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Direct-drive permanent magnet generators are becoming an attractive option for highly efficient small-scale wind turbines due to their high-power density and size reduction capabilities. In this study, the optimal shape design of a direct-drive permanent magnet generator for 1 kW-class wind turbines was conducted while considering power generation and weight. Half of the geometry of a single stage in the generator was considered for a electromagnetic analysis under given electrical parameters. In order to construct a response surface model, a sensitivity analysis was conducted on seven design parameters of the proposed generator. The desirability function was used to minimize the weight of the generator while meeting a requirement of the target specification. The results indicated that the optimized design parameters for the generator met the target specification while maintaining the generator’s weight at the same level as the initial design model. From the comparisons with other research, the optimized generator exhibited a higher power generation/weight ratio than the generator with a rated capacity under 3 kW.

As the public interest in healthcare increases, illegal dietary supplements, foods, and drugs containing unauthorized pharmaceutical ingredients, including nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, have been identified. Excessive and unintentional consumption is toxic to the gastrointestinal tract, kidneys, and liver; therefore, these pharmaceuticals must be monitored using analytical methods.A rapid and reliable analysis system involving liquid chromatography-quadrupole orbitrap mass spectrometry (LC-Q-Orbitrap/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established and validated to identify and quantify 30 NSAIDs and acetaminophen. In addition, we obtained the MSThe analytical method was applied to 505 samples of illicitly distributed dietary supplements, foods, and pharmaceuticals. Non-steroidal analgesics were detected in 126 samples. Carbamazepine (42.9%) and diclofenac (30.2%) were the most detected components in the samples; other pharmaceutical adulterants were also detected in some cases. Additionally, we present the identification of an unknown component, dexamethasone (799 μg/g), using LC-Q-Orbitrap/MS in a sample containing the unknown component with meloxicam (15.4 mg/g).The developed analysis system, consisting of qualitative analysis using LC-Q-Orbitrap/MS and quantitative analysis using LC-MS/MS, can rapidly and accurately identify and quantify NSAIDs and acetaminophen while also identifying non-analytical components.

Alzheimer’s disease is one of the most critical brain diseases. The prevalence of the disease keeps rising due to increasing life spans. This study aims to examine the use of hemodynamic signals during hypoxic respiratory challenge for the differentiation of Alzheimer’s disease (AD) and wild-type (WT) mice. Diffuse optical spectroscopy, an optical system that can non-invasively monitor transient changes in deoxygenated (ΔRHb) and oxygenated (ΔOHb) hemoglobin concentrations, was used to monitor hemodynamic reactivity during hypoxic respiratory challenges in an animal model. From the acquired signals, 13 hemodynamic features were extracted from each of ΔRHb and −ΔOHb (26 features total) for more in-depth analyses of the differences between AD and WT. The hemodynamic features were statistically analyzed and tested to explore the possibility of using machine learning (ML) to differentiate AD and WT. Among the twenty-six features, two features of ΔRHb and one feature of −ΔOHb showed statistically significant differences between AD and WT. Among ML techniques, a naive Bayes algorithm achieved the best accuracy of 84.3% when whole hemodynamic features were used for differentiation. While further works are required to improve the approach, the suggested approach has the potential to be an alternative method for the differentiation of AD and WT.

BACKGROUND Unilateral pulmonary hemorrhage is typically reported in young and healthy men with upper respiratory tract obstruction during anesthesia in special situations. Negative pressure in the lungs is created, resulting in negative pressure pulmonary edema (NPPE). CASE SUMMARY A 78-year-old male patient diagnosed with spinal stenosis was admitted to receive a unilateral laminectomy with bilateral decompression. The patient had been diagnosed with hypertension four years earlier and asthma more than 70 years earlier. We experienced a unilateral alveolar hemorrhage associated with NPPE that occurred in a longstanding asthma patient who bit the intubated endotracheal tube for a short period during posture change at the end of surgery. Because diffuse alveolar hemorrhage accompanied by NPPE was caused in this case by airway obstruction in an older patient with asthma without known risk factors, anesthesiologists should be careful not to induce airway irritation during anesthesia awakening in asthma patients. CONCLUSION Because diffuse alveolar hemorrhage accompanied by NPPE can occur, anesthesiologists should take care not to induce airway irritation.

