Development of a digital star-shot analysis system for comparing radiation and imaging isocenters of proton treatment machine.

PURPOSE: To directly compare the radiation and imaging isocenters of a proton treatment machine, we developed and evaluated a real-time radiation isocenter verification system. METHODS: The system consists of a plastic scintillator (PI-200, Mitsubishi Chemical Corporation, Tokyo, Japan), an acrylic phantom, a steel ball on the detachable plate, Raspberry Pi 4 (Raspberry Pi Foundation, London, UK) with camera module, and analysis software implemented through a Python-based graphical user interface (GUI). After kV imaging alignment of the steel ball, the imaging isocenter defined as the position of the steel ball was extracted from the optical image. The proton star-shot was obtained by optical camera because the scintillator converted proton beam into visible light. Then the software computed both the minimum circle radius and the radiation isocenter position from the star-shot. And the deviation between the imaging isocenter and radiation isocenter was calculated. We compared our results with measurements obtained by Gafchromic EBT3 film (Ashland, NJ, USA). RESULTS: The minimum circle radii were averaged 0.29 and 0.41 mm while the position deviations from the radiation isocenter to the laser marker were averaged 0.99 and 1.07 mm, for our system and EBT3 film, respectively. Furthermore, the average position difference between the radiation isocenter and imaging isocenter was 0.27 mm for our system. Our system reduced analysis time by 10 min. CONCLUSIONS: Our system provided automated star-shot analysis with sufficient accuracy, and it is cost-effective alternative to conventional film-based method for radiation isocenter verification.

Flavobacterium humidisoli sp. nov., isolated from riverside soil.

A novel Gram-stain-negative, yellow-pigmented, non-motile and rod-shaped bacterial strain designated MMS21-Er5T was isolated and subjected to polyphasic taxonomic characterization. MMS21- Er5T could grow at 4-34 °C (optimum, 30 °C), at pH 6-8 (optimum, pH 7) and in the presence of 0-2% NaCl (optimum, 1 %). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that MMS21- Er5T showed low levels of sequence similarities with other species, as the highest similarity of 97.83 % was observed with Flavobacterium tyrosinilyticum THG DN8.8T, then 97.68 % with 'Flavobacterium ginsengiterrae' DCY 55 and 97.63 % with Flavobacterium banpakuense 15F3T, which were well below the suggested cutoff for species distinction. The whole genome sequence of MMS21-Er5T consisted of a single contig of 5.63 Mbp, and the DNA G+C content was 34.06 mol%. The in-silico DNA-DNA hybridization and orthologous average nucleotide identity values were highest with Flavobacterium tyrosinilyticum KCTC 42726T (45.7 and 91.92% respectively). The predominant respiratory quinone for the strain was menaquinone-6 (MK-6), the major cellular fatty acid was iso-C15 : 0, and the diagnostic polar lipids were phosphatidylethanolamine and phosphatidyldiethanolamine. The combination of physiological and biochemical tests clearly distinguished the strain from related species of the genus Flavobacterium. On the basis of these results, strain MMS21-Er5T evidently represents a novel species of the genus Flavobacterium, for which the name Flavobacterium humidisoli sp. nov. is proposed (type strain=MMS21-Er5T=KCTC 92256T =LMG 32524T).

Solitalea lacus sp. nov., isolated from pond sediment.

A Gram-stain-negative, strictly aerobic, oxidase-positive, catalase-negative, motile by gliding, creamy white-pigmented bacterium, designated strain S2-8T, isolated from a sediment sample from a Wiyang pond in the Republic of Korea, was subjected to polyphasic taxonomic analysis. Growth was observed at 10-40 °C (optimum: 30 °C), pH 7-8 and 0-0.5% NaCl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain S2-8T belonged to the family Sphingobacteriaceae in the phylum Bacteroidota and was closely related to Solitalea longa HR-AVT, Solitalea canadensis DSM 3403T and Solitalea koreensis R2A36-4T with 97.2, 96.7 and 93.7 % 16S rRNA gene sequence similarities, respectively. Average nucleotide identity and digital DNA-DNA hybridization values for these type strains were 72.0-75.2% and 21.2-21.9 %, respectively. The major respiratory quinone is menaquinone-7. The major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c). The major polar lipids were phosphatidylethanolamine, two unidentified amino acids and four unidentified lipids. The G+C content of genomic DNA was 37.9 mol%. Based on polyphasic taxonomic analysis, it was observed that strain S2-8T is a novel species belonging to the genus Solitalea, for which the name Solitalea lacus sp. nov. is proposed. The type strain is S2-8T (= KACC 22266T= JCM 34533T).

