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Objectives: The purpose of this study was to investigate the effect of weight loss in Korean Medicine (KM) obesity treatment combined with self-monitoring and to identify the relevant factors which are related to successful weight loss. In addition to this, adverse events reported by the patients were analyzed to assess the safety of KM treatments for obesityMethods: This was a retrospective observational study that analyzed the medical records of the patients that participated in the 10-week of KM treatment. All patients took herbal medicine for weight loss and were instructed to reduce calorie intake and adhere to self-monitoring. Clinical data including body weight were collected for evaluating the effect of the treatments. Behavior factors affecting weight loss were collected. The correlation between each factor and weight loss was analyzed. Adverse events (AEs) were collected at each time to evaluate the safety of the intervention.Results: One hundred eighteen patients’ records were included in this study. The average weight loss was 7.64kg(74.59kg to 66.95kg). 94.9% of patients lost 5% or more of their initial weight. The degree of weight loss was identified to be related to self-assessment of diet control and self-assessment of appetite control. The average self-weighing frequency significantly increased(2.45 times/week before treatment and 4.70 times/weeks during treatment). Constipation, insomnia, and dizziness were found to be the most frequent AEs, and except for one case, most AEs were mild cases.Conclusion: From this study, we found that KM obesity treatment combined with self-monitoring showed significant weight loss without serious AE.

Background and Aim Functional dyspepsia (FD) is characterized by chronic and unexplained indigestion at upper abdomen. Because of unsatisfactory effect of conventional treatments, demand is growing for complementary and alternative medicine. Rikkunshito (RKT) is a herbal medicine, which has been widely used for FD in Asia; however, the evidence is lacking. We carried out systematic review and meta‐analysis to evaluate the effect and safety of RKT in the treatment of FD. Methods Electronic databases were searched in April 2019, including PUBMED, EMBASE, and Cochrane Library. All eligible studies should be randomized controlled trials (RCTs) comparing RKT or combination therapy (RKT and western medicine) group to western medicine group. The primary outcome measure was the total clinical efficacy rate (TCE). The secondary outcomes were total dyspepsia symptom scale, gastric emptying rate, gastrin, motilin, recurrence 6 months after treatment, and Hamilton depression rating scale. Results Fifty‐two RCTs with 5475 patients were involved in this systematic review and meta‐analysis. Compared with western medicine, RKT showed significant better result, with higher TCE (relative risk = 1.21, 95% confidence interval 1.17 to 1.25, P

To provide high-quality training to residents in a rapidly changing medical environment, it is very important to improve the annual training curriculum centered on competency and ensure that training hospitals maintain an environment suitable for training. The Korean Society of Radiology (KSR) has been steadily improving the training system and has suggested the improvement of the training system by strengthening the competency-based evaluation and faculty development. Currently, KSR was selected for the second annual training curriculum systematization construction project in July 2021, and developed entrustable professional activities, core competencies, and assessment guidelines required by the construction project. Therefore, the development process and assessment guidelines will be introduced to residents and the faculty.

MicroRNAs (miRNAs) are small non-coding RNAs, which are involved in RNA silencing and post-transcriptional regulation of gene expression. Numerous studies have determined the expression of certain miRNAs in specific tissues and cell types, and their aberrant expression is associated with a variety of serious diseases such as cancers, immune-related diseases, and many infectious diseases. This suggests that miRNAs may be attractive and promising non-invasive biomarkers of diseases. In this study, we established a graphene oxide (GO)-based fluorescence/colorimetric dual sensing platform for miRNA by using a newly designed probe. The probe was designed to form a hairpin-like configuration with a fluorescent dye-labeled long tail, possessing a guanine (G)-rich DNAzyme domain in the loop region and target binding domain over the stem region and tail. By introducing this new hairpin-like probe in a conventional GO-based fluorescence platform, we observed both the miRNA-responsive color change by direct observation and sensitive fluorescence increase even below the nanomolar levels in a single solution without an additional separation step.

