A novel BRCA2 pathogenic variant c.7094_7100del (p.His2365LeufsTer9) in an Italian family with hereditary breast cancer.

BACKGROUND: Breast cancer is the most common type of malignancy and the foremost cause of tumor-related death in women. The two most well-known genes linked to hereditary breast cancer are BRCA1 (MIM#113705) and BRCA2 (MIM#600185). Germline mutations in the tumor-suppressor genes are found in a proportion of this group. CASE REPORT: Family history of breast and ovarian cancer, early-onset breast cancer, and ethnicity constitute the basic criteria for identifying cases affected by BRCA1 or BRCA2 mutations. This study reports a novel BRCA2 pathogenic variant c.7094_7100del (p.His2365LeufsTer9), identified in a family from Basilicata, Italy, with a history of hereditary breast cancer. Genetic tests are available to predict the risk of developing cancer, particularly in cases of hereditary cancer, the predisposition to cancer, and the target organs. CONCLUSIONS: The identification of this variant expands the spectrum of BRCA2 mutations associated with hereditary breast cancer and highlights the importance of genetic testing and counseling for families with a history of breast cancer.

Accuracy evaluation in temperature-dependent EXAFS measurements of CdTe.

The evaluation of uncertainty in temperature-dependent EXAFS measurements is discussed, considering the specific case of a recent experiment performed on CdTe. EXAFS at both Cd and Te K-edges was measured at different times and at different beamlines in a temperature range from 5 to 300 K. Attention is focused on the nearest-neighbours parameters: bond thermal expansion, parallel and perpendicular mean-square relative displacements and the third cumulant. Different causes of uncertainty, a comparison of experimental results with theoretical models, the difference between EXAFS and crystallographic thermal expansions and the meaning of the third cumulant are discussed.

DJ-1 is a Parkinson's disease susceptibility gene in southern Italy.

Mutations in the gene DJ-1 have been shown to be a rare cause of early-onset Parkinson's disease (EOPD). Since DJ-1 mutations have been found in patients with Parkinson's disease (PD) from southern Italy, we aimed to investigate whether polymorphisms within the DJ-1 gene could represent a risk factor for sporadic PD. First, we genotyped 294 patients with PD and 298 controls coming from southern Italy to assess the distribution of the insertion/deletion (Ins/Del) polymorphism. In a second phase, we identified five single-nucleotide polymorphisms (SNPs) useful to delimit a region potentially involved and genotyped all patients and controls for these markers. All the markers analyzed were significantly associated with PD at both allelic and genotypic level. The most significant association with the disease was found at the Ins/Del polymorphism (p = 0.0001; adjusted odds ratio (OR ) = 2.05; confidence interval (CI ) = 1.36-3.08). When we considered a three-marker sliding window, we found a highly significant association between the disease and the haplotypes including markers rs17523802, Ins/Del, and rs3766606 (p = 0.0007) and markers Ins/Del, rs3766606 and rs7517357 (p = 0.0054). Our results indicate that polymorphisms located in a region spanning 3535 bp from the promoter to the intron 2 of the DJ-1 gene confer risk to sporadic PD in southern Italy.

Thermal expansion of silver iodide-silver molybdate glasses at low temperatures.

Ionic glasses obtained combining silver iodide and silver molybdate are characterized by quite low values of the glass transition temperature T(g) around 320-350 K, by high values of the dc ionic conductivity even at room temperature and by a peculiar behavior of the mechanical response at ultrasonic frequencies. In fact, at temperatures well below their glass transition temperature, these glasses exhibit an intense peak of acoustic attenuation well described by two different and almost overlapping relaxational contributions. Considering also that negative thermal expansion has been reported for some molybdate crystalline compounds, we have investigated in this work the thermal expansion of two silver iodomolybdate glasses (AgI)(1-x)(Ag(2)MoO(4))(x) for x=0.25 and x=0.33 in a wide temperature range (4.2-300 K) from cryogenic temperatures up to some 20 K below T(g) using a precision capacitance dilatometer aiming to understand whether the expansivity shows some possible fingerprint corresponding to the above-mentioned mechanical response. Two different measuring methods, a quasiadiabatic and a continuous one, have been used for the thermal expansion measurements. The results are discussed in comparison with the information obtained from previous investigations based on the extended x-ray absorption fine structure (EXAFS) technique and with the behavior of other ionic glasses.

A new tool for nanoscale X-ray absorption spectroscopy and element-specific SNOM microscopy.

