Effects of saline submersion at body temperature on airway supportive devices including a novel nasopharyngeal device produced using 3D-printing.

PURPOSE: This study investigated dimension changes of various nasopharyngeal airways, including a novel self-supporting device, after saline submersion at body temperature to simulate in-vivo use. Dimension changes over time may reduce efficacy during long-term use and require sizing adjustments or limits on duration of use. MATERIALS AND METHODS: Cuffless Covidien endotracheal tubes, pediatric Rusch fixed flange polyvinyl chloride nasal airway tubes, pediatric Rusch Robertazzi style Mediprene nasal airway tubes, and novel silicone elastomer self-supporting nasopharyngeal airways were fully submerged in 0.9 % normal saline solution incubated at 37 degrees Celsius for 15 days. All devices had tube length and wall thickness measured after 0, 1, 2, 3, 4, 5, 10, and 15 days. The 95 % confidence intervals of tube dimensions at each date were compared with the 95 % confidence intervals at day 0. RESULTS: The Covidien ET tube, Rusch PVC NPA, and ssNPA tube lengths and wall thicknesses did not change significantly over 15 days. The Rusch Mediprene NPAs had a statistically significant increase in length starting at day 1 and wall thickness at day 2. CONCLUSIONS: The novel ssNPA did not expand in the in-vitro environment, supporting its safety for extended use. The PVC NPA and ET tube dimensions also remained stable. However, the Rusch Mediprene NPAs had significant length expansion after 1 day of submersion, indicating a considerable risk of expansion during extended use with potential implications for patient care. Silicone and PVC NPA dimensions remained stable when saturated, indicating these materials may be more appropriate for extended use.

Development of a High-Fidelity, 3D Printed Otoplasty Surgical Simulator.

IMPORTANCE: Prominotia has functional and esthetic impact for the child and family and proficiency in otoplasty requires experiential rehearsal. OBJECTIVES: To design and validate an anatomically accurate, 3D printed prominotia simulator for rehearsal of otoplasties. METHODS: A 3D prominotia model was designed from a computed tomographic (CT) scan and edited in 3-matic software. Negative molds were 3D printed and filled with silicone. Expert surgeons performed an otoplasty procedure on these simulators and provided Likert-based feedback. RESULTS: Six expert surgeons with a mean of 14.3 years of practice evaluated physical qualities, realism, performance, and value of the simulator. The simulator was rated on a scale of 1 (no value) to 5 (great value) and scored 3.83 as a training tool, 3.83 as a competency evaluation tool, and 4 as a rehearsal tool. CONCLUSIONS: Expert validation rated the otoplasty simulator highly in physical qualities, realism, performance, and value. With minor modifications, this model demonstrates valuable educational potential.

A Validated 3D Printed Laryngeal Suturing Simulator for Endoscopic Laryngeal Cleft Repair.

OBJECTIVES: Endoscopic laryngeal cleft repair (ELCR) with endolaryngeal suturing is an advanced surgical skill. This study objective was to assess the validity of 3-dimensionally (3D) printed laryngeal suturing simulator for ELCR. STUDY DESIGN: Development and validation of a simulator for ELCR. METHODS: An ELCR model was developed using 3D printed and readily available materials. Participants were surveyed before and after a simulation session using five-point Likert scale questions. Performance data was assessed using blinded expert video review and rated using a novel objective structured assessment of technical skills (OSATS) for endoscopic laryngeal suturing. RESULTS: Twenty-one participants ranging from residents to attendings completed the simulation session. Survey respondents reported on a five-point Likert scale that the model was "easy to use" and "quite realistic" (both mean of 4). Confidence improved significantly in 86% of participants (p < 0.01). Overall OSATS scores (out of a total of 55) showed a median improvement in technical skills of 11.7 points (p = 0.004). OSATS demonstrated good intra-rater (κ = 0.689 and 0.677) and moderate inter-rater (κ = 0.573) reliability. Completion times improved from the first to the last suture by a median time of 512 to 350 s (decrease of 202 s, p = 0.002). Participants with no prior ELCR experience improved more than those with in vivo experience. CONCLUSION: This study demonstrates the validity of a simulator utilizing 3D printed larynges for ELCR. A novel OSATS for endoscopic laryngeal suturing was successfully implemented. Confidence, technical skills, and completion times improved with the use of the model across a variety of participants. Laryngoscope, 133:785-791, 2023.

Preclinical assessment of clinically streamlined, 3D-printed, biocompatible single- and two-stage tissue scaffolds for ear reconstruction.

