A Deeper Insight into Evolutionary Patterns and Phylogenetic History of ORF Virus through the Whole Genome Sequencing of the First Italian Strains

Orf virus (ORFV) is distributed worldwide and is the causative agent of contagious ecthyma that mainly occurs in sheep and goats. This disease was reported for the first time at the end of 18th century in Europe but very little is currently known about the temporal and geographic origins of this virus. In the present study, the use of new Italian whole genomes allowed for better inference on the evolutionary history of ORFV. In accordance with previous studies, two genome types (S and G) were described for infection of sheep and goats, respectively. These two well-differentiated groups of genomes originated for evolutive convergence in the late 1800s in two different areas of the world (Europe for S type and Asia for G type), but it was only in the early 1900s that the effective size of ORFV increased among hosts and the virus spread across the whole European continent. The Italian strains which were sequenced in the present study were isolated on the Mediterranean island of Sardinian and showed to be exclusive to this geographic area. One of them is likely representative of the early European forms of ORFV which infected sheep and became extinct about one century ago. Such an ancient Sardinian strain may have reached the island simple by chance, where it quickly adapted to the new habitat.     

Influence of Nutritional Status and Physical Exercise on Immune Response in Metabolic Syndrome

Metabolic Syndrome (MetS) is a cluster of metabolic alterations mostly related to visceral adiposity, which in turn promotes glucose intolerance and a chronic systemic inflammatory state, characterized by immune cell infiltration. Such immune system activation increases the risk of severe disease subsequent to viral infections. Strong correlations between elevated body mass index (BMI), type-2-diabetes and increased risk of hospitalization after pandemic influenza H1N1 infection have been described. Similarly, a correlation between elevated blood glucose level and SARS-CoV-2 infection severity and mortality has been described, indicating MetS as an important predictor of clinical outcomes in patients with COVID-19. Adipose secretome, including two of the most abundant and well-studied adipokines, leptin and interleukin-6, is involved in the regulation of energy metabolism and obesity-related low-grade inflammation. Similarly, skeletal muscle hormones—called myokines—released in response to physical exercise affect both metabolic homeostasis and immune system function. Of note, several circulating hormones originate from both adipose tissue and skeletal muscle and display different functions, depending on the metabolic context. This review aims to summarize recent data in the field of exercise immunology, investigating the acute and chronic effects of exercise on myokines release and immune system function.     

Compressive and Thermal Properties of Non-Structural Lightweight Concrete Containing Industrial Byproduct Aggregates

This study aimed to investigate the recycling opportunities for industrial byproducts and their contribution to innovative concrete manufacturing processes. The attention was mainly focused on municipal solid waste incineration fly ash (MSWI-FA) and its employment, after a washing pre-treatment, as the main component in artificially manufactured aggregates containing cement and ground granulated blast furnace slag (GGBFS) in different percentages. The produced aggregates were used to produce lightweight concrete (LWC) containing both artificial aggregates only and artificial aggregates mixed with a relatively small percentage of recycled polyethylene terephthalate (PET) in the sand form. Thereby, the possibility of producing concrete with good mechanical properties and enhanced thermal properties was investigated through effective PET reuse with beneficial impacts on the thermal insulation of structures. Based on the obtained results, the samples containing artificial aggregates had lower compressive strength (up to 30%) but better thermal performance (up to 25%) with respect to the reference sample made from natural aggregates. Moreover, substituting 10% of recycled aggregates with PET led to a greater reduction in resistance while improving the thermal conductivity. This type of concrete could improve the economic and environmental aspects by incorporating industrial wastes—mainly fly ash—thereby lowering the use of cement, which would lead to a reduction in CO₂ emissions.     

NF-kappaB pathway: a target for preventing beta-amyloid (Abeta)-induced neuronal damage and Abeta42 production

Beta-amyloid (Abeta) peptides are key proteins in the pathophysiology of Alzheimer's disease (AD). While Abeta42 aggregates very rapidly to form early diffuse plaques, supplemental Abeta40 deposition is required to form mature neuritic plaques. We here investigated the role of nuclear factor-kappaB (NF-kappaB) pathway in Abeta40-mediated neuronal damage and amyloid pathology. In rat primary neurons and human postmitotic neuronal cells, the Abeta peptide induced a dose-dependent neuronal death, reduced the levels of the anti-apoptotic protein Bcl-XL, enhanced the cytosolic release of cytochrome c, and elicited the intracellular accumulation and secretion of Abeta42 oligomers. Moreover, Abeta40 activated the NF-kappaB pathway by selectively inducing the nuclear translocation of p65 and p50 subunits, and promoted an apoptotic profile of gene expression. As inhibitors of the NF-kappaB pathway, we tested the capability of a double-stranded kappaB decoy oligonucleotide, the anti-inflammatory drug aspirin and the selective IkappaB kinase 2 inhibitor, AS602868, to modify the Abeta40-mediated effects. These treatments, transiently applied before Abeta exposure, completely inhibited p50/p65 nuclear translocation and neuronal damage. The kappaB decoy also inhibited the Abeta-induced release of cytochrome c, restored the levels of Bcl-XL, and prevented intraneuronal accumulation and secretion of Abeta42. These results open up interesting perspectives on the development of novel strategies targeting out NF-kappaB p50/p65 dimers for pharmacological intervention in AD.     

