Combination of lumped hydrological and remote-sensing models to evaluate water resources in a semi-arid high altitude ungauged watershed of Sierra Nevada (Southern Spain).

Assessing water resources in high mountain semi-arid zones is essential to be able to manage and plan the use of these resources downstream where they are used. However, it is not easy to manage an unknown resource, a situation that is common in the vast majority of high mountain hydrological basins. In the present work, the discharge flow in an ungauged basin is estimated using the hydrological parameters of an HBV (Hydrologiska Byråns Vattenbalansavdelning) model calibrated in a "neighboring gauged basin". The results of the hydrological simulation obtained in terms of average annual discharge are validated using the VI-ETo model. This model relates a simple hydrological balance to the discharge of the basin with the evaporation of the vegetal cover of the soil, and this to the SAVI index, which is obtained remotely by means of satellite images. The results of the modeling for both basins underscore the role of the underground discharge in the total discharge of the hydrological system. This is the result of the deglaciation process suffered by the high mountain areas of the Mediterranean arc. This process increases the infiltration capacity of the terrain, the recharge and therefore the discharge of the aquifers that make up the glacial and periglacial sediments that remain exposed on the surface as witnesses of what was the last glaciation.

Pathobiological implications of the d16HER2 splice variant for stemness and aggressiveness of HER2-positive breast cancer.

We have previously shown that the d16HER2 splice variant is linked to HER2-positive breast cancer (BC) tumorigenesis, progression and response to Trastuzumab. However, the mechanisms by which d16HER2 contributes to HER2-driven aggressiveness and targeted therapy susceptibility remain uncertain. Here, we report that the d16HER2-positive mammary tumor cell lines MI6 and MI7, derived from spontaneous lesions of d16HER2 transgenic (tg) mice and resembling the aggressive features of primary lesions, are enriched in the expression of Wnt, Notch and epithelial-mesenchymal transition pathways related genes compared with full-length wild-type (WT) HER2-positive cells (WTHER2_1 and WTHER2_2) derived from spontaneous tumors arising in WTHER2 tg mice. MI6 cells exhibited increased resistance to anoikis and significantly higher mammosphere-forming efficiency (MFE) and self-renewal capability than the WTHER2-positive counterpart. Furthermore, d16HER2-positive tumor cells expressed a higher fraction of CD29High/CD24+/SCA1Low cells and displayed greater in vivo tumor engraftment in serial dilution conditions than WTHER2_1 cells. Accordingly, NOTCH inhibitors impaired mammosphere formation only in MI6 cells. A comparative analysis of stemness-related features driven by d16HER2 and WTHER2 in ad hoc engineered human BC cells (MCF7 and T47D) revealed a higher MFE and aldehyde dehydrogenase-positive staining in d16HER2- vs WTHER2-infected cells, sustaining consistent BC-initiating cell enrichment in the human setting. Moreover, marked CD44 expression was found in MCF7_d16 and T47D_d16 cells vs their WTHER2 and Mock counterparts. Clinically, BC cases from two distinct HER2-positive cohorts characterized by high levels of expression of the activated-d16HER2 metagene were significantly enriched in the Notch family and signal transducer genes vs those with low levels of the metagene.

Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts.

It is established that the interaction between microenvironment and cancer cells has a critical role in tumor development, given the dependence of neoplastic cells on stromal support. However, how this communication promotes the activation of normal (NFs) into cancer-associated fibroblasts (CAFs) is still not well understood. Most microRNA (miRNA) studies focused on tumor cell, but there is increasing evidence of their involvement in reprogramming NFs into CAFs. Here we show that miR-9, upregulated in various breast cancer cell lines and identified as pro-metastatic miRNA, affects the properties of human breast fibroblasts, enhancing the switch to CAF phenotype, thus contributing to tumor growth. Expressed at higher levels in primary triple-negative breast CAFs versus NFs isolated from patients, miR-9 improves indeed migration and invasion capabilities when transfected in immortalized NFs; viceversa, these properties are strongly impaired in CAFs upon miR-9 inhibition. We also demonstrate that tumor-secreted miR-9 can be transferred via exosomes to recipient NFs and this uptake results in enhanced cell motility. Moreover, we observed that this miRNA is also secreted by fibroblasts and in turn able to alter tumor cell behavior, by modulating its direct target E-cadherin, and NFs themselves. Consistently with the biological effects observed, gene expression profiles of NFs upon transient transfection with miR-9 show the modulation of genes mainly involved in cell motility and extracellular matrix remodeling pathways. Finally, we were able to confirm the capability of NFs transiently transfected with miR-9 to promote in vivo tumor growth. Taken together, these data provide new insights into the role of miR-9 as an important player in the cross-talk between cancer cells and stroma.

A subset of genetic susceptibility variants for colorectal cancer also has prognostic value.