Development of Novel Musical Stimuli to Investigate the Perception of Musical Emotions in Individuals With Hearing Loss.

BACKGROUND: Many studies have examined the perception of musical emotion using excerpts from familiar music that includes highly expressed emotions to classify emotional choices. However, using familiar music to study musical emotions in people with acquired hearing loss could produce ambiguous results as to whether the emotional perception is due to previous experiences or listening to the current musical stimuli. To overcome this limitation, we developed new musical stimuli to study emotional perception without the effects of episodic memory. METHODS: A musician was instructed to compose five melodies with evenly distributed pitches around 1 kHz. The melodies were created to express the emotions of happy, sad, angry, tender, and neutral. To evaluate whether these melodies expressed the intended emotions, two methods were applied. First, we classified the expressed emotions of melodies with selected musical features from 60 features using genetic algorithm-based k-nearest neighbors. Second, forty-four people with normal hearing participated in an online survey regarding the emotional perception of music based on dimensional and discrete approaches to evaluate the musical stimuli set. RESULTS: Twenty-four selected musical features produced classification for intended emotions with an accuracy of 76%. The results of the online survey in the normal hearing (NH) group showed that the intended emotions were selected significantly more often than the others. K-means clustering analysis revealed that melodies with arousal and valence ratings corresponded to representative quadrants of interest. Additionally, the applicability of the stimuli was tested in 4 individuals with high-frequency hearing loss. CONCLUSION: By applying the individuals with NH, the musical stimuli were shown to classify emotions with high accuracy, as expressed. These results confirm that the set of musical stimuli can be used to study the perceived emotion in music, demonstrating the validity of the musical stimuli, independent of innate musical bias such as due to episodic memory. Furthermore, musical stimuli could be helpful for further studying perceived musical emotion in people with hearing loss because of the controlled pitch for each emotion.

Peripheral CB1R as a modulator of metabolic inflammation.

Obesity is associated with chronic inflammation in insulin-sensitive tissues, including liver and adipose tissue, and causes hormonal/metabolic complications, such as insulin resistance. There is growing evidence that peripheral cannabinoid-type 1 receptor (CB1R) is a crucial participant in obesity-induced pro-inflammatory responses in insulin-target tissues, and its selective targeting could be a novel therapeutic strategy to break the link between insulin resistance and metabolic inflammation. In this review, we introduce the role of peripheral CB1R in metabolic inflammation and as a mediator of hormonal/metabolic complications that underlie metabolic syndrome, including fatty liver, insulin resistance, and dyslipidemia. We also discuss the therapeutic potential of second- and third-generation peripherally restricted CB1R antagonists for treating obesity-induced metabolic inflammation without eliciting central CB1R-mediated neurobehavioral effects, predictive of neuropsychiatric side effects, in humans.

Small heterodimer partner (SHP) aggravates ER stress in Parkinson's disease-linked LRRK2 mutant astrocyte by regulating XBP1 SUMOylation.

BACKGROUND: Endoplasmic reticulum (ER) stress is a common feature of Parkinson's disease (PD), and several PD-related genes are responsible for ER dysfunction. Recent studies suggested LRRK2-G2019S, a pathogenic mutation in the PD-associated gene LRRK2, cause ER dysfunction, and could thereby contribute to the development of PD. It remains unclear, however, how mutant LRRK2 influence ER stress to control cellular outcome. In this study, we identified the mechanism by which LRRK2-G2019S accelerates ER stress and cell death in astrocytes. METHODS: To investigate changes in ER stress response genes, we treated LRRK2-wild type and LRRK2-G2019S astrocytes with tunicamycin, an ER stress-inducing agent, and performed gene expression profiling with microarrays. The XBP1 SUMOylation and PIAS1 ubiquitination were performed using immunoprecipitation assay. The effect of astrocyte to neuronal survival were assessed by astrocytes-neuron coculture and slice culture systems. To provide in vivo proof-of-concept of our approach, we measured ER stress response in mouse brain. RESULTS: Microarray gene expression profiling revealed that LRRK2-G2019S decreased signaling through XBP1, a key transcription factor of the ER stress response, while increasing the apoptotic ER stress response typified by PERK signaling. In LRRK2-G2019S astrocytes, the transcriptional activity of XBP1 was decreased by PIAS1-mediated SUMOylation. Intriguingly, LRRK2-GS stabilized PIAS1 by increasing the level of small heterodimer partner (SHP), a negative regulator of PIAS1 degradation, thereby promoting XBP1 SUMOylation. When SHP was depleted, XBP1 SUMOylation and cell death were reduced. In addition, we identified agents that can disrupt SHP-mediated XBP1 SUMOylation and may therefore have therapeutic activity in PD caused by the LRRK2-G2019S mutation. CONCLUSION: Our findings reveal a novel regulatory mechanism involving XBP1 in LRRK2-G2019S mutant astrocytes, and highlight the importance of the SHP/PIAS1/XBP1 axis in PD models. These findings provide important insight into the basis of the correlation between mutant LRRK2 and pathophysiological ER stress in PD, and suggest a plausible model that explains this connection.

