Long-Term Follow-Up of Inpatients with Rotator Cuff Tear Who Received Integrative Korean Medicine Treatment: A Retrospective Analysis and Questionnaire Survey.

CONTEXT: Rotator cuff tear is one of the most common causes of shoulder pain and has become a prominent disease most frequently treated by surgery. OBJECTIVES: To investigate the long-term therapeutic effect of integrative Korean medicine (KM) as a conservative treatment in treating rotator cuff tears. DESIGN: A multicenter observational study. SETTINGS: The settings involve four regional network KM hospitals. PATIENTS: The study participants are 288 patients aged 19-70 with rotator cuff tear identified by radiologist based on magnetic resonance imaging who received integrative KM treatment for the chief complaint of shoulder pain between 1 January 2015 and 31 March 2020. INTERVENTION: None. MAIN OUTCOMES: The primary outcome was the pain score in the affected shoulder, measured by the numeric rating scale (NRS). The secondary outcomes were Shoulder Pain and Disability Index (SPADI), 5-Level Quality of life: EuroQol 5-Dimension (EQ-5D-5L), Patient Global Impression of Change (PGIC), and range of motion (ROM) scores. RESULTS: Eligible patients for MCID achievement analysis for minimally clinical important change were 167, and 109 completed the follow-up survey. The mean NRS pain score in the affected shoulder was 5.80 ± 1.27 at admission, 3.50 ± 1.32 at discharge, and 3.83 ± 2.04 at follow-up.The mean SPADI score was 51.48 ± 20.18 at admission, 37.76 ± 19.23 at discharge, and 24.26 ± 21.80 at follow-up. The improvement at discharge (P-value < 0.001) and follow-up (P-value < 0.001) compared to those at admission was statistically significant. The results also presented a significant improvement in ROM for all motions at discharge after treatment (P-value < 0.001). The number of patients who achieved minimal clinically important difference in NRS was 116 (69.5%) at discharge and 71 (65.1%) at follow-up, and in SPADI was 82 (50.9%) at discharge and 77 (70.6%) at follow-up. CONCLUSION: The results of this study suggested that integrative KM treatment can help improve pain, functional impairment, QoL, and ROM in patients with a rotator cuff tear TRIAL REGISTRATION: NCT04566939.

Synthesis of Isolated DNA Aptamer and Its Application of AC-Electrothermal Flow-Based Rapid Biosensor for the Detection of Dengue Virus in a Spiked Sample.

Dengue fever is an infectious disease caused by the dengue virus (DENV) and is transmitted by mosquitoes in tropical and subtropical regions. The early detection method at a low cost is essential. To address this, we synthesized the isolated DENV aptamer for fabricating a rapid electrochemical biosensor on a Au interdigitated microgap electrode (AuIMGE). The DENV aptamers were generated using the SELEX (systemic evolution of ligands by exponential enrichment) method for binding to DENV surface envelope proteins. To reduce the manufacturing cost, unnecessary nucleotide sequences were excluded from the isolation process of the DENV aptamer. To reduce the detection time, the alternating current electrothermal flow (ACEF) technique was applied to the fabricated biosensor, which can shorten the detection time to 10 min. The performance of the biosensor was evaluated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). In the diluted DENV protein solution, the linear range of the concentrations was from 1 pM to 1 µM and the LOD was 76.7 fM. Moreover, the proposed biosensor detected DENV in a diluted spiked sample at a linear range of 10-6 to 106 TCID50/mL, while the detection performance was proven with an LOD of 1.74 × 10-7 TCID50/mL along with high selectivity.

Extended-Gate Field-Effect Transistor Consisted of a CD9 Aptamer and MXene for Exosome Detection in Human Serum.

Cancer progresses silently to the terminal stage of the impossible operable condition. There are many limitations in the treatment options of cancer, but diagnosis in an early stage can improve survival rates and low recurrence. Exosomes are the biomolecules released from cancer cells and are promising candidates for clinical diagnosis. Among them, the cluster of differentiation 9 (CD9) protein is an important exosomal biomarker that can be used for exosome determination. Therefore, here, a CD9 aptamer was first synthesized and applied to an extended-gate field-effect transistor (EGFET)-type biosensor containing a disposable sensing membrane to suggest the possibility of detecting exosomes in a clinical environment. Systematically evaluating ligands using the exponential enrichment (SELEX) technique was performed to select nucleic acid sequences that can specifically target the CD9 protein. Exosomes were detected according to the electrical signal changes on a membrane, which is an extended gate using an Au microelectrode. The fabricated biosensor showed a limit of detection (LOD) of 10.64 pM for CD9 proteins, and the detection range was determined from 10 pM to 1 µM in the buffer. In the case of the clinical test, the LOD and detection ranges of exosomes in human serum samples were 6.41 × 102 exosomes/mL and 1 × 103 to 1 × 107 exosomes/mL, respectively, showing highly reliable results with low error rates. These findings suggest that the proposed aptasensor can be a powerful tool for a simple and early diagnosis of exosomes.

Fast-response electrochemical biosensor based on a truncated aptamer and MXene heterolayer for West Nile virus detection in human serum.

