Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

<p>Abstract</p> <p>Background</p> <p>Two high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the <it>CDK4 </it>gene reported to date. Beside those high penetrance genes, certain allelic variants of the <it>MC1R </it>gene modify the risk of developing the disease.</p> <p>The aims of our study were: to determine the prevalence of germline <it>CDKN2A </it>mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible <it>CDK4 </it>mutations, and to determine the frequency of variations in the <it>MC1R </it>gene.</p> <p>Methods</p> <p>From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing.</p> <p>Results</p> <p>Seven families with CDKN2A mutations were discovered (7/25 or 28.0%). The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54). One p14ARF variant was discovered in the control group and no mutations of the <it>CDK4 </it>gene were found.</p> <p>Most frequently found variants of the <it>MC1R </it>gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant.</p> <p>Conclusion</p> <p>The present study has shown high prevalence of p16INK4A mutations in Slovenian population of familial melanoma patients (37%) and an absence of p14ARF or <it>CDK4 </it>mutations.</p

Strength properties of Scots pine from harbour piles degraded by erosion bacteria

140-year-old Scots pine piles displaying various levels of degradation by erosion bacteria were excavated from the harbour of Hamburg and investigated. Bending and compression strength correlated to the basic density, moisture content and lignin content. The compression strength was determined both on samples with dimensions of 30 mm × 20 mm × 20 mm and using 6.6 mm-increment cores taken perpendicular to the grain direction. Both sizes of the samples showed almost identical results. The sapwood of all samples was completely water-saturated; the heartwood did not even achieve 50% water saturation. The sapwood samples showed a good correlation between moisture content and strength properties, whereas basic density correlated well with the strength properties of both sapwood and heartwood. With increasing bacterial attack and resulting lower basic density, the lignin content increased in relation to holocellulose. The measured lignin content of the sapwood showed a good conformity with all strength properties. Determination of the lignin content represents an alternative method for predicting strength values of waterlogged wood while leaving most of the test material intact

Nutritional predictors of early mortality in incident hemodialysis patients

Low serum albumin concentration and low dietary protein intake are associated with protein-energy wasting (PEW) and higher mortality in maintenance hemodialysis patients. The role of these nutritional markers is less clear in clinical outcomes of the first several months of dialysis therapy, where mortality is exceptionally high. In a cohort of 17,445 incident hemodialysis patients, we examined variation in serum albumin and the normalized protein catabolic rate (nPCR), a surrogate of dietary intake, and quarterly mortality in the first 2 years of dialysis therapy. Cox proportional hazard models were fitted to estimate the association between mortality and combined albumin/nPCR categories for eight quarters. We investigated the associations between mortality and baseline and subsequent serum albumin levels per cohort quarter as well as changes in albumin and nPCR over time. Patients were 64 +/- A 15 years old (mean +/- A SD) and included 45 % women, 24 % African Americans and 58 % diabetics. Correlations between quarterly serum albumin and nPCR varied from 0.18 to 0.25. Serum albumin +0.2 g/kg/day) showed reverse effect on mortality from the 2nd to the last quarter. Low serum albumin and nPCR are associated with mortality. A rapid rise in nPCR by the end of the second year may indicate pre-existing PE