To accurately interpret knee MRI, it is important not only to know the basic meniscal anatomy but also to distinguish it from that under pathological conditions. Thus, it would be helpful to know the normal meniscus variants (false positives) that could be mistaken for meniscal tears, and tears that could easily be missed and incorrectly diagnosed as normal (false negatives). False positives include synovial recesses, meniscal flounce, the relationship between the popliteus tendon and lateral meniscus, transverse ligament, the anterior root of the meniscus, and meniscofemoral ligament. False negatives include focal radial tears, flap tears, posterior root tears, meniscocapsular separation, and discoid meniscal tears. In this pictorial essay, we reviewed the imaging data obtained in the aforementioned cases.무릎 MRI를 정확하게 판독하려면 기본적인 반월연골 해부학을 아는 것뿐만 아니라 병적 상태와 구별하는 것이 중요하다. 따라서 반월연골 열상으로 쉽게 오인될 수 있는 정상 변이(위양성)와 쉽게 놓쳐서 자칫 정상으로 오인될 수 있는 반월연골열상들(위음성)을 아는 것이 판독에 도움이 될 것이다. 위양성에는 활막 오목, 반월연골 주름, 슬와 힘줄과 외측 반월연골 사이의 관계, 가로 인대, 반월연골 앞 근 및 반월대퇴 인대가 포함된다. 위음성에는 국소 방사열상, 피판 열상, 뒤 근 열상, 반월연골-관절낭 분리, 원반모양반월연골의 열상이 있다. 이번 임상화보에서는 앞서 언급한 상황들로부터 얻은 영상자료들을 검토해보았다.

Acetobacter pasteurianus AFY-4 was isolated from fermented vinegar in Hongcheon-gun, Gangwon-do. The A. pasteurianus AFY-4 strain had a higher tolerance to low-pH. Optimization of acetic acid fermentation of hardy kiwi (Actinidia arguta) was conducted using the A. pasteurianus AFY-4 strain based on the response surface methodology (RSM). The optimization of acetic acid fermentation for producing hardy kiwi vinegar was determined by five levels of initial ethanol, initial acetic acid, and acetic acid bacteria (AAB) inoculum volume, using the central composite design. The acetic acid yield and residual ethanol for acetic acid fermentation of hardy kiwi optimized by the RSM were significantly different. The optimal conditions for acetic acid fermentation of hardy kiwi vinegar were 8.95% of the initial ethanol, 1.86% of the initial acetic acid, and 25.02% of the AAB inoculum volume.

Two zinc-aminoclays [ZnACs] with functionalized primary amines [(-CH2)3NH2] were prepared by a simple sol-gel reaction using cationic metal precursors of ZnCl2 and Zn(NO3)2 with 3-aminopropyl triethoxysilane [APTES] under ambient conditions. Due to the facile interaction of heavy metals with primary amine sites and Zn-related intrinsic antimicrobial activity, toxicity assays of ZnACs nanoparticles (NPs) prior to their environmental and human-health applications are essential. However, such reports remain rare. Thus, in the present study, a cell viability assay of in-vitro HeLa cells comparing ZnCl2, Zn(NO3)2 salts, and ZnO (~50 nm average diameter) NPs was performed. Interestingly, compared with the ZnCl2, and Zn(NO3)2 salts, and ZnO NPs (18.73/18.12/51.49 µg/mL and 18.12/15.19/46.10 µg/mL of IC50 values for 24 and 48 h), the two ZnACs NPs exhibited the highest toxicity (IC50 values of 21.18/18.36 µg/mL and 18.37/17.09 µg/mL for 24 and 48 h, respectively), whose concentrations were calculated on Zn elemental composition. This might be due to the enhanced bioavailability and uptake into cells of ZnAC NPs themselves and their positively charged hydrophilicity by reactive oxygen species (ROS) generation, particularly as ZnACs exist in cationic NP's form, not in released Zn2+ ionic form (i.e., dissolved nanometal). However, in an in-vivo embryotoxicity assay in zebrafish, ZnACs and ZnO NPs showed toxic effects at 50–100 µg/mL (corresponding to 37.88–75.76 of Zn wt% µg/mL). The hatching rate (%) of zebrafish was lowest for the ZnO NPs, particularly where ZnAC-[(NO3)2] is slightly more toxic than ZnAC-[Cl2]. These results are all very pertinent to the issue of ZnACs’ potential applications in the environmental and biomedical fields.

