Lateral Distance From the Osteotomy Hinge Point to the Tibial Cortex Is Associated With Lateral Hinge Fracture Type and Fracture Occurrence Time After Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To verify whether the distance from the hinge point to the tibial cortex affects the occurrence time and characteristics of the lateral hinge fracture (LHF) in medial open-wedge high tibial osteotomy. METHODS: We retrospectively reviewed 171 knees in 171 patients (121 women, 50 men; mean age, 53.9 years; range, 36-67 years) who had undergone medial open-wedge high tibial osteotomy with locking plate fixation between January 2011 and December 2020. Osteotomy hinge point and LHFs were identified on intraoperative fluoroscopy and immediate postoperative radiographs. LHF type was classified as suggested by Takeuchi et al. Acute fracture was defined as a fracture that occurred during surgery, and delayed fracture was defined as a fracture observed after 1 month postoperatively. The nearest distances from osteotomy hinge point to lateral, distal, and proximal cortex were measured on postoperative radiographs. We compared the distance between the different types and between acute and delayed LHFs. RESULTS: There were 55 LHFs (32%) (type I, 40 knees; type II, 14 knees; type III, 1 knee) that occurred acutely in 41 knees and were found as delayed fractures in 14 knees. The patient demographics were not significantly different between non-LHFs and each type of LHFs. Proximal and distal distances were not statistically different among fracture types and between occurrence times. However, lateral distances were significantly shorter in type I LHFs (6.2 ± 1.8 mm) and longer in type II LHFs (9.3 ± 2.3 mm) than in non-LHFs (7.1 ± 2.7 mm) (P = .020 and .004, respectively). The lateral cortical distances were also different between acute LHFs (6.4 ± 1.9 mm) and delayed LHF (9.0 ± 2.7 mm) (P < .001). In the case of fracture type, the frequency of type I decreases with increase in the lateral distance, whereas that of type II increases with increase in the lateral cortical distance. In acute fracture, type I was dominant (85.4%), whereas in delayed fracture, type II was dominant (57.2%). CONCLUSIONS: The lateral cortical distance from the hinge point was significantly associated with LHF occurrence. Shorter distance increased the risk for acute type I LHF, whereas longer distance increased the risk for delayed type II LHFs. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation.

In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3ß-mediated STAT2 phosphorylation facilitated STAT2-FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, STAT2 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated STAT2 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.

Lateral Meniscal Allograft Transplantation Provides a Chondroprotective Effect on Articular Cartilage: Quantitative 3-T Magnetic Resonance Imaging T2 Mapping.

PURPOSE: This study aimed to assess the cartilage status in patients who underwent isolated lateral meniscus allograft transplantation (MAT) using preoperative and postoperative quantitative 3-T magnetic resonance imaging T2 mapping at midterm follow-up period. METHODS: Patients who underwent lateral MAT without cartilage treatment procedures between 2010 and 2019 were assessed by quantitative magnetic resonance imaging preoperatively and postoperatively. On the sagittal section image following the center of the lateral femoral condyle, the weight-bearing area of the articular cartilage was divided into 6 segments based on the meniscal coverage area from anterior to posterior direction. The mean T2 values of each of the 6 segments were measured for 3 regions of interest: overall, deep, and superficial layers. The change in T2 values was statistically analyzed by paired t-tests. The Lysholm score was used to evaluate clinical function. RESULTS: A total of 105 patients were included in the study. The mean follow-up period was 3.2 years (range 2.0-5.4 years). Among the 6 segments, the mean T2 value showed significant improvement in the overall layer of F2 (the middle weight-bearing area of femoral condyle) and TP3 (the posterior weight-bearing area of tibia condyle) segments (P = .013 and .021, respectively) and the superficial layer of the F3 (the posterior weight-bearing area of femoral condyle) segments (P = .028). The mean T2 value of all the other segments did not show a statistically significant change. The mean Lysholm score significantly improved from 66.5 ± 15.8 to 89.3 ± 10.0 (P < .001). Overall, 73.3% and 96.2% of the patients met the minimal clinically important difference and patient acceptable symptomatic state, respectively. CONCLUSIONS: The mean T2 value of the articular cartilage of the weight-bearing area was either maintained or showed statistically significant improvement depending on the location following isolated lateral MAT. Thus, the transplanted meniscus seems to have a chondroprotective effect on the weight-bearing cartilage. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic case series.

