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Familial adenomatous polyposis (FAP) is a rare genetic disorder caused mainly by monoallelic mutations of APC gene. The hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominantly inherited disease, which mostly predisposes to breast and ovarian cancers as a result of germline mutations in BRCA1 or BRCA2 genes. In a family, mutations in two cancer susceptibility genes are extremely rare. We studied a family with a case of a 46 years-old woman affected with FAP and ovarian cancer. The patient was affected with profuse FAP since the age of 18 years and a serous ovarian cancer was diagnosed at the age of 45 years. She reported other FAP cases and one case of breast cancer in maternal family. Initially, she was tested for FAP predisposition with mutational analysis of APC gene that revealed the presence of a frameshift mutation, c.3927_3931delAAAGA (p.Glu1309AspfsX4). The presence of ovarian cancer in the patient and of a breast cancer case in the maternal family, suggested an extended analysis to HBOC susceptibility genes that led to the detection of a frameshift mutation, c.3756_3759delGTCT (p.Ser1253Argfs), in BRCA1 gene. The genetic analysis was extended also to family members. The occurrence of the double mutation in APC and BRCA1 genes in the patient was responsible for the onset of FAP and ovarian cancer respectively. The genetic counselling in hereditary cancer with a careful analysis of the pedigree allows identifying the gene to be analyzed. The development of multi-gene panels testing for cancer predisposition, with next generation sequencing (NGS), may reveal mutations in genes of high and moderate penetrance for cancer, although at a low frequency and allows diagnosing a possible double heterozygosity. This enables an adjusted treatment for the affected patient and is critical as it allows initiation of early risk-reducing measures for identified mutation carriers among family members.

Serum concentrations of interleukin-6 (IL-6), IL-6-soluble receptor (sIL-6R), IL-6 gp130-soluble receptor (sgp130), ligand of receptor activator of nuclear factor (NF)-kappaB (RANKL), and osteoprotegerin (OPG) were determined in 42 patients with polyostotic Paget's disease of bone (PDB) and acquired resistance to clodronate (M/F ratio 23:19; mean age 58.5 +/- 9.4 years) in acute phase of disease and after oral risedronate treatment (30 mg/day for 8 weeks). At baseline, pagetic patients showed higher levels of OPG, sIL-6R, and IL-6 with lower levels of sgp130 compared to 24 age- and sex-matched controls (respectively, 4.69 +/- 1.27 vs. 2.87 +/- 0.54 pmol/L; 40.89 +/- 8.61 vs. 30.98 +/- 4.24 ng/ml; 3.59 +/- 0.97 vs. 1.8 +/- 0.9 pg/ml; 327.34 +/- 43.41 vs. 411.7 +/- 79.5 ng/ml). Response to treatment is related to a significant increase of OPG levels in all patients (from 4.69 +/- 1.27 to 5.48 +/- 1.31 pmol/L). The disease remission, that is, total alkaline phosphatase (tALP) levels within the normal range after therapy, was associated with a simultaneous increase in OPG and sgp130 levels. In patients with tALP higher than the normal range after therapy, the OPG increase was associated with a parallel increase in RANKL levels. Our data suggest that serum levels of components of RANKL/OPG and IL-6 systems, before and after treatment, may be used to better define a therapeutical strategy in pagetic patients.

The aim of this paper is to advance the numerical investigation of unsteady thermocapillary migration of gas bubbles in a fully confined non-isothermal liquid. The relevance of the study is twofold: to support space experiments such as the Italian experiment on board of the Spacelab IML-2 Mission and to fill a lack in thermocapillary migration studies mainly devoted to slow motion in infinite medium (so that no comparison is possible with experimental results). The motion due to surface tension gradients of one and two spherical bubbles inside a liquid filling a cylindrical box, with differentially heated ends disks, is herein analysed, both for linear and quadratic temperature dependence of the surface tension at the bubble-liquid interface. A Galerkin finite elements method is employed to solve the unsteady axisymmetric governing equations casted under a velocity, vorticity, temperature formulation. The flow field into the liquid medium, the net force exerted on the bubbles, the bubbles speed and location are determined as a function of the time; pressure and temperature fields around the bubble are reported.