OBJECTIVES: The purpose of this study was to investigate optimization of spray drying conditions for water-soluble powder using response surface methodology that is a statistical procedure used for optimization studies. METHODS: First, conditions of the extract used for spray drying were set. We compared heat water extraction (60–100 °C) with ethanol extraction (10–50%). After final selection of the method of extract used for spray drying, spray drying conditions were set. Independent variables included the additive contents of maltodextrin (X(1)), inlet temperature (X(2)), and air flow rate (X(3)). The dependent variables were yield, water absorption index (WAI) and total phenolic compounds. RESULTS: The yield was highest in 100 °C heat water extraction. The content of rutin was 29.77 mg/100 g in 90 °C heat water extraction, 28.07 mg/100 g in 100 °C heat water extraction and 24.24 mg/100 g in 10% ethanol extraction. The heat water extraction method at 100 °C was selected as an extract of the spray dryer. Statistical analysis revealed that independent variables significantly affected all the responses. A maximum yield was obtained at 15.55% of X(1), 167.87 °C of X(2) and 50.00 mL/min of X(3). The water absorption index of asparagus increased with increasing MD ratio (X(1)), higher inlet temperature (X(2)) and higher air flow rate (X(3)). The total polyphenol contents of asparagus were higher when the MD addition ratio (X(1)) was 16.56%, the inlet temperature (X(2)) was higher and the air flow rate (X(3)) was higher. CONCLUSIONS: In this study, extracts of asparagus using different extraction methods were compared for yield and spray-dried asparagus powders were investigated for their physicochemical characteristics. We were vary the range of the temperature, air flow rate, dextrin rate and set the best method for the functionality content of asparagus. Asparagus was spray - dried using 100 °C water extraction with high yield and high rutin content. The maximum spray drying yield was obtained at 15.55% of MD ratio, 167.87 °C of inlet temperature and 50.00 mL/min of air flow rate. There will be additional processed goods development made with what we have found. FUNDING SOURCES: This study was supported by 2018 Regional Specialized Technology Development Project, Rural Development Administration, Republic of Korea. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

A rapid diagnostic test (RDT) kit was developed to detect non-structural protein 1 (NS1) of yellow fever virus (YFV) using monoclonal antibody. NS1 protein was purified from the cultured YFV and used to immunize mice. Monoclonal antibody to NS1 was selected and conjugated with colloidal gold to produce the YFV NS1 RDT kit. The YFV RDTs were evaluated for sensitivity and specificity using positive and negative samples of monkeys from Brazil and negative human blood samples from Korea. Among monoclonal antibodies, clones 3A11 and 3B7 proved most sensitive, and used for YFV RDT kit. Diagnostic accuracy of YFV RDT was fairly high; Sensitivity was 0.0% and specificity was 100% against Dengue viruses type 2 and 3, Zika, Chikungunya and Mayaro viruses. This YFV RDT kit could be employed as a test of choice for point-of-care diagnosis and large scale surveys of YFV infection under clinical or field conditions in endemic areas and on the globe.

The objective of this study was to investigate quality properties of ‘Cheonghyang’ wine using different commercial yeast strains. Soluble solid content, pH level and total acidity of ‘Cheonghyang’ grape were 20 °Bx, pH 3.5 and 0.66%, respectively. Total acidity ranged from 0.91∼1.06% in the middle stage of fermentation and decreased to 0.77∼0.82% when alcoholic fermentation finished. Alcohol content in wines ranged from 12.5% to 12.9% showing no significant difference in yeast strains. Wine fermented with Red Fruit had high volatile acid content (189.0 ㎎/L) whereas wine fermented with Fermivin indicated low volatile acid content (77.7 ㎎/L). Wines made with Montrachet, Fermivin and Aroma White had low brightness (L-value) compared to others. Results from sensory evaluation demonstrated that commercial wine yeasts, Montrachet and Fermivin, can be applied to improve sensory properties of ‘Cheonghyang’ wine such as aroma, acidity and transperency. On the other hand, preferences of wine fermented with EC-1118 strain containing lots of tannins and total polyphenols were significantly reduced.

