Osteoimmunology of Spondyloarthritis

: The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. we summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA

Computed micro-tomographic evaluation of glide pathwith nickel-titanium rotary pathFile in maxillary firstmolars curved canals

Introduction: X-ray computed micro-tomography scanning allows high-resolution 3-dimensional imaging of small objects. In this study, micro-CT scanning was used to compare the ability of manual and mechanical glide path to maintain the original root canal anatomy. Methods: Eight extracted upper first permanent molars were scanned at the TOMOLAB station at ELETTRA Synchrotron Light Laboratory in Trieste, Italy, with a microfocus cone-beam geometry system. A total of 2,400 projections on 360 degrees have been acquired at 100 kV and 80 mu A, with a focal spot size of 8 mu m. Buccal root canals of each specimen (n = 16) were randomly assigned to Path File (P) or stainless-steel K-file (K) to perform glide path at the full working length. Specimens were then microscanned at the apical level (A) and at the point of the maximum curvature level (C) for post-treatment analyses. Curvatures of root canals were classified as moderate (<= 35 degrees) or severe (>= 40 degrees). The ratio of diameter ratios (RDRs) and the ratio of cross-sectional areas (RAs) were assessed. For each level of analysis (A and C), 2 balanced 2-way factorial analyses of variance (P < .05) were performed to evaluate the significance of the instrument factor and of canal curvature factor as well as the interactions of the factors both with RDRs and RAs. Results: Specimens in the K group had a mean curvature of 35.4 degrees +/- 11.5 degrees; those in the P group had a curvature of 38 degrees +/- 9.9 degrees. The instrument factor (P and K) was extremely significant (P < .001) for both the RDR and RA parameters, regardless of the point of analysis. Conclusions: Micro-CT scanning confirmed that NiTi rotary Path File instruments preserve the original canal anatomy and cause less canal aberrations. (J Endod 2012;38:389-393

Antibiotic Resistance in Paediatric Febrile Urinary Tract Infections

: Febrile urinary tract infection (UTI) is currently considered the most frequent cause of serious bacterial illness in children in the first 2 years of life. UTI in paediatrics can irreversibly damage the renal parenchyma and lead to chronic renal insufficiency and related problems. To avoid this risk, an early effective antibiotic treatment is essential. Moreover, prompt treatment is mandatory to improve the clinical condition of the patient, prevent bacteraemia, and avoid the risk of bacterial localization in other body sites. However, antibiotic resistance for UTI-related bacterial pathogens continuously increases, making recommendations rapidly outdated and the definition of the best empiric antibiotic therapy more difficult. Variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. Moreover, proper identification of cases at increased risk of difficult-to-treat UTIs can reduce the risk of ineffective therapy. In this review, the problem of emerging antibiotic resistance among pathogens associated with the development of paediatric febrile UTIs and the best potential solutions to ensure the most effective therapy are discussed. Literature analysis showed that the emergence of antibiotic resistance is an unavoidable phenomenon closely correlated with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. An increased use of antibiotic stewardship can be greatly effective in this regard

Le epistemologie nascoste. La costruzione del soggetto vulnerabile nell’immaginario educativo italiano. Un approccio grounded

Il volume dà conto del percorso di costruzione condivisa della teoria grounded: L’inclusione si costruisce facendo: dalla progettualità finalizzata all’etica della relazione, che nasce dal progetto di ricerca biennale dipartimentale “Le epistemologie nascoste. La costruzione del soggetto vulnerabile nell’immaginario educativo italiano. Un approccio Grounded”. Tra gli obiettivi-meta della ricerca vi è quello di individuare uno sfondo integratore che dia conto delle radici culturali dalle quali proviene l’attuale clima normativo-culturale-educativo relativo alle pratiche di inclusione in Italia (Canevaro, 2006; Ferri, 2018) e, ancora, disvelare epistemologie implicite e prassi che legittimano esclusione, patologizzazione e subalternità (hooks, 1990, 1998; Spivak, 1998). La teoria elaborata vuole essere strumento di supporto operativo per la formazione iniziale e in servizio di insegnanti, educatori e professioni a valenza pedagogica

