Long-term treatment with high-dose of sildenafil in a thalassemic patient with pulmonary hypertension

We report a case of a 37-years-old man, affected by thalassemia major, hypogonadotropic hypogonadism, chronic HCV-hepatitis, diabetes mellitus, severe osteoporosis, prior septic pulmonary embolism and pulmonary artery hypertension was performed a long-term treatment with highdose of sildenafil (120 mg/die) with reduction of pulmonary arterial systolic pressure and of the dyspnea

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

Many species of ganglioside GM1, differing for the sialic acid and ceramide content, have been characterized and their physico\u2010chemical properties have been studied in detail since 1963. Scientists were immediately attracted to the GM1 molecule and have carried on an ever\u2010increasing number of studies to understand its binding properties and its neurotrophic and neuroprotective role. GM1 displays a well balanced amphiphilic behavior that allows to establish strong both hydrophobic and hydrophilic interactions. The peculiar structure of GM1 reduces the fluidity of the plasma membrane which implies a retention and enrichment of the ganglioside in specific membrane domains called lipid rafts. The dynamism of the GM1 oligosaccharide head allows it to assume different conformations and, in this way, to interact through hydrogen or ionic bonds with a wide range of membrane receptors as well as with extracellular ligands. After more than 60 years of studies, it is a milestone that GM1 is one of the main actors in determining the neuronal functions that allows humans to have an intellectual life. The progressive reduction of its biosynthesis along the lifespan is being considered as one of the causes underlying neuronal loss in aged people and severe neuronal decline in neurodegenerative diseases. In this review, we report on the main knowledge on ganglioside GM1, with an emphasis on the recent discoveries about its bioactive component

Polyphase folding at upper structural levels in the Borbera valley (Northern Apennines, Italy): implications for the tectonic evolution of the linkage area between Alps and Apennines

The Borbera Valley (northwestern Italy) is located in a complex geological area where the linkage between Alps and Apennines occurs. In this area the Antola Unit (Late Cretaceous–Palaeocene) is unconformably overlain by the Upper Eocene–Miocene succession of the Tertiary Piedmont Basin. The structural analysis indicates the occurrence of a folding phase of Late Oligocene–Early Miocene age, characterised by recumbent F2 folds. These folds are superposed onto D1 structures related to an early folding phase of Middle Eocene, affecting only the Antola Unit. The occurrence of map-scale D2 folding phase structures that affect the Tertiary Piedmont Basin succession suggests that the linkage area between Alps and Apennines was reactivated during the Late Oligocene–Early Miocene

Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity

MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development from Drosophila to mammals. Cells expressing low levels of MYC, called losers, are committed to die by nearby cells with high MYC activity, called winners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC's consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised. Here we show stereotypical patterns of MYC-mediated cell competition in human cancers: MYC-upregulating cells and apoptotic cells were indeed repeatedly found at the tumour-stroma interface and within the tumour parenchyma. Cell death amount in the stromal compartment and MYC protein level in the tumour were highly correlated regardless of tumour type and stage. Moreover, we show that MYC modulation in heterotypic co-cultures of human cancer cells is sufficient as to subvert their competitive state, regardless of genetic heterogeneity. Altogether, our findings suggest that the innate role of MYC-mediated cell competition in development is conserved in human cancer, with malignant cells using MYC activity to colonise the organ at the expense of less performant neighbours

Characterization of the GM1 oligosaccharide transport across the blood-brain-barrier

Ganglioside GM1 has demonstrated to attenuate Parkinson Disease (PD) symptoms in clinical and preclinical trials. Nevertheless, the GM1 efficacy revealed in vitro is critically reduced in vivo, because of the amphiphilic behavior that limits the passage across the blood brain barrier (BBB). In vitro and in vivo experiments showed that GM1 exerts neurotrophic functions by interacting with plasma membrane (PM) proteins throughout its oligosaccharide portion (OligoGM1). Furthermore, OligoGM1 intravenously or subcutaneously injected into mice is absorbed and taken up by different organs and tissues, including brain. In order to take advantage of GM1 oligosaccharide properties and to overcome GM1 pharmacological limitation, this study has been aimed by the investigation of the OligoGM1 transportthrough the BBB, by using a human in vitro model for human brain-like endothelial cells (hBLEC). Ruled out the toxicity of OligoGM1 on hBLEC, the OligoGM1 transport across the hBBB has been analyzed, finding out a 20 fold higher rate than GM1 and a time and concentration dependence. In order to characterize the OligoGM1 passage, a direct evaluation of the OligoGM1 interaction with the ABC-transporters was carried on, leaving out this way for OligoGM1 transport. Moreover, inverse- and 4\ub0C-transport experiments were performed excluding the implication of the active transport for OligoGM1 passage across the hBLEC, leading to consider the passive-paracellular route. Furthermore, after the hBLEC transport, OligoGM1 maintained its stability and capacity to induce neuritogenesis in the mouse neuroblastoma cells line Neuro2a. This preliminary study has improved the knowledge about the GM1 pharmacological potential by proving that OligoGM1 can cross advantageously the BBB, offering a new promising therapeutic strategy