Surface-enhanced Raman spectroscopy (SERS)-based protein analysis is a promising alternative to existing early stage diagnoses. However, SERS research conducted thus far accompanies challenges such as nonuniformity of plasmonic nanostructures, irregular coating of analytes, and denaturation of proteins, which seriously limit the practicability of suggested approaches. Here, we introduce a carboxylic acid-functionalized and graphitic nanolayer-coated three-dimensional SERS substrate (CGSS) fabricated by sequential nanotransfer printing. The substrate consists of well-defined, uniform gold nanowire arrays for effective Raman signal enhancement and a strong protein-immobilization layer. With an enhancement factor (EF) of 5.5 × 105, on par with the highest ever reported values, the CGSS allows the detection of protein conformational changes and the determination of protein concentration via Raman measurements. Exploiting the CGSS, we successfully measured the SERS spectra of Alzheimer's biomarkers, tau protein and amyloid β, based on which secondary structural changes were analyzed quantitatively.

Background: Cervical interlaminar epidural steroid injection (CIESI) is increasingly used as an interventional treatment for pain originating from the cervical spine. However, serious neurological complications may occur during CIESI because of direct nerve damage following inappropriate needle placement. Case report: A 35-year-old woman presented with posterior neck pain radiating to the left upper arm. Cervical magnetic resonance imaging (MRI) revealed left C6 nerve impingement. CIESI under fluoroscopic guidance was performed at another hospital using the left C5/6 interlaminar approach. Immediately after the procedure, the patient experienced dizziness, decreased blood pressure, motor weakness in the left upper arm, and sensory loss. She visited our emergency department with postdural puncture headache (PDPH) that worsened after the procedure. Post-admission cervical MRI revealed intramedullary T2 high signal intensity and cord swelling from the C4/5 to C6/7 levels; thus, a diagnosis of spinal cord injury was made. The patient’s PDPH spontaneously improved after 48 h. However, despite conservative treatment with steroids, the decrease in abduction of the left fifth finger and loss of sensation in the dorsum of the left hand persisted for up to 6 months after the procedure. As noticed in the follow-up MRI performed 6 months post-procedure, the T2 high signal intensity in the left intramedullary region had decreased compared to that observed previously; however, cord swelling persisted. Furthermore, left C7/8 radiculopathy with acute denervation was confirmed by electromyography performed 6 months after the procedure. Conclusions: Fluoroscopy does not guarantee the prevention of spinal cord penetration during CIESI. Moreover, persistent neurological deficits may occur, particularly due to intrathecal perforation or drug administration during CIESI. Therefore, in accordance with the recommendations of the Multisociety Pain Workgroup, we recommend performing CIESI at the C6/7 or C7/T1 levels, where the epidural space is relatively large, rather than at the C5/6 level or higher.

With an increase in the number of individuals opting for illegal abortion, the use of counterfeit abortion medicines is increasing throughout the black market. In the present study, a rapid and simultaneous liquid chromatography–tandem mass spectrometry method for detecting abortion-inducing drugs in counterfeit medicines was developed. The parameters used for validating the method using tablet-, powder- and capsule-type matrix-blank samples were limit of detection (0.10–5.00 ng/mL), limit of quantitation (0.31–15.00 ng/mL), linearity (r2 > 0.998), recovery of spiked matrix-blank samples (83.1–114.5%), intraday and interday accuracy (86.4–113.5%) and precision (≤ 9.7% RSD) and stability (≤ 13.3% RSD). Seized tablet-type drugs, advertised for their abortion-inducing activity, were analysed using an established method and were observed to be adulterated with mifepristone and misoprostol in a concentration of 0.02–293.80 mg/g, which can pose a risk to public health. This study demonstrates the successful application of a fast and reliable screening method for detecting illegal abortion-inducing drugs.

Background: Complex regional pain syndrome is a disease characterized by chronic pain caused by tissue damage and worsens over time. The quality of randomized controlled trials on complex regional pain syndrome is low due to the rarity of the disease and difficulty in designing studies. Therefore, we evaluated the completeness of evidence by assessing the quality. Methods: We searched articles that were published between 1998 and 2017. The quality was assessed using the Jadad scale, van Tulder scale, and the Cochrane collaboration risk of bias tool.Results: A total of 72 articles on complex regional pain syndrome have been published. Only 31 articles were found to have a low risk of bias according to the Cochrane Collaboration. On the Jadad and van Tulder scale, 52 and 58 articles, respectively, were assessed as high quality. Only a few trials described the randomization method adequately and presented allocation concealment correctly. We also found that research trials with funding statements had higher Jadad scales than unfunded (P = 0.03). Furthermore, articles that described the sample size were of significantly higher quality (P < 0.01) than those that did not. Conclusions: There was no observed improvement in quality over time. In particular, the performance rate of the allocation concealment for the analyzed papers was low. In addition, we found that the number of high-quality articles increased when institutional review board approval was granted and funding provided. For the future, we recommend that researchers focus their efforts on conducting high-quality studies.

