Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multicentre nation-wide cohort

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3-13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1-1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1-1.4, P

Multiprofessional and intrahospital experience for diagnosis and treatment of pulmonary arterial hypertension.

Background. Referral centres for pulmonary hypertension will provide care by a multiprofessional team, which should as a minimum comprise: consultant physicians with a special interest in PH, clinical nurse specialist, radiologist, cardiologist with expertise in echocardiography. Aims. this study sought to determine whether the experience of the establishment of a clinic for pulmonary arterial hypertension, initially created only for the treatment and diagnosis of heart failure, may be considered positive. Methods. From 1 July 2008 to January 1, 2012 we evaluated 80 patients in our ambulatory dedicated to the diagnosis and treatment of PAH. All patients were performed to clinical evaluation, ECG, and echocardiography with estimation of the sPAP. Then we evaluated the functional capacity through cardiopulmonary exercise testing or six minute walking test (6MWT). RHC was required to confirm the diagnosis of pulmonary arterial hypertension. Results. 80 patients (mean age: 50.9 ± 18.68 years, 31 males) were evaluated in our center; the largest groups subjected to screening were thalassemia (21 subjects), rheumatologic patients (18 patients), respirators, suspected of "outof Proportion" (12 patients) and 4 patients with OSAS. 8 adult congenital heart patients. A diagnosis of PAH after right heart catheterization was possible in 25 cases. In particular, among patients with pulmonary arterial hypertension, 8 had a rheumatic etiology (systemic sclerosis), 2 postthromboembolic disease, 5 patients had congenital heart disease, 1 patient with HIV infection, 1 patient with thalassemia major, 1 chronic lymphocytic leukemia and 1 with myelodysplasia. Conclusions. The initial experience of our center and network within our hospital may be considered positive, because it permitted to patients easy access to hospital services, to undertake a comprehensive prognostic stratification and to recognize the early signs of worsening in subsequent tests

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Fluorescent Probes for Applications in Bioimaging

Optical bioimaging has played a central role in fundamental research and clinical practice. The signals emitted by biological tissues can provide molecular information about various physiological and pathophysiological processes. NIR light (650–1700 nm) can penetrate the blood and biological tissues more profoundly and effectively because, at longer wavelengths, less light is diffused and absorbed. Therefore, many probes have been developed for bioimaging in the NIR window for real-time, high-sensitivity deep tissue imaging. The library of optical probes has been expanded in recent years to include a wide range of probes with emission in the Red-NIR window. The emergence of these new contrast media has provided an essential alternative for realizing the full potential of bioimaging. The most recent advances in small molecule potential probes for detection and imaging in biological systems are examined below

Yada: a novel tool for molecular docking calculations

Molecular docking is a computational method employed to estimate the binding between a small ligand (the drug candidate) and a protein receptor that has become a standard part of workflow in drug discovery. Generally, when the binding site is known and a molecule is similar to known ligands, the most popular docking methods are rather accurate in the prediction of the geometry. Unfortunately, when the binding site is unknown, the blind docking analysis requires large computational resources and the results are often not accurate. Here we present Yada, a new tool for molecular docking that is capable to distribute efficiently calculations onto general purposes computer grid and that combines biological and structural information of the receptor. Yada is available for Windows and Linux and it is free to download at www.yada.unisa.it

Descriptive Proximities. Properties and Interplay Between Classical Proximities and Overlap

The theory of descriptive nearness is usually adopted when dealing with subsets that share some common properties, even when the subsets are not spatially close. Set description arises from the use of probe functions to define feature vectors that describe a set; nearness is given by proximities. A probe on a nonempty set X is an n-dimensional, real-valued function that maps each member of X to its description. We establish a connection between relations on an object space X and relations on the corresponding feature space. In this paper, the starting point is what is known as (Formula presented.) proximity (two sets are (Formula presented.)-near or (Formula presented.)-descriptively near if and only if their (Formula presented.)-descriptions intersect). We extend, elucidate and explain the connection between overlap and strong proximity in a theoretical approach to a more visual form of proximity called descriptive proximity, which leads to a number of applications. Descriptive proximities are considered on two different levels: weaker or stronger than the (Formula presented.) proximity. We analyze the properties and interplay between descriptions on the one hand and classical proximities and overlap relations on the other hand. Axioms and results for a descriptive Lodato strong proximity relation are given. A common descriptive proximity is an EfremoviÄ\u8d proximity, whose underlying topology is (Formula presented.) (symmetry axiom) and Alexandroff-Hopf. For every description (Formula presented.), any Ä\u8cech, Lodato or EF (Formula presented.)-descriptive proximity is at the same time a Ä\u8cech, Lodato or EF-proximity, respectively. But, the converse fails. A detailed practical application is given in terms of the construction of EfremoviÄ\u8d descriptive proximity planograms, which complements recent operations research work on the allocation of shelf space in visual merchandising. Specific instances of applications of descriptive proximity are also cited

A Water Soluble 2-Phenyl-5-(pyridin-3-yl)-1,3,4-oxadiazole Based Probe: Antimicrobial Activity and Colorimetric/Fluorescence pH Response

The growing demand of responsive tools for biological and biomedical applications pushes towards new low-cost probes easy to synthesize and versatile. Current optical probes are theranostic tools simultaneously responsive to biological parameters/analyte and therapeutically operating. Among the optical methods for pH monitoring, simple small organic molecules including multifunc-tional probes for simultaneous biological activity being highly desired by scientists and technicians. Here, we present a novel pH-responsive probe with a three-ring heteroaromatic pattern and a flexible cationic chain. The novel molecule shows real-time naked-eye colorimetric and fluorescence response in the slightly acidic pH range besides its excellent solubility both in the organic phase and in water. In addition, the small probe shows significant antibacterial activity, particularly against Escherichia coli. Single-crystal X-ray study and density functional theory (DFT) calculations rationalize the molecule spectroscopic response. Finally, molecular dynamics (MD) elucidate the interactions between the probe and a model cell membrane