Prevention and modulation of aminoglycoside ototoxicity (Review)

More than 60 years after their isolation and characterization, aminoglycoside (AG) antibiotics remain powerful agents in the treatment of severe gram-negative, enterococcal or mycobacterial infections. However, the clinical use of AGs is hampered by nephrotoxicity and ototoxicity, which often develop as a consequence of prolonged courses of therapy, or of administration of increased doses of these drugs. The discovery of non-ototoxic antibacterial agents, showing a wider spectrum of activity, has gradually decreased the use of AGs as first line antibiotics for many systemic infections. However, AGs are now undergoing an unexpected revival, being increasingly indicated for the treatment of severe emerging infections caused by organisms showing resistance to most first-line agents (e.g., multidrug-resistant tuberculosis, complicated nosocomially-acquired acute urinary tract infections). Increasing adoption of aminoglycosides poses again to scientists and physicians the problem of toxicity directed to the kidneys and to the inner ear. In particular, aminoglycoside-induced deafness can be profound and irreversible, especially in genetically predisposed patients. For this reason, an impressive amount of molecular strategies have been developed in the last decade to counteract the ototoxic effect of aminoglycosides. The present article overviews: i) the molecular mechanisms by which aminoglycosides exert their bactericidal activity, ii) the mechanisms whereby AGs exert their ototoxic activity in genetically-predisposed patients, iii) the drugs and compounds that have so far proven to prevent or modulate AG ototoxicity at the preclinical and/or clinical level, and iv) the dosage regimens that have so far been suggested to decrease the incidence of episodes of AG-induced ototoxicity

Vernalization affects the germination performance of the wetland endangered species Eleocharis carniolica

Eleocharis carniolica W.D.J. Koch (Cyperaceae) is an endangered wetland spike rush mainly threatened by habitat loss and fragmentation. Understanding the germination ecology of this species is essential to perform successful conservation and restoration actions. In this study, we investigated the effect of vernalization (i.e. cold stratification), gibberellic acid (GA3) and chemical scarification on seed germination of E. carniolica from wild populations in northern Italy. The results showed that vernalization (i.e. 8-weeks at 4 °C) significantly improved germination probability, speed, and uniformity compared to non-stratified seeds. Gibberellic acid treatment alone or in combination with vernalization did not show a significant improvement in germination. Chemical scarification using sodium hypochlorite increased germination probability, with 8 h of scarification showing the highest success rate. However, 24-h scarification had a negative impact on germination. Overall, vernalization was found to be the most effective method to enhance germination in E. carniolica. These findings provide valuable insights into the seed germination ecology of this endangered species, aiding in its exsitu conservation, propagation, and in-situ restoration efforts. Moreover, they have important implications on future germination dynamics of this endangered species, especially with predicted climate change scenarios

Connexin-Mediated Signaling in Nonsensory Cells Is Crucial for the Development of Sensory Inner Hair Cells in the Mouse Cochlea

Mutations in the genes encoding for gap junction proteins connexin 26 (Cx26) and connexin 30 (Cx30) have been linked to syndromic and nonsyndromic hearing loss in mice and humans. The release of ATP from connexin hemichannels in cochlear nonsensory cells has been proposed to be the main trigger for action potential activity in immature sensory inner hair cells (IHCs), which is crucial for the refinement of the developing auditory circuitry. Using connexin knock-out mice, we show that IHCs fire spontaneous action potentials even in the absence of ATP-dependent intercellular Ca(2+) signaling in the nonsensory cells. However, this signaling from nonsensory cells was able to increase the intrinsic IHC firing frequency. We also found that connexin expression is key to IHC functional maturation. In Cx26 conditional knock-out mice (Cx26(Sox10-Cre)), the maturation of IHCs, which normally occurs at approximately postnatal day 12, was partially prevented. Although Cx30 has been shown not to be required for hearing in young adult mice, IHCs from Cx30 knock-out mice exhibited a comprehensive brake in their development, such that their basolateral membrane currents and synaptic machinery retain a prehearing phenotype. We propose that IHC functional differentiation into mature sensory receptors is initiated in the prehearing cochlea provided that the expression of either connexin reaches a threshold level. As such, connexins regulate one of the most crucial functional refinements in the mammalian cochlea, the disruption of which contributes to the deafness phenotype observed in mice and DFNB1 patients. SIGNIFICANCE STATEMENT: The correct development and function of the mammalian cochlea relies not only on the sensory hair cells, but also on the surrounding nonsensory cells. Although the nonsensory cells have been largely implicated in the general homeostasis in the mature cochlea, their involvement in the initial functional differentiation of the sensory inner hair cells is less clear. Using mutant mouse models for the most common form of congenital deafness in humans, which are knock-outs for the gap-junction channels connexin 26 and connexin 30 genes, we show that defects in nonsensory cells prevented the functional maturation of inner hair cells. In connexin knock-outs, inner hair cells remained stuck at a prehearing stage of development and, as such, are unable to process sound information

Recent Advances in the Use of Green Corrosion Inhibitors to Prevent Chloride-Induced Corrosion in Reinforced Concrete

Inhibitors for the prevention of corrosion in reinforced concrete are chemical substances able to reduce carbon steel reinforcements corrosion without altering the overall properties of concrete. Today, many commercially available substances have a negative impact on human safety during either the inhibitor synthesis, their handling or application in field. Green corrosion inhibitors are nontoxic, biodegradable and environmentally biocompatible substances. They are generally made of extracts from natural plants or waste, which are abundantly available in several countries. The majority of green inhibitor molecules usually contain multiple bonds, aromatic rings, polar functional groups and electronegative atoms as P, N, S or O; the latter are able to coordinate with metal cations to form protective layers on the metallic surface of the reinforcements, so as to inhibit the development (initiation and/or propagation) of the corrosion process. In this review, the most recent achievements on the study and investigation of green corrosion inhibitors for concrete structures are presented and discussed. Inhibitors are classified based on their nature and inhibition mechanism. The inhibition effectiveness of the substances is compared with the well-established effective nitrite-based inhibitor, distinguishing between accelerated and long-term tests. Based on the available data, a summary of corrosion inhibitors efficiency is reported