Recent studies have revealed that protein arginine methyltransferases (PRMTs) are responsible for diverse neurodegenerative diseases. However, their pathophysiological role in dopaminergic neuronal death in Parkinson's disease (PD) has not been evaluated. In this study, we demonstrated that 1-Methyl-4-phenylpyridinium iodide (MPP+), rotenone and paraquat, which cause dopaminergic neuronal cell death, increased PRMT1 expression in dopaminergic cell line. Dopaminergic neuronal cell death was increased by PRMT1 overexpression. MPP+-induced cell death was attenuated by PRMT1 knockdown. Poly (ADP-ribose) polymerase-1 (PARP1) expression and activity, poly-ADP-ribosylation (PARylation), were elevated by MPP+. Moreover, we found that PRMT1 positively regulates nuclear translocation of apoptosis-inducing factor (AIF). Elevated PRMT1 expression was observed in the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Furthermore, MPTP-induced dopaminergic neuronal death was reduced in PRMT1 haploinsufficient (prmt1+/-) mice. These data suggest that PRMT1 is implicated in PARP1/AIF-mediated dopaminergic neuronal cell death, which might be involved in the pathology of PD. Therefore, our results propose PRMT1 as a new target to develop a potential treatment of PD.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by cognitive dysfunction and memory loss as the main symptoms. The deposition of amyloid beta (Aβ) and tau hyperphosphorylation are hallmarks of AD and are major therapeutic targets. However, the exact etiology has not yet been fully elucidated; thus, no drug that cures the disease has been approved. JBPOS0101 is a phenyl carbamate compound that has been tested as a drug for epileptic diseases. In our previous study, we showed that JBPOS0101 attenuated the accumulation of Aβ as well as the deficits in learning and memory in the 5xFAD mouse model. Here, we tested the dose effect (70 or 35 mg/kg) of JBPOS0101 on the memory defect and pathological markers and further investigated the underlying mechanisms in 5xFAD mice. In the behavior tests, JBPOS0101 treatment ameliorated deficits in learning and memory. Moreover, JBPOS0101 attenuated Aβ accumulation and tau phosphorylation. The elevated phosphorylation levels of the active GSK3β form (GSK3β-y216) in 5xFAD, which are responsible for tau phosphorylation, decreased in the JBPOS0101-treated groups. Furthermore, the elevation of reactive astrocytes and microglia in 5xFAD mice was attenuated in JBPOS0101-treated groups. These data suggest that JBPOS0101 may be a new drug candidate to lessen amyloid- and tau-related pathology by regulating glial cells.

Background and objectiveDespite the awareness of the important roles of physical activity (PA), the majority of cancer survivors fail to meet PA guidelines due to a lack of access to facilities or motivation. The purpose of this study is to examine the effectiveness of lifestyle intervention in prostate cancer (PC) patients receiving androgen deprivation therapy (ADT). Material and methodsA total of 23 PC patients (aged 75.26 ± 6.9 years) receiving ADT at least 3 months were randomized into an intervention group (n=12) and a control group (n=11). The intervention group received lifestyle intervention in the form of education program. Levels of PA, body composition, physical function, disease-specific quality of life (QoL), and fatigue were assessed before and after the 12-week intervention. ResultsThe intervention group showed improvements in the level of PA (step count: p=0.028, moderate to vig-orous PA: p=0.013) compared with the control group. Thigh circumference (p=0.002), physical function (grip strength: p=0.034; knee extensor: p=0.004, up and go: p=0.001; 2-min step: p=0.001), QoL (p

PURPOSE To assess the quality of randomized controlled trials (RCTs) on varicocele published from 1979 to 2017. MATERIALS AND METHODS We searched for original RCT on varicocele published between 1979 and 2017. Jadad scale, van Tulder scale, and Cochrane Collaboration Risk of Bias Tool were used to analyze RCT quality over time. Effects on RCT quality including funding source, Institutional Review Board (IRB) approval, and intervention were assessed. Treatment parameters of varicocele were also analyzed. RESULTS Blinding and allocation concealment were described in 25.9% and 9.4% of RCT, respectively. Both tended to increase and a sharp dip in allocation concealment was observed in 2010-2017. Jadad scores increased steadily from 1979 to 2017 (1.28±0.59 to 2.19±1.10, p

