Diabetic retinopathy, oxidative stress and sirtuins: an in depth look in enzymatic patterns and new therapeutic horizons

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. DR represents the most common microvascular complication of diabetes, and its incidence is constantly rising. The complex interactions between inflammation, oxidative stress, and the production of free oxygen radicals caused by prolonged exposure to hyperglycemia determine the development of DR. Sirtuins (SIRTs) are a recently discovered class of 7 histone deacetylases involved in cellular senescence, regulation of cell cycle, metabolic pathways, and DNA repair. SIRTs participate in the progress of several pathologies such as cancer, neurodegenerative and metabolic diseases. In DR, sirtuins 1,3,5 and 6 play an important role as they regulate the activation of the inflammatory response, insulin sensibility, and both glycolysis and gluconeogenesis. A wide spectrum of direct and indirect activators of SIRTs pathways (e.g. antagomiR, resveratrol, or glycyrrhizin) is currently being developed to treat the inflammatory cascade occurring in DR. We focuse on the main metabolic and inflammatory pathways involving SIRTs and DR, as well as recent evidence on SIRTs activators that may be employed as novel therapeutic approaches to DR

Wild ungulates as sentinels of flaviviruses and tick-borne zoonotic pathogen circulation: an Italian perspective

Background: Vector-borne zoonotic diseases are a concerning issue in Europe. Lyme disease and tick-borne encephalitis virus (TBEV) have been reported in several countries with a large impact on public health; other emerging pathogens, such as Rickettsiales, and mosquito-borne flaviviruses have been increasingly reported. All these pathogens are linked to wild ungulates playing roles as tick feeders, spreaders, and sentinels for pathogen circulation. This study evaluated the prevalence of TBEV, Borrelia burgdorferi sensu lato, Rickettsia spp., Ehrlichia spp., and Coxiella spp. by biomolecular screening of blood samples and ticks collected from wild ungulates. Ungulates were also screened by ELISA and virus neutralization tests for flaviviral antibody detection. Results: A total of 274 blood samples were collected from several wild ungulate species, as well as 406 Ixodes ricinus, which were feeding on them. Blood samples tested positive for B. burgdorferi s.l. (1.1%; 0-2.3%) and Rickettsia spp. (1.1%; 0-2.3%) and showed an overall flaviviral seroprevalence of 30.6% (22.1-39.2%): 26.1% (17.9-34.3%) for TBEV, 3.6% (0.1-7.1%) for Usutu virus and 0.9% (0-2.7%) for West Nile virus. Ticks were pooled when possible and yielded 331 tick samples that tested positive for B. burgdorferi s.l. (8.8%; 5.8-11.8%), Rickettsia spp. (26.6%; 21.8-31.2%) and Neoehrlichia mikurensis (1.2%; 0-2.4%). TBEV and Coxiella spp. were not detected in either blood or tick samples. Conclusions: This research highlighted a high prevalence of several tick-borne zoonotic pathogens and high seroprevalence for flaviviruses in both hilly and alpine areas. For the first time, an alpine chamois tested positive for anti-TBEV antibodies. Ungulate species are of particular interest due to their sentinel role in flavivirus circulation and their indirect role in tick-borne diseases and maintenance as Ixodes feeders and spreaders

Relativistic three-body bound states and the reduction from four to three dimensions

Beginning with an effective field theory based upon meson exchange, the Bethe-Salpeter equation for the three-particle propagator (six-point function) is obtained. Using the one-boson-exchange form of the kernel, this equation is then analyzed using time-ordered perturbation theory, and a three-dimensional equation for the propagator is developed. The propagator consists of a pre-factor in which the relative energies are fixed by the initial state of the particles, an intermediate part in which only global propagation of the particles occurs, and a post-factor in which relative energies are fixed by the final state of the particles. The pre- and post-factors are necessary in order to account for the transition from states where particles are off their mass shell to states described by the global propagator with all of the particle energies on shell. The pole structure of the intermediate part of the propagator is used to determine the equation for the three-body bound state: a Schr{\"o}dinger-like relativistic equation with a single, global Green's function. The role of the pre- and post-factors in the relativistic dynamics is to incorporate the poles of the breakup channels in the initial and final states. The derivation of this equation by integrating over the relative times rather than via a constraint on relative momenta allows the inclusion of retardation and dynamical boost corrections without introducing unphysical singularities.Comment: REVTeX, 21 pages, 4 figures, epsf.st

Features of Mild-to-Moderate COVID-19 Patients with Dysphonia

Introduction To explore the prevalence of dysphonia in European patients with mild-to-moderate COVID-19 and the clinical features of dysphonic patients. Methods The clinical and epidemiological data of 702 patients with mild-to-moderate COVID-19 were collected from 19 European Hospitals. The following data were extracted: age, sex, ethnicity, tobacco consumption, comorbidities, general and otolaryngological symptoms. Dysphonia and otolaryngological symptoms were self-assessed through a 4-point scale. The prevalence of dysphonia, as part of the COVID-19 symptoms, was assessed. The outcomes were compared between dysphonic and non-dysphonic patients. The association between dysphonia severity and outcomes was studied through Bayesian analysis. Results A total of 188 patients were dysphonic, accounting for 26.8% of cases. Females developed more frequently dysphonia than males (p=0.022). The proportion of smokers was significantly higher in the dysphonic group (p=0.042). The prevalence of the following symptoms was higher in dysphonic patients compared with non-dysphonic patients: cough, chest pain, sticky sputum, arthralgia, diarrhea, headache, fatigue, nausea and vomiting. The severity of dyspnea, dysphagia, ear pain, face pain, throat pain and nasal obstruction was higher in dysphonic group compared with non-dysphonic group. There were significant associations between the severity of dysphonia, dysphagia and cough. Conclusion Dysphonia may be encountered in a quarter of patients with mild-to-moderate COVID-19 and should be considered as a symptom list of the infection. Dysphonic COVID-19 patients are more symptomatic than non-dysphonic individuals. Future studies are needed to investigate the relevance of dysphonia in the COVID-19 clinical presentation

Italian consensus conference on guidelines for conservative treatment on lower limb muscle injuries in athlete.

