CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4–32.6, P=0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency.     

Microbiological study on the prognosis of immediate implant and periodontal disease]

AIM: The aim of the present study was to investigate the prevalence of periodontal marker organisms and specific interleukin-1 (IL-1) gene polymorphisms (which show a close association with periodontitis) and their effect on the success of immediate implant placement postextraction in the patient with periodontal disease. PATIENTS AND METHODS: A group of 59 patients (22 men and 37 women aged 20-81 years, median age 55 years, 18 smokers) with chronic adult periodontitis participated in the study which included a 1-year observation period postoperatively. Prior to tooth extraction two DNA samples were obtained for the microbiological diagnosis of five anaerobic gram-negative pathogens (Haemophilus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia sensu stricto, Treponema denticola) and to identify the IL-1 gene polymorphisms. Patients were treated with a total of 95 immediate dental implants (26 Ankylos/Friadent and 69 Camlog Root-Line/Camlog Biotechnologies) placed into extraction sites, 78 of which were loaded immediately. After 1 year four failures were observed; all of these patients were smokers. RESULTS: None of these patients showed a positive IL-1 genotype; periodontal marker organisms were only found in one patient. No significant difference was seen in the microbiological pathogens between smokers and nonsmokers. Of 59 patients, 23 (39%) tested positive for IL-1 genotype polymorphism. Smoking was shown to increase the risk of implant failure. No association was observed between failures and the IL-1 gene polymorphisms or pathogens. CONCLUSION: In conclusion, our study shows that periodontally infected sites do not seem to be a contraindication for immediate implantation.     

Akt signalling through GSK-3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy

Skeletal muscle size is tightly regulated by the synergy between anabolic and catabolic signalling pathways which, in humans, have not been well characterized. Akt has been suggested to play a pivotal role in the regulation of skeletal muscle hypertrophy and atrophy in rodents and cells. Here we measured the amount of phospho-Akt and several of its downstream anabolic targets (glycogen synthase kinase-3β (GSK-3β), mTOR, p70^s6k and 4E-BP1) and catabolic targets (Foxo1, Foxo3, atrogin-1 and MuRF1). All measurements were performed in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. Following resistance training a muscle hypertrophy (∼10%) and an increase in phospho-Akt, phospho-GSK-3β and phospho-mTOR protein content were observed. This was paralleled by a decrease in Foxo1 nuclear protein content. Following the de-training period a muscle atrophy (5%), relative to the post-training muscle size, a decrease in phospho-Akt and GSK-3β and an increase in Foxo1 were observed. Atrogin-1 and MuRF1 increased after the hypertrophy and decreased after the atrophy phases. We demonstrate, for the first time in human skeletal muscle, that the regulation of Akt and its downstream signalling pathways GSK-3β, mTOR and Foxo1 are associated with both the skeletal muscle hypertrophy and atrophy processes.     

Tailoring intervention procedures to routine primary health care practice; an ethnographic process evaluation

Background  

Tailor-made approaches enable the uptake of interventions as they are seen as a way to overcome the incompatibility of general interventions with local knowledge about the organisation of routine medical practice and the relationship between the patients and the professionals in practice. Our case is the Quattro project which is a prevention programme for cardiovascular diseases in high-risk patients in primary health care centres in deprived neighbourhoods. This programme was implemented as a pragmatic trial and foresaw the importance of local knowledge in primary health care and internal, or locally made, guidelines. The aim of this paper is to show how this prevention programme, which could be tailored to routine care, was implemented in primary care.