Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium

Objective: This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration. Methodology: Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination. Results: Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the ca p. Conclusion: The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation

Preclinical Analysis of Irreversible Electroporation on Rat Liver Tissues Using a Microfabricated Electroporator

A microfabricated electroporator (MFE) for the irreversible electroporation (IRE) of tissues has been developed by miniaturizing a clinical electroporator with a two-needle array while keeping the same electric field strength distribution. Since IRE was brought to special attention as one of the local tissue ablation techniques to treat tumors, many preclinical studies have been conducted to investigate the efficacy of IRE on animal tissues. However, some technical difficulties have been frequently encountered due to the macroscale dimension of clinical electroporators, particularly in experiments on small animal models such as the mouse or rat. Here, the MFE was proposed to solve the associated problems, resulting in time-and cost-effective experimental procedures. With the developed MFE, the effect of IRE on rat liver tissues was analyzed with time by immunohistological stainings and electrical measurement, and the experimental results were compared with those operated with the corresponding real-scale clinical electroporator.Choi YS, 2009, ANAL CHEM, V81, P3517, DOI 10.1021/ac900055rMaor E, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0004757Pavlin M, 2008, BIOELECTROCHEMISTRY, V74, P38, DOI 10.1016/j.bioelechem.2008.04.016Sersa G, 2008, EJSO-EUR J SURG ONC, V34, P232, DOI 10.1016/j.ejso.2007.05.016Rubinsky B, 2007, TECHNOL CANCER RES T, V6, P255Onik G, 2007, TECHNOL CANCER RES T, V6, P295Al-Sakere B, 2007, TECHNOL CANCER RES T, V6, P301Maor E, 2007, TECHNOL CANCER RES T, V6, P307Garon EB, 2007, INT J CANCER, V121, P675, DOI 10.1002/ijc.22723Esser AT, 2007, TECHNOL CANCER RES T, V6, P261Lee EW, 2007, TECHNOL CANCER RES T, V6, P287Kimelman N, 2007, TISSUE ENG, V13, P1135, DOI 10.1089/ten.2007.0096Lavee J, 2007, HEART SURG FORUM, V10, pE162, DOI 10.1532/HSF98.20061202Rubinsky B, 2007, TECHNOL CANCER RES T, V6, P37Liu L, 2006, CANCER RES, V66, P11851, DOI 10.1158/0008-5472.CAN-06-1377Marty M, 2006, EJC SUPPL, V4, P3, DOI 10.1016/j.ejcsup.2006.08.002Sersa G, 2006, EJC SUPPL, V4, P52, DOI 10.1016/j.ejcsup.2006.08.007Edd JF, 2006, IEEE T BIO-MED ENG, V53, P1409, DOI [10.1109/TBME.2006.873745, 10.1109/TMBE.2006.873745]Miller L, 2005, TECHNOL CANCER RES T, V4, P699Sel D, 2005, IEEE T BIO-MED ENG, V52, P816, DOI 10.1109/TBME.2005.845212Davalos RV, 2005, ANN BIOMED ENG, V33, P223, DOI 10.1007/s10439-005-8981-8Pliquett U, 2004, BIOELECTROCHEMISTRY, V62, P83, DOI 10.1016/j.biolechem.2003.11.001Davalos RV, 2003, BIOELECTROCHEMISTRY, V61, P99, DOI 10.1016/j.bioelechem.2003.07.001Weaver JC, 2003, IEEE T DIELECT EL IN, V10, P754, DOI 10.1109/TDEI.2003.1237325Gothelf A, 2003, CANCER TREAT REV, V29, P371, DOI 10.1016/S0305-7372(03)00073-2Gehl J, 2003, ACTA PHYSIOL SCAND, V177, P437Leu JI, 2003, J CLIN INVEST, V111, P129, DOI 10.1172/JCI200316712Deng ZS, 2001, PHYSICA A, V300, P521Ryttsen F, 2000, BIOPHYS J, V79, P1993Dev SB, 2000, IEEE T PLASMA SCI, V28, P206, DOI 10.1109/27.842905Duffy DC, 1998, ANAL CHEM, V70, P4974Boone K, 1997, J MED ENG TECHNOL, V21, P201Weaver JC, 1996, BIOELECTROCH BIOENER, V41, P135*I LAB AN RES NAT, 1996, GUID CAR US LAB ANABIDOR IG, 1993, BIOCHIM BIOPHYS ACTA, V1152, P207DILLER KR, 1992, MODELING BIOHEAT TRAMIR LM, 1991, CR ACAD SCI III-VIE, V313, P613DUCK FA, 1990, PHYS PROPERTIES ISSUKINOSITA K, 1979, BIOCHIM BIOPHYS ACTA, V554, P479PENNES HH, 1948, J APPL PHYSIOL, V1, P93

