Efficacy of AZM therapy in patients with gingival overgrowth induced by Cyclosporine A: a systematic review

<p>Abstract</p> <p>Background</p> <p>In daily clinical practice of a dental department it's common to find gingival overgrowth (GO) in periodontal patients under treatment with Cyclosporine A (CsA). The pathogenesis of GO and the mechanism of action of Azithromycin (AZM) are unclear. A systematic review was conducted in order to evaluate the efficacy of Azithromycin in patients with gingival overgrowth induced by assumption of Cyclosporine A.</p> <p>Methods</p> <p>A bibliographic search was performed using the online databases MEDLINE, EMBASE and Cochrane Central of Register Controlled Trials (CENTRAL) in the time period between 1966 and September 2008.</p> <p>Results</p> <p>The literature search retrieved 24 articles; only 5 were Randomised Controlled Trials (RCTs), published in English, fulfilled the inclusion criteria. A great heterogeneity between proposed treatments and outcomes was found, and this did not allow to conduct a quantitative meta-analysis. The systematic review revealed that a 5-day course of Azithromycin with Scaling and Root Planing reduces the degree of gingival overgrowth, while a 7-day course of metronidazole is only effective on concomitant bacterial over-infection.</p> <p>Conclusion</p> <p>Few RCTs on the efficacy of systemic antibiotic therapy in case of GO were found in the literature review. A systemic antibiotic therapy without plaque and calculus removal is not able to reduce gingival overgrowth. The great heterogeneity of diagnostic data and outcomes is due to the lack of precise diagnostic methods and protocols about GO. Future studies need to improve both diagnostic methods and tools and adequate classification aimed to determine a correct prognosis and an appropriate therapy for gingival overgrowth.</p

Power profiles of competitive and noncompetitive mountain bikers

The performance of Olympic distance cross-country mountain bikers (XCO-MTB) is affected by constraints such as erosion of track surfaces and mass start congestion which can affect race results. Standardized laboratory assessments quantify interseasonal and intraseasonal cycling potential through the assessment of multiple physiological capacities. Therefore, this study examined whether the power profile assessment (PPA) could discriminate between competitive XCO-MTB and noncompetitive mountain bikers (NC-MTB). Second, it aimed to report normative power profile data for competitive XCO-MTB cyclists. Twenty-nine male participants were recruited across groups of XCO-MTB (n = 14) and NC-MTB (n = 15) mountain bikers. Each cyclist completed a PPA that consisted of increasing duration maximal efforts (6, 15, 30, 60, 240, and 600 seconds) that were interspersed by longer rest periods (174, 225, 330, 480, and 600 seconds) between efforts. Normative power outputs were established for XCO-MTB cyclists ranging between 13.8 ± 1.5 W·kg -1 (5-second effort) and 4.1 ± 0.6 W·kg -1 (600-second effort). No differences in absolute peak power or cadence were identified between groups across any effort length (p > 0.05). However, the XCO-MTB cyclists produced greater mean power outputs relative to body mass than the NC-MTB during the 60-second (6.9 ± 0.8 vs 6.4 ± 0.6 W·kg -1 ; p = 0.002), 240-second (4.7 ± 0.7 vs. 3.8 ± 0.4 W·kg -1 ; p < 0.001), and 600-second (4.1 ± 0.6 vs. 3.4 ± 0.3 W·kg -1 ; p < 0.001) efforts. The PPA is a useful discriminative assessment tool for XCO-MTB and highlights the importance of aerobic power for XCO-MTB performanc

Adapting Neutralizing Antibodies to Viral Variants by Structure-Guided Affinity Maturation Using Phage Display Technology

Neutralizing monoclonal antibodies have achieved great efficacy and safety for the treatment of numerous infectious diseases. However, their neutralization potency is often rapidly lost when the target antigen mutates. Instead of isolating new antibodies each time a pathogen variant arises, it can be attractive to adapt existing antibodies, making them active against the new variant. Potential benefits of this approach include reduced development time, cost, and regulatory burden. Here a methodology is described to rapidly evolve neutralizing antibodies of proven activity, improving their function against new pathogen variants without losing efficacy against previous ones. The reported procedure is based on structure-guided affinity maturation using combinatorial mutagenesis and phage display technology. Its use against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is demonstrated, but it is suitable for any other pathogen. As proof of concept, the method is applied to CoV-X2, a human bispecific antibody that binds with high affinity to the early SARS-CoV-2 variants but lost neutralization potency against Delta. Antibodies emerging from the affinity maturation selection exhibit significantly improved neutralization potency against Delta and no loss of efficacy against the other viral sequences tested. These results illustrate the potential application of structure-guided affinity maturation in facilitating the rapid adaptation of neutralizing antibodies to pathogen variants