Development of a miniaturized, reconnectable, and implantable multichannel connector.

Objective. Connectors for implantable neural prosthetic systems provide several advantages such as simplification of surgery, safe replacement of implanted devices, and modular design of the implant systems. With the rapid advancement of technologies for neural implants, miniaturized multichannel implantable connectors are also required. In this study, we propose a reconnectable and area-efficient multichannel implantable connector.Approach. A female-to-female adapter was fabricated using the thermal-press bonding of micropatterned liquid crystal polymer films. A bump inside the adapter enabled a reliable electrical connection by increasing the contact pressure between the contact pads of the adapter and the inserted cable. After connection, the adapter is enclosed in a metal case sealed with silicone elastomer packing. With different sizes of the packings, leakage current tests were performed under accelerated conditions to determine the optimal design for long-term reliability. Repeated connection tests were performed to verify the durability and reconnectability of the fabricated connector. The connector was implanted in rats, and the leakage currents were monitored to evaluate the stability of the connectorin vivo. Main results. The fabricated four- and eight-channel implantable connectors, assembled with the metal cases, had a diameter and length of 6 and 17 mm, respectively. Further, the contact resistances of the four- and eight-channel connectors were 53.2 and 75.2 mΩ, respectively. The electrical contact remained stable during repeated connection tests (50 times). The fabricated connectors with packings having 125%, 137%, and 150% volume ratios to the internal space of the metal case failed after 14, 88, and 14 d, respectively, in a 75 °C saline environment. In animal tests with rats, the connector maintained low leakage current levels for up to 92 d.Significance. An implantable and reconnectable multichannel connector was developed and evaluated. The feasibility of the proposed connector was evaluated in terms of electrical and mechanical characteristics as well as sealing performance. The proposed connector is expected to have potential applications in implantable neural prosthetic systems.

Surface Wettability Prediction Using Image Analysis and an Artificial Neural Network.

In this study, a wettability-predicting method that uses an artificial neural network (ANN) by learning from digital images of the actual surface structures was developed. Polyester film surfaces were treated with oxygen plasma to realize various nanostructured surfaces. Surface structural characteristics from SEM images were quantified in a multifaceted way using a box-counting algorithm, a gray-level co-occurrence matrix algorithm, and binary image analysis. An ANN model that can predict wettability from surface structures was developed using the quantified surface structure and the resulting wettability as learning data. Furthermore, a surface with an optimal nanostructure to achieve superhydrophobicity was suggested by considering extracted surface structural parameters that significantly affect the surface wettability.

Molecular and Serological Investigation of Severe Fever with Thrombocytopenia Syndrome Virus in Cats.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis in China, the Republic of Korea (ROK), and Japan. The presence of the SFTS virus (SFTSV) in companion, livestock, and wild animals has been reported. Recently, human SFTS-like clinical symptoms in cats and cheetahs have been reported in Japan. Therefore, the prevalence of the SFTSV gene or antibody in cats is important for public health as well as veterinary medicine. Materials and Methods: Sera were collected from 201 feral and house cats in the ROK in 2017. Samples were analyzed for the presence of the SFTSV gene after RT-nested PCR amplification and for anti-SFTSV antibodies after enzyme linked immunosorbent assay. Results: Eight (4.0%) and nine (4.5%) of 201 cat sera were found to be positive for the SFTSV gene and anti-SFTSV nucleocapsid protein antibodies, respectively. Specifically, 5.9% feral and 2.0% house cats were positive for the SFTSV gene, and 6.9% feral and 2.0% house cats were positive for anti-SFTSV antibodies. All sequences of the SFTSV S segment obtained were included in Japanese/Korean SFTSV clades, as opposed to the Chinese clade. Conclusions: This study constitutes the first serological study of SFTSV in house and feral cats in the ROK. Evidence of SFTSV in companion animals indicates that SFTSV can circulate in homes and that more intensive precautions and education measures are needed for companion animal guardians and veterinarians.

Objective quantification of surface roughness parameters affecting superhydrophobicity.