Amyloidosis is a disease characterized by the deposition of non-soluble fibrous protein in multiple tissues with a number of possible causes. This protein deposition can occur in any tissue, yet is most commonly seen in kidneys, heart, and gastrointestinal tracts. However, invasion to bone tissues is not often reported. The deposition of amyloid proteins in bone tissues may result in joint pain and pathological fractures; it is important to elucidate the causes and detect early to determine prognosis and treat optimally. In the present case report, with relevant literature review, the authors report a case of total hip arthroplasty in an amyloidosis patient.

Polyene macrolides such as nystatin A1 and amphotericin B belong to a large family of very valuable antifungal polyketide compounds typically produced by soil actinomycetes. Recently, nystatin-like Pseudonocardia polyene (NPP) A1 has been identified as a unique disaccharide-containing tetraene antifungal macrolide produced by Pseudonocardia autotrophica. Despite its significantly increased water solubility and decreased hemolytic activity, its antifungal activity remains limited compared with that of nystatin A1. In this study, we developed NPP B1, a novel NPP A1 derivative harboring a heptaene core structure, by introducing two amino acid substitutions in the putative NADPH-binding motif of the enoyl reductase domain in module 5 of the NPP A1 polyketide synthase NppC. The low level NPP B1 production yield was successfully improved by eliminating the native plasmid encoding a polyketide biosynthetic gene cluster present in P. autotrophica. In vitro and in vivo antifungal activity and toxicity studies indicated that NPP B1 exhibited comparable antifungal activity against Candida albicans and was less toxic than the most potent heptaene antifungal, amphotericin B. Moreover, NPP B1 showed improved pharmacokinetic parameters compared to those of amphotericin B, suggesting that NPP B1 could be a promising candidate for development into a pharmacokinetically improved and less-toxic polyene antifungal antibiotic.

Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer's disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy. [BMB Reports 2016; 49(6): 337-342].

The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. However, how these mutations affect the trafficking of TREM2, which may affect the normal functions of TREM2, was not known. In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease.

Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have considerable potential as treatment for osteoporosis as well as metabolic syndrome including type 2 diabetes mellitus. Here, we investigated the anti-diabetic, anti-adipogenic, and anti-osteoporotic activity of KR-67500, as a novel selective 11β-HSD1 inhibitor. Cellular 11β-HSD1 activity was tested based on a homogeneous time-resolved fluorescence method. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) levels were measured in diet-induced obese (DIO)-C57BL/6 mice administered KR-67500 (50 mg/kg per day, p.o.) for 28 days and, additionally, its anti-diabetic effect was evaluated by OGTT and ITT. Thein vitroanti-adipogenic effect of KR-67500 was determined by Oil Red O Staining. Thein vitroanti-osteoporotic activity of KR-67500 was evaluated using bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model systems. KR-67500 improved thein vivoglucose tolerance and insulin sensitivity in DIO-C57BL/6 mice. KR-67500 suppressed cortisone-induced differentiation of 3T3-L1 cells into adipocytes. KR-67500 enhanced BMP2-induced osteoblastogenesis in C2C12 cells and inhibited RANKL-induced osteoclastogenesis in mouse bone marrow-derived macrophages. KR-67500, a new selective 11β-HSD1 inhibitor, may provide a new therapeutic window in the prevention and/or treatment of type 2 diabetes, obesity, and/or osteoporosis.

BACKGROUND During an epidemic of a novel infectious disease, many healthcare workers suffer from mental health problems. OBJECTIVES The aims of this study were to test the following hypotheses: stigma and hardiness exert both direct effects on mental health and also indirect (mediated) effects on mental health through stress in nurses working at a government-designated hospital during a Middle East Respiratory Syndrome coronavirus (MERS-CoV) epidemic. METHODS A total of 187 participants were recruited using a convenience sampling method. The direct and indirect effects related to the study hypotheses were computed using a series of ordinary least-squares regressions and 95% bootstrap confidence intervals with 10,000 bootstrap resamples from the data. DISCUSSIONS The influences of stigma and hardiness on mental health were partially mediated through stress in nurses working at a hospital during a MERS-CoV epidemic. Their mental health was influenced more by direct effects than by indirect effects., HIGHLIGHTS • During an epidemic of a novel infectious disease, nurses can suffer from mental health problems. • Stigma and hardiness exert both direct effects on mental health in nurses. • Stigma and hardiness exert both indirect effects on mental health via stress in nurses. • The mental health of nurses was affected more by direct effects than by indirect effects.

The R47H coding variant of the triggering receptor expressed on myeloid cells-2 (TREM2) increases the risk of Alzheimer's disease (AD) similar to apolipoprotein E4. TREM2 R47H has recently been shown to have impaired binding to damage-associated lipid or apolipoprotein ligands. However, it is not known how this R47H variant affects the biochemical characteristics of TREM2 and alters the pathogenesis of AD. We previously reported that TREM2-R47H has a slightly different glycosylation pattern from wild-type. A more detailed characterization in our present study confirms that TREM2 R47H has an altered glycosylation pattern and reduced stability. TREM2 R47H shows different glycosylation profiles from analysis using monensin or kifunensine treatment which were confirmed by mass spectrometry. The solubility of TREM2 R47H and its cleaved products such as intracellular domain (ICD) is also decreased, increasing its proteasomal and lysosomal degradation. The different biochemical characteristics of TREM2 R47H, including glycosylation, solubility and processing, may offer insights into a future therapeutic strategy for AD.

Epiphyseal involvement of a simple bone cyst (SBC) is rare. Furthermore, its pathological variant is even more uncommon. Herein, we report a case of a 22-year-old woman with an SBC containing unusual mesenchymal tissue proliferation with epiphyseal involvement in the proximal fibula. Magnetic resonance imaging showed a cystic lesion that involved the entire epiphysis as well as some soft tissue components. Hence, our initial differential diagnosis did not include SBC. However, pathology confirmed a SBC. Thus, SBC should be considered in the diagnosis of cystic lesions despite the atypical imaging findings.

A new series of cyclic sulfamide derivatives were synthesized and evaluated for their ability to inhibit 11β-HSD1. Among this series, 18e showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, and pharmacokinetic and safety profiles (hERG, CYP, and acute toxicity). Additionally, 18e exhibited good in vivo efficacy in rat and monkey models.

To evaluate the incidence and pattern of spinous process fractures (SPFs) in patients with osteoporotic compression fractures (OCFs) of the thoracolumbar spine.Spinal MRI or CT of 398 female patients (age range 50-89 years, mean age 70 years) who had OCFs in the thoracolumbar spine were retrospectively reviewed. The incidence, location and imaging results for the SPFs were evaluated.Of the 398 patients who had thoracolumbar OCFs, 14 (3.5%) had SPF. In six patients with single compression fractures, the SPF occurred at the level just above the vertebral compression fracture. In six out of seven patients with multiple continuous compression fractures, the SPF occurred just one level above the uppermost level of the compression fracture. The remaining one patient who had thoracolumbar spinal fixation at T12-L2 with continuous compression fractures in T12-L5 had a SPF in L2. In one patient who had multiple compression fractures in discontinuous levels (fractures at T10 and L1, respectively), the SPF occurred at T12. The directions of the fractures were vertical or oblique vertical (perpendicular to the long axis of the spinous process) in all cases.In the presence of an OCF in the thoracolumbar spine, a SPF was found in 3.5% of cases, and most of the fractures were located just one level above the compression fracture. Therefore, in patients who have OCF, the possibility of a SPF in the level just above the compression fracture should be considered.

This study was investigated to find out the change of reproductive and histological biomarkers of Ruditapes philippinarum exposed to nonylphenol (NP). Experimental period was 16 weeks. Experimental groups were composed of one control condition and three NP exposure conditions (0.05, 0.1, 0.2 mg NP L -1 ). Gonad index was higher in exposure group than control in female and higher in control than exposure group in male. Intersexuality in the NP exposure group was 14.56% with male exhibiting higher ratio than female. Histological analysis of organ system illustrated expansion of hemolymph sinus, loss of striated border of inner epidermis and degeneration of mucous cell in the mantle. In the gill partially disappearance of frontal and lateral cilia, degeneration of mucous cell were observed. Also, hyperplasia of epithelium and disappearance of striated border were observed in the foot. As the concentration of NP increased, the accumulation of lipofuscin increased in the digestive gland. The results of this study suggest that NP induces reduction of survival rate, histopathology and intersex of R. philippinarum. Furthermore, it is indentified that NP functions as an estrogenic effector on the reproduction of R. philippinarum.

Objective To compare the elasticity of the supraspinatus tendon (SST) and infraspinatus tendon (IST) in patients with idiopathic adhesive capsulitis of the shoulder (ACS) with those in the control groups and to evaluate the relationship between age and tendon elasticity. Materials and Methods The Institutional Review Board approved this prospective, case-control study, which was conducted between November 2017 and March 2018, and informed consent was obtained from all participants. Control groups comprised healthy individuals or those with asymptomatic contralateral shoulders. Twenty-five shoulders in 20 participants in the ACS group (14 women; 53.5 ± 7.9 years) and 24 shoulders in 18 participants in the control group (6 women; 52.6 ± 10.5 years) were included. Elastography was performed in the oblique coronal plane at the neutral shoulder position. Mean/maximum/minimum velocity and stiffness from the shear-wave ultrasound elastography (SWE) and strain ratio (subcutaneous fat/target-tendon) from the strain ultrasound elastography (SE) of the SST and IST were evaluated. Statistical analyses were performed using the Mann-Whitney U test, receiver operating characteristic (ROC) curve, and Spearman correlation. Results Both velocity and stiffness in SWE were higher, and the strain ratio in SE was lower in participants with symptomatic shoulders than in those with normal shoulders (p < 0.001). SST- and IST-mean velocity, mean stiffness, and strain ratios showed excellent area under the ROC curve (> 0.970). The elastic modulus was little correlated with age (ρ = −0.340–0.239). Conclusion SWE and SE indicated that SST and IST were stiffer in patients with ACS than in those with normal shoulders regardless of aging.

To identify genes involved in etoposide drug response, we used promoter trap mutagenesis to isolate an etoposide-resistant Chinese hamster ovary (CHO) cell line. This resistant CHO-K1 line, named E91, showed cross-resistance to C2-ceramide (N-acetylsphingosine). The promoter trap retrovirus was found integrated into intron 1–2 of the Dlc-2 (Stard13) RhoGap gene. The E91 cells showed elevated guanosine triphosphate (GTP)-bound RhoA levels compared with the parental line, suggesting that retrovirus integration had inactivated one of the Dlc-2 RhoGap alleles. To test whether E91 cells were impaired in an intracellular ceramide-regulated process not directly related to cell killing, we measured mitochondrial phosphatidylglycerolphosphate (PGP) synthase and phospholipase A2 enzyme activities in cells after C2-ceramide addition. Parental cells showed elevated enzyme activities after treatment with C2-ceramide or tumor necrosis factor α, but not the E91 cells. These results suggested that intracellular ceramide signaling was defective in E91 cells due to increased levels of active GTP-bound RhoA. RNA knockdown experiments of the Dlc2 RhoGap resulted in increased GTP-bound RhoA and reduced induction of PGP synthase after C2-ceramide addition compared with controls. Expression of a dominant-negative RhoA in the E91 cell line allowed induction of PGP synthase by ceramide. The RNA interference knockdown cell line also showed increased etoposide resistance. This study is the first report for the regulation of a phospholipid biosynthetic enzyme through RhoGap expression.

Background The optimal duration of antibiotic treatment for hematogenous vertebral osteomyelitis (HVO) should be based on the patient's risk of recurrence, but it is not well established. Methods A retrospective review was conducted to evaluate the optimal duration of antibiotic treatment in patients with HVO at low and high risk of recurrence. Patients with at least 1 independent baseline risk factor for recurrence, determined by multivariable analysis, were considered as high risk and those with no risk factor as low risk. Results A total of 314 patients with microbiologically diagnosed HVO were evaluable for recurrence. In multivariable analysis, methicillin-resistant Staphylococcus aureus infection (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.16-5.87), undrained paravertebral/psoas abscesses (aOR, 4.09; 95% CI, 1.82-9.19), and end-stage renal disease (aOR, 6.58; 95% CI, 1.63-26.54) were independent baseline risk factors for recurrence. Therefore, 191 (60.8%) patients were classified as low risk and 123 (39.2%) as high risk. Among high-risk patients, there was a significant decreasing trend for recurrence according to total duration of antibiotic therapy: 34.8% (4-6 weeks [28-41 days]), 29.6% (6-8 weeks [42-55 days]), and 9.6% (≥8 weeks [≥56 days]) (P = .002). For low-risk patients, this association was still significant but the recurrence rates were much lower: 12.0% (4-6 weeks), 6.3% (6-8 weeks), and 2.2% (≥8 weeks) (P = .02). Conclusions Antibiotic therapy of prolonged duration (≥8 weeks) should be given to patients with HVO at high risk of recurrence. For low-risk patients, a shorter duration (6-8 weeks) of pathogen-directed antibiotic therapy may be sufficient.

