High-intensity exercise training induces morphological and biochemical changes in skeletal muscle

Skeletal muscle shows an elevated plasticity and can adapt its metabolic and contractile properties in response to a variety of stimuli such as physical exercise. This implies a series of biochemical and morphological changes in the recruited muscle, in order to produce the more appropriate functional response dependent on the specific stimulation. To determine the effective role of physical exercise in the muscle plasticity, in the present study we investigated the effect of two different exercise protocols on fiber composition and metabolism of two specific muscles of mice: the quadriceps -a fast-twitch muscle- and the gastrocnemius -a typical slow-twitch muscle. Mice were run daily on a motorized treadmill for 8 weeks, at a velocity corresponding to 60% (low-intensity exercise) or 90% (high-intensity exercise) of the maximal running velocity previously determined by an incremental exercise test. We found that at the end of training the body weight was significantly increased in highintensity exercise mice (18.2 ± 1.4 %) compared to low-intensity exercise (8.7 ± 0.6 %) and control (12.7 ± 0.5 %) groups, and it was lesser in low-intensity exercise mice compared to controls. In contrast, the food intake of both exercise training mice was greater compared to control group. Whereas low-intensity exercise mice, despite consumed significantly more food compared to control mice, increased the weight lesser, the weight increase of high-intensity exercise mice, that consumed significantly more food compared to other experimental groups, was significantly greater. These effects were accompanied by a progressive reduction in blood lactate levels at the end of training in both the exercised mice compared with controls; in particular, blood lactate levels after highintensity exercise were significantly lower than those measured in low-intensity exercise mice. Moreover, in the present study we demonstrated that high-intensity exercise training produced a significant increase in the expression of mitochondrial complex enzymes (significant for the enzymes corresponding to the Complex IV, II and I of mitochondrial chain) both in gastrocnemius and quadriceps muscle, compared with controls. These changes were associated with an increase in the amount of slow fibers in both these muscle of high-intensity exercise mice. No changing in the expression of mitochondrial enzymes and in the percentage of slow fibers were found in low-intensity exercise mice

Influence of implant mucosal thickness on early bone loss: A systematic review with meta-analysis

Purpose: Marginal bone loss (MBL) is an important clinical issue in implant therapy. One feature that has been cited as a contributing factor to this bone loss is peri-implant mucosal thickness. Therefore, in this report, we conducted a systematic review of the literature comparing bone remodeling around implants placed in areas with thick (≥2-mm) vs. thin (<2-mm) mucosa. Methods: A PICO question was defined. Manual and electronic searches were performed of the MEDLINE/PubMed and Cochrane Oral Health Group databases. The inclusion criteria were prospective studies that documented soft tissue thickness with direct intraoperative measurements and that included at least 1 year of follow-up. When possible, a meta-analysis was performed for both the overall and subgroup analyses. Results: Thirteen papers fulfilled the inclusion criteria. A meta-analysis of 7 randomized clinical trials was conducted. Significantly less bone loss was found around implants with thick mucosa than around those with thin mucosa (difference,-0.53 mm; P<0.0001). Subgroups were analyzed regarding the apico-coronal positioning, the use of platform-matched vs. platform-switched (PS) connections, and the use of cement-retained vs. screw-retained prostheses. In these analyses, thick mucosa was found to be associated with significantly less MBL than thin mucosa (P<0.0001). Among non-matching (PS) connections and screw-retained prostheses, bone levels were not affected by mucosal thickness. Conclusions: Soft tissue thickness was found to be correlated with MBL except in cases of PS connections used on implants with thin tissues and screw-retained prostheses. Mucosal thickness did not affect implant survival or the occurrence of biological or aesthetic complications

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

PURPOSE. To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).CASES AND METHODS. Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intraarterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG).RESULTS. After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors.CONCLUSIONS. CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB