Search

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae and the treatment of choice is ofloxacin (OFX). Specific amino acid substitutions in DNA gyrase of M. leprae have ...

Aims: Quinolone-resistant nontyphoidal Salmonella having serine replaced by isoleucine at the 83rd amino acid in GyrA (GyrA-Ser83Ile) has recently been found in Asian countries. In this study, we aimed to examine the direct effect of substitution Ser83Ile on DNA gyrase activity and/or resistance to quinolones. Materials and Methods: Using 50% of the maximal inhibitory concentrations (IC(50)s) of quinolones, recombinant wild type (WT) and seven mutant DNA gyrases having amino acid substitutions, including Ser83Ile, were screened for enzymatic activity that causes supercoils in relaxed plasmid DNA and resistance to quinolones. Results: Little differences in supercoiling activity were observed between WT and mutant DNA gyrases. By contrast, the IC(50)s of ciprofloxacin and norfloxacin against GyrA-Ser83Ile/GyrB-WT were 11.6 and 73.3 mu g/mL, respectively, which were the highest used against the DNA gyrases examined in this study. Conclusion: Ser83Ile in GyrA was shown to confer high-level quinolone resistance to DNA gyrases of nontyphoidal Salmonella, with no loss of supercoiling activity. Salmonella strain carrying GyrA with Ser83Ile may emerge under a high-concentration pressure of quinolones and easily spread even with no selection bias by quinolones. Hence, avoiding the overuse of quinolones is needed to prevent the spread of Salmonella with Ser83Ile in GyrA.

Aims Open discectomy (OD) is the standard operation for lumbar disc herniation (LDH). Percutaneous endoscopic lumbar discectomy (PELD), however, has shown similar outcomes to OD and there is increasing interest in this procedure. However despite improved surgical techniques and instrumentation, reoperation and infection rates continue and are reported to be between 6% and 24% and 0.7% and 16%, respectively. The objective of this study was to compare the rate of reoperation and infection within six months of patients being treated for LDH either by OD or PELD. Methods In this retrospective, nationwide cohort study, the Korean National Health Insurance database from 1 January 2007 to 31 December 2018 was reviewed. Data were extracted for patients who underwent OD or PELD for LDH without a history of having undergone either procedure during the preceding year. Individual patients were followed for six months through their encrypted unique resident registration number. The primary endpoints were rates of reoperation and infection during the follow-up period. Other risk factors for reoperation and infection were also evalulated. Results Out of 549,531 patients, 522,640 had undergone OD (95.11%) and 26,891 patients had undergone PELD (4.89%). Reoperation rates within six months were 2.28% in the OD group, and 5.38% in the PELD group. Infection rates were 1.18% in OD group and 0.83% in PELD group. The risk of reoperation was lower for patients with OD than for patients with PELD (adjusted hazard ratio (HR) 0.38). The risk of infection was higher for patients with OD than for patients undergoing PELD (HR, 1.325). Conclusion Compared with the OD group, the PELD group showed higher reoperation rates and lower infection rates. Cite this article: Bone Joint J 2021;103-B(8):1392–1399.

Accumulation of reactive oxygen species (ROS) is associated with the development of various diseases. However, the molecular mechanisms underlying oxidative stress that lead to such diseases like autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Here, we observed that oxidative stress markers were increased in Pkd1f/f:HoxB7-Cre mice. Forkhead transcription factors of the O class (FOXOs) are known key regulators of the oxidative stress response, which have been observed with the expression of FoxO3a in an ADPKD mouse model in the present study. An integrated analysis of two datasets for differentially expressed miRNA, such as miRNA sequencing analysis of Pkd1 conditional knockout mice and microarray analysis of samples from ADPKD patients, showed that miR-132-3p was a key regulator of FOXO3a in ADPKD. miR-132-3p was significantly upregulated in ADPKD which directly targeted FOXO3 in both mouse and human cell lines. Interestingly, the mitochondrial gene Gatm was downregulated in ADPKD which led to a decreased inhibition of Foxo3. Overexpression of miR-132-3p coupled with knockdown of Foxo3 and Gatm increased ROS and accelerated cyst formation in 3D culture. This study reveals a novel mechanism involving miR-132-3p, Foxo3, and Gatm that is associated with the oxidative stress that occurs during cystogenesis in ADPKD.

We aimed to investigate change the instrument-assisted soft tissue mobilization (IASTM) rehabilitation exercise on range of motion (ROM), isokinetic ankle strength, and balance. We included 20 elite taekwondo players (chronic ankle instability) in Korea. They were divided into the IASTM group (n=10), control group (n=10). IASTM group were exercised with IASTM rehabilitation exercise four times per week for 8 weeks. The remaining control group did not receive exercise intervention between tests and served as the control. A goniometer was used to measure dorsi-flexion (D/F), plantar-flexion (P/F), a dynamometer was used to measure ankle isokinetic strength, and plantar foot pressure was used to measure static balance. The data were analyzed using repeated-measures analysis of variance. Significant differences were observed between the two groups in IASTM group and control group: ROM (right P/F, P

BACKGROUND Patient blood management (PBM) programmes minimise red blood cell (RBC) transfusion and improve patient outcomes worldwide. This study evaluated the effect of a multidisciplinary, collaborative PBM programme on the appropriateness of RBC transfusion in medical and surgical departments at a hospital level. METHODS/MATERIALS In 2018, the revised PBM programme was launched at the Korea University Anam Hospital, a tertiary hospital with 1048 hospital beds and the first Asian institution where a new computer PBM programme was implemented. Monthly RBC usage and adequacy were analysed from January 2018 to December 2019. The trend of adequacy over time was assessed. RESULTS A total of 2 201 021 patients were hospitalised and visited an outpatient clinic. The number of RBC units transfused per 10 000 patients decreased from 139.8 for 2018 to 137.3 for 2019. The proportion of patients with Hb

House load operation (HLO) occurs when the generator supplies power to the house load without triggering reactor trips during grid disturbances. In Korea, the HLO capability of optimized power reactor 1000 (OPR1000) plants has prevented several reactor trips. Operational experiences demonstrate the difference in the reactor trip incidence due to grid disturbances between OPR1000 plants and Westinghouse plants in Korea, attributable to the availability of the HLO capability. However, probabilistic safety assessments (PSAs) for OPR1000 plants have not considered their specific design features in the initiating event analyses. In an at-power PSA, the HLO capability can affect the initiating event frequencies of general transients (GTRN) and loss of offsite power (LOOP), resulting from transients within the grid system. The initiating event frequencies of GTRN and LOOP for an OPR1000 plant are reduced by 17.7% and 78.7%, respectively, compared to the Korean industry-average initiating event frequencies, and its core damage frequency from internal events is reduced by 15.2%. The explicit consideration of the HLO capability in initiating event analyses makes significant changes in the risk contributions of the initiating events. Consequently, for more realistic at-power PSAs in Korea, we recommend incorporating plant-specific HLO-related design features when estimating initiating event frequencies.

