Antioxidant and Anti-Fatigue Effects of a Standardized Botanical Extract Fraction (HemoHIM) in Forced-Exercised Aged Mice.

HemoHIM is a standardized medicinal herbal preparation consisting of extracts of Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia lactiflora Pallas that possesses immune regulatory activities. This study aimed to research the potential antioxidant effects of HemoHIM and its capacity for reducing fatigue in aged mice subjected to forced exercise. After administering HemoHIM 125 (500 mg/kg orally) for 4 weeks in 8-month-old female C57BL/6 mice (4 groups of 10 mice), various parameters were evaluated. The analyses revealed that HemoHIM enhanced swimming time and grip strength. In addition, it significantly reduced serum lactate levels and increased liver glutathione peroxidase (GPx) levels after exercise challenge. The expression levels of antioxidant enzymes and factors, including nuclear factor erythroid 2-related factor-2 (Nrf-2), heme oxygenase 1, superoxide dismutase, GPx, and glutathione reductase, were significantly higher in liver and muscle tissues of mice treated with HemoHIM. These results indicate that HemoHIM might function as an anti-fatigue and antioxidant agent by modulating the Nrf-2 signaling pathway.

Dual-Mode Graphene Field-Effect Transistor Biosensor with Isothermal Nucleic Acid Amplification.

Despite a substantial increase in testing facilities during the pandemic, access remains a major obstacle, particularly in low-resource and remote areas. This constraint emphasizes the need for high-throughput potential point-of-care diagnostic tools in environments with limited resources. Loop-mediated isothermal amplification (LAMP) is a promising technique, but improvements in sensitivity are needed for accurate detection, especially in scenarios where the virus is present in low quantities. To achieve this objective, we present a highly sensitive detection approach of a dual-mode graphene-based field-effect transistor (G-FET) biosensor with LAMP. The G-FET biosensor, which has a transparent graphene microelectrode array on a glass substrate, detects LAMP products in less than 30 min using both observable color changes and Dirac point voltage measurements, even in samples with low viral concentrations. This dual-mode G-FET biosensor emerges as a potential alternative to conventional RT-PCR for severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-2 detection or point-of-care testing, particularly in resource-constrained scenarios such as developing countries. Moreover, its capacity for colorimetric detection with the naked eye enhances its applicability in diverse settings.

Arthroscopic Implantation of Adipose-Derived Stromal Vascular Fraction Improves Cartilage Regeneration and Pain Relief in Patients With Knee Osteoarthritis.

Purpose: To compare the pain relief and cartilage repair status of patients with knee osteoarthritis who received arthroscopic treatment with or without stromal vascular fraction (SVF) implantation. Methods: We retrospectively evaluated the patients who were examined with 12-month follow-up magnetic resonance imaging (MRI) after arthroscopic treatment for knee osteoarthritis from September 2019 to April 2021. Patients were included in this study if they had grade 3 or 4 knee osteoarthritis according to the Outerbridge classification in MRI. The visual analog scale (VAS) was used for pain assessment over the follow-up period (baseline and at 1-, 3-, 6-, and 12-month follow-ups). Cartilage repair was evaluated using follow-up MRIs based on Outerbridge grades and the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results: Among 97 patients who received arthroscopic treatment, 54 patients received arthroscopic treatment alone (conventional group) and 43 received arthroscopic treatment along with SVF implantation (SVF group). In the conventional group, the mean VAS score decreased significantly at 1-month post-treatment compared with baseline (P < .05), and gradually increased from 3 to 12 months' post-treatment (all P < .05). In the SVF group, the mean VAS score decreased until 12 months post-treatment compared with baseline (all P < .05 except P = .780 in 1-month vs 3-month follow-ups). Significantly greater pain relief was reported in the SVF group than in the conventional group at 6 and 12 months' post-treatment (all P < .05). Overall, Outerbridge grades were significantly greater in the SVF group than in the conventional group (P < .001). Similarly, mean Magnetic Resonance Observation of Cartilage Repair Tissue scores were significantly greater (P < .001) in the SVF group (70.5 ± 11.1) than in the conventional group (39.7 ± 8.2). Conclusions: The results regarding pain improvement and cartilage regeneration and the significant correlation between pain and MRI outcomes at 12-months follow-up indicate that the arthroscopic SVF implantation technique may be useful for repairing cartilage lesions in knee osteoarthritis. Level of Evidence: Level III, retrospective comparative study.

Adipose-Derived Stromal Vascular Fractions Are Comparable With Allogenic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells as a Supplementary Strategy of High Tibial Osteotomy for Varus Knee Osteoarthritis.

Purpose: To compare the clinical, radiologic, and second-look arthroscopic outcomes of high tibial osteotomy (HTO) with stromal vascular fraction (SVF) implantation versus human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) transplantation and identify the association between cartilage regeneration and HTO outcomes. Methods: Patients treated with HTO for varus knee osteoarthritis between March 2018 and September 2020 were retrospectively identified. In this retrospective study, among 183 patients treated with HTO for varus knee osteoarthritis between March 2018 and September 2020, patients treated with HTO with SVF implantation (SVF group; n = 25) were pair-matched based on sex, age, and lesion size with those who underwent HTO with hUCB-MSC transplantation (hUCB-MSC group; n = 25). Clinical outcomes were evaluated using the International Knee Documentation Committee score and Knee Injury and Osteoarthritis Outcome Score. Radiological outcomes evaluated were the femorotibial angle and posterior tibial slope. All patients were evaluated clinically and radiologically before surgery and during follow-up. The mean final follow-up periods were 27.8 ± 3.6 (range 24-36) in the SVF group and 28.2 ± 4.1 (range, 24-36) in the hUCB-MSC group (P = 0.690). At second-look arthroscopic surgery, cartilage regeneration was evaluated using the International Cartilage Repair Society (ICRS) grade. Results: A total of 17 male and 33 female patients with a mean age of 56.2 years (range, 49-67 years) were included. At the time of second-look arthroscopic surgery (mean, 12.6 months; range, 11-15 months in the SVF group and 12.7 months; range, 11-14 months in the hUCB-MSC group, P = .625), the mean International Knee Documentation Committee score and Knee Injury and Osteoarthritis Outcome Score in each group significantly improved (P < .001 for all), and clinical outcomes at final follow-up further improved in both groups when compared with the values at second-look arthroscopic surgery (P < .05 for all). Overall ICRS grades, which significantly correlated with clinical outcomes, were similar between groups with no significant differences (P = .170 for femoral condyle and P = .442 for tibial plateau). Radiologic outcomes at final follow-up showed improved knee joint alignment relative to preoperative conditions but showed no significant correlation with clinical outcomes or ICRS grade in either group (P > .05 for all). Conclusions: Improved clinical and radiological outcomes and favorable cartilage regeneration were seen after surgery for varus Knee OA in both SVF and hUCB-MSC groups. Level of Evidence: Level III, retrospective comparative study.

Gold nanostructures modified carbon-based electrode enhanced with methylene blue for point-of-care COVID-19 tests using isothermal amplification.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) and RNA-dependent RNA polymerase (RdRP) genes were detected via electrochemical measurements using a screen-printed carbon electrode (SPCE) (3-electrode system) coupled with a battery-operated thin-film heater based on the loop-mediated isothermal amplification (LAMP) technique. The working electrodes of the SPCE sensor were decorated with synthesized gold nanostars (AuNSs) to obtain a large surface area and improve sensitivity. The LAMP assay was enhanced using a real-time amplification reaction system to detect the optimal target genes (E and RdRP) of SARS-CoV-2. The optimized LAMP assay was performed with diluted concentrations (from 0 to 109 copies) of the target DNA using 30 µM of methylene blue as a redox indicator. Target DNA amplification was conducted for 30 min at a constant temperature using a thin-film heater, and the final amplicon electrical signals were detected based on cyclic voltammetry curves. Our electrochemical LAMP analysis of SARS-CoV-2 clinical samples showed an excellent correlation with the Ct value of real-time reverse transcriptase-polymerase chain reaction, indicating successful validation of results. A linear relationship between the peak current response and the amplified DNA was observed for both genes. The AuNS-decorated SPCE sensor with the optimized LAMP primer enabled accurate analysis of both SARS-CoV-2-positive and -negative clinical samples. Therefore, the developed device is suitable for use as a point-of-care test DNA-based sensor for the diagnosis of SARS-CoV-2.