We investigated the possible influence of 86 single-nucleotide polymorphisms (SNPs), known to associate with the risk of colorectal cancer (CRC), on overall survival and time to recurrence (TTR) in 733 Italian CRC patients followed up for up to 84 months after surgery. In the Cox multivariate analysis, adjusted for gender, age, pathological stage and adjuvant chemotherapy (yes/no), the risk of death significantly increased by rare allele count (P<0.05) for rs1801133 (MTHFR), rs4939827 (SMAD7), rs2306283 (SLCO1B1) and rs12898159 (BMP4), whereas for rs736775 (GPX3) the opposite was observed. Two additional SNPs associated with TTR, namely rs16892766 (downstream of EIF3H) and rs10749971 (COLCA2). Our findings show that some genetic variants previously found to associate with CRC risk are also associated with survival after treatment. The identification of alleles defining subgroups of patients with worse clinical outcome may have application in developing pharmacogenetic strategies aimed at personalizing CRC treatment.

miR-30e* is an independent subtype-specific prognostic marker in breast cancer.

BACKGROUND: Breast cancer clinical outcome is affected by tumor molecular features, and the identification of subtype-specific prognostic biomarkers is relevant for breast cancer translational research. Gene expression signatures proved to be able to complement prognostic information provided by classical clinico-pathological features. Recently, microRNAs (miRNAs) have been causally linked to tumorigenesis and cancer progression and have been associated with patient outcome, also in breast cancer. METHODS: MicroRNAs associated with the development of distant metastasis were identified in a cohort of 92 ESR1+/ERBB2- lymph node-negative breast cancers from patients not receiving adjuvant treatment. Results were confirmed and further investigated in a total of 1246 miRNA and gene expression profiles of the Molecular Taxonomy of Breast Cancer International Consortium data set. Moderated t-test, univariable and multivariable Cox regression models were used for statistical analyses. RESULTS: miR-30e* was identified as independent protective prognostic factor in lymph node-negative untreated patients with ESR1+/ERBB2- tumours and retained a significant association with a good prognosis in treated patients with the same tumor subtype as well as in the ERBB2+ subtype, but not in ESR1-/ERBB2- tumours. CONCLUSIONS: We highlighted a relevant and subtype-specific role in breast cancer for miR-30e* and demonstrated that adding miRNA markers to gene signatures and clinico-pathological features can help for a better prognostication.

EFFECT OF COPPER OXIDE NANOPARTICLES TO SHEEPSHEAD MINNOW (CYPRINODON VARIEGATUS) AT DIFFERENT SALINITIES.

Nanotechnologies research has become a significant priority worldwide. Many engineered nano-sized materials have been increasingly used in consumer products. But the adverse effects of these nanoparticles on the environment and organisms have recently drawn much attention. The present study investigated the effects of different concentrations of copper oxide nanoparticles (CuO NPs) on the sheepshead minnow (Cyprinodon variegatus) at different salinity regimes, since it is able to withstand a wide range of salinities. The results indicated that CuO NPs could cause behavioral changes in the fish, such as increased mucus secretion, less general activity and loss of equilibrium. No mortality was observed at the presence of CuO NPs during the experiments. But higher oxidative stress was determined at half strength seawater than seawater exposure medium, which can be associated with the decreasing toxicity of CuO NPs as salinity increases. In addition, Cu contents in the tissues of the fish were significantly higher (p<0.05) in the low salinity. The order of Cu accumulation in the fish's organs was intestine > gills > liver.

[Kidney diseases with chronic renal failure in the Italian renal biopsy registries]. / Le nefropatie con insufficienza renale cronica nei registri delle biopsie renali.

The prevalence of chronic renal failure (CRF) at the time of kidney biopsy ranges between 5% and 37% in different renal biopsy registries. This wide variability is mainly dependent on the different definitions of CRF. In the period 1998-2006, the Triveneto Renal Biopsy Registry recorded 816 cases with CRF (defined as serum creatinine persistently > or =1.5 mg/dL), accounting for a prevalence of 27%. At the time of biopsy, the average age and glomerular filtration rate were 54 years and 41 mL/min, respectively; 70% of CRF patients are men and the prevalence of CRF increases with age. IgA nephropathy (IgAN) is the main histological form of glomerulonephritis, accounting for 23% of all cases of CRF. However, in subjects older than 65 years, membranous glomerulonephritis (MG) exceeds IgAN, thus becoming the main diagnosis in elderly patients with renal impairment. With a cutoff value for proteinuria of 3 g/day, the main diagnoses in cases with proteinuria below and above the cutoff are IgAN and MG, respectively. IgAN remains the main histological form of nephropathy throughout all levels of renal failure. These data confirm the findings of the Italian Registry of Renal Biopsies, but correspond only in part with data from other registries. The differences can to a certain extent be explained by the different criteria for the definition of renal impairment, patient selection, and differences in diagnosis among registries.

Genetic mapping of QTLs controlling horticultural traits in diploid roses.