Lateral Meniscal Allograft Transplantation Shows a Long-Term Chondroprotective Effect on Quantitative MRI T2 Mapping at 7 Years' Minimum Follow-Up.

PURPOSE: The purpose of this study was to assess the long-term chondroprotective effect of lateral meniscal allograft transplantation (MAT) using quantitative magnetic resonance imaging (MRI) T2 mapping. METHODS: In patients who underwent isolated lateral MAT, quantitative MRI T2 mapping was conducted preoperatively and postoperatively with at minimum follow-up of 7 years to assess the articular cartilage status. On the sagittal section image bisecting the lateral femoral condyle, the weight-bearing portions of the femoral and tibial articular cartilage were divided into 3 segments each-6 segments in total-based on the meniscal coverage area. The regions of interest analysis were performed on the 6 segments to measure the mean T2 value. Then, the whole layer was divided into deep and superficial layers for further zonal analysis. The longitudinal change in T2 values was statistically analyzed using paired t-tests. Clinical outcome was evaluated using the Lysholm score. RESULTS: A total of 31 patients were included in the study, with the MRI follow-up period of a minimum follow-up of 7 years (mean: 8.9 ± 1.3 years; range: 7.0-11.2 years). The mean T2 value of the whole layer showed significant improvement in all segments of the femoral cartilage and the posterior segment of tibial cartilage. In the zonal analysis, the mean T2 value of the tibial cartilage showed significant improvement in the superficial layer of the mid to posterior portion, while the deep layer remained stable. In contrast, the mean T2 value of the femoral cartilage showed significant improvement in the superficial and deep layers in all segments. The mean Lysholm score significantly improved from 62.6 ± 12.8 to 90.9 ± 10.5 (P < .001). CONCLUSION: This study suggests that MAT appears to have a long-term chondroprotective effect on the articular cartilage as judged by quantitative T2 mapping. LEVEL OF EVIDENCE: Level Ⅳ, case series.

Suitability of visual cues for freezing of gait in patients with idiopathic Parkinson's disease: a case-control pilot study.

BACKGROUND: Freezing of gait (FOG) is one of the most debilitating symptoms in patients with idiopathic Parkinson's disease (IPD). Visual cues can relieve FOG symptoms. However, there is no consensus on patient characteristics that can benefit from visual cues. Therefore, we examined the differences in IPD patient characteristics according to the effectiveness of visual cueing. METHODS: Through gait experiments, we investigated the number of FOG occurrences, average FOG period per episode, proportion of FOG duration in the total gait cycles, and FOG-free period gait spatiotemporal parameters in ten participants diagnosed with FOG due to IPD. Subsequently, the differences between their clinical characteristics and striatal dopamine active transporter availability from six subregions of the striatum were compared by dividing them into two groups based on the three reduction rates: occurrence numbers, mean durations per episode, and proportion of FOG duration in the total gait cycles improved by visual cueing using laser shoes. The relationships among these three reduction rates and other FOG-related parameters were also investigated using Spearman correlation analyses. RESULTS: According to the three FOG-related reduction rates, the group assignments were the same, which was also related to the baseline self-reported FOG severity score (New Freezing of Gait Questionnaire): the more severe the FOG, the poorer the response to the visual cueing. By visual cueing, the better response group demonstrated the characteristics of lower new FOG questionnaire total scores, higher dopamine active transporter availability of the anterior and posterior putamen, and shorter mean duration of FOG per episode in the absence of cueing. These results were replicated using Spearman correlation analyses. CONCLUSIONS: For FOG symptoms following IPD, gait assistance by visual cueing may be more effective when the total NFOGQ score is lower and the DAT of putamen is higher. Through this study, we demonstrated clinical and striatal dopaminergic conditions to select patients who may be more likely to benefit from visual cueing with laser shoes, and these findings lead to the need for early diagnosis of FOG in patients with IPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05080413. Registered on September 14, 2021.

Tear patterns and locations are different between lateral and medial compartments in patients with early anatomical failure after meniscal allograft transplantation.