Cartilage lesion size and number of stromal vascular fraction (SVF) cells strongly influenced the SVF implantation outcomes in patients with knee osteoarthritis.

PURPOSE: This study evaluated outcomes in patients with knee osteoarthritis following stromal vascular fraction implantation and assessed the associated prognostic factors. METHODS: We retrospectively evaluated 43 patients who underwent follow-up magnetic resonance imaging 12 months after stromal vascular fraction implantation for knee osteoarthritis. Pain was assessed using the visual analogue scale and measured at baseline and 1-, 3-, 6-, and 12-month follow-up appointments. In addition, cartilage repair was evaluated based on the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system using the magnetic resonance imaging from the 12-month follow-up. Finally, we evaluated the effects of various factors on outcomes following stromal vascular fraction implantation. RESULTS: Compared to the baseline value, the mean visual analogue scale score significantly and progressively decreased until 12 months post-treatment (P < 0.05 for all, except n.s. between the 1 and 3-month follow-ups). The mean Magnetic Resonance Observation of Cartilage Repair Tissue score was 70.5 ± 11.1. Furthermore, the mean visual analogue scale and Magnetic Resonance Observation of Cartilage Repair Tissue scores significantly correlated 12 months postoperatively (P = 0.002). Additionally, the cartilage lesion size and the number of stromal vascular fraction cells significantly correlated with the 12-month visual analogue scale scores and the Magnetic Resonance Observation of Cartilage Repair Tissue score. Multivariate analyses determined that the cartilage lesion size and the number of stromal vascular fraction cells had a high prognostic significance for unsatisfactory outcomes. CONCLUSION: Stromal vascular fraction implantation improved pain and cartilage regeneration for patients with knee osteoarthritis. The cartilage lesion size and the number of stromal vascular fraction cells significantly influenced the postoperative outcomes. Thus, these findings may serve as a basis for preoperative surgical decisions. LEVEL OF EVIDENCE: IV.

Effect of Back-Channel Surface on Reliability of Solution-Processed In0.51Ga0.15Zn0.34O Thin-Film Transistors with Thin Active Layer.

We have investigated the degradation mechanism of solution-processed indium-gallium-zinc-oxide (IGZO) thin-film transistors. The threshold voltage shift (ΔVth) followed a linear function under negative gate bias stress (NBS), while it showed a stretched-exponential behavior under positive gate bias stress. The slope of ΔVth for stress time was rarely changed with variations below 0.3 mV/s. The thickness of the fabricated IGZO layer (In0.51Ga0.15Zn0.34O) was approximately 10 nm. The Debye length (LD) was larger than IGZO thickness (tIGZO) due to the fully depleted active layer under NBS. Therefore, the degradation phenomenon under NBS was related to the adsorption at back-channel surface. The back-channel surface could be affected by the gate bias under NBS, and the molecules adsorbed at the IGZO layer were positively charged and induced extra electrons by NBS. We verified that the number of positively charged adsorbates had a proportional relationship with the ΔVth based on the two-dimensional technology computer-aided design (TCAD) simulation. Furthermore, we investigated the degradation phenomenon with the ΔVth equation regarding the adsorbates, and the result confirmed that the adsorption process could cause the linear ΔVth. We experimentally confirmed the effect of back-channel surface by comparing the ΔVth between different atmospheric conditions and LD. Consequently, the reaction at the back-channel surface should be considered to develop the metal-oxide semiconductor devices.

Standardized Extract (HemoHIM) Protects against Scopolamine-Induced Amnesia in a Murine Model.

HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia lactiflora Pallas (Paeoniaceae) designed for immune regulation. In the present study, the memory-enhancing effects of a standardized extract (HemoHIM) on scopolamine-induced memory impairment in a murine model was investigated. To induce amnesia, scopolamine (1 mg/kg) was intraperitoneally (i.p.) injected into mice 30 min before the start of behavioral tests. The Y-maze, novel object recognition test (NORT), and passive avoidance task (PAT) were used to evoke memory functions. HemoHIM significantly improved scopolamine-induced memory impairment in ICR mice, which was evidenced by an improvement of spontaneous alternation in the Y-maze, recognition index in NORT, and latency time in PAT. To elucidate the possible mechanism, the cholinergic activity and mRNA levels of choline acetyltransferase (ChAT), muscarinic acetylcholine receptor (mAchR), brain-derived neurotrophic factor (BDNF), and cAMP response element-binding protein (CREB) were measured using reverse transcription (RT-PCR) and western blot analyses, respectively. HemoHIM treatment attenuated the scopolamine-induced hyperactivation of acetylcholinesterase (AchE) activity. In addition, ChAT, mAchR, and CREB mRNA levels were increased in the hippocampus compared with the scopolamine group. Furthermore, HemoHIM treatment resulted in elevated BDNF protein expression. These results indicate that HemoHIM may exert antiamnesic activity by increasing Ach and inhibiting AchE in the hippocampus. In addition, HemoHIM has therapeutic potential by upregulating ChAT, mAchR, and BDNF, which is apparently mediated by activation of the CREB and ERK signaling pathways.

A Graphene-Based Enzymatic Biosensor Using a Common-Gate Field-Effect Transistor for L-Lactic Acid Detection in Blood Plasma Samples.

Lactate is an important organic molecule that is produced in excess during anaerobic metabolism when oxygen is absent in the human organism. The concentration of this substance in the body can be related to several medical conditions, such as hemorrhage, respiratory failure, and ischemia. Herein, we describe a graphene-based lactate biosensor to detect the concentrations of L-lactic acid in different fluids (buffer solution and plasma). The active surface (graphene) of the device was functionalized with lactate dehydrogenase enzyme using different substances (Nafion, chitosan, and glutaraldehyde) to guarantee stability and increase selectivity. The devices presented linear responses for the concentration ranges tested in the different fluids. An interference study was performed using ascorbic acid, uric acid, and glucose, and there was a minimum variation in the Dirac point voltage during detection of lactate in any of the samples. The stability of the devices was verified at up to 50 days while kept in a dry box at room temperature, and device operation was stable until 12 days. This study demonstrated graphene performance to monitor L-lactic acid production in human samples, indicating that this material can be implemented in more simple and low-cost devices, such as flexible sensors, for point-of-care applications.

Antioxidant and antifatigue effect of a standardized fraction (HemoHIM) from Angelica gigas, Cnidium officinale, and Paeonia lactiflora.

CONTEXT: HemoHIM is an herbal preparation containing Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia lactiflora Pallas (Paeoniaceae) developed for immune regulation. To date, studies on the antifatigue effects of HemoHIM have not been conducted. OBJECTIVE: The antifatigue effects of HemoHIM using models of citrinin and exercise-induced chronic fatigue syndrome were investigated. MATERIALS AND METHODS: Citrinin-induced L6 skeletal muscle cells were treated with HemoHIM (125, 250, and 500 µg/mL). The antioxidant factors were analysed. ICR mice were divided into four groups (n = 10): control, HemoHIM 250, 500 mg/kg, and creatine 300 mg/kg, respectively. Mice were orally administered HemoHIM or creatine for three weeks; during this time, both rotarod test and forced swimming test (FST) were conducted. The latency time was investigated and antioxidant, antifatigue factors were analysed. RESULTS: HemoHIM significantly restored reduced antioxidant enzymes (SOD, CAT, Txn, GPx, GSr, and GCLC in HemoHIM 500 µg/mL) compared to the citrinin group in L6 cells. In vivo, HemoHIM significantly improved the latency time (FST; 279.88 ± 50.32 sec, rotarod test; 552.35 ± 23.50 sec in HemoHIM 500 mg/kg). Moreover, the FST-induced reduction in glucose and glutathione significantly increased by 3-fold (HemoHIM 500 mg/kg) and increase in LDH and MDA were significantly inhibited by 1.6, 2.1-fold in the HemoHIM 500 mg/kg compared to the control group.