Alzheimer's disease (AD) is a major neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) in the brain. Defects in Aβ clearance or the interference of Aβ homeostasis could result in Aβ aggregation. JBPOS0101 has been studied for its antiepileptic activity. It showed a neuroprotective effect and prevented memory deficits in lithium-pilocarpine-induced status epilepticus rats. In this study, we tested the effect of JBPOS0101 in an AD model. We showed that JBPOS0101 attenuated the accumulation of Aβ in 5XFAD mouse brains. Moreover, the treatment of JBPOS0101 rescued the deficits in learning and memory in 5XFAD mice. These data suggest that JBPOS0101 could be a potential therapeutic drug candidate for AD.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and dementia with no effective treatment. Here, we investigated a novel compound from oats named avenanthramide-C (Avn-C), on AD-related memory impairment and behavioral deficits in transgenic mouse models. Acute hippocampal slices of wild-type or AD transgenic mice were treated with Avn-C in the presence or absence of oligomeric Aβ42. LTP analyses and immunoblotting were performed to assess the effect of Avn-C on Aβ-induced memory impairment. To further investigate the effect of Avn-C on impaired memory and Aβ pathology, two different AD transgenic mice (Tg2576 and 5XFAD) models were orally treated with either Avn-C or vehicle for 2 weeks. They were then assessed for the effect of the treatment on neuropathologies and behavioral impairments. Avn-C reversed impaired LTP in both ex vivo- and in vivo-treated AD mice hippocampus. Oral administration (6 mg/kg per day) for 2 weeks in AD mice leads to improved recognition and spatial memory, reduced caspase-3 cleavage, reversed neuroinflammation, and to accelerated glycogen synthase kinase-3β (pS9GSK-3β) and interleukin (IL-10) levels. Avn-C exerts its beneficial effects by binding to α1A adrenergic receptors to stimulate adenosine monophosphate-activated kinase (AMPK). All of the beneficial effects of Avn-C on LTP retrieval could be blocked by prazosin hydrochloride, a specific inhibitor of α1A adrenergic receptors. Our findings provide evidence, for the first time, that oats’ Avn-C reverses the AD-related memory and behavioral impairments, and establish it as a potential candidate for Alzheimer’s disease drug development.

Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16‑carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization. Especially, neurodevelopment is regulated by balancing the level of synaptic protein palmitoylation/depalmitoylation. Recently, we revealed the pathological role of the transient receptor potential canonical type 5 (TRPC5) channel in striatal neuronal loss during Huntington's disease (HD), which is abnormally activated by oxidative stress. Here, we report a mechanism of TRPC5 palmitoylation at a conserved cysteine residue, that is critical for intrinsic channel activity. Furthermore, we identified the therapeutic effect of TRPC5 depalmitoylation by enhancing the TRPC5 membrane instability on HD striatal cells in order to lower TRPC5 toxicity. Collectively, these findings suggest that controlling S-palmitoylation of the TRPC5 channel as a potential risk factor can modulate TRPC5 channel expression and activity, providing new insights into a therapeutic strategy for neurodegenerative diseases.

δ-Catenin is abundant in the brain and affects its synaptic plasticity. Furthermore, loss of δ-catenin is related to the deficits of learning and memory, mental retardation (cri-du-chat syndrome), and autism. A few studies about δ-catenin deficiency mice were performed. However, the effect of δ-catenin overexpression in the brain has not been investigated as yet. Therefore we generated a δ-catenin overexpressing mouse model. To generate a transgenic mouse model overexpressing δ-catenin in the brain, δ-catenin plasmid having a Thy-1 promotor was microinjected in C57BL/6 mice. Our results showed δ-catenin transgenic mice expressed higher levels of N-cadherin, β-catenin, and p120-catenin than did wild type mice. Furthermore, δ-catenin transgenic mice exhibited better object recognition, better sociability, and lower anxiety than wild type mice. However, both mice groups showed a similar pattern in locomotion tests. Although δ-catenin transgenic mice show similar locomotion, they show improved sociability and reduced anxiety. These characteristics are opposite to the symptoms of autism or mental retardation, which are caused when δ-catenin is deficient. These results suggest that δ-catenin may alleviate symptoms of autism, Alzheimer's disease and mental retardation.