PURPOSE: To investigate the characteristics of anatomically failed grafts within 1 year after meniscal allograft transplantation (MAT) and compare the differences between lateral and medial MATs. METHODS: The records of consecutive patients with anatomically failed grafts within 1 year after primary MAT between 2005 and 2018 were reviewed. Anatomical failure was defined as a tear covering > 50% of the allograft or an unstable peripheral rim. The pattern and location of the graft tears were analyzed using magnetic resonance imaging or arthroscopy. RESULTS: A total of 21 patients were included. All 21 patients had anatomical failure with tears involving > 50% of the allograft, whereas 15 had an unstable peripheral rim of the allograft. The mean failure time was 6.6 ± 3.6 months in all patients (lateral MAT, n = 15; medial MAT, n = 6). In the lateral MAT group, meniscocapsular separation was the most common pattern (n = 10, 66.7%), followed by complex (n = 3, 20.0%), radial (n = 1, 6.7%), and longitudinal (n = 1, 6.7%) tear. In the medial MAT group, a root tear was the most common pattern (n = 5, 83.3%), followed by a complex tear (n = 1, 16.7%). Meanwhile, in the lateral MAT, the midbody was the most frequently affected location (n = 9, 60.0%), followed by the posterior (n = 5, 33.3%) and anterior (n = 1, 6.7%) areas; in the medial MAT group, the posterior (n = 5, 83.3%) was the most frequently affected location, followed by the anterior area (n = 1, 16.7%). Significant differences in the pattern (P = 0.002) and location (P = 0.043) of the graft tears were found between lateral and medial MATs. CONCLUSION: In patients with early failure after MAT, meniscocapsular separation in the midbody of the lateral compartment and root tears in the posterior area of the medial compartment were the most common. Thus, surgeons are encouraged to pay extra attention to these vulnerable areas during the early period after MAT. LEVEL OF EVIDENCE: IV.

1,2-Diphenyl-o-carborane and Its Chromium Derivatives: Synthesis, Characterization, X-ray Structural Studies, and Biological Evaluations.

The objective of this study is to design and synthesize substituted η6-chromium(0) tricarbonyl metal complexes carrying o-carborane units as potential boron neutron capture therapy (BNCT) agents. In this study, 1,2-diphenyl-o-carborane (1) units were used as starting materials to generate biologically active species. We investigated how the structural changes of 1 substituted with chromium(0) tricarbonyl affect the biological properties, and 1-(Phenyl-η6-chromium(0) tricarbonyl)-2-phenyl-o-carborane (2) and 1,2-bis(phenyl-η6-chromium(0) tricarbonyl)-o-carborane (3) species were produced in moderate yields. The molecular structures of compounds 1-3 were identified and established by infrared (IR); 1H, 11B, and 13C nuclear magnetic resonance (NMR) and X-ray crystallography analyses. Crystal structures of 1,2-diphenyl-o-carborane and the corresponding chromium complexes 1, 2, and 3 were obtained. In an in vitro study using B16 and CT26 cancer cells containing the triphenyl-o-carboranyl chromium(0) complexes Ph3C2BCr2 and Ph3C2BCr3, which we reported previously, compounds 2 and 3 accumulated at higher levels than compounds Ph3C2BCr2 and Ph3C2BCr3. However, the phenylated o-carboranyl chromium complexes have been found to be more cytotoxic than p-boronophenylalanine (BPA).

Null variants in DYSF result in earlier symptom onset.

We investigated the clinical, laboratory, and genetic spectra in Korean patients with dysferlinopathy to clarify its genotype-phenotype correlation. We retrospectively reviewed 101 patients from 96 unrelated families with pathogenic variants of DYSF. The most common initial phenotype was Miyoshi myopathy in 50 patients. Median ages at examination and symptom onset were 23 [interquartile range (IQR): 18-30] and 36 years [IQR: 27-48], respectively. We observed 38 variants, including nine novel variants. Four variants (c.2494C > T, c.1284 + 2 T > C, c.663 + 1G > C, and c.2997G > T) in DYSF accounted for 62% of total allele frequencies of pathogenic variants. To analyze the genotype-phenotype correlation, we compared the clinical phenotype between patients with null/null (N/N; n = 55) and null/missense variants (N/M; n = 35). The N/N group had an earlier symptom onset age (median: 20 years [IQR: 17-25]) than the N/M group (median: 29 years [IQR: 23-35], p < .001). Total manual muscle testing scores in lower extremities were lower in the N/N group (median: 80 [IQR: 56-92]) than in the N/M group (median: 89 [IQR: 78-98], p = .013). Our study is the first to report that null variants in DYSF result in an earlier symptom onset than missense variants.