An acquired plica-induced notch in the medial femoral condyle in a patient with medial patellar plica syndrome: a case report.

BACKGROUND: An inflamed and thickened medial patellar plica (MPP) caused by repeated mechanical irritation from trauma or overuse leads to impingement between the anterior medial femoral condyle and the medial articular facet of the patella and produces pain or clicking, which is known as MPP syndrome. In patients with MPP syndrome, cartilage damage may occur depending on the shape of the MPP and the duration of the impingement. CASE PRESENTATION: Preoperative magnetic resonance imaging in a 17-year-old male patient with MPP syndrome showed a hypertrophic MPP along with an abnormal notch in the articular surface of the medial femoral condyle. We considered that the impinged hypertrophic plica between the anterior medial femoral condyle and the medial articular facet of the patella resulted in cartilage damage on the articular surface of the medial femoral condyle. However, during arthroscopic surgery, we found that the cartilage of the notch, which was located beneath the MPP, was completely intact. We concluded that this abnormal notch had developed gradually in the MPP without cartilage damage. CONCLUSIONS: Surgeons should be mindful that acquired plica-induced notches in the articular surface of the medial femoral condyle can present in patients with MPP syndrome.

Sensitive electrochemical biosensor combined with isothermal amplification for point-of-care COVID-19 tests.

We report an electrochemical biosensor combined with recombinase polymerase amplification (RPA) for rapid and sensitive detection of severe acute respiratory syndrome coronavirus 2. The electrochemical biosensor based on a multi-microelectrode array allows the detection of multiple target genes by differential pulse voltammetry. The RPA reaction involves hybridization of the RPA amplicon with thiol-modified primers immobilized on the working electrodes, which leads to a reduction of current density as amplicons accumulate. The assay results in shorter "sample-to-answer" times than conventional PCR without expensive thermo-cycling equipment. The limits of detection are about 0.972 fg/µL (RdRP gene) and 3.925 fg/µL (N gene), which are slightly lower than or comparable to that of RPA assay results obtained by gel electrophoresis without post-amplification purification. The combination of electrochemical biosensors and the RPA assay is a rapid, sensitive, and convenient platform that can be potentially used as a point-of-care test for the diagnosis of COVID-19.

Factors Influencing Clinical and MRI Outcomes of Mesenchymal Stem Cell Implantation With Concomitant High Tibial Osteotomy for Varus Knee Osteoarthritis.

BACKGROUND: Cartilage repair procedures using mesenchymal stem cells (MSCs) can provide superior cartilage regeneration in the medial compartment of the knee joint when high tibial osteotomy (HTO) is performed for varus knee osteoarthritis (OA). However, few studies have reported the factors influencing the outcomes of MSC implantation with concomitant HTO. PURPOSE: To investigate the outcomes of MSC implantation with concomitant HTO and to identify the prognostic factors that are associated with the outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 71 patients (75 knees) were retrospectively evaluated after MSC implantation with concomitant HTO. Clinical and radiological outcomes were evaluated, and magnetic resonance imaging (MRI) was used to assess cartilage regeneration. Statistical analyses were performed to determine the effect of different factors on clinical, radiographic, and MRI outcomes. RESULTS: Clinical and radiographic outcomes improved significantly from preoperatively to final follow-up (P < .001 for all), and overall cartilage regeneration was encouraging. Significant correlations were found between clinical and MRI outcomes. However, radiographic outcomes were not significantly correlated with clinical or MRI outcomes. Patient age and number of MSCs showed significant correlations with clinical and MRI outcomes. On multivariate analyses, patient age and number of MSCs showed high prognostic significance with poor clinical outcomes. CONCLUSION: MSC implantation with concomitant HTO provided feasible cartilage regeneration and satisfactory clinical outcomes for patients with varus knee OA. Patient age and number of MSCs were important factors that influenced the clinical and MRI outcomes of MSC implantation with concomitant HTO for varus knee OA.