Comparison of the clinical outcomes between antiviral-naïve patients treated with entecavir and lamivudine-resistant patients receiving adefovir add-on lamivudine combination treatment

Background/Aims To analyze the effects of preexisting lamivudine (LAM) resistance and applying antiviral treatment (adefovir [ADV] add-on LAM combination treatment) on long-term treatment outcomes, and comparing the clinical outcomes of antiviral-naïve chronic hepatitis B patients receiving entecavir (ETV) monotherapy. Methods This study enrolled 73 antiviral-naïve patients who received 0.5-mg ETV as an initial therapy and 54 patients who received ADV add-on LAM combination treatment as a rescue therapy from July 2006 to July 2010. Results During 24-month treatments, the decreases in serum log10HBV-DNA values (copies/mL) were significantly greater in the antiviral-naïve patients treated with ETV than the patients receiving ADV add-on LAM combination treatment. The biochemical response rates for alanine aminotransferase normalization at 6 months (ETV) and 12 months (ADV add-on LAM) were 90.4% (66/73) and 77.8% (42/54), respectively (P=0.048). A Kaplan-Meier analysis indicated that the rates of serologic response, viral breakthrough, and emergence of genotypic resistance did not differ significantly between the two patient groups. There were also no significant intergroup differences in the rates of disease progression (PD) and new development of hepatocellular carcinoma (HCC). Conclusion The long-term clinical outcomes of antiviral-naïve patients treated with ETV and LAM-resistant patients receiving ADV add-on LAM combination treatment were comparable in terms of the emergence of HCC and disease progression

High levels of soluble herpes virus entry mediator in sera of patients with allergic and autoimmune diseases

Herpes virus entry mediator (HVEM) is a newly discovered member of the tumor necrosis factor receptor (TNFR) superfamily that has a role in herpes simplex virus entry, in T cell activation and in tumor immunity. We generated mAb against HVEM and detected soluble HVEM (SHVEM) in the sera of patients with various autoimmune diseases. HVEM was constitutively expressed on CD4+ and CD8+ T cells, CD19+ B cells, CD14+ monocytes, neutrophils and dendritic cells. In three-way MLR, mAb 122 and 139 were agonists and mAb 108 had blocking activity. An ELISA was developed to detect sHVEM in patient sera. sHVEM levels were elevated in sera of patients with allergic asthma, atopic dermatitis and rheumatoid arthritis. The mAbs discussed here may be useful for studies of the role of HVEM in immune responses. Detection of soluble HVEM might have diagnostic and prognostic value in certain immunological disorders

A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma

To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) tests sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.This study was supported by grants from the National Research Foundation (NRF) funded by the Ministry of Science & ICT (No. 2017M3A9A7050614, No. 2020R1C1C1012749, and NRF-2017R1D1A1B06029547) and the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (No. HI22C0147

Development and validation of a scoring system for advanced colorectal neoplasm in young Korean subjects less than age 50 years

