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Hiroki Ishikawa,1 Ryuichi Nagashima,1 Yoshihiro Kuno,1,2 Hiraku Sasaki,3 Chikara Kohda,1 Masayuki Iyoda1,2 1Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, 142-8555, Japan; 2Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, 142-8666, Japan; 3Department of Health Science, Faculty of Health and Sports Science, Juntendo University, Inzai, Chiba, 270-1695, JapanCorrespondence: Hiroki Ishikawa, Department of Microbiology and Immunology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan, Tel +81-3-3784-8131, Fax +81-3-3784-3069, Email h_ishikawa@med.showa-u.ac.jpPurpose: The purpose of this study was to investigate whether NKT cells play an important role in preventing or exacerbating diseases caused by high-fat diet (HFD) using CD1d-knockout (KO) mice which lack NKT cells.Methods: Five-week-old male Balb/c (wild-type; WT) or CD1dKO mice were fed with control-diet (CTD) or HFD for 16 weeks.Results: The present study revealed four main findings. First, CD1dKO mice were susceptible to obesity caused by HFD in comparison to WT mice. Second, clinical conditions of fatty liver caused by HFD were comparable between CD1dKO mice and WT mice. Third, HFD-fed WT mice showed high levels of serum biochemical markers, involved in lipid metabolisms, in comparison to WT mice fed a CTD. Notably, the serum concentrations of ALT, T-CHO, TG and HDL-C in CD1dKO mice fed a HFD were almost comparable to those of CD1dKO mice fed a CTD. Fourth, the expression of peroxisome proliferator-activated receptor (PPAR) γ, low-density lipoprotein receptor (LDLR), CD36 of epididymal adipose tissue enhanced and proprotein convertase subtilisin/kexin type (PCSK) 9 in serum decreased.Conclusion: NKT cells were responsible for protection against HFD-induced obesity. However, CD1dKO mice were resistant to serum biochemical marker abnormalities after HFD feeding. One possible explanation is that the epididymal adipose tissue of CD1dKO mice could take up greater amounts of excess lipids in serum in comparison to WT mice.Keywords: NKT cells, high-fat diet, obesity, serum biochemical markers, adipose tissue

Objective: Subchondral bone (SB) is one of the important tissues in development and progression of osteoarthritis (OA). To identify genes involved in the disease process, comprehensive gene expression analysis of SB was performed. Patients and Methods: Medial dominant knee OA patients were selected, and SB of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) was collected at the time of total knee arthroplasty. After RNA extraction, gene expression levels were compared between the MFC and LFC using microarrays. Genes that changed more than two-fold in the MFC were compared with the previously reported gene list from the same type of study that used the affected tibial plateau. Pathway analysis and immuno-histochemical analysis of selected molecules were performed. Results: Eighty genes were identified as commonly affected genes in both the present study and a previous study. Among them periostin was conspicuously up-regulated. Pathway analysis revealed up-regulated osteoclast activities. Periostin was detected in the cytoplasm of mononuclear cells in the SB, except for osteocytes. Conclusions: Among the 80 genes detected and thought to be important, periostin was the most highly up-regulated. Its importance in OA pathogenesis is indicated. [ABSTRACT FROM AUTHOR]

BACKGROUND: In Japan, urea breath-testing includes mouth rinsing with water immediately after the ingestion of (13)C-urea solution, to prevent false-positive results that are caused by oral bacteria with urease activity. Our objective was to evaluate the diagnostic performance of a urea breath test using a film-coated (13)C-urea tablet and omitting mouth rinsing. METHODS: The study was a multicenter trial comparing the solution- and tablet-based urea breath tests (UBTs). Helicobacter pylori status was determined by histology, culture, and rapid urease testing. RESULTS: Of the 255 subjects who completed the study, evaluation of the tablet-based UBT was possible in 254, and comparison of the tablet-based UBT and the solution-based UBT was possible in 250 patients. When the assessment achieved by a combination of biopsy-based methods was used as a reference standard, the sensitivity, specificity, and accuracy of the tablet-based method were determined to be 97.7%, 98.4%, and 98.0%, respectively. When the results of the solution-based UBT were used as a reference standard, the sensitivity, specificity, and accuracy of the tablet-based UBT were determined to be 96.9%, 97.6%, and 97.2%, respectively. CONCLUSIONS: The (13)C-urea tablet-based method proved to be a simple and accurate test for the diagnosis of H. Pylori infection. Mouth rinsing was not required. [ABSTRACT FROM AUTHOR]