Intra-articular injection of human synovium-derived mesenchymal stem cells in beagles with surgery-induced osteoarthritis.

BACKGROUND: Recently, cell-based tissue engineering approaches using mesenchymal stem cells (MSCs) have been used to treat osteoarthritis (OA). However, the efficacy of human synovium-derived MSCs (hSD-MSCs) has not yet been tested in a canine model of OA. The purpose of this study was to investigate the therapeutic effects of intra-articular hSD-MSC injections in a canine OA model. METHODS: Sixty beagles underwent surgical manipulation to induce OA and received intra-articular injection 4 weeks after surgery. The dogs were divided into five groups (n = 12) according to the injection material: G1, sham group; G2, control group injected with phosphate-buffered saline; G3, G4, and G5, experimental groups injected with different hSD-MSC dosages (G3, 2.4 × 106 cells; G4, 4.8 × 106 cells; G5, 9.6 × 106 cells). Magnetic resonance imaging (MRI) and histopathological and immunohistochemical examinations were performed 6 and 24 weeks after injection. RESULTS: MRI revealed significant improvements in synovitis 24 weeks after injection in the hSD-MSC-injected groups (G3-G5). Histopathologic analyses showed that cartilage structure and proteoglycan staining were also significantly improved in these groups (G3-G5) 6 weeks after injection and improved further after 24 weeks. Immunohistochemical analysis revealed significant differences in the levels of collagen types I and II between the hSD-injected groups (G3-G5), indicating a similar extracellular matrix (ECM) composition to naïve articular cartilage. CONCLUSION: Our study demonstrated for the first time that intra-articular hSD-MSC injection ameliorates the progression of canine OA by restoring cartilage, promoting ECM synthesis, and inhibiting the inflammatory response.

Surveillance assessment for veterinary biocidal products in Korea: A laboratory investigation.

Veterinary biocides used in animal husbandry have the potential to cause human health concerns. Biocidal products for veterinary use, which contain pesticides approved in Korea, comprise 49 active ingredients within 234 products. Within 17 of these products there are 3 ingredients which are highly hazardous pesticides: coumaphos, dichlorvos and methomyl. In this study, the content of the active ingredients of 160 products sold domestically was investigated. Samples were collected for 119 biocidal products for veterinary use. These were analysed by high-performance liquid chromatography (HPLC) and gas chromatography (GC). Seventeen products were noncompliant (insufficient or excess quantity of active ingredients). The ingredients that were below the stated concentrations were amitraz, chlorpyrifos-methyl, cypermethrin, cyromazine, dichlorvos, fipronil, muscamone and trichlorfon. The ingredients that exceeded the stated concentrations were abamectin, fluvalinate and pyriproxyfen. The noncompliance rate in biocidal products for veterinary use was 9.19%. The results of this study show that three highly hazardous pesticides (coumaphos, dichlorvos and methomyl) and 10 active ingredients (abamectin, amitraz, chlorpyrifos-methyl, cypermethrin, cyromazine, fipronil, fluvalinate, muscamone, pyriproxyfen and trichlorfon) deviated from the stated concentrations. Thus, management plans should be established to ensure compliant veterinary drugs by post-distribution quality control, such as planning for regular inspection.

Demographic Predictors of Concomitant Osteochondral Lesion of the Talus in Patients With Chronic Lateral Ankle Instability.