Background/Aims Colorectal cancer incidence among patients aged ≤50 years is increasing. This study aimed to develop and validate an advanced colorectal neoplasm (ACRN) screening model for young adults aged <50 years in Korea. Methods This retrospective cross-sectional study included 59,575 consecutive asymptomatic Koreans who underwent screening colonoscopy between 2003 and 2012 at a single comprehensive health care center. Young Adult Colorectal Screening (YCS) score was developed as an optimized risk stratification model for ACRN using multivariate analysis and was internally validated. The predictive power and diagnostic performance of YCS score was compared with those of Asia-Pacific Colorectal Screening (APCS) and Korean Colorectal Screening (KCS) scores. Results 41,702 and 17,873 subjects were randomly allocated into the derivation and validation cohorts, respectively, by examination year. ACRN prevalence was 0.9% in both cohorts. YCS score comprised sex, age, alcohol, smoking, obesity, glucose metabolism abnormality, and family history of CRC, with score ranges of 0 to 10. In the validation cohort, ACRN prevalence was 0.6% in the low-risk tier (score, 0–4), 1.5% in the moderate-risk tier (score, 5–7), and 3.4% in the high-risk tier (score, 8–10). ACRN risk increased 2.5-fold (95% confidence interval [CI], 1.8–3.4) in the moderate-risk tier and 5.8-fold (95% CI, 3.4–9.8) in the high-risk tier compared with the low-risk tier. YCS score identified better balanced accuracy (53.9%) than APCS (51.5%) and KCS (50.7%) scores and had relatively good discriminative power (area under the curve=0.660). Conclusions YCS score based on clinical and laboratory risk factors was clinically effective and beneficial for predicting ACRN risk and targeting screening colonoscopy in adults aged <50 years

Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial

Background This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). Methods This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. Results At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by − 6.60 for CN and − 6.63 for DQ group (all P < 0.0001, P = 0.9739 between groups). TBUT and Schirmer values for CN were significantly improved from the baseline at 4 and 12 weeks (P = 0.0034, P < 0.0001 for TBUT, P = 0.0418, P = 0.0031 for Schirmer test). However, for DQ, TBUT showed significant improvement at 12 weeks only (P = 0.0281). Mean OSDI score differences from the baseline to 12 weeks were improved by − 13.03 ± 19.63 for CN and − 16.11 ± 20.87 for DQ, respectively (all P < 0.0001, P = 0.854 between groups). Regarding drug compliance, the mean instillation frequency of CN was less than that of DQ (P < 0.001). There were no statistically significant intergroup differences in safety evaluation. Conclusions The level of improvement regarding NEI, TBUT, and OSDI scores were not significantly different between the two treatment groups. However, with regards to the early improvement of TBUT and patient compliance, patients using CN improved faster and with greater adherence to drug usage than did those treated with DQ. Trial registration KCT0002180, retrospectively registered on 23 December 2016.This study was supported by an unrestricted educational grant from Taejoon Pharm (Seoul, Korea), which affords funding only, but has not any other contribution to our research

The influence of waist circumference on insulin resistance and nonalcoholic fatty liver disease in apparently healthy Korean adults

Background/AimsWaist circumference (WC) is a risk factor for metabolic syndrome and is related to insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to determine the association between WC and IR and NAFLD in apparently healthy Korean adults.MethodsThe volunteers included in this cross-sectional study comprised 9,159 adults (5,052 men, 4,107 women) who participated in a comprehensive health checkup program. IR was evaluated by the homeostasis model assessment of IR (HOMA-IR) and was considered to be present when the HOMA-IR score was >2. NAFLD was evaluated by ultrasound examination. Elevated alanine aminotransferase (ALT) was defined as >40 IU/L in men and >35 IU/L in women. Logistic regression was performed to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) for NAFLD, IR, and ALT according to categorized levels of WC.ResultsNAFLD was found in 2,553 (27.9%) of the participants (82.6% men, 17.4% women), while IR and elevated ALT were found in 17.2% (68.1% men, 31.9% women) and 10% (83% men, 17% women), respectively. After adjusting for confounding factors, the prevalence of NAFLD, IR, and elevated ALT was significantly associated with increases in WC quartile: highest quartile for NAFLD in men, OR=15.539, 95% CI=12.687-19.033; highest quartile for NAFLD in women, OR=48.732, 95% CI=23.918-99.288 (P<0.001); and highest quartile for IR in men, OR=17.576, 95% CI=13.283-23.255; highest quartile for IR in women, OR=11.078, 95% CI=7.813-15.708 (P<0.001); highest quartile for elevated ALT in men, OR=7.952, 95% CI=6.046-10.459; and highest quartile for elevated ALT in women, OR=8.487, 95% CI=4.679-15.395 (P<0.001).ConclusionsWC contributes to IR and NAFLD in apparently healthy Korean adults, and thus may be an important factor in the development of IR and NAFLD