In-Depth TEM Investigation on Structural Inhomogeneity within a Primary Lix Ni0.835 Co0.15 Al0.015 O2 Particle: Origin of Capacity Decay during High-Rate Discharge.

The structural stability of cathode materials during electrochemical reactions, in particular, under high-rate discharge, is pertinent to the design and development of new electrode materials. This study investigates the structural inhomogeneity that develops within a single LiNi0.835 Co0.15 Al0.015 O2 (NCA83) particle during a fast discharging process under different cutoff voltages. Some of the NCA83 particles discharged from a high cutoff voltage (4.8 V) developed surface areas in which the layered structure was recovered, although the interiors retained the degraded spinel structure. These micro- and nano-scale structural inversions from high cutoff voltage seem highly correlated with structural evolutions in the initial charged state, and may ultimately degrade the cycling stability. This study advances understanding of the structural inhomogeneity within primary particles during various electrochemical processes and may facilitate the development of new Ni-rich cathode materials.

Cilostazol Mono and Combination Treatments in Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

Background and Purpose- We performed a systematic review and meta-analysis to explore the efficacy and safety of cilostazol as a mono or combination (plus aspirin or clopidogrel) treatments compared to conventional single antiplatelet therapy (SAPT, mainly aspirin) for secondary stroke prevention. Methods- Randomized controlled trial studies were searched across multiple comprehensive databases (MEDLINE, EMBASE, and Cochrane) for review. The primary outcome was recurrent stroke comprising ischemic and hemorrhagic stroke. Secondary outcomes included ischemic stroke, hemorrhagic stroke, myocardial infarction, and composite outcomes. We performed an updated systematic review and meta-analysis of the identified reports, including 2 recently published randomized controlled trials. In addition, network meta-analysis was performed to compare the relative effects of mono versus combination cilostazol treatments. Results- Ten studies were included in this review, 5 of which were assigned to the cilostazol mono group (n=5429) and the other 5 to the combination group (n=2456). The relative risks of recurrent stroke, ischemic stroke, and composite outcomes with cilostazol mono as well as combination treatments were significantly lower than with SAPT without any significant heterogeneity. An indirect comparison of these 3 outcomes revealed the cilostazol combination approach to be superior. The cilostazol mono treatment diminished hemorrhagic stroke more significantly than SAPT and the cilostazol combination did not increase hemorrhagic stroke compared to SAPT. The outcomes from the 2 cilostazol regimens were comparable to SAPT in the case of myocardial infarction. Conclusions- Cilostazol is a more effective and safer treatment option than SAPT approaches using mainly aspirin. Cilostazol regimens can also be modified to clinical situations as this drug reduces recurrent and ischemic stroke more efficiently as a combination therapy but is more beneficial for hemorrhagic stroke as a monotherapy.

CNT bundle-based thin intracochlear electrode array.

OBJECTIVE: It is known that the insertion of the intracochlear electrode is critical procedure because the damage around cochlear structures can deteriorate hearing restoration. To reduce the trauma during the electrode insertion surgery, we developed a thin and flexible intracochlear electrode array constructed with carbon nanotube (CNT) bundles. METHODS: Each CNT bundle was used for an individual electrode channel after coated with parylene C for insulation. By encapsulating eight CNT bundles with silicone elastomer, an 8-channel intracochlear electrode array was fabricated. The mechanical and electrochemical characteristics were assessed to evaluate the flexibility and feasibility of the electrode as a stimulation electrode. The functionality of the electrode was confirmed by electrically evoked auditory brainstem responses (eABR) recorded from a rat. RESULTS: The proposed electrode has a thickness of 135 µm at the apex and 395 µm at the base. It was demonstrated that the CNT bundle-based electrodes require 6-fold the lower insertion force than metal wire-based electrodes. The electrode impedance and the cathodic charge storage capacitance (CSCc) were 2.70 kΩ âˆ -20.4° at 1 kHz and - 708 mC/cm2, respectively. The eABR waves III and V were observed when stimulation current is greater than 50 µA. CONCLUSION: A thin and flexible CNT bundle-based intracochlear electrode array was successfully developed. The feasibility of the proposed electrode was shown in terms of mechanical and electrochemical characteristics. A proposed CNT bundle-based intracochlear electrode may reduce the risk of trauma during electrode insertion surgery.