BACKGROUND: Osteochondral lesion of the talus (OLT) is commonly found as a concomitant pathologic lesion in a large proportion of patients with chronic lateral ankle instability (CLAI). This study investigated which characteristics in a patient with CLAI increase the risk for OLT. METHODS: Three hundred sixty-four patients who underwent a modified Broström operation for their CLAI were reviewed retrospectively. The characteristics of each patient and variables associated with OLTs were investigated. Statistical analyses were performed to determine the effect of each potential predictor on the incidence of OLT, and to evaluate the associations between the patient characteristics and variables associated with OLTs. RESULTS: Patients with OLTs were more frequently female (female vs male: 63.1% vs 43.9%, P = .003). In addition, the lesion sizes were larger in female patients (female vs male: 113.9 ± 24.9 mm2 vs 100.7 ± 18.0 mm2, P = .002), and medial lesions were more common in female patients (female vs male; 93.3% vs 81.8%, P = .036). The lesion sizes were larger in patients with a wider talar tilt angle (P < .001), and patients with a medial OLT showed a wider talar tilt angle (12.0 ± 2.0 degrees vs 10.3 ± 2.2 degrees, P = .002). CONCLUSION: In this CLAI patient cohort, we found female patients to be at greater risk for OLTs than male patients. Furthermore, CLAI female patients with concomitant OLT had on average a larger lesion size, more frequent OLT medial position, and were associated with wider talar tilt angles, suggesting that females had more intrinsic ankle instability than males. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Comparative matched-pair cohort analysis of the short-term clinical outcomes of mesenchymal stem cells versus hyaluronic acid treatments through intra-articular injections for knee osteoarthritis.

PURPOSE: Intra-articular injection of hyaluronic acid (HA) has shown promises in reducing pain and improving physical function in knee osteoarthritis (OA). Recently, cell-based therapies using mesenchymal stem cells (MSCs) have emerged as potential treatments. However, few studies have compared the treatment outcomes between MSCs and HA. This study aimed to compare the clinical and radiological outcomes of intra-articular injections of MSCs versus HA in patients with knee OA. METHODS: A cohort of 209 patients with knee OA were retrospectively screened for those who underwent intra-articular injections using MSCs or HA. Thirty MSC-treated patients (MSC group) were pair-matched with thirty HA-treated patients (HA group) based on gender and age. Clinical outcomes were evaluated using the visual analog scale (VAS), International Knee Documentation Committee (IKDC) rating system, and Lysholm scoring system. Radiological evaluation was assessed using the Kellgren-Lawrence (K-L) grading system. RESULTS: MSC treatment yielded consistent significant improvements in VAS, IKDC and Lysholm scores. In the HA group, VAS scores significantly decreased at 1 month, slightly increased at 3 months, and increased significantly from 3 months to 1 year after injection. The IKDC and Lysholm scores improved significantly until 3 months, but gradually worsened thereafter. Significantly greater improvements in VAS (P = 0.041), IKDC (P = 0.014), and Lysholm (P = 0.020) scores were observed in the MSC group compared to those in the HA group at 1-year post-treatment. The K-L grade worsened in a few patients, especially those in the HA group, albeit no significant difference. CONCLUSIONS: MSC group showed better VAS, IKDC, and Lysholm scores at 1-year post-treatment, compared to the HA group, although earlier clinical improvements were superior in the HA group for the initial 3 months. LEVEL OF EVIDENCE: Therapeutic study, Level III.

All-solution-processed colour-tuneable tandem quantum-dot light-emitting diode driven by AC signal.

We demonstrate a novel structure for a quantum-dot light-emitting diode (QD-LED) with wide-range colour-tuneable pixels, fabricated via full solution processing. The proposed device has a symmetrical structure produced via stacking of an inverted-structure diode with a green QD emission layer (EML) and normal-structure diode with a red QD EML. It is an electron-only device; however, a charge generation layer in the middle of the device generates holes for the formation of excitons. Depending on the polarity of the applied voltage, either the bottom inverted unit or the top normal unit is operated, thereby emitting green or red light, respectively. The working mechanism of the device is investigated via analysis of the charge generation mechanism and carrier transport path. In addition, the colour tunability is verified using a simple alternating current (AC) driving scheme; the duty cycle modulation of the AC signal enables fine colour adjustment over a broad range, from pure green to pure red. Thus, our colour-tuneable QD-LED with vertically stacked independently operated sub-pixels can open a promising pathway towards cost-effective ultra-high-resolution displays.