Significance Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, primarily caused by germline mutation of PKD1 or PKD2, leading to end-stage renal disease. There are few cures for ADPKD, although many researchers are trying to find a cure. The Hippo signaling pathway regulates organ growth and cell proliferation. Transcriptional coactivator with PDZ-binding motif (TAZ) is a Hippo signaling effector. In this study, we demonstrated that the PKD1–TAZ–Wnt–β-catenin–c-MYC signaling axis plays a critical role in cystogenesis. Endo IWR1 treatment, which inhibited β-catenin activity via AXIN stabilization, reduced cyst growth in an ADPKD model. Our findings provide a potential therapeutic target against ADPKD and would be important for clinical translation., Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, primarily caused by germline mutation of PKD1 or PKD2, leading to end-stage renal disease. The Hippo signaling pathway regulates organ growth and cell proliferation. Herein, we demonstrate the regulatory mechanism of cystogenesis in ADPKD by transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo signaling effector. TAZ was highly expressed around the renal cyst-lining epithelial cells of Pkd1-deficient mice. Loss of Taz in Pkd1-deficient mice reduced cyst formation. In wild type, TAZ interacted with PKD1, which inactivated β-catenin. In contrast, in PKD1-deficient cells, TAZ interacted with AXIN1, thus increasing β-catenin activity. Interaction of TAZ with AXIN1 in PKD1-deficient cells resulted in nuclear accumulation of TAZ together with β-catenin, which up-regulated c-MYC expression. Our findings suggest that the PKD1–TAZ–Wnt–β-catenin–c-MYC signaling axis plays a critical role in cystogenesis and might be a potential therapeutic target against ADPKD.

We determined the total energy expenditure (TEE) of healthy overweight or obese people, and those with impaired glucose tolerance and/or impaired fasting glycemia (IGT/IFG), or type 2 diabetes (T2DM) using the doubly-labeled water method. As a second purpose, we compared the measured TEE with the target energy intake recommended in the treatment guidelines for diabetes. The participants were normal glucose tolerance (NGT), and IGT/IFG (n=11) and T2DM (n=9) patients, who were 50-59 y and had a body mass index >25 kg/m2. The median TEE/body mass (BM) values were 32.6, 33.3, and 34.4 kcal/kg BM and the TEE/target BM values (target BM: BM at a BMI of 22 kg/m2) were 43.7, 50.2, and 46.5 kcal/kg target BM for each group, respectively, and did not differ significantly among them. Obese Japanese participants with T2DM in this study had lower TEE/BM than previously studied in non-obese participants with T2DM. In IGT/IFG or T2DM patients, if 30 kcal/kg target BM was used as the energy coefficient, on the basis of the treatment guidelines, the difference between TEE and the target energy intake would be -1,174±552 kcal (-38±11%). When 35 kcal/kg target BM was used as the energy coefficient, the difference between TEE and the target energy intake would be -877±542 kcal (-27±13%). Thus, the energy coefficients used to estimate target energy intake during lifestyle modification in obese/overweight patients with T2DM are considered to be quite low during the first step of diet therapy.

[Purpose] The purpose of this study was to investigate the effects of short-term creatine intake on muscle fatigue induced by resistance exercise in healthy adolescent men, i.e., lactic acid concentration and wrist and head tremor measured by an accelerometer. [Methods] Twelve healthy adolescent men who had no experience with creatine intake were included. The subjects were randomly assigned to the creatine group and the placebo group, followed by 5 days of creatine and placebo intake, and 5 times of 5 sets of leg press, leg extension, bench press, and arm curl exercises at 70% repetition maximum (RM). The lactic acid concentration before and after exercising, rate of perceived exertion (RPE), and accelerometer-based wrist tremor and head tremor during exercise were measured. Subsequently, after 7 days to allow for creatine washout, the same exercise treatment and measurement were performed in each group after switching drug and placebo between the groups. [Results] The level of lactic acid before and after the acute resistance exercise trial was significantly lower in the creatine group than in the placebo group (P

Obese individuals are considered to have lower energy expenditure (EE) rates than non-obese individuals. We aimed to investigate the effects of various factors related to food intake on diet-induced thermogenesis (DIT) in the EE of obese individuals. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed relevant literature from PubMed, Embase, and Medline databases from study inception till the end of July 2019. Studies on dietary factors affecting DIT in obese individuals were included. Fifteen studies were included; these studies assessed macronutrient, single-nutrient, or supplement meal compositions, as well as dietary patterns and behaviors. The effect of obesity on DIT was not constant in each study. Differences in DIT pertained to the protein ratio being higher than the fat ratio or the carbohydrate ratio being higher than the fat ratio. High intake of calcium and vitamin D as well as high-oleic peanut supplements increased DIT in obese people. In addition, ascorbic acid intake, fatty acid saturation, and the chain length of various fatty acids had no effects on DIT. In conclusion, the findings suggest that in obese individuals, DIT is associated with various factors related to meal, nutrient, and dietary habits. However, because of the complexity of the relationship between DIT and obesity, it is difficult to determine the critical element underlying this association.

Background Only limited data are available regarding postural stability between anterior cruciate ligament (ACL)-injured patients with medial meniscus (MM) tear and those with lateral meniscus (LM) tear. The purpose of this study was to compare preoperative postural stability for both involved and uninvolved knees in ACL rupture combined with MM and LM tears. It was hypothesized that there would be a significant difference in postural stability between these two groups. Methods Ninety-three ACL-injured patients (53 combined with MM tears vs. 40 combined with LM tears) were included. Static and dynamic postural stability were evaluated with the overall stability index (OSI), anterior–posterior stability index (APSI), and medial–lateral stability index (MLSI) using stabilometry. Knee muscle strength was evaluated using an isokinetic testing device. Results In the static postural stability test, none of the stability indices showed significant differences between the two groups for both knees (p > 0.05). In the dynamic postural stability test for involved side knees, the OSI and APSI were significantly higher in the LM tear group compared to the MM tear group (OSI: 2.0 ± 0.8 vs. 1.6 ± 0.5, p = 0.001; APSI: 1.5 ± 0.6 vs. 1.3 ± 0.5, p = 0.023), but not the MLSI (p > 0.05). In the static and dynamic postural stability tests in each group, there were no significant differences between the involved and uninvolved side knees (p > 0.05). There was no significant difference in the knee muscle strength between the two groups (p > 0.05). All postural stability showed no significant correlation with knee muscle strength (p > 0.05). Conclusion Dynamic postural stability was poorer in patients with ACL rupture combined with LM tear than in those with MM tear. Therefore, close monitoring for postural stability would be necessary during preoperative and postoperative rehabilitation, especially for patients with ACL rupture combined with LM tear. Level of evidence: Level III

ATPase inhibitory factor 1 (IF1) is an ATP synthase–interacting protein that suppresses the hydrolysis activity of ATP synthase. In this study, we observed that the expression of IF1 was up-regulated in response to electrical pulse stimulation of skeletalmuscle cells and in exercized mice and healthy men. IF1 stimulates glucose uptake viaAMPKin skeletalmuscle cells and primary culturedmyoblasts.Reactive oxygen species and Rac family small GTPase 1 (Rac1) function in the upstream and downstream of AMPK, respectively, in IF1-mediated glucose uptake. In diabetic animal models, the administration of recombinant IF1 improved glucose tolerance and down-regulated blood glucose level. In addition, IF1 inhibitsATPhydrolysis byb-F1-ATPase inplasmamembrane, thereby increasing extracellular ATP and activating the protein kinase B (Akt) pathway, ultimately leading to glucose uptake. Thus, we suggest that IF1 is a novel myokine and propose amechanismby which AMPK and Akt contribute independently to IF1-mediated improvement of glucose tolerance impairment. These results demonstrate the importance of IF1 as a potential antidiabetic agent.

The primary cilium is a microtubule-based structure projecting from a cell. Although the primary cilium shows no motility, it can recognize environmental stimuli. Thus, ciliary defects cause severe abnormalities called ciliopathies. Ciliogenesis is a very complex process and involves a myriad of components and regulators. In order to excavate the novel positive regulators of ciliogenesis, we performed mRNA microarray using starved NIH/3T3 cells. We selected 62 murine genes with corresponding human orthologs, with significantly upregulated expression at 24 h after serum withdrawal. Finally, calpain-6 was selected as a positive regulator of ciliogenesis. We found that calpain-6 deficiency reduced the percentage of ciliated cells and impaired sonic hedgehog signaling. It has been speculated that this defect might be associated with decreased levels of α-tubulin acetylation at lysine 40. This is the first study to report a novel role of calpain-6 in the formation of primary cilia. [BMB Reports 2019; 52(10): 619-624].