Prevalence and Socioeconomic Status of Patients with Genetic Myopathy in Korea: A Nationwide, Population-Based Study.

BACKGROUND: Genetic myopathy is a clinically and genetically heterogeneous group of genetic disorders characterized by progressive degeneration of skeletal muscles. Epidemiological studies of genetic myopathy have not yet been performed in Korea. OBJECTIVES: This study used data from the national health insurance claims database to determine the prevalence and socioeconomic status of patients with genetic myopathy in Korea. METHODS: We analyzed the Health Insurance Review and Assessment database from 2007 to 2011. Patients with genetic myopathy were defined based on diagnostic and procedure codes. We then evaluated the prevalence, types of health insurances, and medical expenses of these patients. RESULTS: During the 11-year study period, 2,988 patients with genetic myopathy were enrolled. Among them, 1,762 were men and 1,226 were women. The prevalence per 100,000 population in 2017 was 3.09 (3.94 for men and 2.24 for women). The prevalence of genetic myopathy among men <35 years old (8.33 per 100,000 population) was approximately twice that among women <35 years old (4.06 per 100,000 population). However, there was no significant difference in the prevalence of genetic myopathy among those ≥35 years old according to sex. The ratio of patients using medical aid among all genetic myopathy patients was approximately 4 times than that among the general population in Korea. The medical expenses per person for genetic myopathy increased from USD 2,027 in 2007 to USD 4,810 in 2017. CONCLUSIONS: Our study was the first nationwide epidemiologic study of the prevalence and socioeconomic status of patients with genetic myopathy in Korea. Our results confirmed a sex divergence in a younger population and those with low socioeconomic status among patients with genetic myopathy.

Does arthroscopic preemptive extensive rotator interval release reduce postoperative stiffness after arthroscopic rotator cuff repair?: a prospective randomized clinical trial.

BACKGROUND: To investigate whether preemptive extensive rotator interval (RI) release during arthroscopic rotator cuff repair (ARCR) would reduce postoperative stiffness. METHODS: From July 2015 to September 2016, a total of 80 patients who were scheduled for ARCR were enrolled and randomly allocated into 2 groups: the preemptive extensive RI release group (group 1, n=40) and the RI nonrelease group (group 2, n=40). The American Shoulder and Elbow Surgeons scale, Constant score, Korean Shoulder Scale (KSS), visual analog scale (VAS) pain score, and range of motion (ROM) were evaluated before surgery; 3, 6, and 12 months after surgery; and at last follow-up. Magnetic resonance imaging was performed at postoperative 12 months. RESULTS: The mean follow-up period was 26.5 months. The functional and pain scores in both groups were significantly improved at the last follow-up (P < .05). Group 1 showed a significantly higher sum of ROM with a difference of 27° and 1.6 vertebral level of internal rotation compared to group 2 at postoperative 3 months (P < .05). Constant score and KSS were significantly higher in group 1 than in group 2 at this time point (P < .05). Functional scores and ROM were not significantly different between 2 groups at postoperative 6 or 12 months or at the last follow-up (P > .05). The retear rate and pathologic change of the long head of the biceps tendon during follow-up were not significantly different between the 2 groups (P > .05). CONCLUSION: Arthroscopic preemptive extensive RI release can reduce early postoperative shoulder stiffness after ARCR but does not significantly change the overall clinical outcome after surgery.

RSK2-Mediated ELK3 Activation Enhances Cell Transformation and Breast Cancer Cell Growth by Regulation of c-fos Promoter Activity.