Auricular reconstruction is a technically demanding procedure requiring significant surgical expertise, as the current gold standard involves hand carving of the costal cartilage into an auricular framework and re-implantation of the tissue. 3D-printing presents a powerful tool that can reduce technical demands associated with the procedure. Our group compared clinical, radiological, histological, and biomechanical outcomes in single- and two-stage 3D-printed auricular tissue scaffolds in an athymic rodent model. Briefly, an external anatomic envelope of a human auricle was created using DICOM computed tomography (CT) images and modified in design to create a two-stage, lock-in-key base and elevating platform. Single- and two-stage scaffolds were 3D-printed by laser sintering poly-L-caprolactone (PCL) then implanted subcutaneously in five athymic rats each. Rats were monitored for ulcer formation, site infection, and scaffold distortion weekly, and scaffolds were explanted at 8 weeks with analysis using microCT and histologic staining. Nonlinear finite element analysis was performed to determine areas of high strain in relation to ulcer formation. Scaffolds demonstrated precise anatomic appearance and maintenance of integrity of both anterior and posterior auricular surfaces and scaffold projection, with no statistically significant differences in complications noted between the single- and two-staged implantation. While minor superficial ulcers occurred most commonly at the lateral and superior helix coincident with finite element predictions of high skin strains, evidence of robust tissue ingrowth and angiogenesis was visible grossly and histologically. This promising preclinical small animal model supports future initiatives for making clinically viable options for an ear tissue scaffold.

Hybrid Three-Dimensional-Printed Ear Tissue Scaffold With Autologous Cartilage Mitigates Soft Tissue Complications.

OBJECTIVES/HYPOTHESIS: To analyze the use of highly translatable three-dimensional (3D)-printed auricular scaffolds with and without novel cartilage tissue inserts in a rodent model. STUDY DESIGN: Preclinical rodent animal model. METHODS: This prospective study assessed a single-stage 3D-printed auricular bioscaffold with or without porcine cartilage tissue inserts in an athymic rodent model. Digital Imaging and Communications in Medicine computed tomography images of a human auricle were segmented to create an external anatomic envelope filled with orthogonally interconnected spherical pores. Scaffolds with and without tissue inset sites were 3D printed by laser sintering bioresorbable polycaprolactone, then implanted subcutaneously in five rats for each group. RESULTS: Ten athymic rats were studied to a goal of 24 weeks postoperatively. Precise anatomic similarity and scaffold integrity were maintained in both scaffold conditions throughout experimentation with grossly visible tissue ingrowth and angiogenesis upon explantation. Cartilage-seeded scaffolds had relatively lower rates of nonsurgical site complications compared to unseeded scaffolds with relatively increased surgical site ulceration, though neither met statistical significance. Histology revealed robust soft tissue infiltration and vascularization in both seeded and unseeded scaffolds, and demonstrated impressive maintenance of viable cartilage in cartilage-seeded scaffolds. Radiology confirmed soft tissue infiltration in all scaffolds, and biomechanical modeling suggested amelioration of stress in scaffolds implanted with cartilage. CONCLUSIONS: A hybrid approach incorporating cartilage insets into 3D-printed bioscaffolds suggests enhanced clinical and histological outcomes. These data demonstrate the potential to integrate point-of-care tissue engineering techniques into 3D printing to generate alternatives to current reconstructive surgery techniques and avoid the demands of traditional tissue engineering. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1008-1015, 2021.

Expression of miR-9 and miR-200c, ZEB1, ZEB2 and E-cadherin in Non-Small Cell Lung Cancers in Iran.

MicroRNAs (miRNAs) exert a critical influence on physiological and pathological processes through posttranscriptional modification of their mRNA targets. They play important roles in tumorigenesis and are considered to be potential diagnostic and prognostic biomarkers with various cancers. MiR-200c and miR-9 are regulatory elements that can have dual impacts as oncogenes and/or tumor suppressor genes. MiR-200c regulates two transcription factors, ZEB1 and ZEB2, while miR-9 is a regulatory factor for the E-cadherin protein which has a critical function in cell-cell junctions and is inhibited by two transcription factors ZEB1 and ZEB2. In this study, expression levels of miR-200c and miR-9, ZEB-1, ZEB-2 and E-cadherin were assessed in 30 non-small cell lung cancers (NSCLCs) by real-time qPCR. MiR-9 was down-regulated significantly in tumor tissues compared to normal adjacent tissues, while there was no significant change in expression level of miR-200c. On the other hand, ZEB1 demonstrated significant increase and ZEB2a decrease at the mRNA level. These results indicate roles for miR-9 and ZEB1 in genesis of lung cancer, although clinico-pathological associations were not evident. Further studies are necessary to assess implications for treatment of lung cancer.