Detecting plasma protein loss from the stomach is quite difficult by measuring fecal alpha1-AT clearance because alpha1-AT is rapidly destroyed in the gastric juice at values below pH 3. We examined protein loss from the stomach using fecal alpha1-AT clearance with lansoprazole, a proton pump inhibitor. A 38-year-old Japanese male presented with hypoproteinemia (total serum protein: 4.4 g/dl). Abdominal scintigraphy using technetium-99m-labeled albumin revealed distinct radioactivity accumulation in the small intestine. It strongly suggested excessive protein loss to the gastrointestinal tract. Although, regular fecal alpha1-AT clearance was within the normal range (<13 ml/day), the fecal alpha1-AT clearance with the administration of lansoprazole was 80.5 ml/day. The results indicated that this method using lansoprazole is simple and useful for detecting protein-losing gastropathy. [ABSTRACT FROM AUTHOR]

A patient with primary small cell carcinoma of the esophagus is reported, in whom we have studied the secretion of a variety of hormones and cytokines. The tumor was an intermediate cell type of small cell carcinoma and had either epithelial and neuroendocrinological characteristics. Furthermore, hypercalcemia and neutrophilia were present, and the tumor was shown to produce PTHrp, secretin, and G-CSF. The present case is the first report of primary small cell carcinoma of the esophagus with ectopic production of PTHrp, secretin, and G-CSF. [ABSTRACT FROM AUTHOR]

Objective: This study assessed whether patients with potentially preventable emergency admissions had limited access to outpatient care immediately before admission and whether they received appropriate outpatient care during their outpatient visits., Design: Retrospective observational study., Setting: Linked outpatient and inpatient care records obtained from a nationwide claims database in Japan., Participants: Patients who experienced emergency admissions for ambulatory care-sensitive conditions between April 2005 and March 2020. Patient and regional characteristics were examined to assess the types of patients who faced difficulties with outpatient visits and receiving outpatient care related to the disease that resulted in admissions (hereafter referred to as admission-related outpatient care)., Main Outcome Measures: (1) Whether patients had an outpatient visit during the 2 weeks preceding admission and (2) whether patients received admission-related outpatient care during the 2 weeks before admission., Results: This study included 18 449 emergency admissions for ambulatory care-sensitive conditions, representing 16.3% (18 449/113 669) of all emergency admissions in our data. Among patients with emergency admissions for ambulatory care-sensitive conditions, 37.4% did not have an outpatient visit within the 2 weeks preceding admission and 29.9% did not receive admission-related outpatient care despite having an outpatient visit. In total, 67.4% did not receive admission-related outpatient care during the 2 weeks preceding admission. Patients in their 40s and 50s were less likely to have outpatient visits and receive admission-related outpatient care before admission. No evidence associates regional characteristics with outpatient visits and receiving admission-related outpatient care before admission., Conclusion: Most patients who underwent emergency admissions for ambulatory care-sensitive conditions did not have an outpatient visit or receive admission-related outpatient care, despite having an outpatient visit immediately before admission. Our findings suggest that emergency admissions may be prevented by improving access to timely and effective outpatient care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Chemotherapy-induced peripheral neuropathy (CIPN) is a type of peripheral neuropathy that develops in patients treated with certain anticancer drugs. Oxaliplatin (OXA) causes CIPN in approximately 80-90 % of patients; thus, it is necessary to elucidate its underlying mechanism and develop effective treatments and prevention methods. The purpose of this study was to determine whether the pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1 receptor system in the spinal dorsal horn is involved in OXA-induced acute cold allodynia and examine the effect of a PAC1 receptor antagonist. Administration of OXA induced acute cold allodynia in wild-type mice, but not in PACAP-/- mice. In the dorsal root ganglia, OXA upregulated PACAP expression, particularly in small-sized neurons. OXA-induced cold allodynia was ameliorated by intrathecal (i.t.) injection of PACAP6-38 (peptide antagonist for PACAP receptor) and PA-8 (small-molecule antagonist specific for PAC1 receptor). I.t. PACAP, but not vasoactive intestinal polypeptide, resulted in cold allodynia, which was blocked by PA-8. OXA induced the activation of spinal astrocytes in a PAC1 receptor-dependent manner. The results suggest that spinal PACAP/PAC1 receptor systems are involved in OXA-induced acute cold allodynia through astrocyte activation. Furthermore, we demonstrated that the systemic administration of PA-8 resulted in therapeutic and preventative effects on OXA-induced acute cold allodynia. Because PA-8 did not affect the anticancer effects of OXA, we propose PAC1 receptor inhibition as a new strategy for the treatment and prevention of CIPN. PERSPECTIVE: Cold allodynia is a hallmark of OXA-induced peripheral neuropathy. This study demonstrated the involvement of spinal PACAP/PAC1 receptors in OXA-induced acute cold allodynia. We propose PAC1 receptor inhibition as a new strategy for the treatment and prevention of OXA-induced acute cold allodynia., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to report., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

