Risk assessment of treated municipal wastewater reuse in Sicily.

In Italy, the restrictive approach for treated wastewater reuse in agriculture has led to some difficulties in promoting this practice. In order to assess the health risk associated with the use of wastewater in agriculture, an experiment was conducted in an open field near the constructed wetland (CW) system of San Michele di Ganzaria (Eastern Sicily), during the irrigation seasons 2004-2009. In particular the impact on tomato crops of drip and sub-drip irrigation with treated municipal wastewater, as well as effects of wastewater reuse on the irrigation system, main production features, hydrological soil behaviour, and microbial soil and products contamination were investigated. Notwithstanding the fact that globally CW effluents did not match microbiological standards for wastewater reuse of Italian legislation, the median infection risk (function of the recommended tolerable additional disease burden of 10(-6) DALY (disability-adjusted life year) loss per person per year) suggested by the 2006 World Health Organization Guidelines for rotavirus, Campylobacter and Cryptosporidium for lettuce irrigation under unrestricted irrigation scenario was achieved.

Appropriate management of cutaneous adverse events maximizes compliance with sorafenib treatment: a single-center experience.

AIMS: This report describes a positive experience of adverse event (AE) management of a multidisciplinary clinical team and 18 patients with late-stage renal cell carcinoma and hepatocellular carcinoma attending the Day Hospital Unit of the 'Centro Catanese di Oncologia Humanitas' (Italy) over a 2-year period. METHODS: The management strategy was based on preventive measures for reducing the development of cutaneous AEs, including pain, risk of infection and patient discomfort, while avoiding the discontinuation or the reduction of the sorafenib dosage. RESULTS: As of July 2011, eight patients were still under treatment with sorafenib; seven patients experienced cutaneous AEs and two reported severe cutaneous AEs. CONCLUSION: Our treatment approach seemed to reduce the incidence and/or severity of AEs, keeping patients in treatment, which is essential for good treatment outcomes.

Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study.

Recent studies have reported the potential clinical utility for metastatic breast cancer (MBC) patients of continuing trastuzumab beyond progression. Based on those results, here the authors have examined the benefits of trastuzumab-continuation by specifically evaluating RECIST responses upon first line trastuzumab-treatment as a potential predictive marker for therapeutic effect of trastuzumab-continuation beyond metastatic disease progression. The authors carried out a retrospective analysis of 272 HER2 positive MBC patients under trastuzumab treatment at 22 different oncology Italian centers during the years of 2000 and 2001 who progressed under first line trastuzumab-treatment. The primary end point of the study was the survival from the date of first documented progression upon first line trastuzumab treatment of disease. Data analysis involved the use of matching on propensity score to balance variables between treated and untreated subjects and to reduce bias. Of the 272 HER2-positive MBC patients, 154 (56.6%) continued treatment. 79 (51.3%) of those 154 patients showed responses based on RECIST criteria during first-line trastuzumab-treatment. Of the 118 patients that suspended trastuzumab, RECIST responses had been observed in 44 (37.3%). Cox proportional hazards analysis of progressed patients, matched using propensity score, showed that discontinuation of trastuzumab at metastatic disease progression was a risk factor for significantly reduced overall survival in both responder (HR = 2.23; 95% CI = 1.03-4.82) and non-responder groups (HR = 3.53, 95% CI = 1.73-7.21), with no significant differences in the two estimated HRs (P-value of the likelihood-ratio test = 0.690). Continued trastuzumab treatment after disease progression has clinically and statistically significant effects in both RECIST responder and non-responder MBC patients.

Structure of the cytosolic portion of the motor protein prestin and functional role of the STAS domain in SLC26/SulP anion transporters.

Prestin is the motor protein responsible for the somatic electromotility of cochlear outer hair cells and is essential for normal hearing sensitivity and frequency selectivity of mammals. Prestin is a member of mammalian solute-linked carrier 26 (SLC26) anion exchangers, a family of membrane proteins capable of transporting a wide variety of monovalent and divalent anions. SLC26 transporters play important roles in normal human physiology in different tissues, and many of them are involved in genetic diseases. SLC26 and related SulP transporters carry a hydrophobic membrane core and a C-terminal cytosolic portion that is essential in plasma membrane targeting and protein function. This C-terminal portion is mainly composed of a STAS (sulfate transporters and anti-sigma factor antagonist) domain, whose name is due to a remote but significant sequence similarity with bacterial ASA (anti-sigma factor antagonist) proteins. Here we present the crystal structure at 1.57 A resolution of the cytosolic portion of prestin, the first structure of a SulP transporter STAS domain, and its characterization in solution by heteronuclear multidimensional NMR spectroscopy. Prestin STAS significantly deviates from the related bacterial ASA proteins, especially in the N-terminal region, which-although previously considered merely as a generic linker between the domain and the last transmembrane helix-is indeed fully part of the domain. Hence, unexpectedly, our data reveal that the STAS domain starts immediately after the last transmembrane segment and lies beneath the lipid bilayer. A structure-function analysis suggests that this model can be a general template for most SLC26 and SulP anion transporters and supports the notion that STAS domains are involved in functionally important intramolecular and intermolecular interactions. Mapping of disease-associated or functionally harmful mutations on STAS structure indicates that they can be divided into two categories: those causing significant misfolding of the domain and those altering its interaction properties.

The crystal structure of the superoxide dismutase from Helicobacter pylori reveals a structured C-terminal extension.

Superoxide dismutases (SODs) are key enzymes for fighting oxidative stress. Helicobacter pylori produces a single SOD (HpSOD) which contains iron. The structure of this antioxidant protein has been determined at 2.4 A resolution. It is a dimer of two identical subunits with one iron ion per monomer. The protein shares 53% sequence identity with the corresponding enzyme from Escherichia coli. The model is compared with those of other dimeric Fe-containing SODs. HpSOD shows significant differences in relation to other SODs, the most important being an extended C-terminal tail. This structure provides a model for closely related sequences from species such as Campylobacter, where no structures are currently known. The structure of extended carboxyl termini is discussed in light of putative functions it may serve.

Combined endothelin receptor antagonist and transcatheter interventional therapy of patent ductus arteriosus with severe pulmonary artery hypertension.

The natural history of congenital heart disease (CHD) with left to right shunt and high pulmonary blood flow, is characterized by development of severe Pulmonary Artery Hypertension (PAH); this condition usually contraindicates any type of surgical or interventional cardiac correction because of bad results. We here report the case of an adult patient with a patent ductus arteriosus and severe PAH, treated uneventfully with a staged combined therapy: Bosentan for 3 months and then percutaneous closure with amplatzer duct occluder (AGA Med. Co. Golden Valley, MN). The patient showed a dramatic improvement both of pulmonary hemodynamics and functional capacity at 8 months follow up confirming the efficacy of pulmonary vasodilator therapy in PAH associated to congenital heart disease.