Interventions to prevent urinary catheter-associated infections in children and neonates: a systematic review.

INTRODUCTION: Few data are available to inform strategies for the prevention of catheter-associated urinary tract infection (CAUTI) in children and neonates. Many recommendations are derived from studies in adults and cannot be applied to the paediatric population. OBJECTIVE: This study was aimed to identify all studies that measured the efficacy of an intervention for the prevention of CAUTI in children and neonates. METHODS: A systematic review using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) was conducted. Eligible studies published between January 1st, 1995 and December 31st, 2017, were identified in PubMed, the Cochrane Database of Systematic Reviews, LILACS, SciELO and DOAJ if applying an intervention with the aim of CAUTI prevention in inpatient children, infants or neonates. The following study designs were included: controlled and non-controlled before-and-after studies, (controlled) interrupted time series analyses and randomized controlled trials. Quantitative or qualitative studies on interventions in both adults and children were eligible if data on children could be extracted. Reviews, case series, letters, notes, conference abstracts and opinion articles were excluded. RESULTS: Of 99 articles identified, six were included in the final analysis, after consensus from three independent investigators. Four studies used a multimodal strategy (using at least four or more different components at the same time) as follows: aseptic rules during catheter insertion and removal; cleaning the urethral meatus with sterile water; use of a new silicone catheter per insertion with a closed sterile drainage system by a sterile technique; daily evaluation of catheter requirement; placement of indwelling urinary catheters only for approved indications; reducing of urinary catheter days and positioning of the patient and collection device to assist in urine drainage. One study tested periurethral cleaning intervention to reduce CAUTI. One study described the association of the presence of a physician safety champion with urinary catheter device utilization ratios. Catheter-associated UTI reduction rates were reported in four studies; three achieved statistically significant decreases in CAUTI rates. Positive results were achieved only when a multimodal strategy was used with at least four or more components. This strategy could be adopted for paediatric healthcare institutions to reduce CAUTI rates in children and neonates. CONCLUSION: Evidence exists to support the use of a multimodal strategy for CAUTI reduction in hospitalized children and neonates

Which route of antibiotic administration should be used for third molar surgery? A split-mouth study to compare intramuscular and oral intake

Objectives. To compare the effectiveness of two different routes of antibiotic administration in preventing septic complications in patients undergoing third molar extraction. Materials and Methods. Twenty-four healthy patients requiring bilateral surgical removal of impacted mandibular third molars were successfully enrolled for this study. Depth of impaction, angulation, and relationship of the lower third molars with the mandibular branch had to be overlapping on both sides. A split-mouth design was chosen, so each patient underwent both the first and second surgeries, having for each extraction a different antibiotic route of administration. The second extraction was carried out 1 month later. To compare the effects of the two routes of antibiotic administration, inflammatory parameters, such as edema, trismus, pain, fever, dysphagia and lymphadenopathy were evaluated 2 and 7 days after surgery. Side effects of each therapy were evaluated 48h after surgery. Results. oral and intramuscular antibiotic therapies overlap in preventing post-operative complications in dental surgery (p>0.05), even if the oral intake, seems to promote the onset of significant gastrointestinal disorders (p=0.003). Conclusions. This study could help dentists in their ordinary practice to choose the right route of antibiotic administration in the third molar surgery. At the same effectiveness, the higher cost and the minor compliance of the patient seem not to justify a routine antibiotic intramuscular therapy, reserving it for patients with gastrointestinal disorders

Intermittent vertebral flow in asymptomatic progression of aortic dissection.

Not available