Heart Failure and Biomarkers. Unravelling new pathophysiological pathways, outcome predictors, and therapeutic targets.

The present thesis, result of the international experience I had during the last 3 years in the context of the International Philosophiæ Doctor programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh), disserts on the known and unknown role of biomarkers in HF. The thesis is divided in several chapter, each of them dwelling upon specific aspects that have been investigated during the 3 years of my PhD curriculum. After a generalist paragraph dwelling upon the use of biomarkers in HF, its associated diseases, and the argument around the dilemma of racial differences (chapter 2), the important and emerging role of hormone deficiencies (HD), alone ore combined in the multiple hormone deficiency syndrome (MHDS) is discussed (chapter 3), together with the presentation of the results of the main project of my PhD, the T.O.S.CA. project, an international effort aimed to investigate the role of MHDS in HF. The following chapter (chapter 4) is based on the even strong relationship between the heart and the gut (the so-called Gut Axis), followed by a chapter showing the possible role of novel biomarkers in HF (chapter 5). In conclusion, a last chapter about my other HF research activity (not strictly related to biomarkers) is present

Cardiovascular abnormalities and impaired exercise performance in adolescents with congenital adrenal hyperplasia

Context: Patients with classic Congenital Adrenal Hyperplasia (CAH) are treated with lifelong glucocorticoids (GCS). Cardiovascular (CV) and metabolic effects of such therapy in adolescents have never been quantified. Objective: To investigate left ventricular (LV) morphology, function and exercise performance in adolescents with CAH. Design and Setting: cross-sectional and controlled study conducted at a tertiary referral centre. Patients: Twenty patients with classic CAH (10 females) aged 13.6±2.5 years and 20 healthy controls comparable for sex and pubertal status were enrolled in the study and compared to a group of 18 patients without CAH receiving a similar dose of GCS for Juvenile Idiopathic Arthritis (JIA). Main Outcomes Measures: Echocardiographic assessment and symptom-limited exercise testing were performed. Anthropometric, hormonal and biochemical parameters were also measured. Results: Compared to healthy controls, patients with CAH exhibited an increased BMI (p<0.001), waist-to-height ratio (p<0.001), percentage of body fat (p<0.001) as well as higher insulin concentrations and HOMA index even after adjustment for BMI (p=0.03 and p=0.05, respectively). Moreover, CAH patients exhibited an impaired exercise capacity as shown by reduced peak workload (99±27 vs 126±27 W, p<0.01) and higher systolic blood pressure response at peak (156±18 vs 132±11 mmHg, p<0.01; Δ=45±24 vs 22±10 mmHg, p=0.05) with respect to healthy controls. CAH males displayed mild LV diastolic dysfunction as documented by significant prolongation of both isovolumic relaxation time (IRT) (118±18 vs 98±11ms, p<0.05) and mitral deceleration time (MDT) (138±25 vs 111±15 ms, p<0.01). No significant differences in CV function were found between CAH and JIA patients. Conclusion: Adolescents with CAH exhibit impaired exercise performance and enhanced systolic blood pressure response during exercise. In our population, such abnormalities appear related to GCS therapy rather than CAH per se. CAH males, but no females, present mild LV diastolic dysfunction that correlates with testosterone concentrations suggesting a sex hormone related difference

Interfacially-Located Nanoparticles Anticipate the Onset of Co-Continuity in Immiscible Polymer Blends

The addition of nanoparticles has recently emerged as a clever tool to manipulate the microstructure and, through it, the macroscopic properties of immiscible polymer blends. Despite the huge number of studies in this field, the underlying mechanisms of most of the nanoparticle-induced effects on the blend microstructure remain poorly understood. Among others, the origin of effect of nanoparticles on the transition from distributed (drop-in-matrix) to co-continuous morphology is still controversial. Here we address this issue through a systematic study on a model blend of polystyrene (PS) and poly(methyl methacrylate) (PMMA) filled with small amounts of nanoparticles (organo-modified clay) selectively located at the polymer–polymer interface. Extraction experiments with selective solvents prove that the nanoparticles significantly anticipate the onset of co-continuity with respect to the unfilled blend. Morphological analyses reveal that such an effect is a consequence of the interconnection of nanoparticle-coated polymer domains. Such “ginger-like” clusters get into contact at low content due to their irregular shape, thus anticipating the onset of co-continuity