A novel peripheral cannabinoid 1 receptor antagonist, AJ5012, improves metabolic outcomes and suppresses adipose tissue inflammation in obese mice.

The overactivity of cannabinoid 1 receptor (CB1R) is associated with obesity and type 2 diabetes. First-generation CB1R antagonists, such as rimonabant, offered therapeutic advantages for the control of obesity and related metabolic abnormalities, but their therapeutic potential was limited by undesirable neuropsychiatric side effects. Here, we evaluated AJ5012 as a novel potent peripheral CB1R antagonist and, using this antagonist, investigated the role of peripheral CB1R on adipose tissue inflammation in obese mouse models. AJ5012 had a high degree of CB1R and cannabinoid 2 receptor selectivity but a low brain:plasma concentration ratio without eliciting centrally mediated neurobehavioral effects. In diet-induced obese (DIO) mice, AJ5012 did not reduce food intake but did induce a significant weight loss, likely owing to an increased energy expenditure. It was as effective as rimonabant for the improvement of hormonal or metabolic abnormalities, glycemic control, and insulin sensitivity. The treatment of DIO and leptin receptor-deficient mice with AJ5012 also exhibited effects comparable to rimonabant for the prevention of macrophage infiltration, activation of the nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome, and production of proinflammatory cytokines, which resulted in the suppression of adipose tissue inflammation. In addition to macrophage, activation of CB1R in 3T3-L1 adipocytes induced the expression of proinflammatory genes, which was fully inhibited by AJ5012. Our findings identified AJ5012 as a novel peripheral CB1R antagonist and suggest that peripheral CB1R blockade might break the links between insulin resistance and adipose tissue inflammation.-Han, J. H., Shin, H., Park, J.-Y., Rho, J. G., Son, D. H., Kim, K. W., Seong, J. K., Yoon, S.-H., Kim, W. A novel peripheral cannabinoid 1 receptor antagonist, AJ5012, improves metabolic outcomes and suppresses adipose tissue inflammation in obese mice.

Isothiocyanate groups of 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) inhibit cell penetration of octa-arginine (R8)-fused peptides.

Delivering biomolecules, such as antibodies, proteins, and peptides, to the cytosol is an important and challenging aspect of drug development and chemical biology. Polyarginine-a well-known cell-penetrating peptide (CPP)-is capable of exploiting its positive charge and guanidium groups to carry a fused cargo into the cytosol. However, the precise mechanism by which this occurs remains ambiguous. In the present study, we established a new method of quantitatively assessing cell penetration. The method involves inducing cell death by using a polyarginine (R8) to deliver a peptide-ie, mitochondrial targeting domain (MTD)-to the cytosol. We found that 4,4'-diisothiocyanatostilbene-2,2'-di-sulfonate (DIDS)-an anion channel blocker-inhibited the ability of octa-arginine (R8)-fused MTD to penetrate cells. Other anion channel blockers did not inhibit the penetration of peptides fused with R8. Comparison of DIDS with other structurally similar chemicals revealed that the isothiocyanate group of DIDS may be primarily responsible for the inhibitory effect than its stilbene di-sulfonate backbone. These results imply that the inhibitory effect of DIDS may not be derived from the interaction between stilbene di-sulfonate and the anion channels, but from the interaction between the isothiocyanate groups and the cell membrane. Our new MTD method enables the quantitative assessment of cell penetration. Moreover, further studies on the inhibition of CPPs by DIDS may help clarify the mechanism by which penetration occurs and facilitate the design of new penetrative biomolecules.