To determine the characteristics of the changes in the amplitude of the flicker electroretinograms (ERGs) after combined cataract surgery and vitrectomy for an idiopathic epiretinal membrane (ERM). To accomplish this, we conducted a prospective study on 20 patients. Flicker ERGs and central macular thickness (CMT) were measured before the surgery (baseline), and at 1 week, 1 month, 3 months, and 6 months postoperatively. The mean amplitude of the flicker ERGs increased significantly by 63.5% at 1 week after surgery (P < 0.001) and then gradually decreased. The amplitude at 6 months was not significantly different from the baseline amplitude. This transient increase in the flicker ERG amplitudes after ERM surgery suggests that electrophysiologic evaluations of the therapeutic effects of vitrectomy should be performed 6 months postoperatively. The mean CMT decreased significantly at 1 week postoperatively (P < 0.001) and continued to decrease progressively over six months. The relative increase of amplitude at 1 week was significantly associated with the relative decrease of CMT at 6 months, and evaluation of retinal functional changes at 1 week may be able to predict the postoperative course of the ERM., (© 2024. The Author(s).)

Renal fibrosis is a common pathway of chronic kidney disease (CKD) progression involving primary kidney injury and kidney diseases. Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses irrespective of antigen presentation and play a reno-protective role in kidney injury and disease. In the present study, we observed a decrease in kidney-resident ILC2s in CKD and found that enrichment of ILC2s in the kidney ameliorates renal fibrosis. In CKD kidney, ILC2s preferentially produced IL-13 over IL-5 in response to IL-33 stimulation, regardless of ST2L expression. Moreover, GATA3 expression was decreased in ILC2s, and T-bet+ ILC1s and RORγt+ ILC3s were increased in CKD kidney. Adoptive transfer of kidney ILC2s into adenine-induced CKD model mouse improved renal function and fibrosis. Renal fibroblasts cultured with IL33-activated kidney ILC2s suppressed myofibroblast trans-differentiation through Acta2 and Fn-1 regulation. These results suggest that kidney ILC2s prevent CKD progression via improvement of renal fibrosis. Our findings also suggest that ILC2s may contribute to the development of new therapeutic agents and strategies for tissue fibroses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Intrinsic foot muscles (IFMs) play an important role in lower-limb motor control, including biomechanics and neuromuscular control function. Short foot exercise (SFE) and toe curl exercise (TC) are methods used to train the IFMs, but their effect on lower-limb motor control has not been reported in previous studies. This study evaluated the effects of SFE and TC on lower-limb motor control function during single-leg standing (SLS)., Trial Design: Randomized control trial., Method: Thirty-six participants with flatfoot were randomly assigned to the SFE or TC group and performed exercise for 8 weeks. The assessment items were navicular drop test, toe grip strength (TGS), plantar sensation, and SLS. In the SLS assessment, we measured the mean center of pressure (COP) amplitude in the anteroposterior (AP) and mediolateral (ML) directions, onset time of gluteus maximus (G. max) and gluteus medius (G. med), angle of forefoot/hindfoot protonation and hip adduction, and lateral pelvic shift. Mixed-model repeated-measures analysis of variance and Bonferroni corrections were performed in statistical analysis., Results: The SFE group showed significant differences between pre- and post-intervention for TGS (p < 0.001), COP ML (p = 0.039), and onset times of G. max (p = 0.015), and G. med (p < 0.001). The TC group showed no significant differences in all assessment items., Conclusion: Our finding suggests that SFE contributes to lower neuromuscular control function in people with flatfoot., Trial Registration: UMIN000049963., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

It is a problem that influenza virus infection increases susceptibility to secondary bacterial infection in lungs leading to lethal pneumonia. We previously reported that exopolysaccharides (EPS) derived from Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1) could prevent against influenza virus infection followed by secondary bacterial infection in vitro. Therefore, the present study assessed whether EPS derived OLL1073R-1 protects the alveolar epithelial barrier disfunction caused by influenza virus infection. After A549 cells treated with EPS or without EPS were infected influenza virus A/Puerto Rico/8/34 (IFV) for 12 h, the levels of tight junction genes expression and inflammatory genes expression were measured by reverse transcription polymerase chain reaction. As results, EPS treatment could protect against low-titer IFV infection, but not high-titer IFV infection, followed by suppression of the increased expression of inflammatory cytokine gene levels and recovery of the decrease in the expression level of ZO-1 gene that was caused by low-titer IFV infection, leading to an improvement trend in the barrier function. Our findings showed that EPS derived from OLL1073R-1 could inhibit low-titer IFV infection leading to maintenance of the epithelial barrier function through the suppression of inflammatory cytokine genes expression., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Purpose: To report our findings of reduced full-field electroretinograms (ff-ERGs) and abnormal optical coherence tomographic (OCT) images in a patient with poor visual acuity after cataract surgery who was eventually diagnosed with vitamin A deficiency (VAD)., Methods: This was a clinical study of a patient who complained of blurred vision after cataract surgery. To determine the cause of the reduced vision, we recorded full-field electroretinograms (ff-ERGs) to determine the scotopic and photopic status of the retina. We also performed optical coherence tomography to assess the changes in the retinal structure. Serological tests were performed., Results: A 74-year-old man presented with persistent corneal epithelial damages and reduced vision that developed after conventional cataract surgery. OCT showed an interrupted ellipsoid zone, and fundus autofluorescence (FAF) showed a severe hypofluorescence in the retina of the left eye. The scotopic ff-ERGs were severely reduced, and the photopic ff-ERGs were mildly reduced. Serological examinations revealed a vitamin A concentration < 7 IU/dL (normal, 97-316 IU/dL). Based on these findings, we diagnosed the patient with VAD and started treatment with oral vitamin A supplements. After three months, his visual acuity, ff-ERGs, and OCT findings recovered to normal levels. The amplitudes and implicit times of the RETeval flicker ERGs increased to be within the normal range, and the hypofluorescence of the left eye disappeared. The length of the photoreceptor outer segments increased after the vitamin A supplementation., Conclusion: Our findings indicate that the ERGs are helpful for diagnosing patients with VAD associated with persistent corneal epithelial damages., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A 68-year-old man with a history of valve-sparing aortic root replacement and endoscopic aortic valve replacement was admitted to our hospital with dyspnea. Transthoracic echocardiography revealed severe pulmonary valve regurgitation. The patient had undergone cardiac surgery twice, through median sternotomy and right thoracotomy; therefore, we planned endoscopic pulmonary valve replacement via the left thoracic approach. The patient was placed in a modified right lateral decubitus position and underwent mild hypothermic cardiopulmonary bypass. An on-pump beating-heart technique was used during surgery. The 3D endoscopic system and trocars for surgical instruments were inserted through the left 3rd and 4th intercostal spaces. After incision of the pulmonary artery, the pulmonary cusps were resected. A 27-mm St Jude Medical Epic heart valve was implanted in the intra-annular position. Subsequently, the left atrial appendage was resected. The patient was discharged without complications. To our knowledge, this is the first case of totally endoscopic pulmonary valve replacement.

Intraocular inflammations (IOIs) have been reported to occur after intravitreal injections of brolucizumab, and one of their causes has been suggested to be drug-specific features. We evaluated the anterior chamber by the aqueous flare value (AFV) and the retina by flicker electroretinography (ERG) after the initial intravitreal injection of aflibercept (IVA), brolucizumab (IVBr), or faricimab (IVF) for neovascular age-related macular degeneration (nAMD). The AFV and flicker ERGs were determined before, 2 weeks after, and 4 weeks after the injections in 14 eyes of 14 patients for each drug. After the injections, none of the patients had an IOI, but the AFV increased significantly in the IVA and IVF groups. The increase in the IVF group was +4.6 photon count/ms, which was significantly greater than in the other groups, but was not clinically significant. The implicit time was significantly prolonged in the IVBr group but unchanged in the IVA and IVF groups. These results suggest that brolucizumab, administered at high molar doses, may cause transient retinal disturbances that are not detectable by general ophthalmologic examinations but affect the implicit ERG times.