Assessing the Diagnostic Value of Plasma-Free DNA in Prostate Cancer Screening

Background: Prostate cancer is the second form of cancer among men worldwide. For early cancer detection, we should identify tumors in initial stages before the physical signs become visible. The present study aims to evaluate the diagnostic value of cell-free DNA (cfDNA), its comparison with prostate-specific antigen (PSA) level in prostate cancer screening and also in patients with localized prostate cancer, metastatic form, and benign prostatic hyperplasia (BPH). Methods: The participants of this study were selected from 126 patients with genitourinary symptoms suspected prostate cancer, rising PSA, and/or abnormal rectal examination results and 10 healthy subjects as controls. Peripheral blood plasma before any treatment measures was considered. cfDNA was extracted using a commercial kit, and PSA levels were measured by ELISA. The ANOVA test was used to compare the average serum level of PSA and plasma concentration of cfDNA between the groups. The correlation between variables was measured by the Pearson test. Results: The subgroups consisted of 50 patients with localized prostate cancer, 26 patients with metastatic prostate cancer, 50 patients with BPH, and 10 healthy subjects; the average concentrations of cfDNA in these subgroups were 15.04, 19.62, 9.51, and 8.7 ng/µl, respectively. According to p < 0.0001 obtained from multivariate test, there was a significant difference between all the groups. Conclusion: Our findings indicated significant differences between cfDNA levels of patients with localized and metastatic prostate cancer, and differences of these two groups from BPH and healthy cases show the importance of this biomarker in non-invasive diagnostic procedures.

Detection of Loss of Heterozygosity (LOH) Using Circulating Cell-free DNA (cfDNA) by Fluorescence-based Multiplex PCR for Identification of Patients With Prostate Cancer.

Several lines of evidence suggest that loss of heterozygosity (LOH) in specific chromosomal regions is a common mechanism for the inactivation of tumor-suppressor genes that are implicated in the pathogenesis of prostate cancer (PCa). Short tandem repeat (STR) sequences are extremely reliable genetic markers for the detection of LOH associated with cancers. Hence, in the current study, we investigated the detection of LOH at 6 STR markers (D8S360, D9S1748, D9S171, D8S137, D6S1631, and THRB) using blood circulating cell-free DNA (cfDNA), which can be used to distinguish PCa from benign prostatic hyperplasia (BPH). A total of 136 individuals were included in the study, 76 male patients diagnosed with PCa (50 male patients with localized PCa and 26 male patients with metastatic PCa) as experimental subjects and 60 male patients with BPH as controls. Circulating cfDNA was extracted from plasma samples and amplified with fluorescence-labeled primers specific for known STR markers. We also evaluated the serum prostate-specific antigen in both groups. Our findings revealed that the frequency of LOH at D8S360, D9S1748, D9S171, D8S137, and D6S1631 was significantly higher in PCa subjects than in controls (P<0.05). Of the 6 STR markers, LOH at D8S360 could discriminate metastatic PCa from localized PCa. We found that 71.05% of patients with PCa and 1.66% of BPH subjects had LOH at least at 3 of the markers in cfDNA. Our findings provide additional evidence to support the hypothesis that analysis of LOH at D8S360, D9S1748, D9S171, D8S137, and D6S1631 STR markers using cfDNA can be applied as a noninvasive diagnostic approach for the detection of PCa.

Porous architected biomaterial for a tibial-knee implant with minimum bone resorption and bone-implant interface micromotion.

This investigation presents the numerical development of a fully porous tibial knee implant that is suggested to alleviate the clinical problems associated with current prostheses that are fully solid. A scheme combining multiscale mechanics and topology optimization is proposed to handle the homogenized analysis and property tailoring of the porous architecture with the aim of reducing the stiffness mismatch between the implant and surrounding bone. The outcome of applying this scheme is a graded lattice microarchitecture that can potentially offer the implant an improved degree of load bearing capacity while reducing concurrently bone resorption and interface micromotion. Asymptotic Homogenization theory is used to characterize the mechanics of its building block, a tetrahedron based unit cell, and the Soderberg fatigue criterion to represent the implant fatigue resistance under multiaxial physiological loadings. The numerical results suggest that the overall amount of bone resorption around the graded porous tibial stem is 26% lower than that around a conventional, commercially available, fully dense titanium implant of identical shape and size. In addition, an improved interface micromotion is observed along the tibial stem, with values at the tip of the stem as low as 17µm during gait cycle and 22µm for deep bend compared to a fully dense implant. This decrease in micromotion compared to that of an identical solid implant made of titanium can reasonably be expected to alleviate post-operative end of stem pain suffered by some patients undergoing surgery at the present time.

Analysis of Nonlinear Thermoelastic Dissipation in Euler-Bernoulli Beam Resonators.

The linear theory of thermoelastic damping (TED) has been extensively developed over the past eight decades, but relatively little is known about the different types of nonlinearities that are associated with this fundamental mechanism of material damping. Here, we initiate the study of a dissipative nonlinearity (also called thermomechanical nonlinearity) whose origins reside at the heart of the thermomechanical coupling that gives rise to TED. The finite difference method is used to solve the nonlinear governing equation and estimate nonlinear TED in Euler-Bernoulli beams. The maximum difference between the nonlinear and linear estimates ranges from 0.06% for quartz and 0.3% for silicon to 7% for aluminum and 28% for zinc.

Melatonin modulates the expression of BCL-xl and improve the development of vitrified embryos obtained by IVF in mice.

PURPOSE: Antioxidant and anti-apoptotic effects of melatonin on development of in vitro fertilization (IVF)/vitrified two-cell mouse embryos were evaluated in this study. METHODS: The IVF two-cell embryos were vitrified by cryotop, and were cultured in KSOM medium in different concentrations of melatonin (10(-6), 10(-9), 10(-12) M) and without melatonin. The blastocyst cell number, apoptotic cells and glutathione (GSH) level were evaluated by differential, TUNEL and cell tracker blue staining, respectively. The expression of Bax and Bcl-xl genes was evaluated by qPCR. The expression of melatonin receptors (Mtnr1a and Mtnr1b) in mouse 2-cell embryos and blastocysts was evaluated by RT-PCR. RESULTS: Melatonin increased the rate of cleavage and blastulation at 10(-12) M concentration (p < 0.05). The number of trophectoderm and inner cell mass showed a significant increase (p < 0.05) in 10(-9) M melatonin. The 10(-9) M and 10(-12) M melatonin treatments significantly reduced (p < 0.05) the apoptotic index. The significant increase in the expression of Bcl-xl observed at 10(-9) M concentration however, reduced expression of Bax was not statistically significant. The levels of GSH in 10(-9) and 10(-12) M groups were significantly improved relative to the control group (p < 0.05). The Mtnr1a was expressed in 2-cell embryos and blastocysts in all groups, but the expression of Mntr1b was not detected. CONCLUSION: Melatonin may have a special role against oxidative stress in protection of IVF/vitrified embryos.

Novel molecular anti-colorectalcancer conjugate:chlorambucil-adipic acid dihydrizide-glutamine.

Cancer is one of the most fatal diseases in the world and it has been years that finding new drugs and chemotherapeutic techniques with lowest side effects become one of the most important challenging matters needs really hard efforts. Chlorambucil (CBL), an ancient direct-acting alkylating anticancer agent, is commonly used for initial treatment of some kinds of cancers but the use of CBL is often limited because of the unpleasant side effects due to its lack of specificity for targeting cancer cells. In this research we tried to increase the specificity of CBL by producing a novel conjugate by using glutamine amino acid (Glut). Based on previous studies, poly amines and nitrogen compounds noticeably are used by cancer cells increasingly; therefore we decided to increase the efficiency and specificity of CBL by designing and producing a novel anti cancer conjugate using glutamine amino acid as an uptake enhancer, CBL, and Adipic acid Dihydrazide (ADH) as a spacer and linker. The biological tests were carried out on HT29 colorectal cancer cell line to evaluate its anticancer properties. Biological tests like MTT assay, finding IC50, evaluating the induced mechanism of the death of our novel CBL-Glutamine conjugate on HT29 cells, testing abnormal toxicity of this conjugate on mice in comparison with CBL drug were careid out. We found that not only CBL-Glutamine conjugate preserved its anti cancer property with regard to CBL drug, but also it represent lower abnormal toxicity in mice. Apoptosis was detected as its mechanism of the death. Our present study provides a promising strategy for targeting cancer cells using amino acids nano-conjugate drugs. The future perspectives have also been highlighted in continuing similar and relative researches.