Complications and treatment errors in nonsurgical periodontal therapy

Nonsurgical periodontal therapy can be subject to iatrogenesis, which includes all the complications directly or indirectly related to a treatment. These complications include both operator-dependent harms and errors and the consequences and adverse effects of the therapeutic procedures. The complications arising following nonsurgical periodontal treatment can be categorized as intraoperative and postoperative and can affect both soft and hard tissues at an intra-oral and extraoral level. Soft-tissues damage or damage to teeth and restorations can occur while performing the procedure. In the majority of cases, the risk of bleeding associated with nonsurgical therapy is reported to be low and easily controlled by means of local hemostatic measures, even in medicated subjects. Cervicofacial subcutaneous emphysema is not a frequent extraoral intraoperative complication, occurring during the use of air polishing. Moreover, side effects such as pain, fever, and dentine hypersensitivity are frequently reported as a consequence of nonsurgical periodontal therapy and can have a major impact on a patient's perception of the treatment provided. The level of intraoperative pain could be influenced by the types of instruments employed, the characteristics of tips, and the individual level of tolerance of the patient. Unexpected damage to teeth or restorations can also occur as a consequence of procedural errors.     

Effects of memantine on mania-like phenotypes exhibited by Drosophila Shaker mutants

Introduction

Increased glutamate levels and electrolytic fluctuations have been observed in acutely manic patients. Despite some efficacy of the non-competitive NMDA receptor antagonist memantine (Mem), such as antidepressant-like and mood-stabilizer drugs in clinical studies, its specific mechanisms of action are still uncertain. The present study aims to better characterize the Drosophila melanogaster fly Shaker mutants (SH), as a translational model of manic episodes within bipolar disorder in humans, and to investigate the potential anti-manic properties of Mem.

Methods and Results

Our findings showed typical behavioral abnormalities in SH, which mirrored with the overexpression of NMDAR-NR1 protein subunit, matched well to glutamate up-regulation. Such molecular features were associated to a significant reduction of SH brain volume in comparison to Wild Type strain flies (WT). Here we report on the ability of Mem treatment to ameliorate behavioral aberrations of SH (similar to that of Lithium), and its ability to reduce NMDAR-NR1 over-expression.

Conclusions

Our results show the involvement of the glutamatergic system in the SH, given the interaction between the Shaker channel and the NMDA receptor, suggesting this model as a promising tool for studying the neurobiology of bipolar disorders. Moreover, our results show Mem as a potential disease-modifying therapy, providing insight on new mechanisms of action.     

Real-world clinical outcome and safety of adjuvant therapy in stage III melanoma patients: Data from two Academic Italian Institutions

Adjuvant immunotherapy (IO) and targeted therapy (TT) have improved relapse-free survival (RFS) in patients with stage III melanoma, although about 25% of them relapse within a year. However, real-world data on treatment efficacy and safety as well as management of treatment recurrences are still limited. We retrospectively analyzed 113 patients with stage III melanoma who received at least one cycle of anti-PD-1 (nivolumab or pembrolizumab) or dabrafenib + trametinib as adjuvant therapy. Most of patients included into the analyses harbor BRAV600E mutation (66.4%) and had a stage IIIC melanoma (63.7%). Immunotherapy was administered in 48.7% of patients, whereas targeted therapy in 51.3% At data cut-off, median RFS was not reached with 12- and 24-months RFS of 81% and 64%, respectively. No new adverse events were registered. Thirty patients (26.5%) relapsed, mainly at distant sites. Patient treated with IO recurred mostly during adjuvant treatment (ON-treatment) while patients treated with TT relapsed at the end of treatment (OFF-treatment). At relapse, surgery, radiotherapy and systemic therapy were used alone or in combination. Among patients who started a first-line therapy, an excellent response switching to a different treatment was observed. Real-world outcomes and safety of adjuvant treatment for resected stage III melanoma appear comparable to clinical trials data. Moreover, management of recurrences depends on type of relapse (loco-regional vs distant) and timing (during vs OFF treatment). Furthermore, patients who relapse after adjuvant TT respond well to subsequent anti-PD1 based therapy.     

Expression of NADPH-diaphorase and colocalization with Fos in the brain neurons of the rat following visceral noxious stimulation

We used double staining immunocytochemical techniques to determine whether nitric oxide (NO) and Fos immunoreactivity induced by noxious visceral stimulation were colocalized in the neurons of the supraspinal areas. We observed a considerable increase in Fos-positive neurons in many brain areas after noxious stimulation but only 15% of the Fos-positive neurons colocalized Nicotinamide Adenine Dinucleotide Phosphate Diaphorase (NADPH-d). The NADPH-d positive cells showed perikarya and cytoplasmic processes laying next to or more frequently apposed to Fos-positive neurons. This anatomical finding supported the hypothesis that also at supraspinal level NO is released near the neurons specifically activated and diffuses through the source cells to act on adjacent neurons playing a role in the central processing of pain transmission and modulation.