NAB2 is a novel immune stimulator of MDA-5 that promotes a strong type I interferon response

Novel adjuvants are needed to increase the efficacy of vaccine formulations and immune therapies for cancer and chronic infections. In particular, adjuvants that promote a strong type I IFN response are required, since this cytokine is crucial for the development of efficient anti-tumoral and anti-viral immunity. Nucleic acid band 2 (NAB2) is a double- stranded RNA molecule isolated from yeast and identified as an agonist of the pattern- recognition receptors TLR3 and MDA-5. We compared the ability of NAB2 to activate innate immunity with that of poly(I:C), a well-characterized TLR3 and MDA-5 agonist known for the induction of type I IFN. NAB2 promoted stronger IFN-α production and induced a higher activation state of both murine and human innate immune cells compared to poly(I:C). This correlated with a stronger activation of the signalling pathway downstream of MDA-5, and IFN-α induction was dependent on MDA-5. Upon injection, NAB2 induced higher levels of serum IFN-α in mice than poly(I:C). These results suggest that NAB2 has the potential to become an efficient adjuvant for the induction of type-I IFN responses in therapeutic immunization against cancer or infections

Class III Orthodontic Camouflage: Is the “Ideal” Treatment Always the Best Option? A Documented Case Report

Angle’s Class III is one of the most complex malocclusions to treat. In nongrowing skeletal class III malocclusions, the choice between orthognathic surgery and camouflage treatment remains a challenge to the orthodontist. In class III borderline cases, clinicians are called to find the best compromise between functional and aesthetics outcomes, with the latter which often turns in avoiding worsening of profile characteristics, which makes the treatment of these patients quite challenging. This case report describes a borderline nongrowing patient with skeletal class III malocclusion, upper incisor proclination and spacing, lower crowding, and arch width discrepancy, which has already undergone previous orthodontic treatment. The orthodontic treatment involved the mandibular first premolar extraction, resulting in class I canine relation with good overjet and overbite as well as good arch coordination. The orthodontic camouflage improved the dental relationship with normalization of upper incisor inclination without a relevant retroclination of lower incisors; the skeletal facial pattern of the patient experienced a slight improvement. The tendency to skeletal class III has remained nearly unaffected. Treatment outcomes were stable after 1-year posttreatment follow-up

Evaluation of cyclic fatigue resistance of modern Nickel–Titanium rotary instruments with continuous rotation

Abstract Aim The aim of present study was to compare cyclic fatigue resistance of three modern Ni–Ti instruments used with continuous rotation. Materials and methods For this study 3 groups of rotating instruments with continuous rotation (HyFlex EDM, Twisted File Adaptive, Revo S SU) have been used, each group consisted of 20 files. The various groups were subjected to cyclic fatigue testing through an artificial metal device. A statistical analysis with Kruskal–Wallis test and Mann–Whitney test was performed. Results There were statistically significant differences between the three groups. The HyFlex EDM instruments have a fracture resistance slightly higher than the Twisted file and far higher than Revo S SU. Conclusions Modern Ni–Ti alloys increase resistance of the rotating instruments to cyclic fatigue

Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation

Although immunotherapy shows great promise for the long-term control of cancer, many tumors still fail to respond to treatment. To improve the outcome, the delivery of immunostimulants to the lymph nodes draining the tumor, where the antitumor immune response is initiated, is key. Efforts to use nanoparticles as carriers for cancer immunotherapy have generally required targeting agents and chemical modification of the drug, and have unfortunately resulted in low delivery and therapeutic efficiency. Here, we report on the efficacy of gold nanoparticles with approximately 5 nm hydrodynamic diameter coated with a mixture of 1-octanethiol and 11- mercaptoundecanesulfonic acid for the delivery of an immunostimulatory TLR7 ligand to tumor-draining lymph nodes. The drug was loaded without modification through nonspecific adsorption into the ligand shell of the nanoparticles, taking advantage of their amphiphilic nature. After loading, nanoparticles retained their stability in solution without significant premature release of the drug, and the drug cargo was immunologically active. Upon subcutaneous injection into tumor-bearing mice, the drug-loaded particles were rapidly transported to the tumor-draining lymph nodes. There, they induced a local immune activation and fostered a cytotoxic T-cell response that was specific for the tumor. Importantly, the particle-delivered TLR7 ligand blocked the growth of large established tumors and significantly prolonged survival compared to the free form of the drug. Thus, we demonstrate for the first time that nanoparticle delivery of a TLR7 immunostimulant to the tumor-draining lymph nodes enhances antitumor immunity and improves the outcome of cancer immunotherapy

To Wean or Not to Wean: The Role of Autologous Reconstructive Surgery in the Natural History of Pediatric Short Bowel Syndrome on Behalf of Italian Society for Gastroenterology, Hepatology and Nutrition (SIGENP)

Pediatric Short Bowel Syndrome (SBS) can require prolonged parenteral nutrition (PN). Over the years, SBS management has been implemented by autologous gastrointestinal reconstructive surgery (AGIR). The primary objective of the present review was to assess the effect of AGIR on weaning off PN. We also evaluated how AGIR impacts survival, the need for transplantation (Tx) and the development of liver disease (LD). We conducted a systematic literature search to identify studies published from January 1999 to the present and 947 patients were identified. PN alone was weakly associated with higher probability of weaning from PN (OR = 1.1, p = 0.03) and of surviving (OR = 1.05, p = 0.01). Adjusting for age, the probability of weaning off PN but of not surviving remained significantly associated with PN alone (OR = 1.08, p = 0.03). Finally, adjusting for age and primary diagnosis (gastroschisis), any association was lost. The prevalence of TX and LD did not differ by groups. In conclusion, in view of the low benefit in terms of intestinal adaptation and of the not negligible rate of complications (20%), a careful selection of candidates for AGIR should be required. Bowel dilation associated with failure of advancing EN and poor growth, should be criteria to refer for AGIR