A new potential anti-cancer beta-carboline derivative decreases the expression levels of key proteins involved in glioma aggressiveness: A proteomic investigation

Gliomas remain highly fatal due to their high resistance to current therapies. Deregulation of protein synthesis contributes to cancer onset and progression and is a source of rising interest for new drugs. CM16, a harmine derivative with predicted high blood–brain barrier penetration, exerts antiproliferative effects partly through translation inhibition. We evaluated herein how CM16 alters the proteome of glioma cells. The analysis of the gel-free LC/MS and auto-MS/MS data showed that CM16 induces time- and concentration-dependent significant changes in the total ion current chromatograms. In addition, we observed spontaneous clustering of the samples according to their treatment condition and their proper classification by unsupervised and supervised analyses, respectively. A two-dimensional gel-based approach analysis allowed us to identify that treatment with CM16 may downregulate four key proteins involved in glioma aggressiveness and associated with poor patient survival (HspB1, BTF3, PGAM1, and cofilin), while it may upregulate galectin-1 and Ebp1. Consistently with the protein synthesis inhibition properties of CM16, HspB1, Ebp1, and BTF3 exert known roles in protein synthesis. In conclusion, the downregulation of HspB1, BTF3, PGAM1 and cofilin bring new insights in CM16 antiproliferative effects, further supporting CM16 as an interesting protein synthesis inhibitor to combat glioma.     

Influence of controlled immediate loading and implant design on peri-implant bone formation

AIM: Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. MATERIAL AND METHODS: A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance. RESULTS: A significantly higher bone area fraction was observed for SL compared with SU (p<0.0001). The mineralized bone fraction was the highest for SL and significantly different from SU (p<0.0001). The chance that osteoid- and bone-to-implant contact occurred was the highest for SL and significantly different from SU (p<0.0001), but not from CL. When bone-to-implant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. CONCLUSIONS: Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant.     

Case for staged thyroidectomy

Recent modifications in the management of well‐differentiated thyroid cancer have resulted in significant alterations in clinical approach. Utilizing a series of preoperative and postoperative risk factors involving both the patient and the disease pathology, we offer the term “staged thyroidectomy” to help organize these risk factors for patients and the endocrine team to optimize management. This approach is intended to incorporate our latest nuanced understanding of certain endocrine pathology and may serve to optimize patient outcomes.     

Load Sharing and Ligament Strains in Balanced,Overstuffed and Understuffed UKA. A Validated Finite Element Analysis

The aim of this study was to quantify the effects of understuffing and overstuffing UKA on bone stresses, load distribution and ligament strains. For that purpose, a numerical knee model of a cadaveric knee was developed and was validated against experimental measurements on that same knee. Good agreement was found among the numerical and experimental results. This study showed that, even if a medial UKA is well-aligned with normal soft tissue tension and with correct thickness of the tibia component, it induces a stiffness modification in the joint that alters the load distribution between the medial and lateral compartments, the bone stress and the ligament strain potentially leading to an osteoarthritic progression.     

A Systematic Review of the Predictive Value of 18FDG-PET in Esophageal and Esophagogastric Junction Cancer After Neoadjuvant Chemoradiation on the Survival Outcome Stratification

Purpose

We studied the predictive value of [¹⁸?F]fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) for assessing disease-free (DFS) and overall survival (OS) in esophageal and esophagogastric junction cancer.

Materials and methods

A literature search (PUBMED/MEDLINE, EMBASE, Cochrane) was performed to identify full papers with ¹⁸FDG-PET and survival data, using indexing terms and free text words. Studies with >10 patients with locally advanced esophageal cancer, presenting sequential or at least one post-adjuvant treatment ¹⁸FDG-PET data and Kaplan–Meier survival curves with >6 months median follow-up period were included. We performed a meta-analysis for DFS and OS using the hazard ratio (HRs) as outcome measure. Sources of heterogeneity study were also explored.

Results

We identified 26 eligible studies including a total of 1,544 patients (average age 62 years, 82 % males). The TNM distribution was as follows: stage I 7 %, II 24 %, III 53 % and IV 15 %. The pooled HRs for complete metabolic response versus no response were 0.51 for OS (95 % CI, 0.4–0.64; P?<?0.00001) and 0.47 for DFS (95 % CI, 0.38–0.57; P?<?0.00001), respectively. No statistical heterogeneity was present. To explore sources of clinical heterogeneity, we also realised subgroup and regression analyses. Taken into account the moderate correlation between OS and DFS (ρ?=?0.54), we used joint bivariate random regression model. These analyses did not show a statistically significant impact of study characteristics and PET modalities on the pooled outcome estimates.

Conclusion

Despite methodological and clinical heterogeneity, metabolic response on ¹⁸FDG-PET is a significant predictor of long-term survival data.     

Research strategy for health sciences: Facebook friend request is non‐differentially accepted in a diverse,young adult population

Social media is being used for recruitment and the study of health‐care choices and behavior, and could be particularly helpful to reach young adult populations outside of a 4 year college setting. The aim of this study was to report on overall success of recruiting young adults in diverse settings with respect to education and employment into a study using Facebook (FB). Young adults (n = 380, 50% male, 44% white) who had been involved in a longitudinal research project received a friend request from the research study group's profile. Acceptance rates of friend requests and sociodemographic and mental health factors associated with acceptance were evaluated. Approximately 67% of 318 participants who received a friend request accepted the request. Sociodemographic and mental health characteristics were similar between those who did and did not accept friend requests, suggesting non‐differential recruitment through FB. Friending through FB is a feasible way to reach young adults involved in health and behavioral research, and could be a way to expand the populations that are studied in health science research to maximize generalizability of the conclusions drawn.