Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections.

Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying.

5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-β-synthase in colon cancer cells lacking p53.

Recent findings revealed in cancer cells novel stress response pathways, which in response to many chemotherapeutic drugs causing nucleolar stress, will function independently from tumor protein p53 (p53) and still lead to cell cycle arrest and/or apoptosis. Since it is known that most cancers lack functional p53, it is of great interest to explore these emerging molecular mechanisms. Here, we demonstrate that nucleolar stress induced by 5-fluorouracil (5-FU) in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 (rpL3) as proapoptotic factor.

l-Cys/CSE/H2S pathway modulates mouse uterus motility and sildenafil effect.

Sildenafil, a selective phosphodiesterase type 5 (PDE5) inhibitor, commonly used in the oral treatment for erectile dysfunction, relaxes smooth muscle of human bladder through the activation of hydrogen sulfide (H2S) signaling. H2S is an endogenous gaseous transmitter with myorelaxant properties predominantly formed from l-cysteine (l-Cys) by cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). Sildenafil also relaxes rat and human myometrium during preterm labor but the underlying mechanism is still unclear.

The Ankylosing Spondylitis-associated HLA-B*2705 presents a B*0702-restricted EBV epitope and sustains the clonal amplification of cytotoxic T cells in patients.

HLA-B*27 is strongly associated with an inflammatory autoimmune disorder, the Ankylosing Spondylitis (AS) and plays a protective role in viral infections. The two aspects might be linked. In this work, we compared in B*2705/B*07 positive patients with AS, the CD8+ T cell responses to two immunodominant EBV-derived epitopes restricted for either the HLA-B*27 (pEBNA3C) or the HLA-B*07 (pEBNA3A).

In vitro analysis of the fracture resistance of CAD-CAM monolithic zirconia molar crowns with different occlusal thickness.

Objectives: To compare the fracture resistance and mode of failure of CAD-CAM monolithic zirconia crowns with different occlusal thickness.

Material And Methods: Forty CAD-CAM monolithic zirconia crowns with different occlusal thickness were randomly distributed into 4 experimental groups: 2.0mm (group 1), 1.

Combined microcomputed tomography, biomechanical and histomorphometric analysis of the peri-implant bone: a pilot study in minipig model.

Objectives: To present a practical approach that combines biomechanical tests, microcomputed tomography (μCT) and histomorphometry, providing quantitative results on bone structure and mechanical properties in a minipig model, in order to investigate the specific response to an innovative dental biomaterial.

Methods: Titanium implants with innovative three-dimensional scaffolds were inserted in the tibias of 4 minipigs. Primary stability and osseointegration were investigated by means of insertion torque (IT) values, resonance frequency analysis (RFA), bone-to-implant contact (BIC), bone mineral density (BMD) and stereological measures of trabecular bone.

Large Porous Particles for Sustained Release of a Decoy Oligonucelotide and Poly(ethylenimine): Potential for Combined Therapy of Chronic Pseudomonas aeruginosa Lung Infections.

We have recently demonstrated that the specific inhibition of nuclear factor-κB by a decoy oligonucleotide (dec-ODN) delivered through inhalable large porous particles (LPP) made of poly(lactic-co-glycolic acid) (PLGA) may be highly beneficial for long-term treatment of lung inflammation. Nevertheless, besides chronic inflammation, multifunctional systems aimed to control also infection are required in chronic lung diseases, such as cystic fibrosis (CF). In this work, we tested the hypothesis that engineering PLGA-based LPP with branched poly(ethylenimine) (PEI) may improve LPP properties for pulmonary delivery of dec-ODN, with particular regard to the treatment of Pseudomonas aeruginosa lung infections.

3-Year Randomized Controlled Prospective Clinical Trial on Different CAD-CAM Implant Abutments.

Background: Zirconia abutments were introduced to restore esthetic regions and showed sufficient stability to support implant restorations. Nonetheless, to date the observation periods are shorter than those of titanium abutments.

Purpose: To assess the survival of implant crowns supported by computer aided design-computer aided manufacturing (CAD-CAM) abutments after 3 years.

Data in support of Gallium (Ga(3+)) antibacterial activities to counteract E. coli and S. epidermidis biofilm formation onto pro-osteointegrative titanium surfaces.

This paper contains original data supporting the antibacterial activities of Gallium (Ga(3+))-doped pro-osteointegrative titanium alloys, obtained via Anodic Spark Deposition (ASD), as described in "The effect of silver or gallium doped titanium against the multidrug resistant Acinetobacter baumannii" (Cochis et al. 2016) [1]. In this article we included an indirect cytocompatibility evaluation towards Saos2 human osteoblasts and extended the microbial evaluation of the Ga(3+) enriched titanium surfaces against the biofilm former Escherichia coli and Staphylococcus epidermidis strains.

Extraction of chronically implanted coronary sinus leads active fixation vs passive fixation leads.

Background: The Medtronic model 4195 (StarFix) left ventricular lead is an active fixation lead that provides additional support within the coronary sinus (CS) via deployable lobes. While this lead has been shown to have excellent stability within the CS, concerns about its extractability have been raised.

Objective: The aim of this study was to compare the safety and efficacy of the extraction of the model 4195 lead vs other Medtronic CS leads in a prospective cohort study.

Inflammatory mediators in a short-time mouse model of doxorubicin-induced cardiotoxicity.