Analysis of the Zn-Binding Domains of TRIM32, the E3 Ubiquitin Ligase Mutated in Limb Girdle Muscular Dystrophy 2H

8siMembers of the tripartite motif family of E3 ubiquitin ligases are characterized by the presence of a conserved N-terminal module composed of a RING domain followed by one or two B-box domains, a coiled-coil and a variable C-terminal region. The RING and B-box are both Zn-binding domains but, while the RING is found in a large number of proteins, the B-box is exclusive to the tripartite motif (TRIM) family members in metazoans. Whereas the RING has been extensively characterized and shown to possess intrinsic E3 ligase catalytic activity, much less is known about the role of the B-box domains. In this study, we adopted an in vitro approach using recombinant point- and deletion-mutants to characterize the contribution of the TRIM32 Zn-binding domains to the activity of this E3 ligase that is altered in a genetic form of muscular dystrophy. We found that the RING domain is crucial for E3 ligase activity and E2 specificity, whereas a complete B-box domain is involved in chain assembly rate modulation. Further, in vitro, the RING domain is necessary to modulate TRIM32 oligomerization, whereas, in cells, both the RING and B-box cooperate to specify TRIM32 subcellular localization, which if altered may impact the pathogenesis of diseases.openopenLazzari, Elisa; El-Halawany, Medhat; De March, Matteo; Valentino, Floriana; Cantatore, Francesco; Migliore, Chiara; Onesti, Silvia; Meroni, GermanaLazzari, Elisa; El-Halawany, Medhat; De March, Matteo; Valentino, Floriana; Cantatore, Francesco; Migliore, Chiara; Onesti, Silvia; Meroni, German

The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties

Natural products have been used in medicine for thousands of years. Given their potential health benefits, they have gained significant popularity in recent times. The administration of phytochemicals existed shown to regulate differential gene expression and modulate various cellular pathways implicated in cell protection. Curcumin is a natural dietary polyphenol extracted from Curcuma Longa Linn with different biological and pharmacological effects. One of the important targets of curcumin is Toll-like receptor-4 (TLR-4), the receptor which plays a key role in the modulation of the immune responses and the stimulation of inflammatory chemokines and cytokines production. Different studies have demonstrated that curcumin attenuates inflammatory response via TLR-4 acting directly on receptor, or by its downstream pathway. Curcumin bioavailability is low, so the use of exosomes, as nano drug delivery, could improve the efficacy of curcumin in inflammatory diseases. The focus of this review is to explore the therapeutic effect of curcumin interacting with TLR-4 receptor and how this modulation could improve the prognosis of neuroinflammatory and rheumatic diseases

6-Monoacetylmorphine-antibody distribution in tissues from heroin-related death cases: An experimental study to investigate the distributive response

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6-diacetyl ester of morphine (diacetylmorphine). The post-mortem diagnosis of heroin-related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post-mortem anti-6-MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin-related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post-mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications

A Low-Voltage Chopper-Stabilized Amplifier for Fetal ECG Monitoring With a 1.41 Power Efficiency Factor

This paper presents a low-voltage current-reuse chopper-stabilized frontend amplifier for fetal ECG monitoring. The proposed amplifier allows for individual tuning of the noise in each measurement channel, minimizing the total power consumption while satisfying all application requirements. The low-voltage current reuse topology exploits power optimization in both the current and the voltage domain, exploiting multiple supply voltages (0.3, 0.6 and 1.2 V). The power management circuitry providing the different supplies is optimized for high efficiency (peak charge-pump efficiency = 90%).The low-voltage amplifier together with its power management circuitry is implemented in a standard 0.18 μm CMOS process and characterized experimentally. The amplifier core achieves both good noise efficiency factor (NEF=1.74) and power efficiency factor (PEF=1.05). Experiments show that the amplifier core can provide a noise level of 0.34 μVrms in a 0.7 to 182 Hz band, consuming 1.17 μW power. The amplifier together with its power management circuitry consumes 1.56 μW, achieving a PEF of 1.41. The amplifier is also validated with adult ECG and pre-recorded fetal ECG measurements