Large N Analysis of TTˉT\bar{T}-deformation and Unavoidable Negative-norm States

We study non-perturbative quantum aspects of $T\bar{T}$-deformation of a free $O(N)$ vector model by employing the large $N$ limit. It is shown that bound states of the original field appear and inevitably become negative-norm states. In particular, the bound states can be regarded as the states of the conformal mode in a gravitational theory, where the Liouville action is induced with the coefficient proportional to the minus of central charge. To make the theory positive-definite, some modification is required so as to preserve diffeomorphism invariance due to the Faddeev-Popov ghosts with a negative central charge.Comment: 1+20 pages, 1 figur

Porphyromonas gingivalis attenuates the insulin-induced phosphorylation and translocation of forkhead box protein O1 in human hepatocytes

Objective: Porphyromonas gingivalis (P. gingivalis) is a pathogen involved in periodontal disease. Recently, periodontal disease has been demonstrated to increase the risk of developing diabetes mellitus, although the molecular mechanism is not fully understood. Forkhead box protein O1 (FoxO1) is a transcriptional factor that regulates gluconeogenesis in the liver. Gluconeogenesis is a key process in the induction of diabetes mellitus; however, little is known regarding the relationship between periodontal disease and gluconeogenesis. In this study, to investigate whether periodontal disease influences hepatic gluconeogenesis, we examined the effects of P. gingivalis on the phosphorylation and translocation of FoxO1 in insulin-induced human hepatocytes. Design: The human hepatocyte HepG2 was treated with insulin and Akt and FoxO1 phosphorylation was detected by western blot analysis. The localization of phosphorylated FoxO1 was detected by immunocytochemistry and western blot analysis. HepG2 cells were treated with SNAP26b-tagged P. gingivalis (SNAP-P. g.) before insulin stimulation, and then the changes in Akt and FoxO1 were determined by western blot analysis and immunocytochemistry. Results: Insulin (100 nM) induced FoxO1 phosphorylation 60 min after treatment in HepG2 cells. Phosphorylated FoxO1 translocated to the cytoplasm. SNAP-P.g. internalized into HepG2 cells and decreased Akt and FoxO1 phosphorylation induced by insulin. The effect of insulin on FoxO1 translocation was also attenuated by SNAP-P.g. Conclusions: Our study shows that P. gingivalis decreases the phosphorylation and translocation of FoxO induced by insulin in HepG2 cells. Our results suggest that periodontal disease may increase hepatic gluconeogenesis by reducing the effects of insulin on FoxO1

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence

ヒト社会に貢献する動物に対するGABAのストレス軽減効果の検証

γ-アミノ酪酸 (GABA) の経口投与が肉用牛の長距離輸送および出荷・屠畜時のストレスを低減するかどうかを調べた。試験1では，対照区の去勢牛4頭に20mLの蒸留水を，処理区の去勢牛4頭に体重当たり10mgのGABA粉末を20mLの蒸留水に溶解した水溶液を，それぞれ130.1kmの陸路輸送直前に経口投与した。分散分析の結果，供試牛の唾液中コルチゾール濃度に対する処理と輸送経過時間との交互作用は，経過時間が60分までは有意 (P<0.05) であったが，120分以降については有意ではなくなった。試験2では，肥育牛20頭を5頭ずつ4処理区に分け，屠畜場への輸送前と翌朝の屠畜直前に，G区には13gのGABA粉末を100mLの蒸留水に溶解した水溶液を，S区には100mLの生理食塩水を，SG区には輸送前に生理食塩水と屠畜直前にGABA溶液を，それぞれ経口投与した。C区には輸送前も屠畜直前にも何も投与しなかった。多重比較検定の結果，いずれの処理区のウシの血漿コルチゾール濃度も，C区のウシよりも有意に低かった (全てP<0.01)。血漿アドレナリン濃度も，C区に比べ，S区のウシで有意に低く (P<0.05)，G区のウシで低い傾向 (P<0.10) がみられた。これらの結果から，GABAの経口投与は，肉用牛の輸送および屠畜時のストレスを投与後数十分間は低減させることが確認された。We examined whether orally administered γ-aminobutyric acid (GABA) would reduce stress of applied animals such as cattle, sheep, pigs and dogs. We report here only about the results of tests of transport and handling stress in cattle. In test 1, 20 mL of GABA solution containing 10 mg of GABA powder per kg body weight was administered to a group of 4 steers. Twenty mL of deionized water was administered to another group of 4 steers. Both groups of steers were then transported together 130.1 km by road. A significant interaction between group and salivary cortisol level for transport times up to 60 min was shown in two-way repeated-measure ANOVA (P<0.05). In test 2, 100 mL of GABA solution containing 13 g of GABA powder was administered to 5 steers twice, just before transport and before slaughter (group G). One hundred mL of normal saline solution (NSS) was administered to 5 steers (group S); 100 mL of NSS and 100 mL of the GABA solution were administered to 5 steers just before transport and before slaughter, respectively (group SG). The remaining 5 steers did not receive any solutions (group C). Significantly lowered concentration of plasma cortisol in groups G, S and SG compared to group C was shown in multiple comparisons (all P<0.01). The concentration of plasma adrenaline was significantly lowered in group S (P<0.05) and tended to be lower in group G (P<0.10) compared to group C. These results indicate that orally administered GABA can be a kind of stress reliever for cattle transported and handled by human

Detection of Transgenes in Gene Delivery Model Mice by Adenoviral Vector Using ddPCR

With the rapid progress of genetic engineering and gene therapy, the World Anti-Doping Agency has been alerted to gene doping and prohibited its use in sports. However, there is no standard method available yet for the detection of transgenes delivered by recombinant adenoviral (rAdV) vectors. Here, we aim to develop a detection method for transgenes delivered by rAdV vectors in a mouse model that mimics gene doping. These rAdV vectors containing the mCherry gene was delivered in mice through intravenous injection or local muscular injection. After five days, stool and whole blood samples were collected, and total DNA was extracted. As additional experiments, whole blood was also collected from the mouse tail tip until 15 days from injection of the rAdv vector. Transgene fragments from different DNA samples were analyzed using semi-quantitative PCR (sqPCR), quantitative PCR (qPCR), and droplet digital PCR (ddPCR). In the results, transgene fragments could be directly detected from blood cell fraction DNA, plasma cell-free DNA, and stool DNA by qPCR and ddPCR, depending on specimen type and injection methods. We observed that a combination of blood cell fraction DNA and ddPCR was more sensitive than other combinations used in this model. These results could accelerate the development of detection methods for gene doping

児童青年期を対象とした認知行動療法における個別化に必要なアセスメントの観点の検討 -ストレスマネジメント教育とソーシャルスキルトレーニングにおける個別化の試み-

departmental bulletin pape

Decreases in the Serum VLDL-TG/Non-VLDL-TG Ratio from Early Stages of Chronic Hepatitis C: Alterations in TG-Rich Lipoprotein Levels

BACKGROUND: The liver secretes very-low-density lipoproteins (VLDLs) and plays a key role in lipid metabolism. Plasma total triglyceride (TG) level variations have been studied in patients with hepatitis C virus (HCV)-related chronic hepatitis (CH-C). However, the results of these studies are variable. A homogenous assay protocol was recently proposed to directly measure the TG content in VLDL (VLDL-TG) and VLDL remnants. METHODOLOGY/PRINCIPAL FINDINGS: Using the assay protocol, we determined serum VLDL-TG levels in 69 fasting patients with biopsy-proven HCV-related chronic liver disease and 50 healthy subjects. Patients were classified into stages F0-F4 using the 5-point Desmet scale. Serum total TG levels in patients with non-cirrhotic (F1-F3) CH-C did not demonstrate significant differences compared with healthy subjects, but serum VLDL-TG levels did demonstrate significant differences. Mean serum VLDL-TG levels tended to decrease with disease progression from F1 to F4 (cirrhosis). Compared with healthy subjects, serum non-VLDL-TG levels significantly increased in patients with stages F2 and F3 CH-C; however, we observed no significant difference in patients with liver cirrhosis. Furthermore, the serum VLDL-TG/non-VLDL-TG ratio, when taken, demonstrated a significant decrease in patients with CH-C from the mildest stage F1 onward. CONCLUSIONS/SIGNIFICANCE: The decrease in serum VLDL-TG levels was attenuated by increase in non-VLDL-TG levels in patients with non-cirrhotic CH-C, resulting in comparable total TG levels. Results of previous studies though variable, were confirmed to have a logical basis. The decrease in the serum VLDL-TG/non-VLDL-TG ratio as early as stage F1 demonstrated TG metabolic alterations in early stages of CH-C for the first time. The involvement of TG metabolism in CH-C pathogenesis has been established in experimental animals, while conventional TG measurements are generally considered as poor indicators of CH-C progression in clinical practice. The serum VLDL-TG/non-VLDL-TG ratio, which focuses on TG metabolic alterations, may be an early indicator of CH-C

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS