Experimental analysis and numerical fatigue life prediction of 3D-Printed osteosynthesis plates.

The trend towards patient-specific medical orthopedic prostheses has led to an increased use of 3D-printed surgical implants made of Ti6Al4V. However, uncertainties arise due to varying printing parameters, particularly with regards to the fatigue limit. This necessitates time-consuming and costly experimental validation before they can be safely used on patients. To address this issue, this study aimed to employ a stress-life fatigue analysis approach coupled with a finite element (FE) simulation to estimate numerically the fatigue limit and location of failure for 3D-printed surgical osteosynthesis plates and to validate the results experimentally. However, predicting the fatigue life of 3D components is not a new concept and has previously been implemented in the medical device field, though without experimental validation. Then, an experimental fatigue test was conducted using a proposed modification to the staircase method introduced in ISO 12107. Additionally, a FE model was developed to estimate the stress cycles on the plate. The stress versus number of cycles to failure curve (S-N) obtained from the minimum mechanical properties of 3D-printed Ti6AI4V alloy according to ASTM F3001-14 to predict the fatigue limit. The comparison between experimental results and fatigue numerical predictions showed very good agreement. It was found that a linear elastic FE model was sufficient to estimate the fatigue limit, while an elastic-plastic model led to an accurate prediction throughout the implant's cyclic life. The proposed method has great potential for enhancing patient-specific implant designs without the need for time-consuming and costly experimental regulatory testing.

Upregulation of Interleukin-6 in HPV-Positive Breast Cancer Patients.

BACKGROUND: Interleukin-6 (IL-6) is a well-known proinflammatory cytokine with tumor promoting capacity in various forms of malignancies including breast cancer (BC). Data highlighted the substantial role of HPV in the pathogenesis of BC. Compelling evidence suggests the contribution of HPV in carcinogenesis through triggering inflammatory cytokines such as IL-6. OBJECTIVE: Here, we assessed the correlation between the presence of HPV infection and the status of IL-6 expression and serum level in BC. METHODS: 72 tissue specimens including tumoral (Case; n=36) and their adjacent normal tissues (Control; n=36) were used. Nested-PCR and Real-Time PCR were employed to identify HPV DNA and assess the expression of IL-6, respectively. In addition, 72 sera samples from BC patients (n=36) and an age-matched healthy control group (n=36) were taken to measure the IL-6 serum level by ELISA. RESULTS: Overall, the HPV DNA was detected in 19.4% (14/72) of samples. 33.33% (12/36) of cases and 5.5% (2/36) of the controls were found to be positive for HPV (P=0.003). The overexpression of IL-6 was observed in HPV+ samples compared to HPV- samples (P=0.05). However, the concentration of IL-6 serum level was remarkably different between patients and normal controls (P=0.0001. Intriguingly, IL-6 serum level was connected to the advanced clinical stage (III/IV), high grade (II/III), metastasis and, ER+ status of patients. CONCLUSIONS: Our finding indicated that the overexpression of the IL-6 may be connected to HPV infection in BC. Furthermore, the results reinforced the clinical significance and prognostic value of the serum IL-6 in BC patients.

MiRNA-218 Is Frequently Downregulated in Malignant Breast Tumors: A Footprint of Epstein-Barr Virus Infection.

BACKGROUND & OBJECTIVE: The role of Epstein-Barr Virus in development of breast cancer is frequently studied. In this regard, miRNAs are among the contributing elements in the molecular pathophysiology of EBV-related diseases. In addition, a growing number of host miRNAs are believed to be implicated in pathogenesis of breast cancer. MiR-218 is a tumor suppressive miRNA that is subjected to dysregulation in various EBV-associated cancers. We aimed to investigate the frequency of EBV and its relationship with expression status of tumor suppressive miR-218 in breast cancer and adjacent normal tissue. METHODS: A total number of 51 fresh malignant breast cancer tissues (cases) and their adjacent normal tissues (controls) were collected. Nested-PCR and RT-qPCR were set to identify EBV frequency and miR-218 expression in cases and controls, respectively. RESULTS: Out of all samples, 6.8% (7/102) comprising 11.6% (6/51) in malignant tissues and 1.9% (1/51) in normal control tissues were positive for EBV (P<0.05). Quantitative data showed that miR-218 was significantly downregulated in malignant tissues compared to control tissues (P<0.0001). In addition, reduced expression of miR-218 was associated with adverse clinical outcomes, metastasis, and higher grades of malignancy. Given the presence of EBV, lower expression of miR-218 was observed in breast cancer group in comparison with normal group (P<0.05). CONCLUSION: Our results raise the possibility of the relation between EBV infection and miR-218 downregulation in breast cancer and propose further investigations in this regard.