Mild parkinsonian signs and psycho-behavioral symptoms in subjects with mild cognitive impairment

BACKGROUND: Mild cognitive impairment (MCI) may be accompanied by extra pyramidal signs (EPS), which are related to the severity and type of cognitive impairment. We aimed to elucidate further the relationship between MCI and EPS, analyzing the correlation between the severity of EPS and cognitive functions, and the presence of EPS and neuro-psychiatric features. METHODS: Data were obtained from a longitudinal study of 150 MCI outpatients. Participants underwent a clinical assessment including the Unified Parkinson Disease Rating Scale, the Neuropsychiatric Inventory, the Tinetti Scale, and a standardized neuropsychological battery. Mild EPS could be defined as being present (MCI with mild EPS) using a subscale of UPDRS, based on three specific symptoms: bradykinesia, rigidity and tremor. RESULTS: The two groups, one with mild EPS (24%) and one without EPS (76%), differed in gait abnormalities and presence of extrapyramidal symptoms. Groups did not differ in terms of general cognitive functions evaluated using the Mini-mental State Examination, while subjects with MCI with mild EPS performed significantly worse than those with MCI without EPS in total global score and in non-memory items of the Alzheimer's Disease Assessment Scale. Moreover, severity of EPS was significantly correlated with low performance on executive functions and with high performance on episodic memory. The group with MCI with mild EPS were observed to have a greater prevalence of patients with anxiety, depression, apathy and sleep disturbances than in MCI without EPS. CONCLUSION: MCI may be associated with mild parkinsonian signs, the severity of which are related to the severity of cognitive impairment, in particular of non-memory functions, and to a differential pattern of psycho-behavioral symptoms.     

Differences in the force/endurance relationship between young and older men

The aim of the present study was to ascertain if in six young (23–35 years) and in six older (70–72 years) healthy men matched for comparable absolute and specific maximal force of the dominant elbow flexors, differences in isometric endurance, myoelectrical fatigability, and shortening velocity are still recognizable. To assess the specific force, the muscle cross sectional area (CSA) was determined from magnetic resonance imaging (MRI) scans. The performance of the elbow flexors was studied by assessing the isometric endurance times (ET) at different percentages of maximal isometric contraction (MVC), the average muscle fibre conduction velocity of action potentials (CV), and the median frequency (MDF) of the surface electromyogram (sEMG) of the biceps brachii. Finally, the torque-velocity curve was assessed by means of maximal isokinetic contractions at six fixed angular velocities. All data were expressed as the mean (SD). The results showed that: (1) the ET was longer in the older subjects at the highest levels of isometric contraction, independently from the absolute force; (2) the modifications of muscle fibre CV during isometric effort progressed less rapidly in the older than the younger groups, as did those of MDF; and (3) at the same angular velocity, the older subjects exerted less absolute force than the younger subjects. These results suggest an impairment of the neuromuscular system of older men, which is less powerful and less fatigable than that of young men.     

Management of psoriatic arthritis in rheumatology and dermatology settings: sub-analysis of the Italian population from the international LOOP study

Clinical Rheumatology - Psoriatic arthritis (PsA) patients are often treated by dermatology and rheumatology specialities and may receive different treatments. To evaluate the impact of...     

Tocilizumab for the treatment of adult-onset Still’s disease: results from a case series

Adult-onset Still’s disease (AOSD) is a chronic inflammatory disease of unknown etiology which commonly affects young adults. Treatment of AOSD patients includes nonsteroidal anti-inflammatory drugs, corticosteroids, and DMARDs. Interleukin (IL)-6 blockade is an attractive therapeutic option for AOSD because this cytokine contributes to the pathogenesis of major AOSD symptoms. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that blocks the effects of IL-6. Preliminary results of TCZ in AOSD have been promising. Here, we reported our experience evaluating both the safety and the efficacy of 12 months therapy with TCZ in 11 patients with AOSD refractory to corticosteroids and MTX therapy, followed for 18 months, including the first 12 months of active treatment and the last 6 months to evaluate the activity of the disease when the treatment was discontinued. The main outcome measures were the European League Against Rheumatism (EULAR) improvement criteria and improvement of systemic symptoms at the 3, 6, 12, and 18-months follow-up periods. Our patients rapidly responded and experienced a sustained clinical remission over time during active treatment. Disease Activity Score 28 decreased from 5.62 (3.75–8.28) [median (range)] at baseline to 1.61(0.49–3.5) at month 12. EULAR remission was achieved in 81.82 % at 12 months. Tender joint and swollen joint counts displayed a progressive reduction during active therapy study period. During treatment, we observed a resolution of fever in our AOSD patient. In conclusion, TCZ might represent a suitable option for the therapy of refractory AOSD patients.