The RIBES strategy for ex situ conservation: conventional and modern techniques for seed conservation

The Italian seed bank network (RIBES) aims to improve the quality and safety of the germplasm reserves of native plant species in Italy to ensure the long-term conservation of endangered and/or endemic flora. The strategy includes traditional methods to secure seed conservation. A comprehensive priority list for seed collection is being defined, it was prepared by crossing data of various checklists (red lists, endemics) and will soon be cross-referenced with an updated list of accessions of the whole network. A safety-backup program of duplicates will quickly be implemented to secure the conservation of the most threatened species in at least two seed banks of the network. On the other hand, the RIBES strategy also includes research by applying modern techniques. In collaboration with the Millennium Seed Bank, research on the storage behaviour of seeds and spores through thermal analysis is ongoing to inform conservation. Using the Differential Scanning Calorimetry (DSC), we could evaluate seed lipid properties such as glass transition temperature, melting, crystallization, oxidation behaviour, and thermal stability. Finally, RIBES participates as a co-funder in the LIFE Nature project SEEDFORCE, coordinating 11 seed banks of the network for collecting seeds/spores of 29 threatened species of EU interest

The RIBES strategy for ex situ conservation: conventional and modern techniques for seed conservation

The Italian seed bank network (RIBES) aims to improve the quality and safety of the germplasm reserves of native plant species in Italy to ensure the long-term conservation of endangered and/or endemic flora. The strategy includes traditional methods to secure seed conservation. A comprehensive priority list for seed collection is being defined, it was prepared by crossing data of various checklists (red lists, endemics) and will soon be cross-referenced with an updated list of accessions of the whole network. A safety-backup program of duplicates will quickly be implemented to secure the conservation of the most threatened species in at least two seed banks of the network. On the other hand, the RIBES strategy also includes research by applying modern techniques. In collaboration with the Millennium Seed Bank, research on the storage behaviour of seeds and spores through thermal analysis is ongoing to inform conservation. Using the Differential Scanning Calorimetry (DSC), we could evaluate seed lipid properties such as glass transition temperature, melting, crystallization, oxidation behaviour, and thermal stability. Finally, RIBES participates as a co-funder in the LIFE Nature project SEEDFORCE, coordinating 11 seed banks of the network for collecting seeds/spores of 29 threatened species of EU interest

High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study

Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 \ub1 87 vs. 16 \ub1 41 mg/L; p < 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend <0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23; p < 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p < 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome

Metastatic gastric cancer presenting with shoulder-hand syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Shoulder-hand syndrome is a relatively rare clinical entity classified as a complex regional pain syndrome type 1 and consisting essentially of a painful 'frozen shoulder' with disability, swelling, vasomotor or dystrophic changes in the homolateral hand. The pathophysiology is not completely clear but a predominant 'sympathetic' factor affecting the neural and vascular supply to the affected parts seems to be involved. Shoulder-hand syndrome has been related to many surgical, orthopedic, neurological and medical conditions; it is more often seen after myocardial infarction, hemiplegia and painful conditions of neck and shoulder, such as trauma, tumors, cervical discogenic or intraforaminal diseases and shoulder calcific tendinopathy, but has also been associated with herpetic infections, brain and lung tumors, thoracoplasty and drugs including phenobarbitone and isoniazid. The diagnosis of shoulder-hand syndrome is primarily clinical, but imaging studies, particularly bone scintigraphy, may be useful to exclude other disorders.</p> <p>Case presentation</p> <p>We report the case of a 67-year-old woman who presented with shoulder-hand syndrome as the initial manifestation of gastric cancer which had metastasized to bone.</p> <p>Conclusion</p> <p>Wider investigations are advisable in patients with atypical shoulder-hand syndrome. To the best of the authors' knowledge this is the first case of shoulder-hand syndrome associated with metastatic gastric cancer.</p

Tourismes 3 - La révolution durable

Tourismes 3 poursuit la réflexion entreprise depuis 2002 dans Tourismes 1, lieux communs et Tourismes 2, moments de lieux. Cet ouvrage aborde les temps longs du tourisme en montrant et en expliquant les logiques qui ont contribué à assurer sa durabilité. Inventé il y a plus de deux siècles et réservé alors à une élite, le tourisme est devenu progressivement planétaire, « milliardaire » en personnes concernées et en recettes engrangées, exponentiel dans les tendances à l\u27oeuvre. Face à la révolution industrielle, les territoires et les sociétés touchés précocement ou plus tardivement par le tourisme le restent, voire continuent de se développer. Il y aurait donc une formidable pérennité des pratiques touristiques et une remarquable adaptabilité des lieux touristiques face à l\u27évolution du monde en général et de l\u27univers touristique en particulier. Le tourisme apparaît alors comme cette autre révolution, la révolution silencieuse, la révolution ignorée, mais aussi la révolution durable, au sens où elle n\u27a pas fini de produire des effets sur la Terre et sur le Monde. La trilogie s\u27achève, mais la réflexion se poursuit via la conclusion qui propose deux projets scientifiques d\u27importance : la construction d\u27une théorie générale du tourisme et la mise à l\u27épreuve des sciences sociales par le tourisme