In this research, a multi-slit prompt-gamma camera was developed to locate the distal dose falloff of the proton beam spots in spot scanning proton therapy. To see the performance of the developed camera, therapeutic proton beams were delivered to a solid plate phantom and then the prompt gammas from the phantom were measured using the camera. Our results show that the camera locates the 90% distal dose falloff (= d90%), within about 2–3 mm of error for the spots which are composed 3.8 × 108 protons or more. The measured location of d90% is not very sensitive to the irradiation depth of the proton beam (i.e., the depth of proton beam from the phantom surface toward which the camera is located). Considering the number of protons per spot for the most distal spots in typical treatment cases (i.e., 2 Gy dose divided in 2 fields), the camera can locate d90% only for a fraction of the spots depending on the treatment cases. However, the information of those spots is still valuable in that, in the multi-slit prompt-gamma camera, the distal dose falloff of the spots is located solely based on prompt gamma measurement, i.e., not referring to Monte Carlo simulation. Keywords: Proton therapy, Prompt gamma, Beam range verification, Distal dose falloff

Primary cilia and autophagy are two distinct nutrient-sensing machineries required for maintaining intracellular energy homeostasis, either via signal transduction or recycling of macromolecules from cargo breakdown, respectively. Potential correlations between primary cilia and autophagy have been recently suggested and their relationship may increase our understanding of the pathogenesis of human diseases, including ciliopathies and cancer. In this review, we cover the current issues concerning the bidirectional interaction between primary cilia and autophagy and discuss its role in cancer with cilia defect.

Background/objectives The objectives of this study were to evaluate the accuracy of the Dietary Reference Intakes (DRI) for estimating the energy requirements of older adults, and to develop and validate new equations for predicting the energy requirements of this population group. Materials/methods The study subjects were 25 men and 23 women with a mean age of 72.2 ± 3.9 years and 70.0 ± 3.3 years, and mean BMI of 24.0 ± 2.1 and 23.9 ± 2.7, respectively. The total energy expenditure (TEE) was measured by using the doubly labeled water (DLW) method, and used to validate the DRI predictive equations for estimated energy requirements (EER) and to develop new EER predictive equations. These developed equations were cross-validated by using the leave-one-out technique. Results In men, the DRI equation had a -7.2% bias and accurately predicted the EER (meaning EER values within ±10% of the measured TEE) for 64% of the subjects, whereas our developed equation had a bias of -0.1% and an accuracy rate of 84%. In women, the bias was -6.6% for the DRI equation and 0.2% for our developed equation, and the accuracy rate was 74% and 83%, respectively. The predicted EER was strongly correlated with the measured TEE, for both the DRI equations and our developed equations (Pearson's r = 0.915 and 0.908, respectively). Conclusions The DRI equations provided an acceptable prediction of EER in older adults and these study results therefore support the use of these equations in this population group. Our developed equations had a better predictive accuracy than the DRI equations, but more studies need to be performed to assess the performance of these new equations when applied to an independent sample of older adults.

Background X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. TRAPPC2 gene, which is important for collagen secretion, has been reported as causative for SEDT-XL. Case presentation Here, we report two variants of TRAPPC2 gene of SEDT-XL patients, a missense variant of start codon, c.1A > T, and a deletion variant, c.40delG. To understand molecular consequence of the variants, we establish an in vitro gene expression assay system and demonstrate that both mutated genes are transcribed, but are not properly translated, indicative of the pathogenic nature of those TRAPPC2 variants. Conclusions In the current study, we provide additional experimental data showing that loss-of-function TRAPPC2 variants are probably causative for SEDT-XL phenotype. These findings further contribute to the understanding the clinical picture related to TRAPPC2 gene.

The mechanical-collimation imaging is the most mature technology in prompt gamma (PG) imaging which is considered the most promising technology for beam range verification in proton therapy. The purpose of the present study is to compare the performances of two mechanical-collimation PG cameras, knife-edge (KE) camera and multi-slit (MS) camera. For this, the PG cameras were modeled by Geant4 Monte Carlo code, and the performances of the cameras were compared for imaginary point and line sources and for proton beams incident on a cylindrical PMMA phantom. From the simulation results, the KE camera was found to show higher counting efficiency than the MS camera, being able to estimate the beam range even for 107 protons. Our results, however, confirmed that in order to estimate the beam range correctly, the KE camera should be aligned, at least approximately, to the location of the proton beam range. The MS camera was found to show lower efficiency, being able to estimate the beam range correctly only when the number of the protons is at least 108. For enough number of protons, however, the MS camera estimated the beam range correctly, errors being less than 1.2 mm, regardless of the location of the camera. Keywords: Proton therapy, Beam range verification, Prompt gamma, Knife-edge camera, Multi-slit camera

[Purpose] The goal of this study was to review data on physical activity level (PAL), a crucial index for de­termining estimated energy requirement (EER), calcu­lated as total energy expenditure (TEE, assessed with doubly labeled water [DLW]) divided by resting meta­bolic rate (RMR, PAL = TEE/RMR) in female athletes and to understand the methods of assessing athletes’ EERs in the field. [Methods] For the PAL data review among female athletes, we conducted a PubMed search of the avail­able literature related to the DLW method. DLW studies measuring TEE and RMR were included for the pres­ent review. [Results] Briefly, the mean PAL was 1.71 for colle­giate swimmers with moderate training, which was rela­tively low, but the mean PAL was 3.0 for elite swimmers during summer training camp. This shows that PAL can largely vary even within the same sport depending on the amount of training, and the differences in PAL were remarkable depending on the sport. Aside from the DLW method, there is currently no research tool related to athletes’ EERs that can be used in the field. [Conclusion] Briefly, the mean PAL was 1.71 for collegiate swimmers with moderate training, which was relatively low, but the mean PAL was 3.0 for elite swimmers during summer training camp. This shows that PAL can largely vary even within the same sport depending on the amount of training, and the differences in PAL were remarkable depending on the sport. Aside from the DLW method, there is currently no research tool related to athletes’ EERs that can be used in the field.

After decades-long efforts to diagnose and treat breast cancer, the management strategy that has proved most successful to date is molecular-subtype-specific inhibition of the hormone receptors and HER2 that are expressed by individual cancers. Melanoma-associated antigen (MAGE) proteins comprise &gt, 40 highly conserved members that contain the MAGE homology domain. They are often overexpressed in multiple cancers and contribute to cancer progression and metastasis. However, it remains unclear whether the biological activity arising from MAGE gene expression is associated with breast cancer subtypes. In this study, we analyzed the RNA-sequencing (RNA-seq) data of 70 breast cancer cell lines and found that MAGEA12 and MAGEA3 were highly expressed in a subset of these lines. Significantly, MAGEA12 and MAGEA3 expression levels were independent of hormone receptor expression levels but were closely associated with markers of active histone modifications. This indicates that overexpression of these genes is attributable to epigenetic deregulation. RNA-seq of MAGEA12-depleted cells was then used to identify 382 candidate targets of MAGEA12 that were downregulated by MAGEA12 depletion. Furthermore, our gain-of-function experiments showed that MAGEA12 overexpression promoted aggressive behaviors of malignant breast cancer cells, including enhancing their cell migration and invasion. These changes were associated with increased epigenetic deregulation of the MAGEA12 signature genes. Thus, MAGEA12 may play an important role in breast cancer malignancy. Taken together, our findings suggest that MAGEA12 could be a promising therapeutic target in breast cancer, and its overexpression and epigenetic changes could serve as subtype classification biomarkers.

Osteoid osteomas are benign bone-forming lesions that usually present in adolescence. In patients with severe pain and those not responding to medication, surgical treatment should be considered. Medulloscopy is a standard arthroscopic technique for visualizing the intramedullary canal of the tibia. Herein, we report two patients with intramedullary osteoid osteomas in the posterior area of the tibia, which were successfully treated using medulloscopy. Hence, medulloscopy is an effective minimally invasive method in patients with intramedullary osteoid osteomas in the posterior tibial area.

Background Polycystic kidney disease (PKD) involves renal cysts arising from proliferating tubular cells. Autophagy has been recently suggested as a potential therapeutic target in PKD, and mammalian target of rapamycin (mTOR) is a key negative regulator of autophagy. However, the effect of autophagy regulation on cystogenesis has not been elucidated in PKD mice. Methods Clinical validation was performed using GEO datasets and autosomal dominant polycystic kidney disease (ADPKD) patient samples. Newly established PKD and LC3 transgenic mice were used for in vivo verifications, and additional tests were performed in vitro and in vivo using multiple autophagy drugs. Findings Neither autophagy stimulation nor LC3 overexpression alleviated PKD. Furthermore, we observed the inhibitory effect of an autophagy inhibitor on cysts, indicating its possible therapeutic use in a specific group of patients with ADPKD. Interpretation Our findings provide a novel insight into the pathogenesis related to autophagy in PKD, suggesting that drugs related to autophagy regulation should be considered with caution for treating PKD. Funding Sources This work was supported by grants from the Bio & Medical Technology Development Program; the Collaborative Genome Program for Fostering New Post-Genome Industry of the NRF; the Basic Science Program.

Background Unnecessary costs and complications can be reduced by increasing hemoglobin (Hb) levels and minimizing blood transfusions in patients who underwent total knee arthroplasty (TKA). This study aimed to determine the effects of intravenous iron monotherapy before TKA on preoperative iron deficient anemia and postoperative transfusion rates. Methods This prospective cohort study included 45 patients scheduled for TKA in the experimental group (Group I) and 221 patients who underwent TKA in 2015 and 2018 in the control group (Group C). One thousand milligrams of ferric carboxymaltose was administrated 1 month before TKA in group I. Intergroup comparison of the rate and total volume of transfusion, perioperative changes in Hb and analysis of iron metabolism variables in group I were performed. Subgroup analysis of Group I was conducted according to the response to iron monotherapy. Results Although Hb levels increased after intravenous iron monotherapy in Group I, postoperative transfusion rates in Groups I and C were 17.8% and 18.6%, respectively, without significant intergroup differences in the rate and total units of transfusion. Ferritin level and transferrin saturation were corrected in both subgroups of Group I. Only 17 patients (37.78%) showed response to iron monotherapy, with an Hb increase of 1.0 g/dL or more. Subgroup analysis showed lower proportions of coexisting chronic diseases, including chronic kidney disease in responders. Conclusion IV iron monotherapy was shown to be insufficient in successfully treating preoperative iron-deficient anemia to reduce postoperative allogenic blood transfusion in patients who underwent TKA. As preoperative anemia should be managed due to the high rates of postoperative transfusion for this surgery, clinicians should consider the complex interplay among the causal factors of anemia, apart from ID, in patients with preoperative anemia who are scheduled for TKA.

Although postoperative delirium is a common complication in older patients, few papers have described risk factors after of spinal surgery. The purpose of this study was to analyze various perioperative risk factors for delirium after spinal surgery in older patients. This study was performed on retrospective data collection with prospective design. We analyzed 138 patients over 65 years of age who underwent spinal surgery. Preoperative factors were cognitive function (Mini-Mental State Examination-Korean (MMSE-K) and the Korean version of the Delirium Rating Scale-Revised-98 (K-DRS 98)), age, sex, type of admission, American Society of Anesthesiologist classification, metabolic equivalents, laboratory findings, visual analog scale, and Oswestry Disability Index. Intraoperative factors were operation time, blood loss, and type of procedure. Postoperative factors were blood transfusion and type of postoperative pain control. Postoperative delirium developed in 25 patients (18.16%). Patients were divided into two groups: Group with delirium (group A) and group without delirium (group B). MMSE-K scores in Group A were significantly lower than in Group B (p

Autophagy is a catabolic process required for maintaining intracellular energy homeostasis. It eliminates harmful proteins and recycles functional macromolecules back into the cell via cargo breakdown. Autophagy is generally suppressed under fed conditions and induced by serum starvation; therefore, it is considered to be a nutrient-sensing mechanism. Cilia, finger-like organelles harboring multiple receptors along their surface, are energy-sensing structures that are also triggered by serum deprivation. Herein, we verified the effect of autophagy alterations on cilia assembly and the specific underlying mechanisms. Autophagy flux altered either by drugs or autophagy-targeting siRNAs strongly inhibited ciliogenesis, and this inhibition was affected by p62, an autophagy regulator, via Pten/Dvl2/AurKA signaling.

OBJECTIVEBiportal endoscopic spinal surgery has been performed for several years, and its effectiveness is well known; however, no studies on its safety, specifically intracranial pressure, have been conducted to date. The authors sought to evaluate the effect of biportal endoscopic lumbar discectomy on intracranial pressure by monitoring cervical epidural pressure (CEP) changes throughout the procedure.METHODSTwenty patients undergoing single-level biportal endoscopic lumbar discectomy were enrolled in this study. CEPs were monitored throughout the procedure, consisting of phase 1, establishing the surgical portal and working space; phase 2, performing decompression and discectomy; and phase 3, turning off the fluid irrigation system. After discectomy was completed, the authors evaluated changes in CEP as the irrigation pressure increased serially by adding phase 4, increasing irrigation pressure with outflow open; and phase 5, increasing irrigation pressure with outflow closed.RESULTSThe mean baseline CEP was measured as 16.65 mm Hg. In phase 1, the mean CEP was 17.3 mm Hg, which was not significantly different from the baseline CEP. In phase 2, the mean CEP abruptly increased up to 35.1 mm Hg when the epidural space was first connected with the working space, followed by stabilization of the CEP at 31.65 mm Hg. In phase 4, the CEP increased as the inflow pressure increased, showing a linear correlation, but not in phase 5. No patients experienced neurological complications.CONCLUSIONSIt is important to ensure that irrigation fluid is not stagnant and is maintained continuously. More attention must be paid to keeping pressures low when opening the epidural space.

Checkpoint kinase 1 (Chk1) expression is enhanced in most cancers owing to oncogenic activation and constant replicative stress. Chk1 inactivation is a promising cancer therapy, as its inactivation leads to genomic instability, chromosomal catastrophe, and cancer cell death. Herein, we observed that miR-320c, downregulated in triple-negative breast cancer (TNBC) patients, can target Chk1. In addition, downregulated miR-320c expression was associated with poor overall survival in TNBC patients. As Chk1 was associated with the DNA damage response (DDR), we investigated the effect of miR-320c on DDR in TNBC cells. To induce DNA damage, we used platinum-based drugs, especially oxaliplatin, which is most effective with miR-320c. We observed that overexpression of miR-320c in TNBC regulated the oxaliplatin responsiveness by mediating DNA damage repair through the negative regulation of Chk1 in vitro. Furthermore, using a xenograft model, a combination of miR-320c mimic and oxaliplatin effectively inhibited tumor progression. These investigations indicate the potential of miR-320c as a marker of oxaliplatin responsiveness and a therapeutic target to increase the efficacy of chemotherapy in TNBC.

Background: Polycystic kidney disease (PKD) is a hereditary disease characterized by cyst formation in the kidneys bilaterally. It has been observed that semaphorin-3C (SEMA3C) is overexpressed in polycystic kidney epithelial cells. It is hypothesized that upregulated SEMA3C would contribute to survival of polycystic kidney epithelial cells. Furthermore, as the kidney is a highly vascularized organ, the secreted SEMA3C from PKD epithelial cells will affect glomerular endothelial cells (GECs) in a paracrine manner. Methods: To evaluate the effect of SEMA3C on renal cells, siSEMA3C-treated PKD epithelial cells were used for further analysis, and GECs were exposed to recombinant SEMA3C (rSEMA3C). Also, co-culture and treatment of conditioned media were employed to confirm whether PKD epithelial cells could influence on GECs via SEMA3C secretion. Results: SEMA3C knockdown reduced proliferation of PKD epithelial cells. In case of GECs, exposure to rSEMA3C decreased angiogenesis, which resulted from suppressed migratory ability not cell proliferation. Conclusions: This study indicates that SEMA3C is the aggravating factor in PKD. Thus, it is proposed that targeting SEMA3C can be effective to mitigate PKD.

Altered miRNA (miR) expression occurs in various diseases. However, the therapeutic effect of miRNAs in autosomal dominant polycystic kidney disease (ADPKD) is unclear. Genome-wide analyses of miRNA expression and DNA methylation status were conducted to identify crucial miRNAs in end-stage ADPKD. miR-192 and -194 levels were down-regulated with hypermethylation at these loci, mainly in the intermediate and late stages, not in the early stage, of cystogenesis, suggesting their potential impact on cyst expansion. Cyst expansion has been strongly associated with endothelial-mesenchymal transition (EMT). Zinc finger E-box-binding homeobox-2 and cadherin-2, which are involved in EMT, were directly regulated by miR-192 and -194. The therapeutic effect of miR-192 and -194 in vivo and in vitro were assessed. Restoring these miRs by injection of precursors influenced the reduced size of cysts in Pkd1 conditional knockout mice. miR-192 and -194 may act as potential therapeutic targets to control the expansion and progression of cysts in patients with ADPKD.-Kim, D. Y., Woo, Y. M., Lee, S., Oh, S., Shin, Y., Shin, J.-O., Park, E. Y., Ko, J. Y., Lee, E. J., Bok, J., Yoo, K. H., Park, J. H. Impact of miR-192 and miR-194 on cyst enlargement through EMT in autosomal dominant polycystic kidney disease.

[Purpose] The purpose of this study was to investigate the relationship of various aspects of daily physical activity, such as the number of steps, time spent in moderate to vigorous intensity physical activity (MVPA), and locomotive and non-locomotive MVPA measured by a triaxial accelerometer, with the functional fitness in healthy elderly men. [Methods] The subjects of this study were 22 healthy elderly men aged over 65 years. The participants wore a triaxial accelerometer for two weeks to estimate their daily physical activities. The level of functional fitness was measured based on "National Fitness Award 100 in Korea" immediately after the measurement of two weeks of daily physical activities. [Results] The results showed that active healthy elderly men with more than 6,500 walking steps per day and more than 60 min per day spent in MVPA showed a significantly higher 2-min marching in place and index of cardiorespiratory endurance compared to less physically active participants. Particularly, locomotive MVPA was significantly associated with cardiorespiratory endurance levels (r = 0.50), whereas non-locomotive MVPA was not associated with other measurements of functional fitness. [Conclusion] Increased MVPA time, especially the locomotive MVPA, can effectively suppress the decrease in cardiorespiratory endurance level in elderly men. However, no association was observed between non-locomotive MVPA, such as household activities, and functional fitness in healthy elderly men.

[Purpose] Brown adipose tissue (BAT) plays an important role in metabolizing different substances, including androgens. The aim of this study was to determine whether a single bout of aerobic exercise would increase the androgen hormone concentration in mouse BAT and whether its increase was associated with uncoupling protein-1 (UCP-1), protein kinase A (PKA)-related mechanism in BAT. [Methods] Twenty, 9-week-old ICR adult male micewere randomly divided into three groups: Control (n=6, CON), Exercise (n=7, EX), and Exercise + SRD5A1A2 inhibitor (n=7, EXIN). SRD5A1A2 is an enzyme needed when free testosterone is metabolized to dihydrotestosterone (DHT). SRD5A1A2 was administered intraperitoneally in the EXIN group, while the CON and EX groups were treated with the vehicle only. One hour later, exercise was performed at 60–70% V˙O2max for 30minutes. The levels of testosterone and DHT in BAT were determined by ELISA, and UCP-1 mRNA level was examined by RT-PCR. UCP-1 and PKA protein levels were determined by western blotting. [Results] After a single period of exercise, testosterone and DHT concentrations in BAT were significantly higher in EX than those in CON, and lower in EXIN than those in EX. The ratio of phosphorylated PKA to total PKA in BAT was significantly higher in EX than that in CON, and lower in EXIN than that in EX. UCP-1 levels in BAT were not different in the three groups. [Conclusion] Aerobic exercise increased bioactive androgen hormone levels in BAT in association with the increase in phosphorylated PKA levels. In contrast, 30minutes of treadmill exercise did not affect UCP-1 expression.

[Purpose] Dihydrotestosterone (DHT) plays an important role in various processes that utilize energy, including fat and carbohydrate oxidation. The purpose of this study was to determine the effect of inhibiting DHT formation during mid-intensity running exercise on energy expenditure and fat and carbohydrate oxidation in the whole body using a calorimetric chamber. [Methods] Twelve ICR adult male mice, 9 weeks of age, were randomized into two groups: CON (n = 6, no treatment with exercise) and CONIN (n = 6, DHT inhibitor treatment with exercise, SRD5A1A2 is an enzyme involved in the metabolism of free testosterone into DHT). Inhibitor was administered to the CONIN group intraperitoneally, while the CON group was treated with vehicle (corn oil 2 mg/kg). After 3 days of administration of the inhibitor or vehicle, exercise was performed at 60-70% VO2max for 30 min on a treadmill in a calorimetric chamber. The O2 uptake, CO2 production, carbohydrate and fat oxidation, and respiratory exchange ratio (RER) during 30-min exercise were measured using a calorimeter. [Results] During a single bout of exercise, the CONIN group showed a significantly higher area under the curve (AUC) of O2 uptake and CO2 production from 20 min into exercise than the CON group (p < 0.001). The CONIN group showed a significantly higher AUC for carbohydrate oxidation from 20 min into exercise than the CON group (p < 0.001), whereas no difference was found in fat oxidation between groups (p = 0.067). The CONIN group had a significantly higher AUC of RER from 20 min into exercise than the CON group (p < 0.001). [Conclusion] We observed increased energy consumption at the later phase of 30-min moderate-intensity treadmill running when DHT production was inhibited. Furthermore, when DHT production during exercise was inhibited, whole-body fat utilization was inhibited and carbohydrate oxidation was substantially increased at the later phase of exercise compared to in the control group. Therefore, changes in DHT concentration in the body during exercise may be involved in whole-body fat utilization, suggesting that DHT may be an important factor affecting endurance exercise capacity.

Purpose The purpose of the study was to perform a comparative analysis of the YANG Hak Seon technique carried out by "K" athlete with the kinematical data of "Y" athlete and propose a method to improve the YANG Hak Seon technique of "K" athlete Method The subject recruited for the study was a male athlete from Korean national team (Age: 21, height: 1.65 m, body weight: 59.6 kg, and career: 11 years). Four high - speed cameras were used to analyze the 3D motion of the YANG Hak Seon technique performed by "K" athlete. The variables selected for analysis were the velocity of COM, displacement of COM, the rotational & torsional angle of the trunk and rotational & torsional angular velocity of the trunk. The results obtained were compared to the preexisting data of the "Y" athlete (data set from the published research) Results Firstly, the horizontal displacement of the YANG Hak Seon technique of the "K" athlete was observed to be shorter along with lower vertical displacement during landing compared to “Y” athlete. In addition, the overall horizontal velocity was low and vertical velocity was not generated which rises during the BC (board contact) phase. Although the rotational angular velocity of the trunk was lower during the BC, HC (horse contact) phase and LD (landing) phase, torsional angular velocity was higher during the LD Conclusion In order to improve the completeness of the YANG Hak Seon technique of the K player, it is necessary to enter with a fast and low posture on the footplate during the initial phase. In the BC phase, it is essential to raise the COM simultaneously while landing on the footplate and increase the rotational angular velocity of the trunk.

[Purpose] Physical inactivity behavior at middle age or older is a major risk factor for cardiovascular disease. However, the effects of levels of habitual physical activity on arterial stiffness in elderly population remain unclear currently. Therefore, the purpose of this study was to demonstrate whether the effects of habitual physical activity could attenuate arterial stiffness in elderly individuals via a meta-analysis. [Methods] We searched the Medline and Embase databases from January 1997 through November 2017, using the medical subject headings “older population”, “physical activity” (e.g., walking, cycling, climbing, and any participation in sports), “arterial stiffness”, “pulse wave velocity”, and “cardiovascular health” published in English. Six articles (2,932 participants) were included in this meta-analysis. We investigated the effects of habitual physical activity on arterial stiffness, which was measured by the pulse wave velocity. [Results] Results confirmed heterogeneity (Q-value = 160.691, p = 0.000, I2 = 96.888) between individual studies. The effect size was calculated using random effect model. It has shown that physically active individuals have significantly lower arterial stiffness than their sedentary peers do (standardized mean difference: -1.017 ± 0.340, 95% confidence interval: -1.684 ~ -0.350, p = 0.003). [Conclusion] Findings of our systematic review and meta-analysis indicate that habitual physical activity can significantly ameliorate arterial stiffness in the elderly population.

Purpose The purpose of this study was to evaluate the anatomical similarity of three-dimensional (3D) morphometric parameters between right and left knees. Materials and methods Ten fresh-frozen paired cadaveric knees were tested. Following dissection, footprint areas of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were measured. Surface scanning was performed using a 3D scanner. Scanned data were reproduced and morphometric parameters were measured on specialized software. After making mirror models, we compared footprint center positions of the ACL and PCL of both sides and calculated the average deviation of 3D alignment between the right- and left-side models. Results No significant side-to-side differences were found in any morphometric parameters. Bony shapes displayed a side-to-side difference of 〈1 mm. Distal femoral and proximal tibial volumes did not present side-to-side differences, either; the average 3D deviations of alignment between the right and left sides were 0.8±0.4/1.1±0.6 mm (distal femur/proximal tibia). Center-to-center distances between the right and left ACL footprints were 2.6/2.7 mm (femur/tibia) for the anteromedial bundle and 2.4/2.8 mm for the posterolateral bundle. They were 1.9/1.5 mm for the anterolateral bundle and 2.2/1.8 mm for the posteromedial bundle of the PCL. Conclusions There was a remarkable 3D morphometric similarity between right and left knees. Our results might support the concept of obtaining morphologic reference data from the uninvolved contralateral knee.

Osteogenesis imperfecta (OI) is a heritable skeletal disorder characterized by bone fragility and low bone mass. Recently, loss-of-function mutations of WNT1 have been reported to be causative in OI or osteoporosis. We report an OI patient with novel compound heterozygous WNT1 missense mutations, p.Glu123Asp and p.Cys153Gly. Both mutations are found in the exon 3, and the p.Glu123Asp is the most proximal N-terminus missense mutation among the reported WNT1 missense mutations in OI patients. In vitro functional analysis reveals that while expression of wildtype WNT1 stimulates canonical WNT1-mediated β-catenin signaling, that of individual WNT1 mutant fails to do so, indicative of the pathogenic nature of the WNT1 variants. Although the pathogenic mechanism of WNT1 defects in OI has yet to be uncovered, these findings further contribute to the implications and importance of functional relevance of WNT1 in skeletal disorders.

[Purpose] This study examined the effects of daily physical activity level on health-related factors according to gender and identified age-specific differences among Korean adults. [Methods] Using data from the Korea National Health and Nutrition Examination Survey VI (2014-2015), we selected adults aged 19-64 years who participated in both a health examination and health interview survey. The study included 6,457 participants 19-64 years of age (2,611 men, 3,846 women). [Results] Assessment of the differences in health-related factors according to age and physical activity in men and women by repeated two-way analysis of variance (ANOVA) revealed significant interaction effects on total cholesterol (TC) and triglyceride (TG) levels and diastolic blood pressure (DBP) in male participants, but there were no significant interaction effects for any health-related factors in female participants. The group of female participants aged 40-64 years with daily physical activity levels over 200 kcal showed a significantly increased prevalence of 46% for dyslipidemia compared to that in female participants with daily physical activity levels below 200 kcal. Physical activity was positively correlated with weight and high-density lipoprotein cholesterol (HDL-C) levels in men 19-39 years of age, compared to weight, waist circumference (WC), body mass index (BMI), and DBP in men 40-64 years of age, and weight, WC, BMI, glycated hemoglobin (HbA1c) and triglyceride (TG) levels in women 19-39 years of age. In women 40- 64 years of age, physical activity was especially significantly positively correlated with weight, BMI, HDL-C and negatively correlated with fasting glucose and TG levels. [Conclusion] In male and female participants, the 40-64-year age group showed negative results for health-related factors compared to those in the 19-39-year age group. The higher the weight, WC, BMI, the higher is the physical activity level. Physical activity levels were significantly positively correlated with health-related variables.

In proton therapy, for both therapeutic effectiveness and patient safety, it is very important to accurately measure the proton dose distribution, especially the range of the proton beam. For this purpose, recently we proposed a new imaging method named gamma electron vertex imaging (GEVI), in which the prompt gammas emitting from the nuclear reactions of the proton beam in the patient are converted to electrons, and then the converted electrons are tracked to determine the vertices of the prompt gammas, thereby producing a 2D image of the vertices. In the present study, we developed a prototype GEVI system, including dedicated signal processing and data acquisition systems, which consists of a beryllium plate (= electron converter) to convert the prompt gammas to electrons, two double-sided silicon strip detectors (= hodoscopes) to determine the trajectories of those converted electrons, and a plastic scintillation detector (= calorimeter) to measure their kinetic energies. The system uses triple coincidence logic and multiple energy windows to select only the events from prompt gammas. The detectors of the prototype GEVI system were evaluated for electronic noise level, energy resolution, and time resolution. Finally, the imaging capability of the GEVI system was tested by imaging a 90 Sr beta source, a 60 Co gamma source, and a 45-MeV proton beam in a PMMA phantom. The overall results of the present study generally show that the prototype GEVI system can image the vertices of the prompt gammas produced by the proton nuclear interactions.

[Purpose] The purpose of this study was to determine whether exercise or/and cold exposure regulate mitochondria biogenesis-related gene expression in soleus and inguinal adipose tissue of mice. [Methods] Forty ICR 5-week old male mice were divided into four groups: thermoneutrality-untrained (23 ± 1 °C in room temperature, n=10), cold-water immersion (24 ± 1 °C, n=10), exercise in neutral temperature (34 ± 1 °C, n=10), and exercise in cold temperature (24 ± 1 °C, n=10). The mice performed swimming exercise (30 min to 60 min, 5 times) for 8 weeks. After 8 weeks, we confirmed mitochondrial biogenesis-related gene expression changes for peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear respiratory factors 1 (NRF1), and mitochondrial transcription factor A (Tfam) in soleus muscle and inguinal adipose tissue, and the related protein expression in soleus muscle. [Results] In soleus muscle, PGC-1α expression significantly increased in response to cold exposure (p = 0.006) and exercise (p = 0.05). There was also significant interaction between exercise and cold exposure (p = 0.005). Only exercise had a significant effect on NRF1 relative expression (p=0.001). Neither cold exposure nor the interaction showed significant effects (p = 0.1222 and p = 0.875, respectively). Relative Tfam expression did not show any significant effect from exercise. In inguinal adipose tissue, relative PGC-1α expression did not significantly change in any group. NRF1 expression showed a significant change from exercise (p = 0.01) and cold exposure (p = 0.011). There was also a significant interaction between exercise and cold exposure (p = 0.000). Tfam mRNA expression showed a significant effect from exercise (p=0.000) and an interaction between exercise and cold exposure (p=0.001). Only temperature significantly affected PGC-1α protein levels (p=0.045). Neither exercise nor the interaction were significant (p = 0.397 and p = 0.292, respectively). NRF1 protein levels did not show a significant effect in any experimental treatments. Tfam protein levels showed a significant effect in the exercise group (p=0.012), but effects of neither cold exposure nor the interaction were significant (p = 0.085 and p=0.374, respectively). [Conclusion] Exercise and cold exposure promoted increased expression of mitochondrial biogenesis- related genes in soleus muscle. Only cold exposure had a significant effect on PGC-1α protein expression and only exercise had a significant effect on Tfam protein expression. In inguinal adipose tissue, there was interaction between exercise and cold exposure in expression of mitochondrial biogenesis-related genes.

This study was designed to evaluate the accuracy of ultrasound-guided injection targeting EPB tendon sheath and influenceable anatomical variances to the accuracy in the first extensor compartment of fresh cadaver wrists.Thirty wrists of 15 cadavers were used. The wrists were divided into right-sided wrists (control group) and left-sided wrists (group A) to compare the accuracy of the manual injection technique (control group) and ultrasound-guided injection technique (group A) targeting EPB tendon sheath. To estimate the influence of anatomical variances within first extensor compartment to the accuracy of each injection techniques, control group (manual injection group) was divided into Control group I (right-sided wrists without septum) and II (right-sided wrists with septum) and group A (ultrasound-guided injection group) was also divided into group AI (left-sided wrists without septum) and group AII (left-sided wrists with septum), respectively. After the methylene blue dye injection, the location of methylene blue dye and anatomical variances in the first extensor compartment was identified by dissection.The accuracy was higher in the group A (93.3%) than in control group (40.0%, p 0.05). The accuracy in control group I (55.6%) was higher than in control group II (16.7%, p 0.05). The accuracy between group AI (100%) and group AII (85.7%) was not significantly different (p 0.05). Wrists with more EPB or APL tendon slips showed a tendency not to have septum and all intratendinous injections was occurred in the wrist with 1 EPB tendon slip or 1 or 2 APL tendon slip.Ultrasound-guided injection targeting EPB tendon ensures correct needle placement through the visualization of compartmental anatomy and improves accuracy of injection though the septum in first extensor compartment encourage inaccurate injections.

The purpose of this study was to examine the accuracy of uni- and triaxial accelerometers in monitoring step counts and gait intensity in older people who did or did not use an assistive device. Forty-nine healthy and frail older adults wore uniaxial (Lifecorder, Suzuken Co. Ltd.) and triaxial accelerometers (Activity Monitor, Matsushita Electronic Works, Ltd., and Active Style Pro, Omron Healthcare Co., Ltd.) during three trials at different gait speeds. All accelerometers gave relatively accurate step counts for healthy older participants compared with direct observation; however, the error was greater for frail older people with assistive devices. Gait intensity detection error was unaffected by gait speed. Among frail older people with assistive devices, the gait intensity error was smaller than for step count error. To accurately assess the steps walked or the gait intensity among frail older people using assistive devices, more study is needed on these groups of participants.

OBJECTIVEAlthough endoscopic procedures for lumbar disc herniation have improved greatly and offer many advantages, the indications are limited mostly to nonmigrated or low-grade migrated disc herniation. Endoscopic application in migrated disc herniation cases is still challenging and technically demanding. The goal in this study was to determine the feasibility of biportal endoscopic discectomy for removal of high-grade migrated disc herniation.METHODSA retrospective review was performed in 262 patients who had undergone biportal endoscopic discectomy after the diagnosis of lumbar herniated disc. According to preoperative MRI findings, disc herniation was classified into 5 zones based on the direction and distance from the disc space. Patients were divided into 2 groups—a high-grade migration group and a low-grade migration group. Clinical outcomes were evaluated using the Oswestry Disability Index (ODI), visual analog scale (VAS), and modified Macnab criteria, and those outcomes and operation time were compared between the 2 groups.RESULTSThere were 10 patients with “high-grade up,” 8 with “low-grade up,” 98 with disc-level, 102 with “low-grade down,” and 44 with “high-grade down” herniation, thereby yielding 54 patients in the high-grade group and 208 in the low-grade group. Demographic data for the 2 groups showed no significant difference. There was no significant difference between the 2 groups in ODI, VAS, and modified Macnab criteria. Operation time between the 2 groups was not significantly different (60.74 vs 65.63 minutes, p > 0.05).CONCLUSIONSBiportal endoscopic discectomy can be effective for high-grade migrated lumbar disc herniation with no prolonged operation time and satisfactory clinical outcomes.

Background Androgen hormone levels are strongly associated with obesity in adult mammals, especially with advanced age. We investigated androgen receptor inhibition on fat metabolism and long-chain fatty acid (LCFA) transport proteins in skeletal muscle during exercise. Methods Male ICR mice were randomly divided into three groups: CON (control), EX (exercise), and EXIN (exercise + androgen receptor inhibition). EX and EXIN groups were trained on a treadmill five times a week. After 4 weeks, the fat metabolism of each group was measured using open-circuit calorimetry during 1 hour of exercise. After the metabolism measurement, the expression levels of LCFA transport proteins (FAT/CD36, CPTI) were analyzed in skeletal muscle. Results Weight gain and final body weight were significantly lower in the EX group than in either the CON or EXIN groups. Conversely, food intake was significantly higher in the EX group than it was in the CON and EXIN groups. The total weight (CON; 2.07 ± 0.6, EX; 1.64 ± 0.2, EXIN; 1.95 ± 0.2) of the abdominal adipose tissue were significantly lower in the EX group than in the CON and EXIN groups (P P P P P P Conclusion Exercise training increases the expression of LCFA transport proteins (FAT/CD36, CPTI). Blocking androgen receptors can decreases the expression of CPTI in the skeletal muscle, which reduces fat metabolism. Thus, reducing sex hormones or suppressing the sensitivity of AR receptors can inhibit energy efficiency and fat metabolism by suppressing CPTI.

Background: Mycobacterium leprae causes leprosy and ofloxacin is used to control this bacterium. However, specific amino acid substitutions in DNA gyrases of M. leprae interferes with the effect of ofloxacin. Methodology/principal findings: Here we tested the inhibitory effect of WQ-3810 on DNA gyrases in M. leprae, using recombinant gyrases. We theorized that WQ-3810 and DNA gyrases interacted, which was tested in silico. Compared with control drugs like ofloxacin, WQ-3810 showed a better inhibitory effect on ofloxacin-resistant DNA gyrases. The in-silico study showed that, unlike control drugs, a specific linkage between a R1 group in WQ-3810 and aspartic acid at position 464 in the subunit B of DNA gyrases existed, which would enhance the inhibitory effect of WQ-3810. This linkage was confirmed in a further experiment, using recombinant DNA gyrases with amino acid substitutions in subunits B instead. Conclusions/significance: The inhibitory effect of WQ-3810 was likely enhanced by the specific linkage between a R1 group residue in its structure and DNA gyrases. Using interactions like the one found in the present work may help design new fluoroquinolones that contribute to halt the emergence of antibiotic-resistant pathogens. (c) 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Rationale: Plantar fasciitis is a common cause of foot pain presenting with morning stiffness and plantar area pain. This case study is to optimize the management in patient with plantar fasciitis accompanied by apparent high-arch foot. Patient concerns: A 55-year-old women presented with plantar fasciitis accompanied by apparent high-arch foot. The pain presents for the heel and pelvic areas with long-distance walking. Diagnoses: She was diagnosed with plantar fasciitis accompanied by apparent high-arch foot for physical examination and plain radiographs. In muscle performance and dynamic postural stability tests, indicated the muscle weakness and postural instability. Interventions: The patient was treated with manual therapy such as joint and soft tissue mobilization interventions including plantar fascia and gastrocnemius stretching, but the heel and pelvic pain were aggravated during long-distance walking. After hip strengthening exercises, the heel and pelvic pain significantly improved. Outcomes: The 3-month follow-up revealed that the heel and pelvic pain did not occur in the long-distance walking, and there was no pain and discomfort at one year follow-up. Lessons: To optimize the management in patient with plantar fasciitis accompanied by apparent high-arch deformity, clinicians should try to identify the hip abductor muscles weakness, and therapists should consider incorporating hip strengthening exercises.

[PURPOSE]: To date, there have been no studies on the response of wrist tremor to increased muscle activity during exercise. This study aimed to evaluate the wrist tremor response with increasing muscle activity during bench press exercise. [METHODS]: Triceps muscle activity and wrist tremor response were measured by electromyography and an accelerometer, respectively, during bench press exercise in 11 healthy men without weight-training experience. Subjects performed bench press at 30% repetition maximum (RM), and the rating of perceived exertion (RPE) and lactate concentration were measured before and after exercise. One week later, an equivalent number of bench presses at 30% RM was performed without weight load as a control trial (CT). [RESULTS]: RPEs and lactate concentrations significantly increased after resistance exercise (30% RM) from 7.4 to 14.3 and 1.7 to 4.9, respectively (P

Patient blood management (PBM) is defined as treatment of a patient who is at risk of transfusion to minimize the need for transfusion and improve the probability of an optimal clinical outcome. We performed the present study to examine the effects of PBM in spinal fusion surgery.A total of 154 patients who had undergone 1- and 2-level posterior lumbar interbody fusion for degenerative lumbar disease were included. We retrospectively reviewed the data from 101 patients from 2012 to 2016 as the pre-PBM group. We recruited 53 patients from 2017 to 2018 for the post-PBM group. Intravenous iron was administered 2-4 weeks before surgery, and intravenous tranexamic acid was administered intraoperatively in the post-PBM group. The primary outcome was the reduction of hemoglobin (Hb). The secondary outcomes included perioperative blood loss, Hemovac drain output, postoperative transfusion, complications, and length of hospital stay.Intravenous iron was administered 17.4 days before surgery in the post-PBM group. The reduction in Hb was not significantly different statistically between the 2 groups (3.06 vs. 3.33 g/dL; P0.05). Of the 101 patients in the pre-PBM group, 24 (24%) underwent transfusion. In contrast, no patient in the post-PBM group had required a transfusion (P0.001). The average hospital stay was 10.15 days in the pre-PBM group and 8.33 days in the post-PBM group (P = 0.02). The average operative time was 146 minutes in the pre-PBM group and 133 minutes in the post-PBM group (P = 0.03). The Hb decrease and total Hemovac drain output did not differ significantly between the 2 groups.Implementation of PBM is an effective strategy for reducing the rate of transfusion in patients undergoing lumbar spinal fusion surgery without significant complications.

Bisphosphonates are the most commonly used drugs for osteoporosis and long-term use of bisphosphonates may affect fusion rate after spinal fusion surgery. There was significant delayed union after 6 months in long-term bisphosphonates users; however, there were no significant difference in fusion rate of long-term bisphosphonate users. Therefore, spinal fusion surgery should not be hesitated in long-term bisphosphonates users.Bisphosphonates (BPs) are the most popular class of drugs for treatment of postmenopausal osteoporosis. Long-term use of BPs may also inhibit the spinal fusion process after posterior lumbar interbody fusion (PLIF). We compared bone fusion rates of long-term BPs users and non-users after undergoing spinal fusion surgery.A total of 97 postmenopausal women who were candidates for single-level PLIF were recruited from 2015 to 2016. Participants were divided into two groups, with 63 patients in a long-term BPs user group and 34 patients in a non-user group. Serum C-terminal cross-linking telopeptide (CTX) levels were checked for bone resorption markers. Bone fusion rates were calculated at 6 months and 1 and 2 years after the surgery. Clinical outcomes were measured using the Oswestry Disability Index (ODI) and visual analog scale (VAS).Serum CTX level was dramatically decreased in the long-term BPs user group (p 0.05). Fusion rates at 6 months after surgery were 42% in the non-user group and 26% in the long-term BPs user group (p = 0.035). However, fusion rates were 82% in the long-term BPs user group and 87% in the non-user group at 2 years after surgery (p 0.05). There was no significant difference between the two groups in ODI or VAS.Even though there was significant delayed union after 6 months in long-term BPs users, at the 2-year postoperative follow-up, there was no significant difference in bone fusion rate between the two groups. Long-term BPs users showed fusion rates greater than 80% and clinical outcome improvements that were comparable to those in non-users. No significant effect on fusion rate after PLIF was found in long-term BPs users.

Triple negative breast cancer (TNBC) has higher aggressiveness and poorer outcomes compared with other subtypes of breast cancer. However, the genomic and molecular aberrations of TNBC are largely unknown. In this study, miR-374a-5p was discovered as a novel TNBC-specific miRNA and its functions and the molecular mechanisms involved were investigated. Combined gene expression profiling of miRNA-microarray and human transcriptome dataset analysis revealed that miR-374a-5p is specifically upregulated in TNBC patients. Functional studies using in vitro and in vivo models indicated that upregulated miR-374a-5p promotes tumor progression in TNBC. miR-374a-5p was also found to directly target arrestin beta 1 (ARRB1) that is specifically downregulated in TNBC patients in several human genomic datasets. Overexpressed ARRB1 reduced TNBC cell growth and migration, and the ARRB1 expression level is inversely correlated with the histological grade of the breast cancer and positively associated with TNBC patient survival, suggestive of a tumor-suppressive function of ARRB1 in breast cancer. Interestingly, increased ARRB1 activates AMPK in TNBC cells, associated with the expression of miR-374a-5p. Taken together, the findings suggest that miR-374a-5p is a potential prognostic marker of TNBC.