Ribosomal S6 kinase 2 (RSK2), regulated by Ras/Raf/MEKs/ERKs, transmits upstream activation signals to downstream substrates including kinases and transcription and epigenetic factors. We observed that ELK members, including ELK1, 3, and 4, highly interacted with RSK2. We further observed that the RSK2-ELK3 interaction was mediated by N-terminal kinase and linker domains of RSK2, and the D and C domains of ELK3, resulting in the phosphorylation of ELK3. Importantly, RSK2-mediated ELK3 enhanced c-fos promoter activity. Notably, chemical inhibition of RSK2 signaling using kaempferol (a RSK2 inhibitor) or U0126 (a selective MEK inhibitor) suppressed EGF-induced c-fos promoter activity. Moreover, functional deletion of RSK2 by knockdown or knockout showed that RSK2 deficiency suppressed EGF-induced c-fos promoter activity, resulting in inhibition of AP-1 transactivation activity and Ras-mediated foci formation in NIH3T3 cells. Immunocytofluorescence assay demonstrated that RSK2 deficiency reduced ELK3 localization in the nucleus. In MDA-MB-231 breast cancer cells, knockdown of RSK2 or ELK3 suppressed cell proliferation with accumulation at the G1 cell cycle phase, resulting in inhibition of foci formation and anchorage-independent cancer colony growth in soft agar. Taken together, these results indicate that a novel RSK2/ELK3 signaling axis, by enhancing c-Fos-mediated AP-1 transactivation activity, has an essential role in cancer cell proliferation and colony growth.

Risk factors for osteoporosis in chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients possess multiple risk factors for osteoporosis, but few studies have evaluated bone mineral density (BMD) in CIDP patients. METHODS: We retrospectively compared the BMD of CIDP patients with that of normal controls, and evaluated the clinical factors associated with osteoporosis. RESULTS: Total BMD was lower in CIDP patients than in normal controls (P = 0.017). In a comparison of 16 osteoporotic CIDP patients with 25 non-osteoporotic patients, the cumulative prednisolone dose was lower (P = 0.022) and the duration from disease onset to BMD measurement was shorter (P = 0.014) in osteoporotic patients than in non-osteoporotic patients. Function, as measured by modified Rankin scale score within 3 years of the BMD measurement, was worse in osteoporotic than in non-osteoporotic patients (P = 0.008). DISCUSSION: BMD in CIDP patients was significantly lower than in normal controls. Functional status rather than cumulative steroid dose was associated with osteoporosis. Muscle Nerve 58: 407-412, 2018.

Antibacterial Cyclic Lipopeptide Enamidonins with an Enamide-Linked Acyl Chain from a Streptomyces Species.

Three cyclic lipopeptides, including one known (1) and two new (2 and 3) compounds, that possess the rare enamide linkage group were discovered from Streptomyces sp. KCB14A132, an actinobacterium isolated from a soil sample collected from Jeung Island, Korea. The NMR and MS-based characterization showed that they differed in the amino acid residues in the peptide backbone. Application of Marfey's analysis, GITC derivatization, and modified Mosher's method, as well as ECD measurements provided the absolute configurations of enamidonin (1) and those of new compounds enamidonins B and C (2 and 3). The two new enamidonin analogues were shown to exhibit antibacterial activity against Gram-positive bacteria including methicillin-resistant and quinolone-resistant Staphylococcus aureus. Furthermore, evaluation of the extraction conditions and a close inspection of the LC-MS chromatograms revealed that the N, N-acetonide unit of the enamidonin family was formed during the acetone extraction process. The chemically prepared deacetonide derivatives of enamidonins were found to lack antibacterial activity, demonstrating that the dimethylimidazolidinone residue is necessary for antibacterial activity.

'Screening audit' as a quality assurance tool in good clinical practice compliant research environments.

BACKGROUND: With the growing amount of clinical research, regulations and research ethics are becoming more stringent. This trend introduces a need for quality assurance measures for ensuring adherence to research ethics and human research protection beyond Institutional Review Board approval. Audits, one of the most effective tools for assessing quality assurance, are measures used to evaluate Good Clinical Practice (GCP) and protocol compliance in clinical research. However, they are laborious, time consuming, and require expertise. Therefore, we developed a simple auditing process (a screening audit) and evaluated its feasibility and effectiveness. METHODS: The screening audit was developed using a routine audit checklist based on the Severance Hospital's Human Research Protection Program policies and procedures. The measure includes 20 questions, and results are summarized in five categories of audit findings. We analyzed 462 studies that were reviewed by the Severance Hospital Human Research Protection Center between 2013 and 2017. We retrospectively analyzed research characteristics, reply rate, audit findings, associated factors and post-screening audit compliance, etc. RESULTS: Investigator reply rates gradually increased, except for the first year (73% → 26% → 53% → 49% → 55%). The studies were graded as "critical," "major," "minor," and "not a finding" (11.9, 39.0, 42.9, and 6.3%, respectively), based on findings and number of deficiencies. The auditors' decisions showed fair agreement with weighted kappa values of 0.316, 0.339, and 0.373. Low-risk level studies, single center studies, and non-phase clinical research showed more prevalent frequencies of being "major" or "critical" (p = 0.002, < 0.0001, < 0.0001, respectively). Inappropriateness of documents, failure to obtain informed consent, inappropriateness of informed consent process, and failure to protect participants' personal information were associated with higher audit grade (p < 0.0001, p = 0.0001, p < 0.0001, p = 0.003). We were able to observe critical GCP violations in the routine internal audit results of post-screening audit compliance checks in "non-responding" and "critical" studies upon applying the screening audit. CONCLUSIONS: Our screening audit is a simple and effective way to assess overall GCP compliance by institutions and to ensure medical ethics. The tool also provides useful selection criteria for conducting routine audits.

Multifunctionalized Reduced Graphene Oxide Biosensors for Simultaneous Monitoring of Structural Changes in Amyloid-ß 40.

Determination of the conformation (monomer, oligomer, or fibril) of amyloid peptide aggregates in the human brain is essential for the diagnosis and treatment of Alzheimer's disease (AD). Accordingly, systematic investigation of amyloid conformation using analytical tools is essential for precisely quantifying the relative amounts of the three conformations of amyloid peptide. Here, we developed a reduced graphene oxide (rGO) based multiplexing biosensor that could be used to monitor the relative amounts of the three conformations of various amyloid-ß 40 (Aß40) fluids. The electrical rGO biosensor was composed of a multichannel sensor array capable of individual detection of monomers, oligomers, and fibrils in a single amyloid fluid sample. From the performance test of each sensor, we showed that this method had good analytical sensitivity (1 pg/mL) and a fairly wide dynamic range (1 pg/mL to 10 ng/mL) for each conformation of Aß40. To verify whether the rGO biosensor could be used to evaluate the relative amounts of the three conformations, various amyloid solutions (monomeric Aß40, aggregated Aß40, and disaggregated Aß40 solutions) were employed. Notably, different trends in the relative amounts of the three conformations were observed in each amyloid solution, indicating that this information could serve as an important parameter in the clinical setting. Accordingly, our analytical tool could precisely detect the relative amounts of the three conformations of Aß40 and may have potential applications as a diagnostic system for AD.

Significantly Increased Solubility of Carbon Nanotubes in Superacid by Oxidation and Their Assembly into High-Performance Fibers.

This study demonstrates that small amount of oxygen incorporated into carbon nanotubes (CNTs) during the purification process greatly increases their solubility in chlorosulfonic acid (CSA). Using as-purchased and unpurified CNT powders, the optimal purification process is established to significantly increase the solubility of CNTs in CSA, and spin CNT fibers with high mechanical strength (0.84 N tex-1 ) and electrical conductivity (1.4 MS m-1 ) from the CNT liquid crystal dope with high concentration of CNTs in CSA. The knowledge obtained here may guide development of a way to dissolve extremely long CNTs at high concentration and thereby to enable production of CNT fibers with ultimate properties.

Spinal cord involvement in Behçet's disease.

BACKGROUND: Spinal cord involvement in Behçet's disease is not well studied. OBJECTIVE: To evaluate the clinical, laboratory and magnetic resonance imaging characteristics of spinal cord involvement in Behçet's disease. METHODS: We retrospectively reviewed 10 spinal cord involvements in seven patients with Behçet's disease. RESULTS: The median age of onset for spinal cord involvement was 32 (23-45 years). Two patients showed a secondary progressive course. Cerebrospinal fluid findings revealed mild to moderate pleocytosis and/or elevated protein levels. In eight spinal cord involvements, the lesion was longer than three vertebrae. Serum anti-aquaporin-4 antibody was negative in all four patients tested. CONCLUSIONS: Longitudinally extensive transverse myelitis is a characteristic manifestation of spinal cord involvement in Behçet's disease.