Development of a Smartphone-Based Digits-in-Noise Test in Korean: a Hearing Screening Tool for Speech Perception in Noise.

BACKGROUND: The digits-in-noise (DiN) test is a speech-in-noise test to measure speech recognition threshold in noise adaptively. Herein, we aimed to develop the Korean version of the DiN test to provide a useful hearing screening tool for clinical as well as research purposes. METHOD: Spoken monosyllabic digits from 0 to 9 were recorded by a female speaker. The test list was constructed such that each digit was placed in three different positions. An optimization procedure was conducted to equate the audibility of each digit. After the optimization, the smartphone application for the Korean DiN (K-DiN) test was developed. For the adaptive measurement procedure, 180 new DiN triplets separated into six lists of 30 were created. Mean speech recognition threshold values for each list and session were measured to examine the test-retest and training effects of the test materials. In addition, speech recognition threshold values measured by different devices were compared to determine whether the speech recognition threshold levels differed. RESULTS: Optimization results showed that the mean speech recognition threshold and slope were ?11.55 dB signal-to-noise ratio and 10.21%/dB, respectively, which are comparable to levels shown in different-language versions of the DiN test. The results of the test-retest and training effects revealed no significant differences among the test sessions and lists. Additionally, the mean speech recognition threshold values measured by four different devices were not different, indicating the reliability of the test materials. CONCLUSION: We believe this study is the first to attempt to develop a K-DiN test. Our results indicate that this test can be used as a potentially reliable hearing screening tool.

A peptide containing Noxa mitochondrial-targeting domain induces cell death via mitochondrial and endoplasmic reticulum disruption.

Noxa is a weak apoptosis activator consisting of a BH3 domain and a mitochondrial-targeting domain (MTD). BH3 binds Mcl-1 and Bcl2A1 and inactivates their anti-apoptotic activities, while MTD delivers BH3 to mitochondria. Previously we revealed that MTD may also function as an inducer of necrosis via conjugation with octa-arginine, which induces cytosolic Ca2+ influx from mitochondria. However, the mechanism(s) underlying this process has not been elucidated yet. Here, we show that calcium influx induced by an MTD peptide fused with octa-arginine residue (R8:MTD) originates not only from mitochondria but also from the extracellular space. However, calcium spikes were not sufficient for necrosis. R8:MTD induced mitochondrial permeability transition pore opening, fragmentation, and swelling. These mitochondrial events induced by MTD appeared to be necessary for necrosis induction, since DIDS, a VDAC inhibitor, inhibited the mitochondrial swelling and cell death induced by MTD. We show that R8:MTD disrupted endoplasmic reticulum (ER) structures but not peroxisomes or Golgi, indicating that R8:MTD causes necrosis by inducing ER events as well.

Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway.

Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer's disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced ß-secretase and Aß1⁻42 generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity, neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding.

Blockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells.

Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse ß-cell lines, human islets and CB1R-null (CB1R-/- ) mice, we have now investigated the role of CB1Rs in modulating ß-cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP-1-mediated cAMP accumulation and insulin secretion as well as glucose-stimulated insulin secretion in mouse ß-cell lines and human islets. In addition, silencing CB1R in mouse ß cells resulted in an increased expression of pro-insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in ß cells lacking insulin receptor. Furthermore, CB1R-/- mice had increased pro-insulin, GCK and GLUT2 expression in ß cells. Our results suggest that CB1R signalling in pancreatic islets may be harnessed to improve ß-cell glucose responsiveness and preserve their function. Thus, our findings further support that blocking peripheral CB1Rs would be beneficial to ß-cell function in type 2 diabetes.

MTD-like motif of a BH3-only protein, BNIP1, induces necrosis accompanied by an intracellular calcium spike.

The mitochondrial targeting domain (MTD) of Noxa has necrosis-inducing activity when conjugated with cell-penetrating peptide (CPP). In this study, we report another MTD-like motif, B1MLM, found in BNIP1, a pro-apoptotic BH3-only protein found in the endoplasmic reticulum membrane. The B1MLM peptide, conjugated with CPP, induced necrosis in a way similar to that of R8:MTD. R8:B1MLM caused an intracellular calcium spike, mitochondrial reactive oxygen species generation, and mitochondrial fragmentation. The cytosolic calcium spike was likely due to the opening of the mitochondrial permeability transition pore.

Anti-inflammatory effect of astaxanthin in phthalic anhydride-induced atopic dermatitis animal model.

In this study, we investigated anti-dermatitic effects of astaxanthin (AST) in phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. AD-like lesion was induced by the topical application of 5% PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 µL of 1 mg/mL and 2 mg/mL of AST (10 µg or 20 µg/cm2 ) was spread on the dorsum of ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) activity. We also measured tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and immunoglobulin E (IgE) concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). AST treatment attenuated the development of PA-induced AD. Histological analysis showed that AST inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. AST treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as release of TNF-α, IL-1ß, IL-6 and IgE. In addition, AST (5, 10 and 20 µM) potently inhibited lipopolysaccharide (LPS) (1 µg/mL)-induced nitric oxide (NO) production, expression of iNOS and COX-2 and NF-κB DNA binding activities in RAW 264.7 macrophage cells. Our data demonstrated that AST could be a promising agent for AD by inhibition of NF-κB signalling.

Mitochondrial targeting domain of NOXA causes necrosis in apoptosis-resistant tumor cells.

The resistance of tumor cells to apoptosis-inducing anticancer agents is regarded as a major impediment for the treatment of cancer patients. This study aimed to examine the possibility whether a necrosis-inducing peptide containing the mitochondria-targeting domain (MTD) of NOXA kills tumor cells that are resistant to apoptosis-inducing anticancer agents. To examine this possibility, we established doxorubicin-resistant (Dox-Res) cells by treating CT26 cells with increasing amounts of doxorubicin. The apoptosis resistance of the Dox-Res CT26 cells was confirmed by measuring the cell viability and activation of caspases. We showed that the MTD-containing peptide fused to eight arginine residues (R8:MTD), a necrosis-inducing peptide, induced necrosis in the Dox-Res CT26 cells, together with a cytosolic calcium spike, reactive oxygen species production, and the release of high mobility group box 1 into the media. Moreover, we demonstrated the killing effect of R8:MTD in tumor tissues generated using the Dox-Res CT26 cells in a mouse model. Therefore, our results suggest that MTD-containing peptides may provide an alternative tool for the elimination of relapsed tumor cells that are not responsive to apoptosis-inducing anticancer agents.

Pseudogracilibacillus endophyticus sp. nov., a moderately thermophilic and halophilic species isolated from plant root.

A Gram-stain-positive strain, designated DT7-02T, was isolated from the surface-sterilized root of Oenotherabiennis (evening primrose) and subjected to taxonomic characterization. Cells of DT7-02T were slender rod-shaped, motile by means of flagella, and oxidase- and catalase-positive. The colonies were circular, pinkish-yellow, opaque, glistering and 1-2 mm in diameter. The strain was moderately thermophilic and halophilic, as growth occurred at 20-44 °C (optimum 40 °C), pH 7-10 (optimum pH 8-9) and in the presence of 0-8 % of NaCl (optimum 4 %) in tryptic soy broth. The analysis of 16S rRNA gene sequences indicated that the strain represented a member of the genus Pseudogracilibacillus of the family Bacillaceae, and the sequence similarity was 96.5 % with Pseudogracilibacillus auburnensis P-207T and 95.9 % with Pseudogracilibacillus marinus NIOT-bflm-S4T. Other related taxa were Ornithinibacillus contaminans DSM 22953T and Sinibacillus soli KCTC 33117T, with 16S rRNA gene sequence similarities of 95.4 and 94.3 %, respectively. The major cellular fatty acids of DT7-02T were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The DNA G+C content was 35.1 mol%, and the respiratory quinone was MK-7. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The combination of chemotaxonomic properties enabled differentiation of DT7-02T from the other two species of the genus Pseudogracilibacillus. The results of phylogenetic, phenotypic and chemotaxonomic analyses demonstrate that strain DT7-02T (=KCTC 33854T=JCM 31192T) merits recognition as representing a novel species of the genus Pseudogracilibacillus, for which the name Pseudogracilibacillusendophyticus sp. nov. is proposed.

Uliginosibacterium sangjuense sp. nov., isolated from sediment of the Nakdong River.

A Gram-negative, aerobic, motile by flagella, and light yellow bacterium, designated SS1-76T, was isolated from sediment of the Nakdong River in Sangju-si, Republic of Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate SS1-76T belongs to the genus Uliginosibacterium of the family Rhodocyclaceae, exhibiting high sequence similarity with the type strains of Uliginosibacterium gangwonense 5YN10-9T (96.0%) and Uliginosibacterium paludis KBP-13T (94.9%). Strain SS1-76T contains ubiquinone-8 as a respiratory quinone and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0, and C14:0 as major fatty acids. The cellular polar lipids are composed of phosphatidylethanolamine, phosphatidylglycerol, and unidentified aminophospholipids. The DNA G+C content was 65.3 mol%. Phenotypic, chemotaxonomic, and phylogenetic evidence clearly indicated that strain SS1-76T represents a novel species of the genus Uliginosibacterium, for which the name Uliginosibacterium sangjuense sp. nov. is proposed. The type strain is SS1-76T (= KCTC 52159T = JCM 31375T).

Height Changes of Tutoplast-Processed Fascia Lata Over Time After Dorsal Augmentation During Rhinoplasty.

PURPOSE: Tutoplast (Tutogen Medical, Neunkirchen am Brand, Germany)-processed fascia lata (TPFL) has been used for dorsal augmentation in rhinoplasty in the Republic of Korea for approximately 10 years, but few studies have described changes in TPFL in terms of dorsal height over time. We investigated changes in dorsal height after TPFL use as a dorsal implant material during rhinoplasty. MATERIALS AND METHODS: The records of 18 rhinoplasty patients who had undergone dorsal augmentation with TPFL were examined retrospectively. The patients had undergone rhinoplasty from March 2008 to June 2012. Two different ear, nose, and throat doctors analyzed the first follow-up photographs (2 lateral views and 2 oblique views) taken at approximately 1 month postoperatively and the last follow-up photographs taken from 18 to 75 months after surgery. The last follow-up photographs were classified as showing no nasal dorsal height change, slight change, and marked change compared with the first follow-up photographs. RESULTS: Of the 18 patients enrolled, 50% (n = 9) showed no change in the nasal dorsum whereas 33% (n = 6) showed mild depression and 17% (n = 3) showed marked depression of the nasal dorsum at last follow-up. CONCLUSIONS: About half of the patients who had undergone dorsal augmentation using TPFL during rhinoplasty showed mild or marked dorsal depression over time. It is recommended that TPFL be used with another implant during augmentation rhinoplasty or TPFL be used only for a slightly depressed nose. In addition, patients should be informed that TPFL could be resorbed over time.

Frontal Sinus Osteoplastic Flap Surgery Using a Surgical Navigation System.

OBJECTIVE: To report the case of a 38-year-old woman who underwent osteoplastic flap surgery for recurrent frontal sinus mucocele. During surgery, the exact shape of the frontal sinus was duplicated using a surgical navigation system. METHODS: In this case report, the authors suggest intraoperative surgical navigation systems are useful for accurately determining the dimensions of the frontal sinus for osteoplastic flap surgery. RESULTS: The patient underwent successful and safe osteoplastic flap surgery using a surgical navigation system. CONCLUSION: Surgical navigation is useful and safe for frontal sinus osteoplastic flap surgery.

The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE -/- mice fed a western diet.

AIMS/HYPOTHESIS: A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action. METHODS: Forty-eight 5-week-old male ApoE -/- mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0.1 mg/kg, empagliflozin 1 mg/kg and empagliflozin 3 mg/kg (n = 12/group). Plaque size and composition in the aortic arch/valve areas and cardiovascular risk variables in the blood and tissues were evaluated. Insulin resistance was estimated by HOMA and adiponectin levels. Body composition was determined using dual-energy x-ray absorptiometry. RESULTS: After 8 weeks of treatment, the empagliflozin and glimepiride groups exhibited decreased blood glucose levels. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the empagliflozin groups than in the control or glimepiride groups. Insulin resistance and circulating concentrations of TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A and urinary microalbumin decreased after empagliflozin treatment, and this significantly correlated with plaque size. Empagliflozin treatment reduced weight and fat mass, lipid droplets in the liver, fat cell size, mRNA expression of Tnf, Il6 and Mcp-1 (also known as Ccl2) and the infiltration of inflammatory cells in plaque and adipose tissue compared with the control or glimepiride group. Empagliflozin treatment increased adiponectin levels. CONCLUSIONS/INTERPRETATION: Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by empagliflozin.