Doxorubicin (DOXO) is commonly used to treat a wide range of malignant tumors, but its clinical use is limited by acute and chronic cardiotoxicity. The precise mechanism underlying DOXO-induced cardiotoxicity is still not completely elucidated, but cardiac inflammation seems to be involved. Effects of DOXO on proinflammatory cytokines, inflammatory cell infiltration, and necrosis have been proven only when a functional impairment has already occurred, so this study aimed to investigate the acute effect of DOXO administration in mouse heart.

Genomic-based diagnosis of arrhythmia disease in a personalized medicine era.

Introduction: Although thousands of potentially disease-causing mutations have been identified in a handful of genes, the genetic heterogeneity has led to diagnostic confusions, stemming directly from the limitations in our arsenal of genetic tools.

Areas Covered: We discuss the genetic basis of cardiac ion channelopathies, the gaps in our knowledge and how Next-generation sequencing technology (NGS) and can be used to bridge them, and how induced pluripotent stem cell (iPSC) derived-cardiomyocytes can be used for drug discovery.

Expert Commentary: Univariate, arrhythmogenic arrhythmias can explain some congenital arrhythmias, however, it is far from a comprehensive understanding of the complexity of many arrhythmias.

Complete genomic sequence of barley (Hordeum vulgare) endornavirus (HvEV) determined by next-generation sequencing.

Endornaviruses are unusual plant-, fungus- and oomycete-infecting viruses with a large, ca 14- to 17-kb linear double-stranded RNA (dsRNA) genome and a persistent lifestyle. The complete genome sequence of an endornavirus from the barley (Hordeum vulgare) Nerz variety was determined from paired Illumina MySeq reads derived from purified dsRNAs. The genome is 14,243 nt long, with 5' and 3' non-coding regions of 207 and 47 nt, respectively.

The use of transthoracic echocardiography for the assessment of left ventricular systolic and diastolic function in patients with suspected or ascertained chronic heart failure.

Several indices are available to assess left ventricular (LV) function. Although ejection fraction (EF) is widely used, it has many limitations. An assessment of LV longitudinal function should be therefore provided as it precedes the impairment of EF.

Human lung cancer-derived immunosuppressive plasmacytoid dendritic cells release IL-1α in an AIM2 inflammasome-dependent manner.

Plasmacytoid dendritic cells (pDCs) highly populate lung tumor masses and are strictly correlated to bad prognosis, yet their role in lung cancer is controversial. To understand their role in lung cancer, we isolated pDCs from human samples of lung obtained from non-small cell lung cancer patients undergoing thoracic surgery. Tumor masses presented a higher percentage of pDCs than healthy tissues; pDCs were in the immunosuppressive phenotype, as determined by higher levels of CD33 and PD-L1.

Short-term clinical performance of zirconia single crowns with different framework designs: 3-year clinical trial.

Purpose: The present prospective clinical study evaluated the influence of coping design on the fracture resistance of CAD/CAM zirconia single crowns layered with dedicated ceramics.

Methods: 56 subjects were provided with 90 zirconia single crowns in posterior regions. Tooth preparations were standardized and the abutment teeth were randomly distributed into three groups, according to three different coping designs (flat design, FD; porcelain-fused-to-metal-like crowns, PFM; anatomically-guided, AG).

Human Cystathionine-β-Synthase Phosphorylation on Serine227 Modulates Hydrogen Sulfide Production in Human Urothelium.

Urothelium, the epithelial lining the inner surface of human bladder, plays a key role in bladder physiology and pathology. It responds to chemical, mechanical and thermal stimuli by releasing several factors and mediators. Recently it has been shown that hydrogen sulfide contributes to human bladder homeostasis.

Cardiac implantable electronic device infection in patients with end-stage renal disease.

Introduction: Cardiac implantable electronic devices (CIED) are increasingly being used in end-stage renal disease (ESRD) patients. These patients have a high risk of device infection.

Objectives: To study the optimal management of device infections in patients with ESRD.

Hydrogen sulfide inhalation ameliorates allergen induced airway hypereactivity by modulating mast cell activation.

Compelling evidence suggests that hydrogen sulfide represents an important gaseous transmitter in the mammalian respiratory system. In the present study, we have evaluated the role of mast cells in hydrogen sulfide-induced effects on airways in a mouse model of asthma. Mice were sensitized to ovalbumin and received aerosol of a hydrogen sulfide donor (NaHS; 100 ppm) starting at day 7 after ovalbumin challenge.

Label Propagation Prediction of Drug-Drug Interactions Based on Clinical Side Effects.

Drug-drug interaction (DDI) is an important topic for public health, and thus attracts attention from both academia and industry. Here we hypothesize that clinical side effects (SEs) provide a human phenotypic profile and can be translated into the development of computational models for predicting adverse DDIs. We propose an integrative label propagation framework to predict DDIs by integrating SEs extracted from package inserts of prescription drugs, SEs extracted from FDA Adverse Event Reporting System, and chemical structures from PubChem.

Hydrogen Sulfide and Urogenital Tract.

In this chapter the role played by H2S in the physiopathology of urogenital tract revising animal and human data available in the current relevant literature is discussed. H2S pathway has been demonstrated to be involved in the mechanism underlying penile erection in human and experimental animal. Both cystathionine-β synthase (CBS) and cystathionine-γ lyase (CSE) are expressed in the human corpus cavernosum and exogenous H2S relaxes isolated human corpus cavernosum strips in an endothelium-independent manner.

Influence of finish line on the marginal seal of nanohybrid composite crowns after periodontal scaling: a microleakage study.

Aim: The aim of the present microleakage study was to assess the sealing ability of nanohybrid composite crowns with different finish lines exposed to simulated mechanical periodontal treatment (SMPT).

Methods: After sample size calculation (α=0.05; β=0.