Investigations of complex nanostructured materials used in modern technologies require special experimental techniques able to provide information on the structure and electronic properties of materials with a spatial resolution down to the nanometer scale. We tried to address these needs through the combination of X-ray absorption spectroscopy (XAS) using synchrotron radiation microbeams with scanning near-field optical microscopy (SNOM) detection of the X-ray excited optical luminescence (XEOL) signal. The first results obtained with the prototype instrumentation installed at the European Synchrotron Radiation Facility (Grenoble, France) are presented. They illustrate the possibility to detect an element-specific contrast and to perform nanoscale XAS experiments at the Zn K and W L(3)-absorption edges in pure ZnO and mixed ZnWO(4)/ZnO thin films.

On the origin of the differences in the Cu K-edge XANES of isostructural and isoelectronic compounds.

Cu K-edge x-ray absorption near-edge structure (XANES) spectra of trigonal (3R) CuScO(2) and CuLaO(2) and of hexagonal (2H) CuScO(2) were investigated experimentally and theoretically, in order to study differences between spectra of isostructural and isoelectronic compounds. Significant differences were found in the Cu K-edge XANES of 3R CuScO(2) and 3R CuLaO(2); these differences can be understood by considering the calculated polarization dependence of the XANES spectra and the differences between the phaseshifts of Sc and La. Spectra of the 3R and 2H polytypes of CuScO(2) differ only weakly and the difference originates from the long-range order. The pre-edge peak around 8980 eV is generated by the same mechanism as the pre-edge peak in Cu(2)O, i.e. involving scattering by the Cu atoms in the plane which is perpendicular to the O-Cu-O axis.

[Study by multiplex PCR of Listeria monocytogenes serotypes isolated in Argentine]. / Estudio mediante PCR múltiple de serotipos de Listeria monocytogenes aislados en Argentina.

A multiplex PCR assay, recently validated to characterize the serotypes of Listeria monocytogenes was evaluated in comparison to conventional serotyping. Three hundred forty two L. monocytogenes strains isolated from human, food, animal and environmental sources during the 1992-2005 period were assayed. The concordance between the two methods for serotypes 1/2a, 1/2b and 1/2c was 100%, whereas for serotype 4b it was 98%. Serotyping is a useful tool for first line strain differentiation during epidemiological surveillance and outbreaks. The multiplex PCR assay offers a fast and low-cost alternative, which is easily adaptable to clinical bacteriology and bromatology laboratories.

Alpha-synuclein promoter haplotypes and dementia in Parkinson's disease.

Dementia is a common complication of Parkinson's disease (PD). It correlates significantly with the presence of cortical, limbic or nigral Lewy bodies, mainly constituted of alpha-synuclein. Mutations of the alpha-synuclein gene (SNCA) have been linked to rare familial forms of PD, while association studies on the promoter polymorphisms have given conflicting results in sporadic patients. We have performed a case control study to investigate whether genetic variability in the promoter of the alpha-synuclein gene could predispose to dementia in PD. A total of 114 demented patients and 114 non-demented patients with sporadic PD were included in the study. Six polymorphic loci (including the Rep1 microsatellite) in the promoter of the SNCA gene were examined. Each marker, taken individually, did not show association to dementia and no significant differences were observed in the inferred haplotype frequencies of demented and non-demented patients. Our data suggest the lack of involvement of the SNCA promoter in the pathogenesis of dementia in PD. Further studies in other populations are needed to confirm these results.

Clinical outcome of patients examined by capsule endoscopy for suspected small bowel Crohn's disease.

BACKGROUND: Capsule endoscopy has a greater diagnostic yield than radiology for detecting subtle inflammatory changes of the small bowel mucosa, but the clinical significance of these abnormalities is still uncertain because of the lack of long-term follow-ups. AIM AND METHODS: To verify the accuracy of capsule endoscopy in a cohort of patients with suspected Crohn's disease of the small bowel, taking as 'gold standard' the final diagnosis made after a long follow-up. From April 2002 to March 2005, we enrolled and examined by capsule endoscopy 27 consecutive patients with abdominal pain and diarrhea lasting more than 3 months and at least one of the following: anaemia, weight loss, fever, extra-intestinal manifestation(s) of inflammatory bowel disease. All patients already had an unremarkable pan-endoscopy, serology for celiac disease and intestinal radiology inconclusive for small bowel abnormality. On the basis of capsule endoscopy findings, patients were distributed in three groups; Group A had severe stricturing lesions requiring surgery; Group B, moderate inflammatory lesions further investigated invasively; Group C, minimal inflammatory changes or normal findings, clinically observed every 3 months (median 21 months, range 15-29). RESULTS: Small bowel inflammatory lesions were found in 16 of the 27 patients (diagnostic yield 59%). Three had surgery (Group A) and Crohn's disease was confirmed in two; the remainder had ileal adenocarcinoma in a pathological context of chronic inflammation. Crohn's disease was histologically confirmed in four of the five patients in Group B. Group C comprised 19 patients; Crohn's disease was confirmed in seven out of eight with positive capsule endoscopy, while only one of the patients with normal findings later developed overt ileal Crohn's disease. Sensitivity, specificity, positive and negative likelihood ratio were, respectively, 93%, 84%, 5.8 and 0.08. Assuming a 50% pre-test probability of disease, capsule endoscopy gave a post-test probability of 85%. CONCLUSIONS: In our selected cohort, capsule endoscopy was highly sensitive in detecting small bowel inflammatory changes, enhancing by nearly 35% the pre-test probability of structural small bowel disease. Focal erythema and luminal debris may limit the specificity of capsule endoscopy.