Objective To evaluate whether an early bone marrow edema pattern predicts vertebral deformity types and prognosis in osteoporotic vertebral compression fracture (OVCF). Methods This retrospective study enrolled 64 patients with 75 acute OVCFs who underwent early MRI and followed up MRI. On early MRI, the low SI pattern of OVCF on T1WI were assessed and classified into 3 types (diffuse, globular or patchy, band-like). On followed up MRI, the vertebral deformity types (anterior wedge, biconcave, crush), degree of vertebral body height loss, incidence of vertebral osteonecrosis and spinal stenosis were assessed for each vertebral fracture types. Results According to the early bone marrow edema pattern on T1WI, 26 vertebrae were type 1, 14 vertebrae were type 2 and 35 vertebrae were type 3. On followed up MRI, the crush-type vertebral deformity was most frequent among the type 1 OVCFs, the biconcave-type vertebral deformity was most frequent among the type 2 OVCFs and the anterior wedge-type vertebral deformity was most frequent among the type 3 OVCFs (p

Musculoskeletal (MSK) infections, such as osteomyelitis, infectious arthritis and spondylitis have variable radiographic findings depending on their underlying cause and clinical infection stage. Other disease entities, ranging from simple degenerative lesions to tumorous bone conditions, in which there is no evidence of infectious origin, can share similar radiographic findings. It is important to be aware, when interpreting radiographic features that are typically associated with MSK infections, that a non-infectious MSK disease may be mimicking the radiographic findings of infectious diseases.

Purpose To determine the reliability of edema grading of the psoas and paraspinal muscles on axial T2-weighted magnetic resonance (MR) image (T2WI) for the detection of lumbar transverse process (TP) fractures. Materials and Methods A retrospective review of lumbar spine MR images of 56 patients (mean age = 56.1 years, age range = 17–87 years, male:female = 28:28) was conducted by 2 radiologists. Based on the axial T2WI at the disc level, the paraspinal muscles were classified into 4 compartments and muscle edema (increased signal intensity on axial T2WI) grading performed for each quadrant. Results A total of 486 TPs (with fracture: 24, without fracture: 462) of 56 patients were evaluated. Muscle edema grade showed moderate correlation with the presence of TP fracture (ρ = 0.466). When the total score of muscle edema was 2.50, the receiver operating characteristic curve showed a sensitivity of 72.7% and a specificity of 90.7%. A higher edema grade had a significantly higher probability of concomitant TP fracture [any sided (total): odds ratio = 1.704 (95% confidence interval = 1.410–2.060)]. Conclusion Edema grading of the psoas and paraspinal muscles on axial T2WI of lumbar spine can be helpful in the detection of TP fracture.

The precise mechanisms of resistance to camptothecin (CPT)-derived DNA topoisomerase (topo I) inhibitors and the determinants remain unclear. We found that a DNA repair protein, O(6)-methylguanine-DNA methyltransferase (MGMT), participated in resistance to irinotecan hydrochloride (CPT-11), its active metabolite SN-38, and a novel CPT derivative, DX-8951f. In 17 human cancer cell lines, MGMT gene expression level closely correlated with sensitivity to the CPT derivatives, and inhibition of MGMT activity by nontoxic 5 microM O(6)-benzylguanine augmented the drug activity in relation to the MGMT expression levels in 8 cell lines examined. Transfection of pCR / MGMT-sense into U-251MG and pCR / MGMT-antisense into T98G and HEC-46 cells revealed that increased MGMT expression decreased the sensitivity to CPT-11, SN-38, and DX-8951f, whereas repressed MGMT expression sensitized cells to the drugs. Western analysis revealed that treatment of MGMT-expressing T98G cells with the drugs caused a decrease of both MGMT and topo I in a dose-dependent manner. Although, in the transfectants, MGMT expression did not so closely correlate with the sensitivity to drugs as to nimustine hydrochloride (ACNU), MGMT is probably an important resistance determinant to CPT derivatives, and may play some role in the topo I-mediated DNA damage and / or the repair process.