Open-wedge high tibial osteotomy (HTO) cannot always accurately correct limb alignment, resulting in under- or over-correction. This study assessed the relationship between soft tissue laxity of the knee joint and alignment correction in open-wedge HTO. This prospective study involved 85 patients (86 knees) undergoing open-wedge HTO for primary medial osteoarthritis. The mechanical axis (MA), weight-bearing line (WBL) ratio, and joint line convergence angle (JLCA) were measured on radiographs preoperatively and after 6 months, and the differences between the pre- and post-surgery values were calculated. Post-operative WBL ratios of 57–67 % were classified as acceptable correction. WBL ratios 67 % were classified as under- and over-corrections, respectively. Preoperative JLCA correlated positively with differences in MA (r = 0.358, P = 0.001) and WBL ratio (P = 0.003). Difference in JLCA showed a stronger correlation than preoperative JLCA with differences in MA (P

Purpose In anatomical single-bundle (SB) anterior cruciate ligament (ACL) reconstruction, the traditional transtibial approach can limit anatomical placement of the femoral tunnel. Surgical Technique We present a novel three-point freehand technique that allows for anatomic SB ACL reconstruction with the transtibial technique. Materials and Methods Between January 2012 and December 2012, 55 ACL reconstructions were performed using the three-point freehand technique. All the patients were followed for a minimum of 12 months post-operatively. Clinical evaluation was done using the Lysholm score and International Knee Documentation Committee (IKDC) grade. All patients were analyzed by 3-dimensional computed tomography (3D CT) at 1 week after surgery. Results The mean Lysholm score improved from 68.2±12.7 points preoperatively to 89.2±8.2 points at final follow-up. At final follow-up, the IKDC grade was normal in 42 patients and nearly normal in 13 patients. None of the patients had a positive pivot shift test, anterior drawer test and Lachman test at final follow-up. The anatomical position of the femoral tunnel was confirmed on 3D CT scans. Conclusions The three-point freehand technique for SB transtibial ACL reconstruction is a simple, anatomic technique showing good clinical results.

The safety of food is occasionally questionable, as there have been some reports of products contaminated with illegal adulterants. In this study, the presence of three aconitum alkaloids (aconitine, mesaconitine, and hypaconitine) in food was determined by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) and quadruple time of flight mass spectrometry (Q-TOF/MS). The LC-MS/MS method was validated. The linearity (R2) was more than 0.999, and the LODs and LOQs ranged from 0.010 to 0.200 ng mL−1 and 0.025 to 0.500 ng mL−1, respectively. The precisions were 0.25–2.27% (intra-day) and 0.44–5.47% (inter-day), and the accuracies were 86.45–106.45% (intra-day) and 87.54–106.95% (inter-day). The mean recoveries of the spiked samples ranged from 99.04% to 102.30%. The relative standard deviation (RSD) of the stability was less than 7.33%. Using the developed method, the aconitum alkaloids were detected in 10 tested samples, obtained between 2012 and 2014, in the following quantities: aconitine, 57.1%; mesaconitine, 7.1%; and hypaconitine, 7.1%. Monitoring the presence of these three aconitum alkaloids in food should be pursued in the interest of human health, and the results of this study confirm that the developed method will be useful towards that end.

Adulterated products are continuously detected in society and cause problems. In this study, we developed and validated a method for determining synthetic sedative-hypnotics and sleep inducers, including barbital, benzodiazepam, zolpidem, and first-generation antihistamines, in adulterated products using Quadrupole-Orbitrap mass spectrometry and ultrahigh performance liquid chromatography with tandem mass spectrometry. In Quadrupole-Orbitrap mass spectrometry analysis, target compounds were confirmed using a combination of retention time, mass tolerance, mass accuracy, and fragment ions. For quantification, several validation parameters were employed using ultrahigh performance liquid chromatography with tandem mass spectrometry. The limit of detection and limit of quantitation was 0.05-53 and 0.17-177 ng/mL, respectively. The correlation coefficient for linearity was more than 0.995. The intra- and interassay accuracies were 86-110 and 84-111%, respectively. Their precision values were evaluated as within 4.0 (intraday) and 10.7% (interday). Mean recoveries of target compounds in adulterated products ranged from 85 to 116%. The relative standard deviation of stability was less than 10.7% at 4°C for 48 h. The 144 adulterated products obtained over 3 years (2014-2016) from online and in-person vendors were tested using established methods. After rapidly screening with Quadrupole-Orbitrap mass spectrometry, the detected samples were quantified using ultrahigh performance liquid chromatography with tandem mass spectrometry. Two of them were adulterated with phenobarbital.