Prenatal Exposure to Perfluoroalkyl Acids and Serum Testosterone Concentrations at 15 Years of Age in Female ALSPAC Study Participants

Background: Exposure to perfluorooctane sulfonic acid (PFOS) or to perfluorooctanoic acid (PFOA) increases mouse and human peroxisome proliferator–activated receptor alpha (PPARα) subtype activity, which influences lipid metabolism. Because cholesterol is the substrate from which testosterone is synthesized, exposure to these substances has the potential to alter testosterone concentrations. Objectives: We explored associations of total testosterone and sex hormone–binding globulin (SHBG) concentrations at age 15 years with prenatal exposures to PFOS, PFOA, perfluorohexane sulfonic acid (PFHxS), and perfluoronanoic acid (PFNA) in females. Methods: Prenatal concentrations of the perfluoroalkyl acids (PFAAs) were measured in serum collected from pregnant mothers at enrollment (1991–1992) in the Avon Longitudinal Study of Parents and Children (ALSPAC). The median gestational age when the maternal blood sample was obtained was 16 weeks (interquartile range, 11–28 weeks). Total testosterone and SHBG concentrations were measured in serum obtained from their daughters at 15 years of age. Associations between prenatal PFAAs concentrations and reproductive outcomes were estimated using linear regression models (n = 72). Results: Adjusted total testosterone concentrations were on average 0.18-nmol/L (95% CI: 0.01, 0.35) higher in daughters with prenatal PFOS in the upper concentration tertile compared with daughters with prenatal PFOS in the lower tertile. Adjusted total testosterone concentrations were also higher in daughters with prenatal concentrations of PFOA (β = 0.24; 95% CI: 0.05, 0.43) and PFHxS (β = 0.18; 95% CI: 0.00, 0.35) in the upper tertile compared with daughters with concentrations in the lower tertile. We did not find evidence of associations between PFNA and total testosterone or between any of the PFAAs and SHBG. Conclusions: Our findings were based on a small study sample and should be interpreted with caution. However, they suggest that prenatal exposure to some PFAAs may alter testosterone concentrations in females

Elucidating an amorphous form stabilization mechanism of tenapanor hydrochloride: crystal structure analysis using Xray diffraction, NMR crystallography and molecular modelling

By the combined use of powder and single crystal X-ray diffraction, solid-state NMR, and molecular modelling, the crystal structures of two systems containing the unusually large tenapanor drug molecule have been determined: the free form, ANHY and a dihydrochloride salt form, 2HCl. Dynamic nuclear polarization (DNP) assisted solid-state NMR (SSNMR) crystallography investigations were found essential for the final assignment, and were used to validate the crystal structure of ANHY. From the structural informatics analysis of ANHY and 2HCl, conformational ring differences in one part of the molecule were observed which influences the relative orientation of a methyl group on a ring nitrogen and thereby impacts the crystallizability of the dihydrochloride salt. From quantum chemistry calculations, the dynamics between different ring conformations in tenapanor is predicted to be fast. Addition of HCl to tenapanor results in general in a mixture of protonated ring conformers and hence a statistical mix of diastereoisomers which builds up the amorphous form, a-2HCl. This was qualitatively verified by 13C CP/MAS NMR investigations of the amorphous form. Thus, to form any significant amount of the crystalline material 2HCl, which originates from the minor (i.e., energetically less stable) ring conformations, one needs to involve nitrogen deprotonation to allow exchange between minor and major conformations of ANHY in solution. Thus, by controlling the solution pH value to well below the pKa of ANHY, the equilibrium between ANHY and 2HCl can be controlled and by this mechanism the crystallization of 2HCl can be avoided and the amorphous form of the dichloride salt can therefore be stabilized

Risk perception of arsenic exposure from rice intake in a UK population

In the UK, consumption of rice and rice-based products is on the rise but, notwithstanding public expressed concerns about such products as an exposure route for arsenic (e.g. BBC News report, 2017“Should I worry about arsenic in my rice?”) there are few, if any published data on public perceptions of risks associated with exposure to arsenic in rice. We therefore aimed to determine the risk perception of arsenic exposure from rice intake and factors that are associated with arsenic knowledge and whether or not this knowledge had an influence on rice consumption and cooking practices. A questionnaire, targeting participation of rice-eating ethnic minorities in Greater Manchester, UK, was administered to 184 participants. A multivariate generalized linear model was used to determine the factors associated with rice consumption behaviour, cooking practices, and risk perception. We show for the first time that the general population did not associate arsenic, which they perceive as toxic to health, with rice consumption. More than half of the participants knew about arsenic as a hazardous substance but less than ten percent knew that rice consumption could be an important route of arsenic exposure. Knowledge of arsenic was significantly lower in Asian/Asian British:Pakistanis (Pakistani) (OR: 0.006; 95% CI:0.00-0.03) and Asian/Asian British:Bangladeshis (Bangladeshi) (OR: 0.064; 95% CI:0.01-0.25) compared to White:English/Welsh/Scottish/Northern Irish/British (White British). Moreover, Bangladeshis consumed three times more rice (OR: 2.92; 95% CI:1.73-4.93) compared to White British. Overall higher rice consumption was not associated with higher knowledge of the nutritional value of rice. Rinsing rice before cooking, an effective arsenic removal technique, was practised by 93% of the participants, however the most popular cooking method was the use of adequate water (rice to water ratio of 1:2) but not excess water (rice to water ratio of > 1:4), the latter being more effective in removing arsenic. Better education, higher weekly expenditure on food and prior knowledge of arsenic hazard were all significant factors positively influencing a change in behaviour to reduce arsenic exposure from rice intake

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

A Multi-Individual Pharmacokinetic Model Framework for Interpreting Time Trends of Persistent Chemicals in Human Populations: Application to a Postban Situation

Ba c k g r o u n d: Human milk and blood are monitored to detect time trends of persistent organic pollutants (POPs) in humans. It is current practice to use log-linear regression to fit time series of averaged cross-sectional biomonitoring data, here referred to as cross-sectional trend data (CSTD). O b j e c t i v e: The goals of our study are to clarify the interpretation of half-lives derived from fitting exponential functions to declining CSTD and to provide a method of estimating human elimina-tion half-lives from CSTD collected in a postban situation. M e t h o d s: We developed a multi-individual pharmacokinetic model framework and present analytical solutions for a postban period. For this case, the framework quantitatively describes the relationships among the half-life for reduction of body burdens of POPs derived from CSTD, the half-life describing decline in daily intake, and the half-life of elimination from the human body. R e s u l t s: The half-life derived from exponential fitting of CSTD collected under postban conditions describes the exposure trend and is independent of human elimination kinetics. We use a case study of DDT (dichlorodiphenyltrichloroethane) to show that CSTD can be combined with exposure data obtained from total diet studies to estimate elimination kinetics of POPs for humans under background exposure conditions. C o n c l u s i o n s: CSTD provide quantitative information about trends in human exposure and can be combined with exposure studies to estimate elimination kinetics. The full utility of these data has not been exploited so far. An efficient and informative monitoring strategy for banned POPs in humans would coordinate sampling of consistent sets of CSTD from young adults with total diet studies.ISSN:1552-9924ISSN:0091-676

Twenty-four hours secretion pattern of serum estradiol in healthy prepubertal and pubertal boys as determined by a validated ultra-sensitive extraction RIA

<p>Abstract</p> <p>Background</p> <p>The role of estrogens in male physiology has become evident. However, clinically useful normative data for estradiol secretion in boys has not previously been established due to the insensitivity of current methods used in clinical routine. By use of a validated ultra-sensitive extraction RIA, our aim was to establish normative data from a group consisting of healthy boys in prepuberty and during pubertal development.</p> <p>Methods</p> <p>Sixty-two 24-hours serum profiles (6 samples/24 hours) were obtained from 44 healthy boys (ages; 7.2–18.6 years) during their pubertal development, classified into five stages: prepuberty (testis, 1–2 mL), early (testis, 3–6 mL), mid (testis, 8–12 mL), late-1 (testis,15–25 mL, not reached final height) and late-2 (testis,15–25 mL, reached final height). Serum estradiol was determined by an ultra- sensitive extraction radioimmunoassay with detection limit 4 pmol/L and functional sensitivity 6 pmol/L.</p> <p>Results</p> <p>Mean estradiol concentrations during 24-hours secretion increased from prepuberty (median: <4 (5–95 percentiles: <4 – 7) pmol/L) to early puberty (6 (<4 – 12 pmol/L) but then remained relatively constant until a marked increase between mid-puberty (8 (4 – 17) pmol/L) and late-1 (21 (12 – 37) pmol/L) puberty, followed by a slower increase until late-2 puberty (32 (20 – 47) pmol/L). The diurnal rhythm of serum estradiol was non-measurable in pre- and early puberty, but discerned in mid-puberty, and become evident in late pubertal stages with peak values at 0600 to 1000 h.</p> <p>Conclusion</p> <p>With the use of an ultra-sensitive extraction RIA, we have provided clinically useful normative data for estradiol secretion in boys.</p

Contaminants and minerals in foods for infants and young children. Part 3, Risk and benefit management

In the present survey the National Food Agency (NFA) analysed and assessed contaminants and minerals in infant formulae and certain foods for children. The analysed items cover the relevant products from all producers present in the Swedish market in spring 2011. In total 92 different products were analysed for arsenic, cadmium and lead unintentionally present in foods, so-called contaminants, as well as the essential minerals manganese, iron and copper

Resmål och potential för kollektivtrafik till och från södra Askim/Hovås/Billdal

Detta arbete tittar på områden i sydvästra Göteborg, specifikt Askim, Hovås och Billdal, vars nyttjande av kollektivtrafik är lågt jämfört med liknande områden kring Göteborg. Arbetet undersöker orsaker till detta, vilka brister som kan finnas hos kollektivtrafiken i området och tittar sedan på potentiella åtgärder. Inledningsvis identifierades anledningarna till det låga utnyttjandet av kollektivtrfiken. Detta gjordes genom kontakt med lokalbefolkningen och andra parter med intressen i området. Deltagande i forskningsprojektet MOSAIC - The Gathering möjliggjorde konversationer med människor från olika delar av samhället som bor och verkar i området. Intervjuer med lokalpolitikerna Axel Josefson (M) och Leif Blomqvist (S) har också genomförts. Enkäter har skickats ut online till grupper med personer med intresse i området. Med hjälp av den insamlade datan och en studie av tidigare forskning på liknande problem runt om i världen har ett antal potentiella lösningar tagits fram och deras möjlighet till tillämpning i sydvästra Göteborg har undersökts. Den främst återkommande anledningen till att bilen väljes är långa restider till destinationer belägna runt omkring centrala Göteborg. På grund av detta undersöks möjliga direktförbindelser till de närliggande knutpunkterna Frölunda torg och Mölndal centrum. En annan idé som undersökts är att förenkla kombination av färdmedel, exempelvis att cykla till busshållplatsen. Ökad avgångsfrekvens på linje 82 undersöks också. Detta kombineras med avlägsnande av hållplatser som idag utnyttjas ytterst lite. Slutligen föreslås en kombination av ovanstående åtgärder som tillsammans kan öka attraktiviteten hos kollektivtrafiken i sydvästra Göteborg

The Public Domain

Background/Aims: Growth Hormone (GH) dosage in childhood is adjusted for body size, but there is no consensus whether body weight (BW) or body surface area (BSA) should be used. We aimed at comparing the biological effect and cost-effectiveness of GH treatment dosed per m(2) BSA in comparison with dosing per kg BW in girls with Turner syndrome (TS). Methods: Serum IGF-I, GH dose, and adult height gain (AHG) from girls participating in two Dutch and five Swedish studies on the efficacy of GH were analyzed, and the cumulative GH dose and costs were calculated for both dose adjustment methods. Additional medication included estrogens (if no spontaneous puberty occurred) and oxandrolone in some studies. Results: At each GH dose, the serum IGF-I standard deviation score remained stable over time after an initial increase after the start of treatment. On a high dose (at 1 m(2) equivalent to 0.056-0.067 mg/kg/day), AHG was at least equal on GH dosed per m(2) BSA compared with dosing per kg BW. The cumulative dose and cost were significantly lower if the GH dose was adjusted for m(2) BSA. Conclusion: Dosing GH per m(2) BSA is at least as efficacious as dosing per kg BW, and is more cost-effective. (c) 2014 S. Karger AG, Basel

Resmål och potential för kollektivtrafik till och från södra Askim/Hovås/Billdal

Detta arbete tittar på områden i sydvästra Göteborg, specifikt Askim, Hovås och Billdal, vars nyttjande av kollektivtrafik är lågt jämfört med liknande områden kring Göteborg. Arbetet undersöker orsaker till detta, vilka brister som kan finnas hos kollektivtrafiken i området och tittar sedan på potentiella åtgärder. Inledningsvis identifierades anledningarna till det låga utnyttjandet av kollektivtrfiken. Detta gjordes genom kontakt med lokalbefolkningen och andra parter med intressen i området. Deltagande i forskningsprojektet MOSAIC - The Gathering möjliggjorde konversationer med människor från olika delar av samhället som bor och verkar i området. Intervjuer med lokalpolitikerna Axel Josefson (M) och Leif Blomqvist (S) har också genomförts. Enkäter har skickats ut online till grupper med personer med intresse i området. Med hjälp av den insamlade datan och en studie av tidigare forskning på liknande problem runt om i världen har ett antal potentiella lösningar tagits fram och deras möjlighet till tillämpning i sydvästra Göteborg har undersökts. Den främst återkommande anledningen till att bilen väljes är långa restider till destinationer belägna runt omkring centrala Göteborg. På grund av detta undersöks möjliga direktförbindelser till de närliggande knutpunkterna Frölunda torg och Mölndal centrum. En annan idé som undersökts är att förenkla kombination av färdmedel, exempelvis att cykla till busshållplatsen. Ökad avgångsfrekvens på linje 82 undersöks också. Detta kombineras med avlägsnande av hållplatser som idag utnyttjas ytterst lite. Slutligen föreslås en kombination av ovanstående åtgärder som tillsammans kan öka attraktiviteten hos kollektivtrafiken i sydvästra Göteborg