To describe the characteristic MRI appearance of squatting-induced rhabdomyolysis involving the thigh muscles.This study consisted of 10 cases obtained at 3 institutions from 2005 to 2015. A retrospective review was performed to obtain clinical information and MR scans for rhabdomyolysis of the thigh muscles. MRI was analyzed according to the distribution and degree of muscle involvement; the degree was assessed and graded as normal, mild or prominent.The mean patient age was 20.2 years (range, 15-24 years), and 7 of the 10 patients were male. All patients had history of excessive squatting action, suffered clinically from bilateral thigh pain and were confirmed to have rhabdomyolysis through analysis of serum creatine kinase (CK) levels. All of the patients (10/10) exhibited diffuse mild to prominent degree involvement of the anterior thigh muscles according to fluid-sensitive MR sequences. Among the anterior thigh muscles, the rectus femoris was spared in 8 patients (8/10) and mild degree involved in 2 patients (2/10). Thus, no cases exhibited prominent degree involvement of the rectus femoris muscle.Preservation of the rectus femoris muscle on MRI in squatting-induced rhabdomyolysis may be useful for differentiating rhabdomyolysis from other aetiologies. Advances in knowledge: Preservation of rectus femoris on MRI is distinguishable finding in squatting-induced rhabdomyolysis and reflects the functional anatomy of anterior thigh muscles.

Background Patients with hematogenous vertebral osteomyelitis (HVO) occasionally require instrumentation for spinal stabilization. However, placing instrumentation in the setting of spinal infection raises concerns about recurrent infection due to bacteria adhering to the foreign material. In this study, we evaluated the therapeutic outcomes of patients with HVO who underwent instrumented surgery. Methods We conducted a retrospective chart review of adult patients with microbiologically diagnosed HVO who underwent surgical intervention in 5 tertiary care hospitals over an 8-year period. Results A total of 153 patients with HVO underwent surgical management for their infections. Of these 153 patients, 94 (61.4%) underwent surgical debridement alone (noninstrumented surgery) and 59 (38.6%) underwent surgical debridement and instrumentation (instrumented surgery). The median durations of antibiotic therapy were 66 and 80 days for the noninstrumentation and instrumentation groups, respectively (P = .22). Clinical outcomes were similar between the groups, including rates of infection-related death (2.1% vs 0%; P = .52), primary failure (1.1% vs 5.1%; P = .30), and recurrence (4.8% vs 6.8%; P = .72). Among the instrumentation group, there was a significant decreasing trend for recurrence according to total duration of antibiotic therapy: 22.2% (4-6 weeks), 9.1% (6-8 weeks), and 2.6% (≥ 8 weeks; P = .04). Duration of pre-instrumentation antibiotic therapy and single-stage operation (vs 2-stage operation) were not risk factors for recurrence. Conclusions Spinal instrumentation in patients with HVO may be safe with pathogen-directed prolonged antibiotic therapy and should not be abandoned or delayed solely because of the risk of recurrence.

The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune-modulatory receptor involved in phagocytosis and inflammation. Mutations of Q33X, Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early onset of dementia and bone cysts. A recent, genome-wide association study also revealed that single nucleotide polymorphism of TREM2, such as R47H, increased the risk of Alzheimer's disease (AD) similar to ApoE4. However, how these mutations affect the trafficking of TREM2, which may affect the normal functions of TREM2, was not known. In this study, we show that TREM2 with NHD mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by γ-secretase. Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine. Our results suggest that the impaired glycosylation and trafficking of TREM2 from endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease.