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Salmonella Enteritidis is a common foodborne pathogen transmitted through poultry products, which are its main carriers. Poultry are vaccinated against Salmonella Enteritidis in many countries, despite the absence of clinical symptoms, using commercially available live-attenuated vaccines. We previously constructed a highly attenuated temperature-sensitive (ts) Salmonella Enteritidis mutant, 2S-G10. In the present study, we describe the construction and attenuation-associated characteristics of 2S-G10. We infected 1-day-old chicks with 2S-G10 and the parental strains to evaluate the attenuation. One week after infection, 2S-G10 was not detected in the liver, cecum, or cecal tonsil tissues of the orally inoculated chicks, contrary to the parental strain. This indicates that 2S-G10 was highly attenuated when compared to the parental stain. In vitro experiments revealed the inability of 2S-G10 to grow at the normal body temperature of chickens and invade chicken liver epithelial cells. Moreover, single nucleotide polymorphism (SNP) analysis between the complete genome sequence of 2S-G10 and its parental strain revealed SNPs in bcsE, recG, rfaF, and pepD_1 genes, which are involved in epithelial cell invasion and persistence in host systems, growth, lipopolysaccharide core biosynthesis, and cellular survival under heat stress, respectively. These potential characteristics are consistent with the findings of in vitro experiments. Conclusively, chemical treatment–induced random genetic mutations highly attenuated 2S-G10, implying its potential to be developed as a novel live-attenuated vaccine against Salmonella Enteritidis.

Background Recent studies on biportal endoscopic spine surgery in patients with lumbar spinal stenosis have reported good clinical results. However, these studies have been limited by the small sample sizes and use of a retrospective study design. Therefore, we aim to compare the efficacy and safety of biportal endoscopic decompressive laminectomy with those of conventional decompressive laminectomy in a multicenter, prospective, randomized controlled trial. Methods This study will include 120 patients (60 per group, aged 20–80 years) with 1- or 2-level lumbar spinal stenosis, who will be recruited from six hospitals. The study will be conducted from July 2021 to December 2024. The primary outcome (Oswestry Disability Index at 12 months after surgery) will be evaluated through a modified intention-to-treat method. The secondary outcomes will include the following: visual analog scale score for low back and lower extremity radiating pain, EuroQol 5-dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scars, and some surgery-related variables. Radiographic outcomes will be analyzed using magnetic resonance imaging or computed tomography. All outcomes will be evaluated before the surgery and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for reporting of clinical trial protocols. Discussion It is hypothesized that the efficacy and safety of biportal endoscopic and conventional decompressive laminectomy will be comparable in patients with lumbar spinal stenosis. The results of this trial will provide a high level of evidence for the efficacy and safety of the biportal endoscopic technique in patients with lumbar spinal stenosis and facilitate the development of clinical practice guidelines. Furthermore, the results of this study may indicate the feasibility of the biportal endoscopic technique for other types of spinal surgery. Trial registration The ENDO-B trial is registered at Clinical Research Information Service (CRIS, cris.nih.go.kr) (KCT0006057; April 52,021).

An ideal vaccine for controlling Salmonella infection in chicken flocks should be safe, inducing both humoral and cellular immunity. Live attenuated vaccines against Salmonella Enteritidis (S. Enteritidis) have been used as a potential control method of Salmonella infection in the poultry industry. However, live attenuated vaccines can persistently infect poultry for long periods and can become virulent revertant strains. In this study, we assessed the immune responses and protective efficacy of a temperature-sensitive attenuated S. Enteritidis mutant as a potential vaccine candidate. In addition, we evaluated the combined vaccine administration methods to maximize both humoral and cellular immune responses in chickens induced by the vaccine candidate. Immune responses and protective efficacy were compared between the Oral/IM group, vaccinated using one oral dose at four weeks old and a booster intramuscular dose at seven weeks old, and the IM/Oral group, vaccinated using one intramuscular dose at four weeks old and a booster oral dose at seven weeks old. The Oral/IM group showed stronger immune responses than those of the IM/Oral group. Spleens from the Oral/IM group showed a promising tendency of reduction of challenged Salmonella compared with those of other groups. Overall, the results indicated that the S. Enteritidis mutant strain is a promising live attenuated vaccine candidate with good efficacy.

Lumbar spinal stenosis is a common spinal degenerative condition. Minimally invasive interlaminar full-endoscopic decompressive laminectomy provides greater patient satisfaction and faster recovery than open decompressive laminectomy. The aim of our randomized controlled trial will be to compare the safety and efficacy of interlaminar full-endoscopic laminectomy and open decompressive laminectomy. Our trial will include 120 participants (60 per group) who will undergo surgical treatment for lumbar spinal stenosis. The primary outcome will be the Oswestry Disability Index measured at 12 months postoperatively. Secondary patient-reported outcomes will include back and radicular leg pain measured via a visual analog scale; the Oswestry Disability Index; the Euro-QOL-5 Dimensions score measured at 2 weeks and at 3, 6, and 12 months postoperatively; and patient satisfaction. The functional measures will include time to return to daily activities postoperatively and walking distance/time. The surgical outcomes will include postoperative drainage, operation time, duration of hospital stay, postoperative creatine kinase (an indicator of muscle injury) level, and postoperative surgical scarring. Magnetic resonance and computed tomography images and simple radiographs will be obtained for all patients. The safety outcomes will include surgery-related complications and adverse effects. All evaluations will be performed by a single assessor at each participating hospital who will be blinded to group allocation. The evaluations will be conducted preoperatively and at 2 weeks and 3, 6, and 12 months postoperatively. The randomized, multicenter design of the trial, blinding, and justification of the sample size will reduce the risk of bias in our trial. The results of the trial will provide data regarding the use of interlaminar full-endoscopic laminectomy as an alternative to open decompressive laminectomy that results in similar surgical findings with less invasiveness. Trial registration: This trial is registered at cris.nih.go.kr. (KCT0006198; protocol version 1; 27 May 2021).

The dramatic spread of Coronavirus Disease 2019 (COVID-19) has profound impacts on every continent and life. Due to human-to-human transmission of COVID-19, nuclear medicine staffs also cannot escape the risk of infection from workplaces. Every staff in the nuclear medicine department must prepare for and respond to COVID-19 pandemic which tailored to the characteristics of our profession. This article provided the guidance prepared by the Korean Society of Nuclear Medicine (KSNM) in cooperation with the Korean Society of Infectious Disease (KSID) and Korean Society for Healthcare-Associated Infection Control and Prevention (KOSHIC) in managing the COVID-19 pandemic for the nuclear medicine department. We hope that this guidance will support every practice in nuclear medicine during this chaotic period.

BACKGROUND: The effect of nano controlled sequential release of trichloroacetic acid (TCA) and epidermal growth factor (EGF) on the oral soft tissue regeneration was determined. METHODS: Hydrophobically modified glycol chitosan (HGC) nano controlled system was developed for the sequential release of TCA and EGF, and the release pattern was identified. The HGC-based nano controlled release system was injected into the critical-sized defects created in beagles’ palatal soft tissues. The palatal impression and its scanned body was obtained on various time points post-injection, and the volumetric amount of soft tissue regeneration was compared among the three groups: CON (natural regeneration control group), EXP1 (TCA-loaded nano controlled release system group), EXP2 (TCA and EGF individually loaded nano controlled release system). DNA microarray analysis was performed and various soft tissue regeneration parameters in histopathological specimens were measured. RESULTS: TCA release was highest at Day 1 whereas EGF release was highest at Day 2 and remained high until Day 3. In the volumetric measurements of impression body scans, no significant difference in soft tissue regeneration between the three groups was shown in two-way ANOVA. However, in the one-way ANOVA at Day 14, EXP2 showed a significant increase in soft tissue regeneration compared to CON. High correlation was determined between the histopathological results of each group. DNA microarray showed up-regulation of various genes and related cell signaling pathways in EXP2 compared to CON. CONCLUSION: HGC-based nano controlled release system for sequential release of TCA and EGF can promote regeneration of oral soft tissue defects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13770-019-00232-9) contains supplementary material, which is available to authorized users.

PSMD14, a subunit of the 19S regulatory particles of the 26S proteasome, was recently identified as a potential prognostic marker and therapeutic target in diverse human cancers. Here, we show that the silencing and pharmacological blockade of PSMD14 in MDA-MB 435S breast cancer cells induce paraptosis, a non-apoptotic cell death mode characterized by extensive vacuolation derived from the endoplasmic reticulum (ER) and mitochondria. The PSMD14 inhibitor, capzimin (CZM), inhibits proteasome activity but differs from the 20S proteasome subunit-inhibiting bortezomib (Bz) in that it does not induce aggresome formation or Nrf1 upregulation, which underlie Bz resistance in cancer cells. In addition to proteasome inhibition, the release of Ca2+ from the ER into the cytosol critically contributes to CZM-induced paraptosis. Induction of paraptosis by targeting PSMD14 may provide an attractive therapeutic strategy against cancer cells resistant to proteasome inhibitors or pro-apoptotic drugs.

The emergence of multidrug-resistant (MDR) bacteria and the spread of antimicrobial resistance among various bacteria are major threats to the global community. Due to the increased failure of classical antibiotic treatments against MDR bacterial infections, probiotics and their antimicrobial compounds have been suggested as promising alternatives to deal with MDR bacteria. Various strains of lactic acid bacteria have been reported to produce antagonistic molecules against pathogens. A new strain of Ligilactobacillus animalis, L. animalis SWLA-1, isolated from the feces of healthy dogs, shows strong antimicrobial activity against not only common pathogens but also MDR bacteria. In this study, we compared the antimicrobial activity of L. animalis SWLA-1 with that of other lactobacilli and antibiotics using an agar spot assay. Additionally, a novel spot inhibition index was developed and validated to quantitively evaluate the inhibitory activities of lactobacilli and antibiotics. A competitive coculture assay of L. animalis SWLA-1 with MDR bacteria further demonstrated its antibacterial activity. Furthermore, we evaluated the antimicrobial activity of the cell-free supernatant (CFS) of L. animalis SWLA-1 and its stability under various conditions in vitro. We found that L. animalis SWLA-1 and its CFS are potential alternatives to classic antimicrobial agents.

Background Biportal endoscopic surgery has recently been performed in lumbar discectomy, with advantages over conventional surgery, such as less skin scarring and muscle damage. However, the clinical results have not been established. Although previous studies reported no difference between the biportal endoscopic and microscopic discectomy clinical results, the evidence was weak. Therefore, this study aims to evaluate the efficacy and safety of the biportal endoscopic discectomy versus the microscopic discectomy. Methods This prospective multicenter randomized controlled equivalence trial is designed to compare the efficacy and safety outcomes of patients who underwent lumbar discectomy using biportal endoscopy or microscopy. We will include 100 participants (50 per group) with a lumbar herniated disc. The primary outcome will be the Oswestry Disability Index (ODI) score 12 months after surgery based on a modified intention-to-treat strategy. The secondary outcomes will include the visual analog scale score for low back and lower extremity radiating pain, the ODI score, the Euro-Qol-5-Dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scar, and surgery-related variables, such as postoperative drainage, operation time, admission duration, postoperative creatine kinase, and implementation status of conversion to open surgery. Radiographic outcomes will also be analyzed using magnetic resonance imaging (MRI) or computed tomography (CT) and simple radiographs. Safety will be assessed by evaluating all adverse and severe adverse events and surgery-related effects. The participants will be assessed by a blinded assessor before surgery (baseline) and 2 weeks and 3, 6, and 12 months after surgery. Discussion This trial will be the first prospective, multicenter, randomized controlled trial to analyze the efficacy and safety of biportal endoscopic discectomy in lumbar herniated disc. This trial is designed for evaluating the equivalence of the results between biportal endoscopic and microscopic discectomy including adequate sample size, blinded analyses, and prospective registration to reduce bias. This trial will provide enough data on the effectiveness and safety of biportal endoscopic surgery and will be an important study that allows clear conclusions. Trial registration Clinical Research Information Service (cris.nih.go.kr.) (KCT0006191). Registered on 27 March 2021

Mycoplasma synoviae (MS) is an avian pathogen that causes respiratory disease, infectious synovitis, and eggshell apex abnormalities in chickens. Nicotinamide adenine dinucleotide (NAD)-independent MS was first reported in 1975. Despite the atypical traits of NAD-independent MS, its independence from NAD has not been studied. In this study, we isolated five NAD-independent strains from Korea and assembled their genomes using sequencing reads obtained from Illumina and Oxford Nanopore Technology platforms. The assembled genomes were compared with the genomes of MS-H vaccine strain and type strain WVU1853. We found that the coding sequences of nicotinate phosphoribosyltransferase and glycerol-3-phosphate acyltransferase, and a unique coding sequence were present only in the genomes of NAD-independent isolates.

Background Advances in minimally invasive surgery have expanded the indications for interlaminar full-endoscopic discectomy. Although the clinical outcomes for this approach may be equivalent to those of conventional microscopic discectomy, the supporting evidence is still based on small, single-center, prospective, and retrospective studies. Therefore, a multicenter randomized controlled trial is warranted. Methods This will be a prospective, multicenter, randomized controlled trial comparing the efficacy and safety of interlaminar full-endoscopic discectomy to those of conventional microscopic discectomy. The trial will enroll 100 participants with a lumbar disc herniation, 50 in each group. The primary outcome will be the Oswestry Disability Index (ODI) score at 12 months post-surgery. Secondary outcomes will be back and leg pain (visual analog scale); the ODI; the EuroQol-5-dimension score; patient satisfaction; and walking distance/time and time to return to daily activities post-surgery. Surgical outcomes will include postoperative drainage, operative time, duration of hospital stay, postoperative creatine kinase level as an indicator of muscle injury, and postoperative scarring. Postoperative magnetic resonance imaging, computed tomography, and simple radiography will be performed to evaluate radiographic outcomes between the two surgical approaches. Surgery-related complications and adverse effects will be evaluated as safety outcomes. A single assessor at each participating hospital, blinded to group allocation, will assess the enrolled participants at baseline, at 2 weeks, and at 3, 6, and 12 months postoperatively. Discussion This trial is designed to determine whether interlaminar full-endoscopic discectomy is clinically comparable to microscopic discectomy to treat lumbar disc herniations. All efforts will be made to reduce bias, including adequate sample size, blinded analyses, and multicenter prospective registration. The outcomes will inform practice, providing the evidence needed for using interlaminar full-endoscopic over microscopic discectomy by confirming the potential of this technique to improve patient satisfaction and clinical outcomes. Trial registration: Clinical Research Information Service; cris.nih.go.kr. (KCT0006277); protocol version (v1, June 8, 2021).

The transferred microbiota from mother to baby constitutes the initial infant gastrointestinal microbiota and has an important influence on the development and health of infants in human. However, the reproductive tract microbiota of avian species and its inheritance have rarely been studied. We aimed to characterize the microbial community in the chicken reproductive tract and determine the origin of the chicken embryo gut microbiota. Microbiota in four different portions of chicken oviduct were determined using 16S rRNA metagenomic approach with the IonTorrent platform. Additionally, we analyzed the mother hen’s magnum and cloaca, descendent egg, and embryo gut microbiota. The microbial composition and relative abundance of bacterial genera were stable throughout the entire chicken reproductive tract, without significant differences between the different parts of the oviduct. The chicken reproductive tract showed a relatively high abundance of Lactobacillus species. The number of bacterial species in the chicken reproductive tract significantly increased following sexual maturation. Core genera analysis detected 21 of common genera in the maternal magnum and cloaca, descendent egg shell, egg white, and embryo gut. Some elements of the maternal oviduct microbiota appear to be transferred to the embryo through the egg white and constitute most of the embryo gut bacterial population.

Accumulating reports demonstrate that apoptosis does not explain all the effects of cancer therapy due to the innate and acquired apoptotic resistance of malignant cancer cells. Recently, paraptosis, a type of programmed cell death accompanied by dilation of mitochondria and/or the endoplasmic reticulum (ER), has garnered interest in cancer research as an alternative way to kill apoptosis-resistant cancers. We describe here the adaptation and validation of a high-content cell-based assay to screen and identify novel paraptotic regulators employing the malignant breast cancer cells undergoing curcumin-induced paraptosis. We used YFP-Mito cells, which express fluorescence selectively in mitochondria, to select paraptosis-related genes whose corresponding siRNAs appeared to modulate mitochondrial dilation, a morphological feature of paraptosis. From the selected 38 candidate genes, we chose ubiquitin specific peptidase 10 (USP10), a ubiquitin specific protease, as a strongly active candidate that warranted further evaluation of its involvement in paraptosis. We found that both siRNA-mediated knockdown of USP10 and treatment with the USP10 inhibitor, spautin-1, effectively attenuated curcumin-induced paraptosis. This systematic assay, in which a siRNA library is screened for the ability to ameliorate paraptotic changes in mitochondria, may enable researchers to identify potent regulators of paraptosis and new candidate genes/drugs to combat malignant breast cancer.

본 연구에서는 지역주민의 정책리터러시 결정요인을 분석하고 정책적 시사점을 논의하고자 하였다. 이를 위해 지방정부에서 추진하고 있는 아동친화정책을 중심으로 지역주민의 개인적 요인인 인구사회학적 요인과 정책효능감, 정책적 요인인 지방정부의 정책PR을 독립변수로 설정하고, 이들 요인이 지역주민의 정책리터러시에 미치는 영향을 분석하였다. 이를 위해 아동친화정책을 시행하고 있는 S시 지역주민들을 대상으로 설문조사를 실시하고 가설을 검증하였다. 위계적 회귀분석 결과, 전통적 정책리터러시에는 인구사회학적 요인인 연령과 자녀수, 정책PR과 정책효능감이 긍정적인 영향을 미치는 것으로 분석되었다. 기능적 정책리터러시에는 성(남성), 정책PR, 정책효능감이, 비판적 정책리터러시에는 연령과 학력, 자녀수, 정책효능감이 긍정적인 영향을 미치는 것으로 분석되었다. 이러한 분석결과를 토대로 본 연구에서는 지역주민의 정책리터러시 향상을 위한 이론적·정책적 시사점을 제시하였다.

Mycoplasma gallisepticum causes chronic respiratory diseases in poultry and economic losses to the chicken and turkey industry. We report the complete genome sequence of the field isolate strain KUVMG001 of Mycoplasma gallisepticum from South Korea.

Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Since paraptosis is morphologically and biochemically different from apoptosis, understanding its regulatory mechanisms may provide a novel therapeutic strategy in malignant cancer cells that have proven resistant to conventional pro-apoptotic treatments. Relatively little is known about the molecular basis of paraptosis, but perturbations of cellular proteostasis and ion homeostasis appear to critically contribute to the process. Ca2+ transport has been shown to be important in the paraptosis induced by several natural products, metal complexes, and co-treatment with proteasome inhibitors and certain Ca2+-modulating agents. In particular, the Ca2+-mediated communication between the ER and mitochondria plays a crucial role in paraptosis. Mitochondrial Ca2+ overload from the intracellular Ca2+-flux system located at the ER–mitochondrial axis can induce mitochondrial dilation during paraptosis, while the accumulation of misfolded proteins within the ER lumen is believed to exert an osmotic force and draw water from the cytoplasm to distend the ER lumen. In this process, Ca2+ release from the ER also critically contributes to aggravating ER stress and ER dilation. This review focuses on the role of Ca2+ transport in paraptosis by summarizing the recent findings related to the actions of Ca2+-modulating paraptosis-inducing agents and discussing the potential cancer therapeutic strategies that may effectively induce paraptosis via Ca2+ signaling.

The Salmonella enterica subspecies serovar Enteritidis is the one of main serovars isolated from human patients with food poisoning and poultry without clinical signs. Consumption of poultry products contaminated with Salmonella Enteritidis is a common source of human salmonellosis. This study was aimed to determine the genetic relationships between Salmonella Enteritidis strains isolated from human patients and those isolated from poultry sources using whole-genome sequencing analysis. Seven of multi-drug resistant (MDR) strains of Salmonella Enteritidis were isolated from 234 retail chicken meats, internal organs of chicken, and straw bedding samples at chicken farms. Whole genome sequences of the MDR strains were determined using the Oxford Nanopore sequencing and compared with available whole genome sequences of the Salmonella Enteritidis strains previously isolated in Korea. Single-nucleotide polymorphism analysis of the whole genomes showed that all MDR Salmonella Enteritidis strains were genetically close and related to the FORC_019 strain isolated from human blood in 2015 in Korea. All of the MDR Salmonella Enteritidis strains contained a 110 kb of plasmid, and comparative plasmid analysis showed that all of the MDR Salmonella Enteritidis strains carried a novel fusion plasmid with genes coding virulence factors and antibiotic resistance proteins. The almost identical plasmid, with an extra 7.5-kb insertion sequence was also found in the FORC_019 strain. These results suggested that the single genetic lineage of MDR Salmonella Enteritidis that can cause salmonellosis in human is currently contaminating the Korean poultry industry.

PURPOSE: This study aimed to construct a database of the effective doses (ED) from F-18 fluorodeoxyglucose (FDG) torso positron emission tomography/computed tomography (PET/CT) in Korea to provide data that supports the reduction of the CT dose of PET/CT and optimization of PET/CT protocols in Korea. METHODS: We investigated data of ED and CT parameters of FDG PET/CT. The data were analyzed by body weight groups. RESULTS: A total of 31 hospitals participated in the survey (99 adults). The mean total EDs (± SD) were 8.77 ± 2.76, 10.93 ± 3.14, and 12.57 ± 3.79 mSv for the 55-, 70-, and 85-kg groups, respectively. The FDG EDs were 4.80 ± 0.98, 6.05 ± 1.15, and 6.89 ± 1.52 mSv, and the CT EDs were 4.00 ± 2.12, 4.88 ± 2.51, and 5.68 ± 2.89 mSv, respectively. Of the enrolled hospitals, 54.5% used ultra-low-dose CT protocols, and their CT ED was significantly lower than low-dose CT group in all groups (2.9 ± 1.0, 3.2 ± 1.1, and 3.3 ± 1.0 mSv vs. 6.6 ± 1.6, 7.2 ± 2.1, and 7.9 ± 2.2 mSv, all p

Anatomically terminal parts of the urinary, reproductive, and digestive systems of birds all connect to the cloaca. As the feces drain through the cloaca in chickens, the cloacal bacteria were previously believed to represent those of the digestive system. To investigate similarities between the cloacal microbiota and the microbiota of the digestive and reproductive systems, microbiota inhabiting the colon, cloaca, and magnum, which is a portion of the chicken oviduct of 34-week-old, specific-pathogen-free hens were analyzed using a 16S rRNA metagenomic approach using the Ion torrent sequencer and the Qiime2 bioinformatics platform. Beta diversity via unweighted and weighted unifrac analyses revealed that the cloacal microbiota was significantly different from those in the colon and the magnum. Unweighted unifrac revealed that the cloacal microbiota was distal from the microbiota in the colon than from the microbiota in the magnum, whereas weighted unifrac revealed that the cloacal microbiota was located further away from the microbiota in the magnum than from the microbiota inhabiting the colon. Pseudomonas spp. were the most abundant in the cloaca, whereas Lactobacillus spp. and Flavobacterium spp. were the most abundant species in the colon and the magnum. The present results indicate that the cloaca contains a mixed population of bacteria, derived from the reproductive, urinary, and digestive systems, particularly in egg-laying hens. Therefore, sampling cloaca to study bacterial populations that inhabit the digestive system of chickens requires caution especially when applied to egg-laying hens. To further understand the physiological role of the microbiota in chicken cloaca, exploratory studies of the chicken's cloacal microbiota should be performed using chickens of different ages and types.

Background/Aims: This study investigated the effect of inducible nitric oxide synthase-loaded mineralized nanoparticles (iNOS-MNPs) on the osteogenic differentiation of mouse embryonic stem cells (ESCs). Methods: We prepared iNOS-MNPs using an anionic block copolymer template-mediated calcium carbonate (CaCO3) mineralization process in the presence of iNOS. iNOS-MNPs were spherical and had a narrow size distribution. iNOS was stably loaded within MNPs without denaturation. In order to confirm the successful introduction of iNOS-MNPs into the cytosol of ESCs, intracellular levels of nitric oxide (NO) was determined with a fluorometric analysis. A NO effector molecule, cyclic guanosine 3’,5’ monophosphate (cGMP) was also quantified with a competitive enzyme immunoassay. Cell viability in response to iNOS-MNP treatment was determined using the cell counting kit-8 (CCK-8) assay. Alkaline phosphatase (ALP) activity assay, intracellular calcium quantification assay, and Alizarin red S staining for matrix mineralization were performed to investigate osteogenic differentiation of ESCs. The protein levels of Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osterix (OSX) as osteogenic-related factors were also assessed by immunofluorescence staining and Western blot analysis. The complex pathways associated with iNOS-MNP-derived osteogenic differentiation of ESCs were evaluated by network-based analysis. Results: Cells with iNOS-MNPs displayed a significant increase in NO and cGMP concentration compared with the control group. When cells were exposed to iNOS-MNPs, there were no adverse effects on cell viability. Importantly, iNOS-MNP uptake promoted the osteogenic differentiation of ESCs. Using transcriptome profiling, we obtained 1,836 differentially-induced genes and performed functional enrichment analysis with ClueGO and KEGG. These analyses identified significantly enriched and interconnected molecular pathways such as protein kinase activity, estrogen receptor activity, bone morphogenetic protein (BMP) receptor binding, ligand-gated ion channel activity, and phosphatidylinositol 3-phosphate binding. Conclusion: These findings suggest that iNOS-MNPs can induce osteogenic differentiation in ESCs by integrating complex signaling pathways.

In this review, we describe the research trends of hybrid nanocarriers developed based on a biomimetic mineralization process, and their recent applications in imaging and therapy of cancers. Organic-inorganic hybrid nanostructures formed by diverse biomimetic mineralization approaches are briefly reviewed, and particularly, the biomedical applications of these hybrid nanocarriers for the diagnosis and therapy of cancers are discussed. Biomineralization is an important process in which living organisms produce biominerals, such as calcium phosphate (CaP), calcium carbonate (CaCO3), and silica (SiO2), to strengthen their tissues, as found in the formation of bone and teeth. Introducing the artificial biomimetic mineralization process to nanobiotechnology has inspired researchers to develop smart stimuli-responsive nanoparticles for multiple purposes, such as improved therapeutic activity and activatable imaging of cancers.

Compressive femoral neuropathy is a disabling condition accompanied by difficulty in hip flexion and knee extension. It may result from retroperitoneal hematoma or bleeding, or from complications associated with pelvic, hip surgery, and renal transplants. A 55-year-old female with autosomal dominant polycystic kidney disease presented with proximal muscle weakness in lower extremities. The patient experienced recurrent renal cyst infection, with aggravated weakness during each event. Electromyography and nerve conduction study revealed bilateral femoral neuropathy. Computed tomography and magnetic resonance images were added to further identify the cause. As a result, a diagnosis of femoral neuropathy caused by enlarged polycystic kidney was made. Cyst infection was managed with antibiotics. Renal function was maintained by frequent regular hemodialysis. While avoiding activities that may increase abdominal pressure, rehabilitation exercises were provided. Motor strength in hip flexion and knee extension improved, and was confirmed via electrodiagnostic studies.

OBJECTIVE To evaluate the diagnostic value of computed tomography-myelography (CTM) compared to that of magnetic resonance imaging (MRI) in patients with lumbar radiculopathy. METHODS The study included 91 patients presenting with radicular leg pain caused by herniated nucleus pulposus or lateral recess stenosis in the lumbar spine. The degree of nerve root compression on MRI and CTM was classified into four grades. The results of each imaging modality as assessed by two different observers were compared. Visual analog scale score for pain and electromyography result were the clinical parameters used to evaluate the relationships between clinical features and nerve root compression grades on both MRI and CTM. These relationships were quantified by calculating the receiver-operating characteristic curves, and the degree of relationship was compared between MRI and CTM. RESULTS McNemar's test revealed that the two diagnostic modalities did not show diagnostic concurrence (p

The purpose of this study was to estimate average radiation exposure from 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) examinations and to analyze possible factors affecting the radiation dose. A nation-wide questionnaire survey was conducted involving all institutions that operate PET/CT scanners in Korea. From the response, radiation doses from injected FDG and CT examination were calculated. A total of 105 PET/CT scanners in 73 institutions were included in the analysis (response rate of 62.4%). The average FDG injected activity was 310 ± 77 MBq and 5.11 ± 1.19 MBq/kg. The average effective dose from FDG was estimated to be 5.89 ± 1.46 mSv. The average CT dose index and dose-length product were 4.60 ± 2.47 mGy and 429.2 ± 227.6 mGy∙cm, which corresponded to 6.26 ± 3.06 mSv. The radiation doses from FDG and CT were significantly lower in case of newer scanners than older ones (P < 0.001). Advanced PET technologies such as time-of-flight acquisition and point-spread function recovery were also related to low radiation dose (P < 0.001). In conclusion, the average radiation dose from FDG PET/CT is estimated to be 12.2 mSv. The radiation dose from FDG PET/CT is reduced with more recent scanners equipped with image-enhancing algorithms., Graphical Abstract

BACKGROUND: We aimed to determine the effect of fibronectin (FN)-immobilized microgrooved titanium (Ti) on human gingival fibroblast proliferation, gene expression and protein expression. METHODS: Photolithography was used to fabricate the microgrooved Ti, and amine funtionalization (silanization) was used for FN immobilization on titanium surfaces. Cell proliferation, gene expression and protein expression were analyzed, followed by multiple regression analysis for determining the influential factors on cell proliferation. RESULTS: FN-immobilized microgrooved Ti significantly enhanced the fibroblast proliferation in various timelines of culture, among which a burst of fivefold increase is induced at 96 h of culture compared to that on the control smooth Ti. We suggest a presence of the synergistic promotion effect of microgrooves and FN immobilization on fibroblast proliferation. Through a series of analyses on the expression of various genes and proteins involved in cell adhesion and proliferation, cyclin-dependent kinase 6, cyclin D1, integrin α5, oncogene c-Src, osteonectin, paxillin and talin-2 were determined as influential factors on promoting fibroblast proliferation induced by FN-immobilized microgrooved Ti. CONCLUSION: FN-immobilized microgrooved Ti can act as an effective surface for enhancing fibroblast proliferation, and can be used for promoting soft tissue response on the connective tissue attachment zone of biomaterial surfaces. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13770-018-0153-7) contains supplementary material, which is available to authorized users.

ImportanceThere have only been a few large-scale studies that have included a risk factor analysis for CTS. No prior study has investigated the relationship between the occurrence of CTS and stratified socioeconomic status, which is closely related to a person’s type of job.ObjectiveTo confirm the known risk factors for CTS and also to determine the correlation between stratified socioeconomic status and the occurrence of CTS.DesignWe conducted this study using a retrospective cohort model based on the combined databases of the Korean National Health Insurance System from 2003–2013, a database compiled using information from a national periodic health-screening program that is used for reimbursement claims.SettingThe setting was a population-based retrospective cohort study.ParticipantsFirst, we randomly sampled 514,795 patients who represented 10% of the 5,147,950 people who took part in periodic health screenings from 2002–2003. Existing CTS patients were excluded from this group. Therefore, this study finally included 512,942 participants and followed their medical records from 2003–2013.Main Outcomes and MeasuresDesired outcomes were the incidence rate of CTS and the hazard ratios according to stratified socioeconomic status.ResultsA correlation analysis showed that CTS was more likely to occur in patients from a lower socioeconomic status.Conclusions and RelevanceCTS was associated with people of a lower socioeconomic status who work in simple but repetitive manual labor jobs. We believe that the results of our study will be helpful to determine the pathophysiology of CTS and to set up a new industrial health policy for this condition.Key PointsQuestionWhat is the relationship between stratified socioeconomic status and the incidence of carpal tunnel syndrome (CTS)?FindingsIn this retrospective population-based cohort study that included 512,942 participants sampled from the Korean National Health Insurance System(KNHIS) database, the incidence rate and hazard ratios for CTS tended to increase with lower socioeconomic status.ImplicationsLow socioeconomic status was identified as a risk factor for the incidence of CTS.

We demonstrate that dual release of bone morphogenic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) by catechol-functionalized adhesive polymer nanoparticles on microgrooved titanium (Ti) surface enhances in vitro osteoblastic differentiation of human mesenchymal stem cells (MSCs). The nanoparticles consisted of three distinct domains, surface Ti-adhesive catechol groups, anionic poly(L-aspartic acid) (PAsp) shells, and hydrophobic poly(L-phenylalanine) (PPhe) cores. The immobilization of the adhesive nanoparticles onto microgrooved Ti surface was verified using various surface analytical tools, such as field-emission scanning electron microscopy (Fe-SEM), X-ray photoelectron spectroscopy (XPS), contact angle measurement. The nanoparticles were immobilized both on the groove bottom surface and the ridge top surface with a similar anchoring density. A fluorescence microscope visualized that BMP-2 and IGF-1 of positive charges were efficiently loaded onto the negatively charged PAsp shells of immobilized nanoparticles. We confirmed the enhanced osteoblastic differentiation of MSCs by presenting the expression results of major osteoblast marker genes and proteins. In addition, overall significant correlations between the experimental results verified the validity of our study. The proposed combined surface of microgrooves and growth factor-releasing nanoparticles can be used as a strong osteogenic promoter on various biomaterial surfaces.

Tentorial dural arteriovenous fistula (DAVF) is a rare vascular disease, which has high risk of intracranial hemorrhage. We present two cases of tentorial DAVF which were successfully treated with single trial of transarterial embolization using Onyx. We briefly reviewed the types of the tentorial DAVF and strategies of treatment.

Objective To evaluate the effect of custom molded foot orthoses on children with growing pains of the lower extremities. Methods Children with growing pains were recruited during a clinic visit. None had any bony deformities, inflammatory joint disease or depression. Resting calcaneal stance position (RCSP) and calcaneal pitch angle were measured, and individual custom molded rigid foot orthoses were prescribed using the inverted orthotic technique to control for foot overpronation using the RCSP angle. Pain sites, degree and frequency of pain, and balance ability were evaluated using Balance Master computerized posturography prior to foot orthosis fitting, and 1 and 3 months later. Results Twenty children completed the study. Seventeen (75%) had overpronated feet. Significant improvements were noted after 1 and 3 months in pain degree and frequency, and after 3 months in balancing ability. Conclusion The use of custom molded foot orthoses is a good method for treating children with multiple musculoskeletal pains in the leg.

We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO3) hybrid nanoparticles (DOX-CaCO3-MNPs) through a block copolymer templated in situ mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO2) bubbles and showed excellent echo persistence. In vivo results demonstrated that the DOX-CaCO3-MNPs generated CO2 bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO3-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO2 bubbles necessary for US contrast. The DOX-CaCO3-MNPs could also trigger the DOX release simultaneously with CO2 bubble generation at the acidic tumoral environment. The DOX-CaCO3-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers.

AIM Oblique lateral interbody fusion (OLIF) is a minimally invasive surgical method that can provide an access to the lumbar spine without direct dissection of psoas muscle and the need for intraoperative neuromonitoring (IOM) is questionable. The aim of this study was to examine and document the transient and persistent perioperative complications in patients who underwent OLIF for degenerative lumbar disease without IOM. MATERIAL AND METHODS A total of 129 consecutive patients who were diagnosed as degenerative spinal disease from L1 to S1 and underwent mini-open OLIF were identified and retrospectively reviewed. All patients were classified as two groups; non-IOM group and IOM group. According to the relation to surgical procedure, the complications were divided into two groups; "procedurerelated" and "procedure-unrelated". Based on the effect of duration, the complications were defined as "transient" where the symptom is relieved within 30 days postoperatively, and "persistent" where the symptom remains for more than 30 days postoperatively. RESULTS The study groups comprised 57 cases in the IOM group and 72 in the non-IOM group. The complication rate was 24.6% (transient; 17.6%, persistent; 7.0%) in the IOM group and 29.2% (transient; 25.0%, persistent; 4.2%) in the non-IOM group. The incidence of postoperative leg symptoms related to lumbar plexus and/or psoas muscle injury was 6 transient and 3 persistent in the IOM group (overall 15.3%), and 12 transient and 3 persistent in the non-IOM group (overall 20.9%). CONCLUSION Mini-open OLIF can be safely carried out without the aid of IOM.

The proliferation status of tumor cells can be imaged using [18F]fluorothymidine ([18F]FLT), which is trapped by cell cycle-dependent thymidine kinase 1 (TK1). Targeting of heat shock protein 90 (HSP90) disrupts multiple client proteins, leading to heterogeneous cell-cycle phenotypes. To investigate whether [18F]FLT uptake reflects the growth arrest caused by various mechanisms of HSP90 inhibition, we used HCT116 cells that were arrested at G0/G1 phase, and Hep3B cells at G2/M phase, by the HSP90 inhibitor 17-AAG. In HCT116 cells, 17-AAG did not induce significant changes in [18F]FLT uptake despite the decreased expression of TK1, cyclin A, and cyclin B. The mRNA level of 5'3'-deoxynucleotidase 1 (NT5C), which antagonizes TK1 by de-phosphorylating [18F]FLT monophosphate, was also decreased in 17-AAG-treated HCT116 cells by 55.3±18.1% compared to vehicle-treated cells. In Hep3B cells, 17-AAG treatment did not induce TK1 expression, TK1 activity nor [18F]FLT uptake. Nucleoside transporter activity in the plasma membrane was unchanged in both cell lines. These results showed that a HSP90 inhibitor exerts multifaceted effects on [18F]FLT uptake before inducing cell death in a cell-cycle-independent manner. Therefore, the use of [18F]FLT-positron emission tomography for monitoring treatment by HSP90 inhibitor would be more appropriate when tumor cell death is induced after growth arrest.

Objective To investigate the correlation between the Montreal Cognitive Assessment (MoCA) and functional outcome among subacute stroke patients with cognitive dysfunction. Methods Records of 61 inpatients were reviewed. Patients were divided into two groups based on their initial MoCA score. MoCA score of 11 was set as the differentiating criterion. We compared the improvements in Modified Barthel Index (MBI) from initial assessment to discharge between the two groups. Results There were no significant differences between the two groups in relation to age, duration from onset to admission, hospitalization period, or years of education. In a comparison of the results of Mini-Mental Status Examinations (MMSE) administered at admission and again at discharge, there was significantly more improvement in MMSE scores in the group with low MoCA scores than in the group with high MoCA scores. However, the group with high MoCA scores also showed high MBI scores at discharge and exhibited greater MBI improvement. Conclusion Higher initial MoCA scores (which reflect preservation of executive function) indicate better functional outcome in the subacute stroke phase.

We developed a calcium phosphate (CaP)-assembled polymer nanocarrier for intracellular doxorubicin (DOX) delivery based on a mussel-inspired mineralization approach. A DOX-loaded core-shell polymer nanoparticle (DOX-NP) consisting of a poly(3,4-dihydroxy-l-phenylalanine) (PDOPA) core and a poly (ethylene glycol) (PEG) shell was utilized as a nanotemplate for CaP mineralization. The mean hydrodynamic diameter of the DOX-loaded CaP-mineralized polymer nanoparticles (DOX-CaP-NPs) was 154.3nm. Energy-dispersive X-ray spectroscopy confirmed that the DOX-CaP-NPs contained substantial amounts of Ca and P, elements found only in the CaP mineral. The loading efficiency and content of DOX, estimated by fluorescence spectroscopy, were 54.0% and 10.8wt%, respectively. The CaP deposited in the PDOPA core domain enabled the DOX-CaP-NPs to maintain a robust structure and effectively inhibit DOX release at extracellular pH, whereas at endosomal pH, the CaP core dissolved to trigger a facilitated DOX release. The DOX-CaP-NPs may serve as robust nanocarriers with a high delivery efficacy for cancer chemotherapy.

Background/Aims: In dementia patients, a deficit in activities of daily living (ADL) is one of the main problems. Our objective was to assess ADL using the Korean Modified Barthel Index (K-MBI) in patients with Alzheimer's disease (AD) plus cerebrovascular disease (CVD) treated with a rivastigmine patch for 24 weeks in an open-label, observational study. Methods: 29 patients were enrolled who met the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ ANDRA) criteria and had a score of 10-26 on the Korean version of the Mini-Mental State Examination (K-MMSE). After the rivastigmine patch had been applied for 24 weeks, changes in self-care activities were assessed using the K-MBI. Results: The average age of the patients was 62.8 years, and they had an average K-MMSE score of 16.2. Patients showed a mean improvement of 21.9 points, as compared with the baseline K-MBI score of 30.3 (p < 0.05). Significantly better outcomes were seen in secondary outcome variables, for example the K-MMSE and backward digit span. The most frequent adverse events were skin problems, such as itching sensation (10%). Conclusion: In this multicenter, open-label, observational study, the rivastigmine patch was associated with improvements in ADL in patients with AD plus CVD.

Destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is a common pathophysiology of Parkinson's disease (PD). Characteristics of PD patients include bradykinesia, muscle rigidity, tremor at rest and disturbances in balance. For about four decades, PD animal models have been produced by toxin-induced or gene-modified techniques. However, in mice, none of the gene-modified models showed all 4 major criteria of PD. Moreover, distinguishing between PD model pigs and normal pigs has not been well established. Therefore, we planned to produce a pig model for PD by chronic subcutaneous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), neurotoxin. Changes in behavioral patterns of pigs were thoroughly evaluated and a new motor scoring system was established for this porcine model that was based on the Unified Parkinson's Disease Rating Scale (UPDRS) in human PD patients. In summary, this motor scoring system could be helpful to analyze the porcine PD model and to confirm the pathology prior to further examinations, such as positron emission tomography-computed tomography (PET-CT), which is expensive, and invasive immunohistochemistry (IHC) of the brain.

The purposes of this study are (1) to examine the relationships among attitude on SNS use, subjective norm, perceived behavioral control, and SNS use, (2) to analyze effect of SNS use on bonding network and bridging network, (3) to consider moderating effect of the gender on the relationship between SNS use and Social network. We conducted a survey for 20-30`s SNS user. The results of analysis using the Structural Equation Model(SEM) represent that attitude on SNS use, subjective norm, and perceived behavioral control are significant determinants of the SNS use. SNS use affects bonding network and bridging network. An interesting result was observed that the gender had moderating effect on the relationship between SNS use and social network. Based on these results, we suggest theoretical and practical implications of this study.

Objective Cerebral aneurysm (CA) is an important acquired cerebrovascular disease that can cause catastrophic results. MicroRNAs (miRNAs) are small non-coding RNAs, playing essential roles in modulating basic physiologic and pathological processes. Currently, evidences have been established about biologic relationship between miRNAs and abdominal aortic aneurysms. However, biologic roles of miRNAs in CA formation have not been explained yet. We employed microarray analysis to detect and compare miRNA expression profiles in late stage of CA in rat model. Methods Twenty-six, 7-week-old male Sprague-Dawley rats underwent a CA induction procedure. The control animals (n=11) were fed a normal diet, and the experimental animals (n=26) were fed a normal diet with 1% normal saline for 3 months. Then, the rats were sacrificed, their cerebral arteries were dissected, and the five regions of aneurysmal dilation on the left posterior communicating artery were cut for miRNA microarrays analysis. Six miRNAs (miRNA-1, miRNA-223, miRNA-24-1-5p, miRNA-551b, miRNA-433, and miRNA-489) were randomly chosen for validation using real-time quantitative PCR. Results Among a set of differentially expressed miRNAs, 14 miRNAs were over-expressed more than 200% and 6 miRNAs were down-expressed lower than 50% in the CA tissues. Conclusion The results show that miRNAs might take part in CA formation probably by affecting multiple target genes and signaling pathways. Further investigations to identify the exact roles of these miRNAs in CA formation are required.