A Finite Element Analysis Study Comparing 3 Internal Fixation Techniques in Mandibular Sagittal Split Osteotomy

Purpose: To analyse, and compare using finite element analysis, the biomechanical properties of the 1.7 mm miniplate fixation against 2 conventional fixation techniques (2.0 mm bi-cortical screws and 2.0 mm miniplate) used in the mandibular sagittal split osteotomy. Methods: A 3-D virtual mandible model was constructed using images from CT scan. Sagittal split osteotomy was carried out virtually, and the fixation techniques were applied onto the model. 9 virtual models consisted of the 3 fixation techniques with mandibular movements of 3 mm setback, 3 mm advancement and 7 mm advancement were developed. Bite forces of 50, 75 and 100 N were applied for incisor bite simulation and 100, 200 and 300 N for molar biting force. Finite element analysis was carried out in Solidworks, and readings of stresses and displacement were recorded. Wilcoxon rank sum test was applied and P-value of 0.05 was set for statistical analysis. Results: In this manuscript the authors have compared 3 internal fixation techniques in mandibular sagittal split osteotomy. There was a statistically significant difference for both stress and displacement readings between the 1.7 mm miniplate, the 2.0 mm bi-cortical screws and the 2.0 mm miniplate for all mandibular movements. For the 1.7 mm miniplate vs 2.0 mm bi-cortical screws, the stress reading was (P = 3.063e-08, W = 314), and for displacement was (P = 5.811e-05, W = 282). For the 1.7 mm miniplate vs 2.0 mm miniplate, the stress reading was (P = 9.862e-4, W = 263) and for displacement was (2.05e-2, W = 235). Conclusion: The 1.7 mm miniplate has adequate strength to be used in mandibular sagittal split osteotomy, although statistically less rigid when compared to the conventional 2.0 mm miniplate and 2.0 mm bi-cortical screws, especially in larger movements.

Non-canonical BRAF variants and rearrangements in hairy cell leukemia

Hairy cell leukemia(HCL)is an uncommon mature B-cell malignancy characterized by a typical morphology,immunophenotype,and clinical profile.The vast majority of HCL patients harbor the canonical BRAF V600E mutation which has become a rationalized target of the subsequently deregulated RAS-RAF-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line therapy.However,several HCL patients with a classical phenotype display non-canonical BRAF mutations or rearrangements.These include sequence variants within alternative exons and an oncogenic fusion with the IGH gene.Care must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon mechanisms.Identification,functional characterization,and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required.

PIM kinase inhibition:co-targeted therapeutic approaches in prostate cancer

PIM kinases have been shown to play a role in prostate cancer development and progression,as well as in some of the hallmarks of cancer,especially proliferation and apoptosis.Their upregulation in prostate cancer has been correlated with decreased patient overall survival and therapy resistance.Initial efforts to inhibit PIM with monotherapies have been hampered by compensatory upregulation of other pathways and drug toxicity,and as such,it has been suggested that co-targeting PIM with other treatment approaches may permit lower doses and be a more viable option in the clinic.Here,we present the rationale and basis for cotargeting PIM with inhibitors of PI3K/mTOR/AKT,JAK/STAT,MYC,stemness,and RNA Polymerase I transcription,along with other therapies,including androgen deprivation,radiotherapy,chemotherapy,and immunotherapy.Such combined approaches could potentially be used as neoadjuvant therapies,limiting the development of resistance to treatments or sensitizing cells to other therapeutics.To determine which drugs should be combined with PIM inhibitors for each patient,it will be key to develop companion diagnostics that predict response to each co-targeted option,hopefully providing a personalized medicine pathway for subsets of prostate cancer patients in the future.

Combined influence of basal media and fibroblast growth factor on the expansion and differentiation capabilities of adipose-derived stem cells

Background: Interest in adipose-derived stem cells (ASCs) has increased in recent years due to their multi-linagedifferentiation capabilities. While much work has been done to optimize the differentiation media, few studies havefocused on examining the influence of different expansion media on cell behavior. In this study, three basal media(low glucose Dulbecco’s modified Eagle’s medium (DMEM), high glucose DMEM and DMEM-F12) supplementedwith or without fibroblast growth factor 2 (FGF) were examined to assess their suitability for expanding ASCs.Findings: Flow cytometry, colony-forming unit assays (CFU-Fs) and differentiation assays were utilized to study cellbehavior. High glucose media CFU-Fs produced fewest colonies while the addition of FGF increased colony size.By passage 2, the majority of cells were positive for CD44, 45, 73, 90 and 105 and negative for CD14, 31 and 45,indicating a mesenchymal phenotype. A sub-population of CD34 positive cells was present among passage 2 cells;however, by passage 4 the cells were negative for CD34. FGF has a negative effective on passage 4 ASC adipogenesisand high glucose media plus FGF-enhanced osteogenic capacity of passage 4 ASCs. FGF supplemented basal mediawere most suitable for chondrogenesis. High glucose media plus FGF appeared to be the most beneficial for primingASCs to induce a keratocyte phenotype.Conclusions: These findings demonstrate the reciprocal effect FGF and basal media have on ASCs. This research hasimplications for those interested regenerating bone, cartilage, cornea or adipose tissues.

感染和非感染人群的外周及胃淋巴细胞对幽门螺杆菌NapA和AphC抗原的不同免疫应答

Background: In this study, we identify the nature of the immunological response of human peripheral blood mononuclear cells (PBMC) and lamina propria gastric lymphocytes (LPL) to two Helicobacter pylori antigens, the neutrophil activating protein (NapA) and alkyl hydroperoxide reductase (AphC). These antigens were identified and selected for study based on the observation that serological recognition of these proteins was associated with H pylori negative status in humans. Aims: The aim was to study the serological, proliferative, and cytokine responses of PBMC and LPL, obtained from H pylori infected and uninfected individuals, to these antigens. Methods: Patient serum, PBMC, and LPL were used to determine antibody isotype, and proliferative and cytokine responses to recombinant forms of NapA and AphC using western blotting and ELISA. Results: Western blotting revealed antibody reactivity to recombinant NapA and AphC among the H pylori negative population studied. Both the proliferative and interferon γ.responses of PBMC and LPL to NapA and AphC were significantly higher in H pylori negative compared with H pylori positive subjects. Analysis of the IgG subclass profiles to both antigens revealed a T helper 1 associated IgG3 antibody response in uninfected individuals. However, interleukin 10 production was greater in H pylori positive individuals in response to these antigens. Conclusions: Taken together these data are consistent with an immune response to these antigens skewed towards a T helper 1 response in the uninfected cohort.