Deposito e autorizzazione sismica

Lo scopo di tale pubblicazione è di offrire una panoramica generale sulle leggi e sulle procedure che disciplinano la denuncia dei lavori per autorizzazione sismica e per deposito sismico delle opere civili sul territorio nazionale e, in particolare, nella Regione Campania. Si intende cioè offrire una lettura semplificata di tali leggi, fornendo indicazioni pratiche e dirette ai professionisti. Il presente lavoro vuole essere di supporto sia per gli operatori del settore delle costruzioni, quali tecnici e costruttori, sia per i committenti per facilitare l’orientamento in un iter burocratico purtroppo spesso poco chiaro e appesantito. Tale lavoro parte da un inquadramento legislativo nazionale, ma inevitabilmente focalizza sulle leggi regionali della Campania poiché ogni regione, nel corso degli anni, si è disciplinata da sé in merito alle procedure di deposito sismico e autorizzazione sismica

Contribution of telomerase RNA retrotranscription to DNA double-strand break repair during mammalian genome evolution

A comparative analysis of two primate and two rodent genomes suggests that telomerase was utilized, in some instances, for the repair of DNA double-strand breaks during mammalian evolution

Redox stress proteins are involved in adaptation response of the hyperthermoacidophilic archaeon Sulfolobus solfataricus to nickel challenge

<p>Abstract</p> <p>Background</p> <p>Exposure to nickel (Ni) and its chemical derivatives has been associated with severe health effects in human. On the contrary, poor knowledge has been acquired on target physiological processes or molecular mechanisms of this metal in model organisms, including Bacteria and Archaea. In this study, we describe an analysis focused at identifying proteins involved in the recovery of the archaeon <it>Sulfolobus solfataricus </it>strain MT4 from Ni-induced stress.</p> <p>Results</p> <p>To this purpose, <it>Sulfolobus solfataricus </it>was grown in the presence of the highest nickel sulphate concentration still allowing cells to survive; crude extracts from treated and untreated cells were compared at the proteome level by using a bi-dimensional chromatography approach. We identified several proteins specifically repressed or induced as result of Ni treatment. Observed up-regulated proteins were largely endowed with the ability to trigger recovery from oxidative and osmotic stress in other biological systems. It is noteworthy that most of the proteins induced following Ni treatment perform similar functions and a few have eukaryal homologue counterparts.</p> <p>Conclusion</p> <p>These findings suggest a series of preferential gene expression pathways activated in adaptation response to metal challenge.</p

Biomimetic Chemistry on Tandem Protein/Lipid Damages under Reductive Radical Stress

The study of radical stress in the biological environment needs a comprehensive vision of all possible reactive species and their mechanisms. Among them, reductive stress is evaluated for its selective target of sulfur-containing compounds. The selective attack of reducing species like H• atoms or eaq?/H+ to sulfur-containing amino acid residues has been proved in different substrates, peptides and proteins. The transformations include methionine to ?-aminobutyric acid and cysteine/cystine residues to alanine, as recognized in several sequences so far, such as RNase A, lysozyme, Met-enkephalin, amyloid ?-peptide and metallothioneins. The amino acid desulfurization is accompanied by the formation of low-molecular-weight sulfur-centered radicals that may cause geometrical cis–trans isomerization of unsaturated fatty acid residues in lipid bilayer. Thus, tandem protein/lipid damage is accomplished. Progress in research has given us a more comprehensive overview of the protein modifications and their roles, and the chemical biology approach will make its vital contribution to the study of free radical reactions, linking chemistry to biology and medicine

Laparoscopic single site (LESS) and classic video-laparoscopic cholecystectomy in the elderly: A single centre experience

Laparoscopic cholecystectomy (LC) is the gold-standard surgical method used to treat gallbladder diseases. Recently Laparoendoscopic single site surgery (LESS) has gained greater interest and diffusion for the surgical treatment of several pathologies. In elderly patients, just few randomized controlled trials are present in the literature that confirm the clinical advantages of LESS compared with the classic laparoscopic procedures.We present in this paper the preliminary results of this randomized prospective study regarding the feasibility and safety of LESS cholecystectomy versus classic laparoscopic technique. We demonstrated that LESS technique compared with traditional technique show some advantages like: acceptable operative times, lower post-operative discomfort and sometimes reduction added complications. In addition we also demonstrate that fewer incisions and less scarring which mean less pain, and fewer parietal complications are related to this surgical procedure. In conclusion in the elderly LESS cholecystectomy technique is to be considered a suitable alternative to traditional three-port cholecystectomy