Bisphenol A is a widely used compound found in large amount of consumer products. As concerns have been raised about its toxicological and public health effect, the use of alternatives to bisphenol A are now increasing. Bisphenol S is one of the analogues being used as a replacement for bisphenol A despite the fact that little is known about the effects of bisphenol S on living organisms. In this study, we investigated the potential endocrine and genotoxic effects of bisphenol A and bisphenol S in juvenile brown trout (Salmo trutta). The fish were exposed to the compounds for either 2 weeks or 8 weeks via sustained-release cholesterol implants containing doses of 2 mg/kg fish or 20 mg/kg fish of the substances. The effects on the thyroid hormone levels and the estrogenic disrupting marker vitellogenin were evaluated, along with the genotoxic markers micronucleated cells and erythrocyte nuclear abnormalities. An increase in plasma vitellogenin was observed in fish exposed to the high dose of bisphenol A for 2 weeks. At this experimental time the level of the thyroid hormone triiodothyronine (T3) in plasma was elevated after bisphenol S exposure at the high concentration, and paralleled by an increase of micronucleated cells. Moreover, bisphenol A induced an increase of micronuclei frequency in fish erythrocytes after the exposure at the lowest dose tested. Taken together the results indicate that both bisphenol A and its alternative bisphenol S cause endocrine disrupting and genotoxic effects in brown trout, although suggesting two different mechanisms of damage underlying bisphenol A and bisphenol S activity.

Two recurrent

(telomerase reverse transcriptase) promoter mutations, C228T and C250T, have been reported in thyroid carcinomas and were correlated with high-risk clinicopathological features and a worse prognosis. Although far more frequent in the poorly differentiated and undifferentiated thyroid cancer, the

promoter mutations play a significant role on PTC recurrence and disease-specific mortality. However, the prevalence varies considerably through studies and it is uncertain if these differences are due to population variation or the methodology used to detect

mutations. In this study we aim to compare three different strategies to detect

promoter mutations in PTC.

DNA was isolated from formalin-fixed paraffin-embedded (FFPE)specimens from 89 PTC and 40 paired lymph node metastases. The prevalence of the hot spot

C228T and C250T mutations was assessed in FFPE samples using TaqMan SNP genotyping assays. Random samples were tested by Sanger Sequencing and droplet digital PCR (ddPCR).

Innd individualized treatment decisions, mainly in highly heterogeneous tumors, require highly sensitive and specific approaches.

This study observed a good concordance among the methodologies used to detect TERT promoter mutations when a high percentage of mutated alleles was present. Sanger analysis demonstrated a limit of detection for mutated alleles. Therefore, the prevalence of TERT promoter mutations in PTC may be higher than previously reported, since most studies have conventionally used Sanger sequencing. Tasquinimod nmr The efficient characterization of genetic alterations that are used as preoperative or postoperative diagnostic, risk stratification of the patient and individualized treatment decisions, mainly in highly heterogeneous tumors, require highly sensitive and specific approaches.

Circulating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined.

In

(n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and

energy intake. In

(n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition.

After adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (β= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7kg (p<0.0001). Lower albumin concentrations were associated with greater weight [β=3.53 kg, p=0.039 (adjusted for age, sex, follow up time), CI 0.16 to 6.21 per 1 g/dl difference albumin concentration] and fat mass (β=2.3 kg, p=0.022), respectively, but not with changes in fat free mass (p=0.06).

Lower albumin concentrations were associated with increased

food intake and weight gain, indicating albumin as a marker of energy intake regulation.

ClinicalTrials.gov, identifiers NCT00340132, NCT00342732.

ClinicalTrials.gov, identifiers NCT00340132, NCT00342732.

To compare metabolic effects of modified release hydrocortisone (MR-HC) with standard hydrocortisone (HC) therapies in adults with Adrenal Insufficiency (AI).

Adult patients (n = 12) with AI, established on HC therapy, were recruited from Endocrinology clinics at University Hospitals Coventry and Warwickshire (UHCW), UK. Baseline (HC) metabolic assessments included fasting serum HbA1C, lipid and thyroid profiles, accurate measures of body composition (BodPod), and 24-h continuous measures of energy expenditure including Sleeping Metabolic Rate (SMR) using indirect calorimetry within the Human Metabolism Research Unit, UHCW. All participants then switched HC to MR-HC with repeat (MR-HC) metabolic assessments at 3 months. Paired-sample t-tests were used for data comparisons between HC and MR-HC assessments P-value <0.05 was considered significant.

Following exclusion of 2 participants, analyses were based on 10 participants. Compared with baseline HC data, following 3 months of MR-HC therapy mean fat mass reduced significantly by -3.2 kg (95% CI -6.0 to -0.4). Mean (SD) baseline HC fat mass vs repeat MR-HC fat mass 31.9kg (15.2) vs 28.7kg (12.8) respectively, P = 0.03. Mean SMR increased significantly by +77 kcal/24h (95% CI 10-146). Mean (SD) baseline HC SMR vs repeat MR-HC SMR 1,517 kcal/24h (301) vs 1,594 kcal/24h (344) respectively, P = 0.03. Mean body fat percentage reduced significantly by -3.4% (95% CI -6.5 to -0.2). Other measures of body composition, energy expenditure, and biochemical analytes were equivalent between HC and MR-HC assessments.

In adults with AI, switching from standard HC to MR-HC associates with early metabolic benefits of reduced fat mass and increased SMR.

In adults with AI, switching from standard HC to MR-HC associates with early metabolic benefits of reduced fat mass and increased SMR.