Sargenthoward5046

A 12-month exercise program reversibly prevented hip bone loss in premenopausal women with early breast cancer. The bone-protective effect was maintained for 2 years after the end of the program but was lost thereafter.

Breast cancer survivors are at an increased risk for osteoporosis and fracture. This 5-year follow-up of a randomized impact exercise intervention trial evaluated the maintenance of training effects on bone among breast cancer patients.

Five hundred seventy-three early breast cancer patients aged 35-68years and treated with adjuvant therapy were allocated into a 12-month exercise program or a control group. Four hundred forty-four patients (77%) were included in the 5-year analysis. The exercise intervention comprised weekly supervised step aerobics, circuit exercises, and home training. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry. Physical activity was estimated in metabolic equivalent (MET) hours per week and physical performance assessed by 2-km walsal breast cancer patients for 3 years. The bone-protective effect was reversible and lost thereafter.A study of 959 black and white women shows that the normal range for 24-h urine calcium excretion in white women is 30-300 mg and 10-285 mg in black women. Clinical laboratories use a normal range for 24-h urine calcium excretion of 100-300 mg; there is a need for them to update their age- and race-specific ranges.

Recommendations for a normal range for 24-h urine calcium vary from a low of 50 mg to a high of 400 mg; most "laboratory normal ranges" based on older literature are incorrect. The objective of this analysis is to define a normal range for young women age 25-45 years and older women age 55-90 years, white and black, for 24-h urine calcium and calcium/creatinine ratio, and to examine the relationship between 24-h urine calcium, calcium absorption, and vitamin D metabolites.

Data from 3 studies was collected on 959 normal black and white women, ages 25-87 years, for 24-h urine calcium, creatinine, calcium intake, serum 25-hydroxyvitamin D (25OHD),1,25 dihydroxyvitamin D (1,25(OH)

D), and calcium OH)

D calcium intake and calcium absorption, but not serum 25OHD. This range will be useful clinically for defining hypercalciuria and for following patients on vitamin D and calcium treatment.

The normal reference interval for 24-h urine calcium for black women is lower than white women. Twenty-four-hour urine calcium was correlated with serum 1,25(OH)2 D calcium intake and calcium absorption, but not serum 25OHD. This range will be useful clinically for defining hypercalciuria and for following patients on vitamin D and calcium treatment.Acrylamide is a suspected human carcinogen formed during high-temperature cooking of starch-rich foods. It is metabolised by cytochrome P450 2E1 to its reactive metabolite glycidamide, which forms pre-mutagenic DNA adducts. Using the human TP53 knock-in (Hupki) mouse embryo fibroblasts (HUFs) immortalisation assay (HIMA), acrylamide- and glycidamide-induced mutagenesis was studied in the tumour suppressor gene TP53. Selected immortalised HUF clones were also subjected to next-generation sequencing to determine mutations across the whole genome. The TP53-mutant frequency after glycidamide exposure (1.1 mM for 24 h, n = 198) was 9% compared with 0% in cultures treated with acrylamide [1.5 (n = 24) or 3 mM (n = 6) for 48 h] and untreated vehicle (water) controls (n = 36). Most glycidamide-induced mutations occurred at adenines with A > T/T > A and A > G/T > C mutations being the most common types. Mutations induced by glycidamide occurred at specific TP53 codons that have also been found to be mutated in human tumours (i.e., breast, ovary, colorectal, and lung) previously associated with acrylamide exposure. The spectrum of TP53 mutations was further reflected by the mutations detected by whole-genome sequencing (WGS) and a distinct WGS mutational signature was found in HUF clones treated with glycidamide that was again characterised by A > G/T > C and A > T/T > A mutations. The WGS mutational signature showed similarities with COSMIC mutational signatures SBS3 and 25 previously found in human tumours (e.g., breast and ovary), while the adenine component was similar to COSMIC SBS4 found mostly in smokers' lung cancer. check details In contrast, in acrylamide-treated HUF clones, only culture-related background WGS mutational signatures were observed. In summary, the results of the present study suggest that glycidamide may be involved in the development of breast, ovarian, and lung cancer.In 2016, the European Commission launched the EU-ToxRisk research project to develop and promote animal-free approaches in toxicology. The 36 partners of this consortium used in vitro and in silico methods in the context of case studies (CSs). These CSs included both compounds with a highly defined target (e.g. mitochondrial respiratory chain inhibitors) as well as compounds with poorly defined molecular initiation events (e.g. short-chain branched carboxylic acids). The initial project focus was on developing a science-based strategy for read-across (RAx) as an animal-free approach in chemical risk assessment. Moreover, seamless incorporation of new approach method (NAM) data into this process (= NAM-enhanced RAx) was explored. Here, the EU-ToxRisk consortium has collated its scientific and regulatory learnings from this particular project objective. For all CSs, a mechanistic hypothesis (in the form of an adverse outcome pathway) guided the safety evaluation. ADME data were generated from NAMs and used for comprehensive physiological-based kinetic modelling. Quality assurance and data management were optimized in parallel. Scientific and Regulatory Advisory Boards played a vital role in assessing the practical applicability of the new approaches. In a next step, external stakeholders evaluated the usefulness of NAMs in the context of RAx CSs for regulatory acceptance. For instance, the CSs were included in the OECD CS portfolio for the Integrated Approach to Testing and Assessment project. Feedback from regulators and other stakeholders was collected at several stages. Future chemical safety science projects can draw from this experience to implement systems toxicology-guided, animal-free next-generation risk assessment.