This study proposes new optical roughness parameters that can be objectively quantified using image processing techniques, and presents an analysis of how these parameters are correlated with the degree of superhydrophobicity. To this end, photolithography and dry etching processes were used to form regular square pillars with different heights and spacings with a length of tens of micro-meters on silicon wafers. Optical roughness parameters of the specimens were obtained using image processing, and surface wettability was characterized using static contact angle and sliding angle measurements for water droplets of volume V D = 3.5 µl or 12 µl. As a result, seven optical roughness parameters were derived to describe the surface roughness topography in a multi-faceted way. Between the Cassie-Baxter state and the Wenzel state, two distinct wetting states intermediate state I, and intermediate state II were observed. Multiple linear regression of optical roughness parameters and superhydrophobicity demonstrated that in the stable Cassie-Baxter state, the contact angle can be increased or sliding angle decreased more effectively by adjusting the spacing between pillars than by just tuning the solid area fraction. However, in the metastable state where the Cassie-Baxter state can be changed to intermediate state I and vice versa by adjusting V D or surface geometry, reducing the solid area fraction is a priority to ensure a stable Cassie-Baxter state. Horizontal-perspective roughness parameters had a great effect on dynamic wettability in the Cassie-Baxter state. The results confirmed that the proposed optical roughness parameters may be useful for quantitative analysis of the complex effects of roughness on superhydrophobic surfaces.

Clinical Potential of Circulating Tumor Cells in Colorectal Cancer: A Prospective Study.

OBJECTIVES: Circulating tumor cells (CTCs) in the blood have been used as diagnostic markers in patients with colorectal cancer (CRC). In this study, we evaluated a CTC detection system based on cell size to assess CTCs and their potential as early diagnostic and prognostic biomarkers for CRC. METHODS: From 2014 to 2015, 88 patients with newly diagnosed CRC, who were scheduled for surgery, and 31 healthy volunteers were enrolled and followed up in Pusan National University Hospital. CTCs were enriched using a centrifugal microfluidic system with a new fluid-assisted separation technique (FAST) and detected by cytomorphological evaluation using fluorescence microscopy. RESULTS: Two or more CTCs were detected using FAST in 74 patients and 3 healthy volunteers. The number of CTCs in the CRC group was significantly higher than that in the healthy volunteers (P < 0.001). When a receiver operating characteristic curve was created to differentiate patients with CRC from healthy volunteers, the sensitivity and specificity were almost optimized when the critical CTC value was 5/7.5 mL of blood. When this value was used, the sensitivity and specificity in differentiating patients with CRC from the healthy controls were 75% and 100%, respectively. In patients with CRC with ≥5 CTCs, vascular invasion was frequently identified (P = 0.035). All patients with stage IV were positive for CTCs. Patients with ≥5 CTCs showed a trend toward poor overall and progression-free survival. DISCUSSION: Our study demonstrated promising results with the use of FAST-based CTC detection for the early diagnosis and prognosis of CRC.

Circulating tumor cells detected by lab-on-a-disc: Role in early diagnosis of gastric cancer.

BACKGROUND: The use of circulating tumor cells (CTCs) as an early diagnostic biomarker and prognostic indicator after surgery or chemotherapy has been suggested for various cancers. This study aimed to evaluate CTCs in patients who underwent gastrectomy for gastric cancer and to explore their clinical usefulness in the early diagnosis of gastric cancer. METHODS: A total of 116 patients with gastric cancer who underwent gastrectomy and 31 healthy volunteers were prospectively included between 2014 and 2015. Peripheral blood samples were collected before gastrectomy, and CTCs were examined using a centrifugal microfluidic system with a new fluid-assisted separation technique. RESULTS: After creating a receiver operating characteristic curve to identify the discriminative CTC value needed differentiate patients with gastric cancer from healthy volunteers, sensitivity and specificity were nearly optimized at a CTC threshold of 2 per 7.5 mL of blood. Of the 102 persons with a CTC level ≥2 per 7.5 mL of blood, 99 (97.1%) had gastric cancer, and of the 45 persons with a CTC level <2 per 7.5 mL of blood, 28 (62.2%) were healthy controls. Accordingly, the sensitivity and specificity for the differentiation of patients with gastric cancer from healthy controls were 85.3% and 90.3%, respectively. However, the presence of CTCs was not associated with any clinicopathologic features such as staging, histologic type, or mucin phenotype. CONCLUSION: Although we could not prove the clinical feasibility of CTCs for gastric cancer staging, our results suggest a potential role of CTCs as an early diagnostic biomarker of gastric cancer.

An epigenomic signature of postprandial hyperglycemia in peripheral blood leukocytes.

Postprandial hyperglycemia is known to be one of the earliest signs of abnormal glucose homeostasis associated with type 2 diabetes. This study aimed to assess clinical significance of a 1-h postprandial glucose level for the development of diabetes, and identify epigenetic biomarkers of postprandial hyperglycemia. We analyzed clinical data from the oral glucose tolerance tests for healthy subjects (n=4502). The ratio (Glu60/Glu0) of 1-h glucose levels to fasting glucose levels was significantly associated with an insulin sensitive index (QUICKI, quantitative insulin sensitivity check index) (ß=0.055, P=1.25E-04) as well as a risk of future pre-diabetic and diabetic conversion. Next, DNA methylation profile analyses of 24 matched pairs of the high and low Glu60/Glu0 ratio subjects showed that specific DNA methylation levels in the promoter region of an olfactory receptor gene (olfactory receptor gene family10 member A4, OR10A4) were associated with the Glu60/Glu0 ratios (ß=0.337, P=0.03). Moreover, acute oral glucose challenges decreased the DNA methylation levels of OR10A4 but not the global DNA methylation in peripheral leukocytes of healthy subjects (n=7), indicating that OR10A4 is a specific epigenomic target of postprandial hyperglycemia. This work suggests possible relevance of olfactory receptor genes to an earlier molecular biomarker of peripheral hyperglycemia and diabetic conversion.

Two-year clinical outcomes of patients with long segments drug-eluting stents: comparison of sirolimus-eluting stent with paclitaxel-eluting stent.

Limited data are available on the long-term clinical efficacy of drug-eluting stent (DES) in diffuse long lesions. From May 2006 to May 2007, a total of 335 consecutive patients (374 lesions) were underwent percutaneous coronary intervention with implantation of long DES (≥ 30 mm) in real world practice. Eight-month angiographic outcomes and 2-yr clinical outcomes were compared between SES (n = 218) and PES (n = 117). Study endpoints were major adverse cardiac events including cardiac death, myocardial infarction, target-lesion revascularization, target-vessel revascularization and stent thrombosis. Baseline characteristics were similar in the two groups as were mean stent length (44.9 ± 15.2 mm in SES and 47.4 ± 15.9 in PES, P = 0.121). Late loss at 8 months follow-up was significantly lower in SES than in PES group (0.4 ± 0.6 mm in SES vs 0.7 ± 0.8 mm in PES, P = 0.007). Mean follow-up duration was 849 ± 256 days, and 2-yr cumulative major adverse cardiac events were significantly lower in the SES than in the PES group (5.5% in SES vs 15.4% in PES, P = 0.003). In conclusion, long-term DES use in diffuse long coronary lesions is associated with favorable results, with SES being more effective and safer than PES in this real-world clinical experience.

Relationship between symptom-onset-to-balloon time and long-term mortality in patients with acute myocardial infarction treated with drug-eluting stents.

BACKGROUND: Time from hospital arrival to reperfusion in ST-segment elevation myocardial infarction (STEMI) has been predictive of in-hospital mortality. The purpose of this study was to evaluate the relationship between symptom-onset-to-balloon time and long-term mortality in patients with STEMI in the drug-eluting stent (DES) era. METHODS: A series of 393 patients with STEMI treated with DES from 2005 to 2007 was stratified according to risk profile and preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow grade, and clinical, angiographic, and follow-up data were collected. RESULTS: A total of 98 (24.9%) low-risk patients and 295 (75.1%) non-low-risk patients were identified. Three-year mortality rate was 3.1% for low-risk patients and 10.2% for non-low-risk patients (p=0.034), respectively; however it did not differ according to symptom-onset-to-balloon time in either low-risk (p=0.333) or non-low-risk patients (p=0.881). Similarly, symptom-onset-to-balloon time and mortality were not related to preprocedural TIMI flow (p=0.474 for TIMI 0-1; p=0.428 for TIMI 2-3). In multivariate analysis, final TIMI flow 0-2, systolic blood pressure <100 mmHg at admission, age ≥70 years, anterior infarction, C-reactive protein level, and peak creatine kinase myocardial band isoenzyme level were identified as independent predictors of 3-year mortality while symptom-onset-to-balloon time and preprocedural TIMI flow were not. CONCLUSIONS: In STEMI patients treated with DES, symptom-onset-to-balloon time does not affect long-term outcomes even in individuals at non-low risk and with poor preprocedural TIMI flow grade.

Clinical and angiographic outcomes of drug-eluting stents in patients with large vessel and single coronary artery lesion.

BACKGROUND: The aim of this study was to evaluate and compare the clinical and angiographic outcomes of 3 drug-eluting stents (DES) in patients with large vessel diameter and single coronary artery lesions. HYPOTHESIS: The efficacy of 3 DESs may be similar. METHODS: A total of 411 consecutive patients who visited 3 university hospitals from June 2004 to December 2007 and had a single coronary lesion which was treated with the use of a DES that was 3.5 mm in diameter were enrolled in this study. Patients were divided into 3 stent groups: Paclitaxel-eluting stent (PES, n = 105), Sirolimus-eluting stent (SES, n = 259), and Zotarolimus-eluting stent (ZES, n = 47). The study end point was a composite of major adverse cardiac events (MACE) including cardiac death, myocardial infarction (MI), and ischemia-driven target-vessel revascularization (TVR) for 12 months. RESULTS: Baseline characteristics were not different. Late loss was higher in the ZES group than the other stents (0.5 +/- 0.4 mm in SES vs 0.3 +/- 0.5 mm in PES, 0.7 +/- 0.5 mm in ZES, P = 0.001). The total MACE-free survival rate was not significantly different between the SES group and the PES group (98.8% in SES vs 97.1% in PES, P = 0.252) or the PES group and the ZES group (97.1% in PES vs 93.6% in ZES, P = 0.301). However, the SES group showed a significantly better MACE-free survival rate compared with the ZES group (98.8% in SES vs 93.6% in ZES, P = 0.018). CONCLUSIONS: Clinical and angiographic outcomes of DES in a large vessel diameter and single coronary artery is excellent and SES appears to show better angiographic and clinical outcomes than ZES.

Therapeutic strategy for in-stent restenosis based on the restenosis pattern after drug-eluting stent implantation.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the outcomes of repeated percutaneous coronary intervention (PCI) based on the restenosis pattern in drug-eluting stent (DES) failure. SUBJECTS AND METHODS: From April 2003 to March 2006, all 67 patients (67 lesions) at our 3 centers who had DES in-stent restenosis (ISR) were enrolled. The patients were divided into 3 groups: group I had focal edge restenosis, group II had focal body restenosis, and group III had non-focal restenosis. All patients were treated with conventional PCI including plain old balloon angioplasty (POBA), cutting balloon angioplasty (CBA), and repeated DES implantation (Re-DES). Angiographic and clinical one year follow-up results for the 3 groups were evaluated. RESULTS: Sixteen patients were enrolled in group I, 36 in group II, and 15 in group III. Baseline clinical and angiographic characteristics and the proportion of patients in each group receiving each type of treatment strategy were not significantly different among the groups. Within each group, a comparison of angiographic and clinical outcomes for each therapeutic modality revealed that restenosis rates were not statistically different. Although rates of major adverse cardiac events (MACE) were not statistically different between groups I and II, in group III, MACE were 3-fold higher for the POBA (4/4, 100.0%) and CBA (4/4, 100.0%) subgroups than for Re-DES (1/3, 33.3%) (p=0.06), but the differences did not reach statistical significance. CONCLUSION: THE PRESENT STUDY SUGGESTS THAT TREATMENT OF DES ISR SHOULD BE INDIVIDUALIZED ACCORDING TO RESTENOSIS PATTERN: any PCI strategy appears appropriate for focal ISR patterns, while Re-DES might be a better choice for non-focal ISR patterns.

Long-term clinical outcomes after angiographically defined very late stent thrombosis of drug-eluting stent.

BACKGROUND: The advent of drug-eluting stent (DES) use has raised concerns regarding later occurring stent thrombosis, especially very late stent thrombosis (VLST), and little is known about long-term clinical outcomes after VLST occurrence. HYPOTHESIS: Long-term clinical outcomes after detection of VLST may be poor. METHOD: We evaluated 3572 consecutive patients who received DES implantation from May 2004 to July 2007 at 3 hospitals. The primary outcomes were a composite of major adverse cardiac events (MACE) including cardiac death, myocardial infarction (MI), target-lesion revascularization (TLR), and target-vessel revascularization (TVR) after VLST occurrence. RESULTS: We identified 19 patients (0.53%) with angiographically documented stent thrombosis developing over 1 year after DES implantation. The mean time to VLST occurrence was 899 days (899 +/- 353). Discontinuation of antiplatelet drugs was noted in 4 (21%) patients and the average duration of discontinuation was 4 days. Clinical presentations of VLST were mainly MI (17 patients, 89%). Balloon angioplasty was only performed in 12 patients (63%) and stent implantation in 7 patients (37%). Mean follow-up duration from VLST occurrence was 620 days (620+/-256). During clinical follow-up after VLST occurrence, no cardiac deaths or MIs were detected. Target-vessel revascularization was done in 2 (11%) patients and TLR in 1 patient (6%). Major adverse cardiac events occurred in 3 (16%) patients during long-term clinical follow-up. CONCLUSIONS: Clinical presentation of VLST after DES implantation is associated with serious adverse events, such as MI. Long-term follow-up outcomes after VLST occurrence appear unfavorable and more data from larger studies are warranted.

Two-year outcomes of the sirolimus-eluting stent according to unprotected left main lesion.

BACKGROUND: The data of long-term outcomes of sirolimus-eluting stent (SES) according to lesion location of unprotected left main coronary artery (LMCA) is scarce. HYPOTHESIS: The purpose of this study was to evaluate the long-term outcomes after implantation of the SES in LMCA. METHODS: A total of 84 patients (51 males) who had undergone SES implantation for the treatment of native LMCA stenosis were enrolled. The patients were divided into 2 groups based on angiographic lesion location: those with significant stenosis in the ostium and/or body (group 1; n = 39) and those involving bifurcation (group 2; n = 45). RESULTS: All of the group 1 patients were treated with simple lesion coverage while different stenting techniques were used in group 2 (cross-over: 44.8%, T: 6.7%, kissing: 37.8%, and crush techniques: 11.1%). The 8-month quantitative angiographic findings and in-hospital and 2 year rates of major adverse cardiac events (MACE) were compared between the 2 groups. Although angiographic success and in-hospital MACE rates were similar in both groups with 1 cardiac death due to acute stent thrombosis in group 2, at 2-year follow-up, the MACE rate was significantly higher in group 2 than in group 1 at 2 years (22.2% vs 2.6%, respectively, P = 0.008). Coronary angiography revealed a significantly higher binary restenosis rate in group 2 compared with group 1 (20% vs 0%, respectively, P = 0.003). CONCLUSIONS: Interventional treatment using SES in left main lesions showed favorable short-term and long-term outcomes in selected patients with lesion location being an important determinant of clinical and angiographic outcomes.