Provide the state of the art concerning (1) biology and aetiology, (2) classification, (3) clinical assessment and (4) conservative treatment of lower limb muscle injuries (MI) in athletes. Seventy international experts with different medical backgrounds participated in the consensus conference. They discussed and approved a consensus composed of four sections which are presented in these documents. This paper represents a synthesis of the consensus conference, the following four sections are discussed: (i) The biology and aetiology of MIs. A definition of MI was formulated and some key points concerning physiology and pathogenesis of MIs were discussed. (ii) The MI classification. A classification of MIs was proposed. (iii) The MI clinical assessment, in which were discussed anamnesis, inspection and clinical examination and are provided the relative guidelines. (iv) The MI conservative treatment, in which are provided the guidelines for conservative treatment based on the severity of the lesion. Furthermore, instrumental therapy and pharmacological treatment were discussed. Knowledge of the aetiology and biology of MIs is an essential prerequisite in order to plan and conduct a rehabilitation plan. Another important aspect is the use of a rational MI classification on prognostic values. We propose a classification based on radiological investigations performed by ultrasonography and MRI strongly linked to prognostic factors. Furthermore, the consensus conference results will able to provide fundamental guidelines for diagnostic and rehabilitation practice, also considering instrumental therapy and pharmacological treatment of MI. Expert opinion, level IV

Evolution of infectious bronchitis virus in the field after homologous vaccination introduction

International audienceAbstractDespite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health

Italian consensus conference on guidelines for conservative treatment on lower limb muscle injuries in athlete

Provide the state of the art concerning (1) biology and aetiology, (2) classification, (3) clinical assessment and (4) conservative treatment of lower limb muscle injuries (MI) in athletes. Seventy international experts with different medical backgrounds participated in the consensus conference. They discussed and approved a consensus composed of four sections which are presented in these documents. This paper represents a synthesis of the consensus conference, the following four sections are discussed: (i) The biology and aetiology of MIs. A definition of MI was formulated and some key points concerning physiology and pathogenesis of MIs were discussed. (ii) The MI classification. A classification of MIs was proposed. (iii) The MI clinical assessment, in which were discussed anamnesis, inspection and clinical examination and are provided the relative guidelines. (iv) The MI conservative treatment, in which are provided the guidelines for conservative treatment based on the severity of the lesion. Furthermore, instrumental therapy and pharmacological treatment were discussed. Knowledge of the aetiology and biology of MIs is an essential prerequisite in order to plan and conduct a rehabilitation plan. Another important aspect is the use of a rational MI classification on prognostic values. We propose a classification based on radiological investigations performed by ultrasonography and MRI strongly linked to prognostic factors. Furthermore, the consensus conference results will able to provide fundamental guidelines for diagnostic and rehabilitation practice, also considering instrumental therapy and pharmacological treatment of MI. Expert opinion, level IV

Targeting cells with single vectors using multiple-feature Boolean logic

Precisely defining the roles of specific cell types is an intriguing frontier in the study of intact biological systems and has stimulated the rapid development of genetically encoded tools for observation and control. However, targeting these tools with adequate specificity remains challenging: most cell types are best defined by the intersection of two or more features such as active promoter elements, location and connectivity. Here we have combined engineered introns with specific recombinases to achieve expression of genetically encoded tools that is conditional upon multiple cell-type features, using Boolean logical operations all governed by a single versatile vector. We used this approach to target intersectionally specified populations of inhibitory interneurons in mammalian hippocampus and neurons of the ventral tegmental area defined by both genetic and wiring properties. This flexible and modular approach may expand the application of genetically encoded interventional and observational tools for intact-systems biology

Detection and Molecular Characterization of a Novel Species of Circovirus in a Tawny Owl (Strix aluco) in Southern Italy

Thanks to recent developments in molecular methods, many new species have been discovered within the genus Circovirus, which comprises viruses of veterinary relevance found in a broad range of hosts. In particular, several circoviruses are known to infect birds, often causing immunosuppression and feathering disorders. Nonetheless, nothing is known about their circulation in birds of prey. In this study, samples from 61 birds of prey representing ten different species, recovered by a wildlife rescue centre in Southern Italy, were taken at necropsy and analysed by PCR with pan-Circovirus primers. Only one sample, collected from a tawny owl (Strix aluco), tested positive. Its genome, sequenced by primer walking, displays the typical features of circoviruses. Based on demarcation criteria, the detected strain qualifies as a novel species, which was named “tawny owl-associated circovirus” (ToCV). Phylogenetically, ToCV clustered with mammalian rather than avian circoviruses, and its closeness to a rodent circovirus suggests that its host may have been a micromammal eaten by the tawny owl. On the other hand, its detection in the spleen fits with the tropism of other avian circoviruses. Little can be therefore said on its biology and pathogenicity, and further efforts are needed to better characterize its epidemiology