A general strategy was developed to transform aptamers into highly sensitive and selective optical sensors. This was accomplished with an unmodified aptamer as the molecular recognition element and a ...competitor oligo, which was completely or partially complementary to the aptamer, as the signal transduction element. Displacement of competitor oligos in the presence of targets resulted in a detectable optical readout. Successful application of this strategy has been demonstrated not only with different types of targets (small molecules and proteins), but also with different types of aptamers (DNA and RNA). This strategy has high potential for various applications in high-throughput drug screening and intracellular studies.
Kidney transplant recipients who have abnormally high creatinine levels in their blood often have allograft dysfunction secondary to rejection. Creatinine has become the preferred marker for renal ...dysfunction and is readily available in hospital clinical settings. We developed a rapid and accurate polymer-based electrochemical point-of-care (POC) assay for creatinine detection from whole blood to identify allograft dysfunction. The creatinine concentrations of 19 blood samples from transplant recipients were measured directly from clinical serum samples by the conducting polymer-based electrochemical (EC) sensor arrays. These measurements were compared to the traditional clinical laboratory assay. The time required for detection was <5 min from sample loading. Sensitivity of the detection was found to be 0.46 mg/dL of creatinine with only 40 μL sample in the creatinine concentration range of 0 mg/dL to 11.33 mg/dL. Signal levels that were detected electrochemically correlated closely with the creatinine blood concentration detected by the UCLA Ronald Reagan Medical Center traditional clinical laboratory assay (correlation coefficient = 0.94). This work is encouraging for the development of a rapid and accurate POC device for measuring creatinine levels in whole blood.
AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma(HCC) recurrence for up to 3 year following curative resection. ...METHODS: A total of 143 patients(83.1% of the 172 participants in the phase Ⅱ study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase Ⅱ trial. Safety parameters and the following efficacy endpoints were investigated:(1) time to recurrence;(2) diseasefree survival; and(3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group:(1) the recurrence-free rate increased from 50% to 63%, and(2) time to recurrence at the 36 th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate(11 out of 54 patients). Additionally, subgroup analyses of patients with(1) multiple tumors or a single tumor ≥ 2 cm; and(2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage(56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.
The creation of micro air vehicles (MAVs) of the same general sizes and weight as natural fliers has spawned renewed interest in flapping wing flight. With a wingspan of approximately 15
cm and a ...flight speed of a few meters per second, MAVs experience the same low Reynolds number (10
4–10
5) flight conditions as their biological counterparts. In this flow regime, rigid fixed wings drop dramatically in aerodynamic performance while flexible flapping wings gain efficacy and are the preferred propulsion method for small natural fliers. Researchers have long realized that steady-state aerodynamics does not properly capture the physical phenomena or forces present in flapping flight at this scale. Hence, unsteady flow mechanisms must dominate this regime. Furthermore, due to the low flight speeds, any disturbance such as gusts or wind will dramatically change the aerodynamic conditions around the MAV. In response, a suitable feedback control system and actuation technology must be developed so that the wing can maintain its aerodynamic efficiency in this extremely dynamic situation; one where the unsteady separated flow field and wing structure are tightly coupled and interact nonlinearly. For instance, birds and bats control their flexible wings with muscle tissue to successfully deal with rapid changes in the flow environment. Drawing from their example, perhaps MAVs can use lightweight actuators in conjunction with adaptive feedback control to shape the wing and achieve active flow control. This article first reviews the scaling laws and unsteady flow regime constraining both biological and man-made fliers. Then a summary of vortex dominated unsteady aerodynamics follows. Next, aeroelastic coupling and its effect on lift and thrust are discussed. Afterwards, flow control strategies found in nature and devised by man to deal with separated flows are examined. Recent work is also presented in using microelectromechanical systems (MEMS) actuators and angular speed variation to achieve active flow control for MAVs. Finally, an explanation for aerodynamic gains seen in flexible versus rigid membrane wings, derived from an unsteady three-dimensional computational fluid dynamics model with an integrated distributed control algorithm, is presented.
Background and Aim
Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are important diagnostic tools for the non‐invasive assessment of hepatic steatosis (HS). This study was ...conducted to compare different magnetic resonance (MR) techniques and correlate the MR findings with histological and intracellular lipid density findings.
Methods
In this institutional review board‐approved, Health Insurance Portability and Accountability Act‐compliant prospective study, 60 patients scheduled for liver resection were included in this study. Fat fraction in the non‐tumorous liver parenchyma was estimated using double‐echo MRI, triple‐echo MRI (TE‐MRI), and MRS. HS was defined by the histologic steatosis percentage (HSP), and intrahepatocellular triglyceride density (IHTGD) of the surgical specimen used as the reference standard. Imaging quantification results were evaluated using Pearson's correlation. Lin's concordance coefficient and Bland–Altman 95% limits of agreement were used to evaluate the concordance of IHTGDs estimated by the three MR techniques. The diagnostic performance was compared using receiver operating characteristic curve analysis.
Results
HS assessed by TE‐MRI and MRS had a stronger relationship with HS assessed by HSP and IHTGD. The TE‐MRI method had the highest concordance correlation coefficients (ρ = 0.881) and percentage (95%, 57/60) within the Bland–Altman 95% limits of agreement. Receiver operating characteristic curve analysis for diagnosing > 5% HSP showed significantly larger area under the curve (0.9783) for TE‐MRI than for double‐echo MRI (0.8773, P = 0.0121).
Conclusions
Among the three MR techniques, TE‐MRI and MRS may be the preferred techniques for non‐invasive assessment of HS.
Background: The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy does not recommended surgery for treating BCLC stage B and C hepatocellular carcinoma (HCC). However, numerous ...Asia-Pacific institutes still perform surgery for this patient group. This consensus report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting aimed to share opinions and experiences pertaining to liver resection for intermediate and advanced HCCs and to provide evidence to issue recommendations for surgery in this patient group. Summary: Thirteen experts from five Asia-Pacific regions were invited to the meeting; 10 of them (Japan: 2, Taiwan: 3, South Korea: 2, Hong Kong: 1, and China: 2) voted for the final consensus. The discussion focused on evaluating the preoperative liver functional reserve and surgery for large tumors, multiple tumors, HCCs with vascular invasion, and HCCs with distant metastasis. The feasibility of future prospective randomized trials comparing surgery with transarterial chemoembolization for intermediate HCC and with sorafenib for advanced HCC was also discussed. The Child-Pugh score (9/10 experts) and indocyanine green retention rate at 15 min (8/10) were the most widely accepted methods for evaluating the preoperative liver functional reserve. All (10/10) experts agreed that portal hypertension, tumor size >5 cm, portal venous invasion, hepatic venous invasion, and extrahepatic metastasis are not absolute contraindications for the surgical resection of HCC. Furthermore, 9 of the 10 experts agreed that tumor resection may be performed for patients with >3 tumors. The limitations of surgery are associated with a poor liver functional reserve, incomplete tumor resection, and a high probability of recurrence. Key Messages: Surgery provides significant survival benefits for Asian-Pacific patients with intermediate and advanced HCCs, particularly when the liver functional reserve is favorable. However, prospective randomized controlled trials are difficult to conduct because of technical and ethical considerations.