Rapid Determination of Benzylpenicillin Resistance in Staphylococcus aureus Bacteraemia Model.

Rapid determination of antimicrobial susceptibility/resistance is an important factor in selecting an appropriate antimicrobial treatment and eradicating infections promptly. Conventional antimicrobial susceptibility tests (ASTs) are very time consuming. Thus, we developed a liquid chromatography-mass spectrometry (LC-MS/MS) method for rapidly determining the resistance of Staphylococcus aureus to penicillin-G in an animal-infection model. This technique will be able to detect those resistant strains whose resistance mechanism specifically controlled by penicillinase. The resistance status of S. aureus against penicillin-G was determined by conventional AST. Cultured S. aureus cells were inoculated to chicken for developing bacteraemia. The solution of penicillin-G was intravenously administered (10 mg/kg b.w.) to chickens just after infection detection. Blood samples were collected at different intervals after drug administration. The concentration of active penicillin-G and its metabolites were determined from the bacteria-free blood supernatant by utilizing the LC-MS/MS method. Evidence of infection in chicken was observed within 5 h of bacterial inoculation. The penicillinase enzyme generated by S. aureus transforms the active penicillin-G to an inactive metabolite by hydrolysis, which is evident by the mass shift from 335.10600 to 353.11579 Da as quantified using liquid chromatography quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS). The signal intensity of inactive/hydrolysed penicillin-G is several-fold greater than that of the active penicillin-G in the blood sample of chicken infected with resistant strain and treated with penicillin-G. The antimicrobial resistance index (ARI) value of resistant S. aureus strain was more than 1, demonstrating the penicillin-G-resistance pattern of that strain. This method is able to determine the extent of ß-lactam antimicrobial resistance within 1.5 h from the patient's blood and is complementary with those existing AST methods which are usually practicing in the evaluation of ß-lactam antibiotic resistance.

Novel Nasal Epithelial Cell Markers of Parkinson's Disease Identified Using Cells Treated with α-Synuclein Preformed Fibrils.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, characterized by olfactory dysfunction in the early stages. α-Synuclein pathologies in the olfactory organs are shown to spread to the brain through the nose-brain axis. We first developed a nasal epithelial PD cellular model by treating RPMI-2650 cells with α-synuclein preformed fibrils (PFF). Upon uptake of PFF, RPMI-2650 cells showed mitochondrial proteome alteration and downregulation of parkin, which has previously been identified as a nasal biomarker of PD. Functional cluster analysis of differentially expressed genes in RPMI-2650 cells revealed various pathways affected by α-synuclein pathology, including the detection of chemical stimulus involved in sensory perception, olfactory receptor activity, and sensory perception of smell. Among genes that were most affected, we validated, by real-time quantitative PCR, the downregulation of MAP3K8, OR10A4, GRM2, OR51B6, and OR9A2, as well as upregulation of IFIT1B, EPN1, OR1D5, LCN, and OTOL1 in PFF-treated RPMI-2650 cells. Subsequent analyses of clinical samples showed a downregulation of OR10A4 and OR9A2 transcripts and an upregulation of IFIT1B in cells isolated from the nasal fluid of PD patients, as compared to those from the controls (cutoff value = 0.5689 for OR9A2, with 72.4% sensitivity and 75% specificity, and 1.4658 for IFIT1B, with 81.8% sensitivity and 77.8% specificity). Expression levels of these nasal PD markers were not altered in nasal fluid cells from SWEDD (scans without evidence of dopaminergic deficits) patients with PD-like motor symptoms. These nasal markers were significantly altered in patients of PD with hyposmia compared to the control hyposmic subjects. Our results validated the α-synuclein-treated nasal epithelial cell model to identify novel biomarkers for PD and suggest the utility of olfactory transcripts, along with olfactory dysfunction, in the diagnosis of PD.