A segregating progeny set of 96 F1 diploid hybrids (2n = 2x = 14) between "Blush Noisette" (D10), one of the first seedlings from the original "Champneys' Pink Cluster", and Rosa wichurana (E15), was used to construct a genetic linkage map of the rose genome following a "pseudo-testcross" mapping strategy. A total of 133 markers (130 RAPD, one morphological and two microsatellites) were located on the 14 linkage groups (LGs) of the D10 and E15 maps, covering total map lengths of 388 and 260 cM, respectively. Due to the presence of common biparental markers the homology of four LGs between parental maps (D10-1/E15-1 to D10-4/E15-4) could be inferred. Four horticulturally interesting quantitative traits, flower size (FS), days to flowering (DF), leaf size (LS), and resistance to powdery mildew (PM) were analysed in the progeny in order to map quantitative trait loci (QTLs) controlling these traits. A total of 13 putative QTLs (LOD > 3.0) were identified, four for FS, two for flowering time, five for LS, and two for resistance to PM. Possible homologies between QTLs detected in the D10 and E15 maps could be established between Fs1 and Fs3, Fs2 and Fs4, and Ls1 and Ls3. Screening for pairwise epistatic interactions between loci revealed additional, epistatic QTLs (EQTLs) for DF and LS that were not detected in the original QTL analysis. The genetic maps developed in this study will be useful to add new markers and locate genes for important traits in the genus providing a practical resource for marker-assisted selection programs in roses.

Role of surgery in the treatment of gastric cancer. Personal experience.

BACKGROUND: Although the decreased incidence of gastric cancer, nevertheless many surgical questions are topical, especially the entity of resection and the extent of lymph node dissection. METHODS: We analyzed retrospectively 38 patients operated for gastric adenocarcinoma in our Surgical Division from January 1997 to December 2001. We excluded cancers of cardia and gastroesophageal junction. We evaluated gastric site, macroscopic and microscopic aspect, TNM staging and grading of gastric cancer (UICC 1997), surgical treatment, postoperative complications and survival, in order to identify the rationale surgical approach to gastric cancer in a suburban hospital. RESULTS: Most of patients affected by gastric cancer were older than 60 years (28/38=73.68%). The cancer was prevalently localized in the antral-pyloric region (21/38=55.27%), in the ulcerated form (27/38=71.05%) and differentiated as intestinal subtype (21/38=55.27%). Regarding the UICC staging we found an almost unvarying distribution, but most of cancers were at stage IV (12/38=31.58%). In 71.05% of cases (27/38) a radical operation was feasible. The most performed operation was a total gastrectomy (19/27=70.37%). We performed a D1 dissection in 85.18% of radical operations (23/27). In the resective surgery we reconstructed the intestinal continuity by a mechanical circular stapler Roux en Y anastomosis. CONCLUSIONS: When possible we perform a total gastrectomy. D1 is our standard lymph node dissection, awaiting a defined D2 role in gastric cancer surgery. In the resective surgery we reconstruct the intestinal continuity by a mechanical circular stapler Roux en Y anastomosis. Morbidity was 10.5% (4/38) and mortality was 7.89% (3/38). Old age and pre-existing pathologies have an important role on surgical outcome. Prognosis of advanced gastric cancer is poor, despite a resective surgical treatment. We emphasize the importance of prevention and early diagnosis as fundamental steps of the oncological gastric surgery.

A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.

To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.

Acute venous thrombosis of spleno-mesenteric portal axis: an unusual localization of thromboembolism in the nephrotic syndrome.

The nephrotic syndrome has been frequently associated with thromboembolic episodes. We report the case of a patient affected by minimal change nephropathy who developed acute thrombosis of the spleno-mesenteric portal axis and partially recovered after thrombolytic and anticoagulant therapy. Unfortunately, the patient died of pulmonary embolism after suspension of the anticoagulant therapy for gastrointestinal bleeding.

[Analysis of 101,379 cases hospitalized for calculi of the bile dusts in the Region of Piedmont]. / Analisi su 101,379 casi di ricovero ospedaliero per patologia litiasica biliare nella Regione Piemonte.

In a study from hospitals in Piemonte (Italy) were identified (from 1976 to 1981) 101,379 recovery for cholelitiasis. Among this group we have examined some factors like sex, age, residence, surgical procedures, etc. It is concluded that there is a continuous decreased in cholecistectomy rate and that can be explained by a simultaneous rise of new instrumental and farmacological procedures in the treatment of this pathology.

Long-term monitoring of renal transplant patients by a CUSUM test on serum creatinine.

A retrospective clinical assessment of kidney function change was performed on 38 kidney transplant patients over a median follow-up period of 128 weeks. Full records of the patients' course were available to the clinician, while only the serum creatinine series of each patient was supplied to the computer on which a bilateral CUSUM test was implemented. The frequency of change assessed by the clinician was 146 out of 2,688 patient-weeks. The computer identified the function changes with 84.9% sensitivity and 94.3% specificity and the function deteriorations attributed to rejection with 88.9% sensitivity and 97.2% specificity. Thus we suggest an efficient long-term monitoring of the graft function with this simple and reliable statistical technique.