Knowledge about genetics and trust in genetic testing in a mid-size city in Argentina / Conocimiento sobre genética y confianza en pruebas genéticas en una ciudad de tamaño medio en Argentina

ABSTRACT Public attitudes about genetics appear to depend on the local context. We analyzed survey responses obtained in 2015 from 293 residents of Luján, a city in the province of Buenos Aires, Argentina, who self-assessed their knowledge about genetics and their trust in genetic tests. The survey integrated a larger research project for which consenting adult participants shared demographic and genealogical information and provided saliva samples for genetic ancestry analyses. Participants reported little knowledge but high trust in genetic testing when questioned about knowledge and trust. Well-known media stories of DNA-based forensic genetic investigations to identify the victims of state repression during the military dictatorship may have contributed to the high self-assessment of their genetic knowledge expressed by some participants, regardless of educational attainment. Our analysis provides information that could be used as a baseline to begin unraveling the current level of public trust in genetics in a region of the Global South where genetic testing has become widespread, but people's knowledge of and trust in genetics remain poorly studied.

RESUMEN Las actitudes del público sobre la genética parecen depender del contexto local. Analizamos las respuestas de una encuesta suministrada en 2015 a 293 residentes de Luján, una ciudad de la provincia de Buenos Aires, Argentina, quienes autoevaluaron su conocimiento sobre genética y su confianza en las pruebas genéticas. La encuesta integraba un proyecto de investigación más amplio en el que los adultos participantes que dieron su consentimiento compartieron información demográfica y genealógica y proporcionaron muestras de saliva para un estudio de ancestría genética. Cuando se les preguntó sobre su conocimiento y confianza, los participantes informaron tener poco conocimiento sobre genética, pero mucha confianza en las pruebas genéticas. Historias muy conocidas de los medios de comunicación sobre investigaciones genéticas forenses basadas en el ADN para identificar a las víctimas de la represión estatal durante la dictadura militar pueden haber contribuido a la alta autoevaluación del propio conocimiento genético manifestado por algunos participantes, independientemente de su nivel educativo. Nuestro análisis proporciona información que podría utilizarse como base para comenzar a desentrañar los niveles actuales de confianza pública en la genética en una región del Sur Global donde las pruebas genéticas se han generalizado, pero el conocimiento y confianza de las personas sobre genética están poco estudiados.

Cell composition of the human pulmonary valve: a comparative study with the aortic valve--the VESALIO Project. Vitalitate Exornatum Succedaneum Aorticum labore Ingegnoso Obtinebitur.

BACKGROUND: Cell populations present in human semilunar valves have not been investigated thoroughly. The aim of this study was to characterize the cell phenotypes in pulmonary valve leaflets (PVL) in comparison with aortic (AVL) valve leaflets. METHODS: AVL and PVL were dissected from hearts (n = 4) harvested from transplanted patients. Leaflets were processed for immunocytochemistry analysis and Western blotting procedures using a panel of monoclonal antibodies specific for cytoskeletal/contractile antigens. RESULTS: The fibrosa and the ventricularis layers of AVL had a higher cellularity than PVL. In PVL and AVL most cells were reactive for vimentin and nonmuscle (NM) myosin, though vimentin-positive cells were more abundant in AVL than in PVL. Sparse cells positive to anti-smooth muscle (SM) alpha-actin, calponin, and anti-SM myosin antibodies were found only at the outer edge of fibrosa. In Western blotting, AVL and PVL extracts were shown to be equally reactive for vimentin, SM alpha-actin, and NM myosin, whereas both valves were negative for SM myosin and SM22. CONCLUSIONS: Three distinct cell phenotypes have been identified in both valves: fibroblasts, myofibroblasts, and fetal-type SM cells whose distribution is specifically related to the valve layers. Although PVL and AVL cell populations differ quantitatively, some minor qualitative differences exist for vimentin and NM myosin distribution. These data are essential for studies aimed at repopulating valve scaffolds by using tissue engineering technology.

Colorectal cancer metastatic phenotype stimulates production by fibroblasts of N-terminal peptide of type III collagen: clinical implications for prognosis.

In this study we assessed whether the serum levels of the N-terminal peptide of type III collagen (PIIIP), an index of type III collagen synthesis, are influenced by colorectal cancer stage, and whether "in vitro" fibroblast growth and PIIIP production could be altered by tumor tissues obtained from metastatic and nonmetastatic colorectal cancer. 208 colorectal cancer patients (115 colon and 93 rectum) were studied; 54 were stage I, 62 stage II, 37 stage III and 55 stage IV. PIIIP serum levels were significantly higher in stage IV as compared to all other patient groups. The 5-year survival of stage I, stage II, stage III and stage IV patients were 87%, 88%, 32% and 20%, respectively. In the subgroup of stage I and stage II patients considered together, PIIIP (> 0.5 U/ml), but not CEA (> 5 microg/l) serum levels, were predictive for survival. Fibroblast growth was significantly inhibited, while PIIIP production was significantly enhanced, when these cells were conditioned with colorectal cancer homogenates obtained from patients with distant metastases, than from those without distant metastases. In conclusion, colorectal tumors, when metastatic, stimulate fibroblasts' PIIIP synthesis and the serum levels of this peptide might predict patients' outcome after radical surgery.

Kappa light chain deposition disease of the liver.

We report the case of a middle-aged woman presenting epigastric discomfort, hepatomegaly, biochemical signs of cholestasis, bone marrow plasmocytosis and Bence Jones proteinuria. Percutaneous liver biopsy disclosed kappa light chain deposition disease of the liver and fine needle aspiration of abdominal fat showed amyloid substance. Renal blood chemistries and urinalysis were repeatedly normal. To our knowledge, this is the first reported case of kappa light chain deposition disease of the liver and concomitant amyloidosis without renal involvement as the first manifestation of plasma cell dyscrasia. This condition should be considered in the differential diagnosis of intrahepatic cholestatic liver disease.

Structural and optical properties of silicon nanocrystals grown by plasma-enhanced chemical vapor deposition.

Silicon nanocrystals (Si-nc) embedded in SiO2 matrix have been prepared by high temperature thermal annealing (1000-1250 degrees C) of substoichiometric SiOx films deposited by plasma-enhanced chemical vapor deposition (PECVD). Different techniques have been used to examine the optical and structural properties of Si-nc. Transmission electron microscopy analysis shows the formation of nanocrystals whose sizes are dependent on annealing conditions and deposition parameters. The spectral positions of room temperature photoluminescence are systematically blue shifted with reduction in the size of Si-nc obtained by decreasing the annealing temperature or the Si content during the PECVD deposition. A similar trend has been found in optical absorption measurements. X-ray absorption fine structure measurements indicate the presence of an intermediate region between the Si-nc and the SiO2 matrix that participates in the light emission process. Theoretical observations reported here support these findings. All these efforts allow us to study the link between dimensionality, optical properties, and the local environment of Si-nc and the surrounding SiO2 matrix.

[Falls in the elderly]. / Le cadute nell'anziano.

Falls are the main causes of accidental death and disability in elderly people, since they may especially cause hip fractures and a number of related complications. Available incidence estimates are surely in defect, because falls are often omitted both by patients, their family and caregivers. Risk factors may be classified in intrinsic and extrinsic; the former include muscular and osteoarticular diseases or other favouring conditions, whilst the latter include environmental or iatrogenic factors, such as drugs or alcohol consumption. Extrinsic factors may be rapidly modified in the elderly and thus prevented. In fact, prevention of falls is the main intervention of geriatrist, both at patient's home and if patient is hospitalized. In order to reduce the risk of falls, it is sometimes sufficient to stop a treatment or to reduce the doses of drugs causing sedation or orthostatic hypotension, to avoid if possible, the use of sedative-hypnotics, to use non-pharmacological methods for treating insomnia. The introduction of the necessary changes in the environment, the promotion of physical activity, the individuation of the subjects with a high risk of falls and the use of hip protectors are useful means for preventing falls and avoiding their harmful consequences.

Evaluation and use of plant biodiversity for food and pharmaceuticals.

Many epidemiological studies have shown the importance of fruit and vegetables in the human diet so as to prevent the onset of cardiovascular disease and several forms of cancer. The use for food and pharmaceuticals of two of the most widely grown and genetically well-known species in the world, the tomato and the potato, is reviewed. Tomatoes are important sources of vitamin C, potassium, folic acid and carotenoids such as lycopene and beta-carotene. It has been demonstrated that lycopene has anti-oxidant properties and interferes with the growth of cancerous cells. At the Department of Agronomy and Plant Genetics in Portici, interesting results have been obtained with the constitution of stable tomato hybrids having a high content of lycopene and vitamin C. Many of the parental lines used in constituting the hybrids come from interspecific crosses. Potato is also very important in the human diet for its content of high quality proteins, mineral salts and vitamins and it has many medicinal properties. The use of diploid wild species to transfer traits such as high content of vitamin C, mineral salts and high quality proteins into the cultivated potato through ploidy manipulation is discussed.