West Nile virus (WNV) is a mosquito-borne flavivirus that can cause West Nile fever, meningitis, encephalitis, and polio. Early detection of WNV is important to prevent infection spread on the field. To commercialize the electrochemical biosensor for WNV, rapid target detection with the cheap manufacture cost is essential. Here, we developed a fast-response electrochemical biosensor consisting of a truncated WNV aptamer/MXene (Ti3C2Tx) bilayer on round-type micro gap. To reduce the target binding time, the application of the alternating current electrothermal flow (ACEF) technology reduced the target detection time to within 10 min, providing a rapid biosensor platform. The MXene nanosheet improved electrochemical signal amplification, and the aptamer produced through systematic evolution of ligands by exponential enrichment process eliminated unnecessary base sequences via truncation and lowered the manufacturing cost. Under optimized conditions, the WNV limit of detection (LOD) and selectivity were measured using electrochemical measurement methods, including cyclic voltammetry and square wave voltammetry. The LOD was 2.57 pM for WNV diluted in deionized water and 1.06 pM for WNV diluted in 10% human serum. The fabricated electrochemical biosensor has high selectivity and allows rapid detection, suggesting the possibility of future application in the diagnosis of flaviviridae virus.

Construction of a rapid electrochemical biosensor consisting of a nanozyme/aptamer conjugate for waterborne microcystin detection.

Microcystin-LR (MC-LR) is a hepatotoxin generated by the excessive proliferation of cyanobacteria, which is a threat to humans and wildlife. Therefore, rapid detection of MC-LR is an important challenge. This study describes a rapid electrochemical biosensor comprising nanozymes and aptamers. Alternating current electrothermal flow (ACEF) significantly reduced the MC-LR detection period to 10 min. We also used MnO2/MC-LR aptamer conjugates to improve the sensitivity to MC-LR detection. Here, MnO2 amplified the electrochemical signal and the aptamer showed high selectivity for MC-LR. Under the optimal conditions, the limit of detection (LOD) and selectivity in freshwater were detected using cyclic voltammetry and differential pulse voltammetry. As a result, an LOD of 3.36 pg mL-1 was observed in the linear concentration range of 10 pg mL-1 to 1 µg mL-1. This study quickly and sensitively detected MC-LR in a situation where it causes serious damage worldwide. In addition, the ACEF technology introduction is the first example of MC-LR detection, suggesting a wide range of possibilities for MC-LR biosensors.

Recent Developments in DNA-Nanotechnology-Powered Biosensors for Zika/Dengue Virus Molecular Diagnostics.

Zika virus (ZIKV) and dengue virus (DENV) are highly contagious and lethal mosquito-borne viruses. Global warming is steadily increasing the probability of ZIKV and DENV infection, and accurate diagnosis is required to control viral infections worldwide. Recently, research on biosensors for the accurate diagnosis of ZIKV and DENV has been actively conducted. Moreover, biosensor research using DNA nanotechnology is also increasing, and has many advantages compared to the existing diagnostic methods, such as polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). As a bioreceptor, DNA can easily introduce a functional group at the 5' or 3' end, and can also be used as a folded structure, such as a DNA aptamer and DNAzyme. Instead of using ZIKV and DENV antibodies, a bioreceptor that specifically binds to viral proteins or nucleic acids has been fabricated and introduced using DNA nanotechnology. Technologies for detecting ZIKV and DENV can be broadly divided into electrochemical, electrical, and optical. In this review, advances in DNA-nanotechnology-based ZIKV and DENV detection biosensors are discussed.

Improving Biosensors by the Use of Different Nanomaterials: Case Study with Microcystins as Target Analytes.

The eutrophication of lakes and rivers without adequate rainfall leads to excessive growth of cyanobacterial harmful algal blooms (CyanoHABs) that produce toxicants, green tides, and unpleasant odors. The rapid growth of CyanoHABs owing to global warming, climate change, and the development of rainforests and dams without considering the environmental concern towards lakes and rivers is a serious issue. Humans and livestock consuming the toxicant-contaminated water that originated from CyanoHABs suffer severe health problems. Among the various toxicants produced by CyanoHABs, microcystins (MCs) are the most harmful. Excess accumulation of MC within living organisms can result in liver failure and hepatocirrhosis, eventually leading to death. Therefore, it is essential to precisely detect MCs in water samples. To date, the liquid chromatography-mass spectrometry (LC-MS) and enzyme-linked immunosorbent assay (ELISA) have been the standard methods for the detection of MC and provide precise results with high reliability. However, these methods require heavy instruments and complicated operation steps that could hamper the portability and field-readiness of the detection system. Therefore, in order for this goal to be achieved, the biosensor has been attracted to a powerful alternative for MC detection. Thus far, several types of MC biosensor have been proposed to detect MC in freshwater sample. The introduction of material is a useful option in order to improve the biosensor performance and construct new types of biosensors. Introducing nanomaterials to the biosensor interface provides new phenomena or enhances the sensitivity. In recent times, different types of nanomaterials, such as metallic, carbon-based, and transition metal dichalcogenide-based nanomaterials, have been developed and used to fabricate biosensors for MC detection. This study reviews the recent advancements in different nanomaterial-based MC biosensors.