Abstract Objective : To evaluate the role of surgery, radiation therapy and chemotherapy in the management of small cell carcinoma of the uterine cervix (SCCC) through a retrospective study of ...Taiwanese Gynecologic Oncology Group. Methods : We reviewed the medical records and histological files of 144 patients with FIGO stages IA–IIB SCCC treated in 11 main hospitals in Taiwan from 1987 to 2009. Results : There were 110 patients receiving primary surgery and 34 primary radiation therapy. Most patients in each group also received chemotherapy as part of primary treatment. A lower loco-regional failure rate was observed in patients who received primary radiation therapy than in those who had primary surgery (6% vs. 27%; P = 0.009). The 5-year overall survival (OS) was 89% for 13 surgically treated patients with cervical tumor ≤ 2 cm and no lymphovascular space involvement (LVSI) in whom recurrence was noted in 2 of 4 patients without receiving adjuvant chemotherapy and none in the 9 patients who had chemotherapy. Excluding these 13 patients, primary radiation therapy with at least 5 cycles of platinum-based chemotherapy ( n = 14, including 12 stages IB2–IIB) resulted in a 5-year OS of 78%, better than that of 46% by primary surgery ( n = 97, including 40 stages IB2–IIB) ( P = 0.046). Conclusions : None of the 9 patients with cervical tumor ≤ 2 cm and no LVSI showed disease recurrence after primary surgery and adjuvant chemotherapy. For most patients with stages I–II, primary radiation therapy with aggressive chemotherapy was associated with better survival than surgery.
Hepatic resection may offer long-term survival for patients with colorectal metastases. However, controversies exist regarding the prognostic factors. Herein, the impact of synchronicity of liver ...metastasis on patient clinicopathological features and prognosis was evaluated.
One hundred and fifty-five patients who underwent hepatectomy for colon cancer metastasis, from 1995 to 2004, were enrolled in this study. Patients were divided into two groups: synchronous and metachronous colorectal liver metastasis. Patient demographics, the nature of the primary and metastatic tumors, surgery-related complications, and long-term outcome were analyzed.
Patients included in the synchronous group tended to be younger than those in the metachronous group. Compared to the metachronous group, patients in the synchronous group showed more metastases (P = 0.008) and bilobarly distributed metastases (P = 0.016). Bile leakage was the most common surgical complication. The estimated 5-year disease-free and overall survival rates were 16.8 and 41.1%, respectively. Univariate analysis indicated that synchronous metastases, advanced stage of the primary tumor, bilobar distribution of the metastases, more than three metastases, and colonic versus rectal location of the primary tumor were prognostic factors of shorter disease-free survival, but not overall survival. Multivariate analysis revealed that synchronous metastases and the advanced stage of the primary tumor were indicators for a worse disease-free survival.
The synchronous presence of primary colon cancer and liver metastasis may indicate a more disseminated disease status and is associated with a shorter disease-free survival than metachronous metastasis. These patients may need more careful monitoring and aggressive chemotherapy following curative resection.
This study is aimed to investigate the risk factors and clinical characteristics of posttransplant lymphoproliferative disorder (PTLD) after conducting Epstein–Barr virus (EBV) viral load monitoring ...in pediatric liver transplant (LT) patients in Taiwan, where EBV infection is endemic.
From 2007 to 2013, pediatric LT recipients who underwent EBV viral load monitoring within 3 months after LT were recruited in this study. The impact of clinical parameters—including age at LT, sex, peak EBV viral load and immunosuppressant levels after LT—on the risk of PTLD were assessed.
A total 39 patients underwent LT at a median age of 1.3 years (range: 0.6–14.0 years), and 5 patients developed PTLD during follow-up. Cox's proportional-hazards model identified two predictors of PTLD: peak EBV viral load within 3 months of LT >4100 copies/μg peripheral blood mononuclear cells (PBMC) DNA and peak tacrolimus level within 3 months of LT >14.8 ng/mL (Hazard ratio = 17.14 and 11.54, P = 0.02 and 0.03, respectively). Kaplan–Meier survival analysis revealed significant higher cumulative incidence rates of PTLD (27.3% and 41.8% at 0.3 and 1.2 years after LT) in subjects with peak EBV viral load >4100 copies/μg PBMC DNA within 3 months after LT. (P = 0.001, log-rank test).
Close monitoring of EBV viral load within 3 months after LT is helpful to predict a high risk of PTLD. Tapering of immunosuppressants is suggested if the EBV viral load is >4100 copies/μg PBMC DNA in LT children.
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