Interactions between immune response to fungal infection and microRNAs: The pioneer tuners

Due to their physiological and biological characteristics, numerous fungi are potentially emerging pathogens. Active dynamicity of fungal pathogens causes life-threatening infections annually impose high costs to the health systems. Although immune responses play crucial roles in controlling the fate of fungal infections, immunocompromised patients are at high risk with high mortality. Tuning the immune response against fungal infections might be an effective strategy for controlling and reducing the pathological damages. MicroRNAs (miRNAs) are known as the master regulators of immune response. These single-stranded tuners (18-23 bp non-coding RNAs) are endogenously expressed by all metazoan eukaryotes and have emerged as the master gene expression controllers of at least 30% human genes. In this review article, following the review of biology and physiology (biogenesis and mechanism of actions) of miRNAs and immune response against fungal infections, the interactions between them were scrutinised. In conclusion, miRNAs might be considered as one of the potential goals in immunotherapy for fungal infections. Undoubtedly, advanced studies in this field, further identifying of miRNA roles in governing the immune response, pave the way for inclusion of miRNA-related immunotherapeutic in the treatment of life-threatening fungal infections.     

Factors accelerating recurrences and secondary tumors in cutaneous squamous cell carcinoma

To investigate factors that affect and also decrease the duration for recurrences and secondary tumors in cSCC.A retrospective study was conducted for all patients who were treated for a cSCC of the head and neck between 2009 and 2016. Anamnestic as well as epidemiological and histological data were noted and correlated with the occurrence of recurrences and secondary cancers. The duration between surgery and these events was used to determine if histological factors accelerate their occurrence.The highest risk for recurrences was seen in patients with previous skin cancers (RR 3.23). Histological ulceration (p = 0.003) and grading (p = 0.031) of the tumor were found as significant factors accelerating the time to relapse. Surrounding chronic precancerotic lesions (p < 0.001) and poor tumor grading (p = 0.035) were found as significant factors accelerating the time until a secondary cSCC was observed.Known risk factors increase not only the risk for a cSCC but also for recurrences. Specific histologic findings can help to adjust follow-up intervals to identify recurrences and secondary tumors at an early stage as these were shown to decrease the duration for a further event.     

Biologic interaction of three-dimensional periodontal fibroblast spheroids with collagen-based and synthetic membranes

Background: Cell‐based therapy using autologous cells has been suggested as a potential approach for periodontal tissue regeneration. Spheroid systems are a form of three‐dimensional cell culture that promotes cell matrix interaction, which could recapitulate the aspect of cell homeostasis in vivo. The aim of this study is to assess the interaction of periodontal fibroblast spheroids with synthetic and collagen‐based membranes that have been used in guided tissue regeneration. Methods: Commercially available normal human periodontal ligament fibroblasts were grown in spheroid forms using a liquid overlay technique and then transplanted onto a collagen‐based and a polyglycolic acid–based membrane. The biologic interaction of the spheroids with the membranes was assessed using basic histology, Alamar blue tissue viability assay, scanning electron microscopy, and immunohistochemical analysis. Results: Periodontal fibroblast spheroids adhered to both membranes, and the cells were able to proliferate and migrate from the spheroids both horizontally and vertically into the membrane scaffolds. Immunohistochemical analysis showed expression of collagen type I, periostin, and Runx2 by the periodontal fibroblasts. Conclusion: Periodontal fibroblast spheroids were able to grow three‐dimensionally on the biologic membranes and may have the potential to be used together with guided tissue regeneration approaches as an adjunct for periodontal regeneration.     

Effect of misoprostol, a prostaglandin E1 analog, on orthodontic tooth movement in rats.

The purpose of this study was to investigate the effects of oral administration of misoprostol, a prostaglandin E1 analog, on orthodontic tooth movement and root resorption in rats. Sixty-four male Sprague-Dawley rats that initially weighed 250 +/- 20 g were used in this study. The animals were randomly assigned to 1 of 6 experimental and 2 control (nonappliance and appliance) groups. The experimental groups received 2.5, 5.0, 10.0, 25.0, 50.0, and 100.0 microg/kg misoprostol by gastric lavage every 24 hours for 2 weeks. A fixed orthodontic appliance consisting of a nickel-titanium closed-coil spring, 5.0 mm long was ligated between the maxillary right incisor and the maxillary right first molar. The initial activating force was 60 g. For analysis of root resorption, 99 maxillary right and left first molars from 61 animals were chosen. Serial histologic sections of the mesial root of the maxillary first molars were made, and histologic analysis of root resorption on the mesial and distal surfaces was performed. The results showed that oral misoprostol did increase the amount of orthodontic tooth movement in all the experimental groups compared with the appliance control group. This increase was statistically significant in doses of 10.0, 25.0, 50.0, and 100.0 microg/kg (P <.001). However, there were no statistically significant differences among these 4 different doses. There were no statistically significant differences in the amount of root resorption among the groups. However, a trend toward more root resorption was registered. On the basis of these findings, oral misoprostol can be used to enhance orthodontic tooth movement with minimal root resorption.     

Processed bovine dentine as a bone substitute

OBJECTIVES: Different forms of allogenic dentine have been studied for their potential use as bone substitutes. We report a new method for processing bovine dentine that results in a sterile bioactive material for repair and regeneration of bone. METHODS: Extracted bovine dentine was processed mechanically and chemically with inorganic and organic solvents, and sterilised. The in vitro biocompatibility on human gingival fibroblasts was assessed by the Alamar Blue assay and the in vivo biocompatibility evaluated by implantation of the processed dentine into rats' femurs. RESULTS: The dentine showed excellent biocompatibility in vitro, stimulated formation of new bone and was completely incorporated into the new bone in vivo. SIGNIFICANCE: Processed bovine dentine has the potential to be used as a suitable substitute in bone repair and regeneration.     

Intrasacral rod fixation for pediatric lumbopelvic fusion

Purpose

This paper reports the authors’ 19 years experience with pediatric intrasacral rod fixation.

Methods

After insertion of two cannulated screws in S1 with and an original template guiding them into the anterior third of the endplate, two short fusion rods were inserted into the sacrum according to Jackson’s technique distally to S3. In neuromuscular scoliosis, pelvic obliquity was reduced by connecting the proximal and distal constructs, distraction or compression, and in situ rod bending. In children with high-grade spondylolisthesis, lumbosacral kyphosis was reduced by rotation of the sacrum and in situ bending.

Results

There were no direct neurological or vascular injuries. The main complication was infection (7 %). No pseudarthrosis or significant loss of correction at the lumbosacral junction was observed during follow-up.

Conclusions

Intrasacral rod fixation appears to be safe and reliable for lumbopelvic fusion in pediatric patients.

     

Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3⁺CD19⁺ cell depletion (CD3/19D) versus CD34⁺ selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios^? FoxP3⁺Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.     

The independent association of massive blood loss with mortality in cardiac surgery

BACKGROUND: Although the association between massive perioperative blood loss (MBL) and adverse outcomes is well recognized, it is unclear whether MBL is an independent risk factor or, instead, simply a marker for other adverse events or severity of illness. The objective of this cohort study was to quantify the independent association of MBL in cardiac surgery with all-cause in-hospital mortality. STUDY DESIGN AND METHODS: Data were prospectively collected on consecutive patients who underwent cardiac surgery with cardiopulmonary bypass at a quaternary-care academic center from 1999 to 2003. The number of red blood cell (RBC) units transfused within 1 day of surgery was used as a surrogate measure of perioperative blood loss. Receiver-operating characteristic curve analyses were employed to identify the most appropriate cutoff for defining MBL. The independent association of MBL with mortality was determined with multivariable logistic regression analyses. Bootstrapping and sensitivity analyses were used to confirm the validity of the results. RESULTS: MBL was defined as receiving at least 5 units of RBCs within 1 day of surgery. Of 9215 patients analyzed, 1.8 percent (n = 169) died and 9.7 percent (n = 890) had MBL. After adjusting for multiple potential confounders (including perioperative adverse events), MBL was associated with an 8.1-fold (95% confidence interval, 3.9-17.0) increase in the odds of death. This risk estimate was stable across different modeling conditions as well as in bootstrap sampling. CONCLUSION: MBL after cardiac surgery has a strong, independent association with in-hospital mortality.