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This algorithm was issued for the appropriate use of drugs for the treatment of type 2 diabetes mellitus in Japan. The revisions include safety considerations, fatty liver disease as a comorbidity to be taken into account and the position of tirzepatide., (© 2024 The Japan Diabetes Society. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

A 64-year-old woman presented with agranulocytosis, anemia, and bacteremia, leading to a diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL). A molecular analysis identified a signal transducer and activator of transcription 3 (STAT3) Y640F variant. Initial treatment with cyclophosphamide and prednisolone did not improve her condition, but serious infections were observed. The patient underwent cord blood transplantation (CBT) after preconditioning with fludarabine, busulfan, and total body irradiation, yielding a STAT3 Y640F variant disappearance, based on allele-specific quantitative polymerase chain reaction (AS-qPCR). In this case, CBT is a promising refractory T-LGLL treatment option, and the STAT3 Y640F variant AS-qPCR is a T-LGLL activity marker.

A 64-year-old woman presented with agranulocytosis, anemia, and bacteremia, leading to a diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL). A molecular analysis identified a signal transducer and activator of transcription 3 (STAT3) Y640F variant. Initial treatment with cyclophosphamide and prednisolone did not improve her condition, but serious infections were observed. The patient underwent cord blood transplantation (CBT) after preconditioning with fludarabine, busulfan, and total body irradiation, yielding a STAT3 Y640F variant disappearance, based on allele-specific quantitative polymerase chain reaction (AS-qPCR). In this case, CBT is a promising refractory T-LGLL treatment option, and the STAT3 Y640F variant AS-qPCR is a T-LGLL activity marker.

The Golgi apparatus, a crucial organelle involved in protein processing, including glycosylation, exhibits complex sub-structures, i.e., cis-, medial, and trans-cisternae. This study investigated the distribution of glycosyltransferases within the Golgi apparatus of mammalian cells via 3D super-resolution imaging. Focusing on human glycosyltransferases involved in N-glycan modification, we found that even enzymes presumed to coexist in the same Golgi compartment exhibit nuanced variations in localization. By artificially making their N-terminal regions [composed of a cytoplasmic, transmembrane, and stem segment (CTS)] identical, it was possible to enhance the degree of their colocalization, suggesting the decisive role of this region in determining the sub-Golgi localization of enzymes. Ultimately, this study reveals the molecular codes within CTS regions as key determinants of glycosyltransferase localization, providing insights into precise control over the positioning of glycosyltransferases, and consequently, the interactions between glycosyltransferases and substrate glycoproteins as cargoes in the secretory pathway. This study advances our understanding of Golgi organization and opens avenues for programming the glycosylation of proteins for clinical applications.Key words: Golgi apparatus, glycosyltransferase, 3D super-resolution imaging, N-glycosylation.

Neurite outgrowth is a crucial process for organizing neuronal circuits in neuronal development and regeneration after injury. Regenerative failure in the adult mammalian central nervous system (CNS) is attributed to axonal growth inhibitors such as the Nogo protein that commonly binds to Nogo receptor-1 (NgR1). We previously reported that lateral olfactory tract usher substance (LOTUS) functions as an endogenous antagonist for NgR1 in forming neuronal circuits in the developing brain and improving axonal regeneration in the adult injured CNS. However, another molecular and cellular function of LOTUS remains unknown. In this study, we found that cultured retinal explant neurons extend their neurites on the LOTUS-coating substrate. This action was also observed in cultured retinal explant neurons derived from Ngr1 -deficient mouse embryos, indicating that the promoting action of LOTUS on neurite outgrowth may be mediated by unidentified LOTUS-binding protein(s). We therefore screened the binding partner(s) of LOTUS by using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). LC-MS/MS analysis and pull-down assay showed that LOTUS interacts with Teneurin-4 (Ten-4), a cell adhesion molecule. RNAi knockdown of Ten-4 inhibited neurite outgrowth on the LOTUS substrate in retinoic acid (RA)-treated Neuro2A cells. Furthermore, a soluble form of Ten-4 attenuates the promoting action on neurite outgrowth in cultured retinal explant neurons on the LOTUS substrate. These results suggest that LOTUS promotes neurite outgrowth by interacting with Ten-4. Our findings may provide a new molecular mechanism of LOTUS to contribute to neuronal circuit formation in development and to enhance axonal regeneration after CNS injury.

Background: Suprapancreatic lymph node metastasis is one of the usual routes for gastric cancer. However, it is rare for the primary lesion to be found several years after resection of the suprapancreatic metastatic lymph node. This is a report of occult gastric carcinoma with microsatellite instability diagnosed 10 years after excision of a metastatic lymph node., Case Presentation: A 55-year-old female presented with suprapancreatic lymph node swelling during a medical examination. Gastroscopy revealed no malignancy. We performed an excisional biopsy via laparotomy and histologically suspected metastatic cancer of unknown origin. After nine and a half years, we detected early gastric cancer by gastroscopy and performed a distal gastrectomy. The gastric tumor was pathologically similar to the previous suprapancreatic tumor. Immunohistochemical examination revealed that both the stomach and suprapancreatic lymph node exhibited microsatellite instability, suggesting that the two lesions were of the same origin., Conclusions: This case is considered valuable because there have been no previous reports of gastric cancer with characteristics of high microsatellite instability in which the primary tumor was identified a long time after resection of metastatic lesions., (© 2024. The Author(s).)

Sudachitin, a member of the flavonoid family, reportedly improves glucose metabolism after long-term administration, but details of the underlying mechanisms are unknown. We found that Sudachitin approximately doubles insulin secretion under high glucose concentrations in mouse pancreatic islets and MIN6 cells. When Sudachitin was orally administered to mice, early-phase insulin secretion was increased and a 30 % reduction in blood glucose levels was demonstrated 30 min after glucose loading. Insulin tolerance tests also showed Sudachitin to increase systemic insulin sensitivity. Additionally, we observed that Sudachitin raised intracellular cAMP levels in pancreatic islets. Phosphodiesterase (PDE) activity assays revealed Sudachitin to inhibit PDE activity and computer simulations predicted a high binding affinity between PDEs and Sudachitin. These findings suggest that Sudachitin enhances both insulin secretion and insulin sensitivity via an increase in intracellular cAMP resulting from PDE inhibition. These insights may facilitate understanding the mechanisms underlying the regulation of glucose metabolism by Sudachitin and other isoflavones., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akihiko Taguchi reports financial support was provided by Taisho Pharmaceutical Co., Ltd. Akihiko Taguchi reports financial support was provided by the 10.13039/501100001691Japan Society for the Promotion of Science. Akihiko Taguchi reports financial support was provided by 10.13039/501100011907Mishima Kaiun Memorial Foundation. Yasuharu Ohta reports financial support was provided by the 10.13039/501100001691Japan Society for the Promotion of Science. Yukio Tanizawa reports financial support was provided by the 10.13039/501100001691Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Perioperative bleeding in total hip arthroplasty (THA) can lead to various problems, so effective management of blood loss is needed. This prospective, single-blind, randomized controlled trial aimed to compare the efficacy of topical administration of SURGICEL ® (a hemostatic agent of oxidized regenerated cellulose) powder (SP) and tranexamic acid (TXA) in controlling perioperative bleeding during THA., Materials and Methods: In total, 114 patients undergoing THA for osteoarthritis were randomized to either group S (THA with SP) or group T (THA with TXA). Data including patient demographics, laboratory data (C-reactive protein [CRP], hemoglobin, and hematocrit), operative time, and intraoperative blood loss were analyzed. Clinical outcomes were assessed using WOMAC, JOA, FJS scores, and visual analog scale (VAS) scores. Primary outcomes were estimated total and postoperative blood loss, while secondary outcomes included hematological test results and various clinical scores., Results: 57 patients were allocated to each group, with 55 in group S and 56 in group T were finally included in the analysis. There was no significant difference (p = 0.141) in estimated total blood loss between group S (788.2 ± 350.1 ml) and group T (714.1 ± 318.4 ml). Hemoglobin and hematocrit levels and WOMAC, and FJS scores were not significantly different between the two groups at any time point. CRP levels were significantly different on postoperative days 4 and 7, and JOA score was significantly different on preoperative and postoperative period. However, the differences in CRP and JOA score values themselves were relatively small and not clinically different., Conclusions: Topical administration of SP is as effective as TXA in reducing perioperative bleeding in patients undergoing THA. Additionally, no significant difference was observed in early postoperative clinical outcomes between SP and TXA., Level of Evidence: Therapeutic Level I., Trial Registration: The University Hospital Medical Information Network (UMIN) registration number UMIN000047607., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dysregulation of the mineralocorticoid hormone aldosterone is an increasingly prevalent cause of hypertension. Aldosterone synthase (CYP11B2) shares 93% homology to 11β-hydroxylase (CYP11B1), which produces cortisol. Lorundrostat, a highly selective inhibitor of CYP11B2, is a potential safe and effective treatment for aldosterone-dependent, uncontrolled hypertension, including treatment-resistant hypertension. Lorundrostat showed highly selective inhibition of CYP11B2 in vitro, with 374-fold selectivity for CYP11B2 vs. CYP11B1. A first-in-human study of single ascending doses ranging from 5 to 800 mg and multiple ascending doses ranging from 40 to 360 mg once daily was conducted in healthy participants. After single- and multiple-dose administration, lorundrostat plasma levels peaked 1-3 h after administration with a t 1/2 of 10-12 h. Plasma aldosterone decreased up to 40% with single 100-mg to 200-mg doses and up to 70% with single 400 to 800-mg doses. Plasma aldosterone returned to baseline within 16 h after single 100-mg doses and multiple once-daily 120-mg doses. Lorundrostat demonstrated a favorable safety profile in healthy participants. Dose- and exposure-dependent inhibition of renal tubular sodium reabsorption was observed across a clinically relevant dose range with no suppression of basal or cosyntropin-stimulated cortisol production and only a modest increase in mean serum potassium., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aim: Malnutrition is a prevalent health issue among hemodialysis patients. Oral frailty, a condition characterized by impairments in multiple oral health aspects and functions, has been associated with nutritional status in the general population. We aimed to determine whether oral frailty was associated with nutritional status in hemodialysis patients aged ≥50 years. Our secondary aim was to determine the prevalence of oral frailty in this population., Methods: This cross-sectional study included hemodialysis patients who were admitted to a single medical center. According to the Oral Frailty 5-item Checklist, oral frailty is characterized by the presence of two or more of the following criteria: (i) fewer teeth, (ii) difficulty in chewing, (iii) difficulty in swallowing, (iv) dry mouth, and (v) low articulatory oral motor skills. Patients' nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI). Multivariable ordinal logistic regression analysis was performed to assess the association between oral frailty and nutritional status (classified into three categories according to the GNRI: >98, 92-98, and <92)., Results: In total, 152 hemodialysis patients (55 women and 97 men) with a mean age of 70.4 years were included. The prevalence of oral frailty was 61.2%. After adjusting for health characteristics and sociodemographic background, oral frailty was associated with poor nutritional status according to the GNRI (odds ratio = 2.04, 95% confidence interval = 1.02-4.09)., Conclusions: In this study, approximately 60% of hemodialysis patients aged ≥50 years exhibited oral frailty, and hemodialysis patients with oral frailty had poor nutritional status according to the GNRI. Geriatr Gerontol Int 2024; ••: ••-••., (© 2024 Japan Geriatrics Society.)

Anti-IgLON5 disease shows various neurological manifestations, of which dysautonomia is one of the major symptoms and is rarely improved by immunotherapy. We herein report a patient with anti-IgLON5 disease who showed several autonomic failures, including vocal cord palsy for four months. The patient presented with cognitive impairments, bulbar symptoms accompanied by myorhythmia in the pharynx and tongue, cerebellar ataxia with tremor, motor neuron symptoms in the limbs, gastrointestinal dysfunction, orthostatic hypotension, non-rapid eye movement sleep disorder on polysomnography, and severe vocal cord palsy. Combined immunotherapy improved his symptoms, including vocal cord palsy, suggesting that combined immunotherapy might improve dysautonomia in anti-IgLON5 disease.

Background: This study aimed to investigate the utility of intensive triamcinolone acetonide (TA) injections after extensive esophageal endoscopic submucosal dissection (ESD)., Methods: This retrospective study included 27 lesions in 27 consecutive patients who underwent ESD (ulcers encompassing ≥3/4 of the esophageal circumference) and received TA injections without oral steroid administration. Groups A and B included patients undergoing ESD with and without complete circumferential resection, respectively. All patients received TA injections (100 mg/session) immediately after ESD. In Group A, weekly based TA injections were performed until near-complete ulcer epithelialization. In Group B, patients did not receive additional injections or received weekly or biweekly TA injections. The primary outcome was stricture rate, and the secondary outcomes were the proportion of patients requiring endoscopic balloon dilation (EBD) and the number of TA injections., Results: Group A included 7 lesions, and Group B included 20 lesions. The median (range) tumor lengths were 40 (30-90) and 45 (30-110) mm in Groups A and B, respectively. In Group A, the median circumferential resection diameter was 40 (20-80) mm. The stricture rate and the proportion of patients requiring EBD were 0 (0%) in Group A and 1 (5.0%) in Group B. The number of TA injection sessions was significantly higher in Group A than in Group B (8 [5-25] vs 1.5 [1-3]; p  < 0.001)., Conclusions: Intensive weekly or biweekly based TA injections might aid in preventing post-ESD stricture and the need for EBD in patients undergoing extensive resection involving the entire esophageal circumference.

Background and Study Aims: The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn's disease., Patients and Methods: This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn's disease who were treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration., Results: The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5 % and 100 %, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53 % and 64 %, respectively. Laboratory data including C-reactive protein, serum albumin, and hemoglobin significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group (25 % vs. 4.5 %, p = 0.0015), but severe adverse events were rare in both groups., Conclusion: The efficacy and safety of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn's disease evaluated by clinical, endoscopic, and laboratory findings. This study establishes the needed groundwork for the development of a strategy for treatment with biologics in patients with Crohn's disease., Competing Interests: Declaration of competing interests 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 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Background: Hydroxyapatite-coated, triple-tapered, shorter-length stems with a medial collar have been reported with good results for a few years. We investigated whether contact between the medial collar and femoral neck affects clinical outcomes and changes in bone mineral density (BMD) in patients who have this type of stem in their total hip arthroplasty construct., Methods: This was a retrospective, single-center study involving 62 patients scheduled for unilateral total hip arthroplasty using a hydroxyapatite-coated, triple-tapered, shorter-length stem who were followed for at least 1 year postoperatively. All patients had a Dorr type B femoral canal shape. Contact between the medial collar and the femoral neck was evaluated by computed tomography at the third postoperative month, and patients were classified into 2 groups. Postoperative clinical outcomes were investigated by the Western Ontario and McMaster Universities Arthritis Index and the Japanese Orthopaedic Association scores; radiological evaluation included stem fixation, spot welds and cortical hypertrophy, postoperative 3-dimensional stem alignment, and periprosthetic BMD changes., Results: There were 51 patients in the Contact + group (collar and neck contact) and 11 in the Contact-group (no contact). There were no differences between the 2 groups in the improvement of Western Ontario and McMaster Universities Arthritis Index and Japanese Orthopaedic Association scores, stem fixation, occurrence of cortical hypertrophy, or 3-dimensional stem alignment. Radiolucent lines were present in zones 3, 4, and 5 in 6 patients (12%) in the Contact + group only, who had no statistical difference between the 2 groups. Bone mineral density (BMD) decreased most in zone 7 in both groups, with no difference between the 2 groups., Conclusions: The presence or absence of contact between the medial collar and femoral neck did not affect postoperative BMD changes or radiological or clinical results., Level of Evidence: Therapeutic Level III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The accuracy of right ventricular (RV) quantification by three-dimensional echocardiography (3DE) has been reported mainly in patients with a normal right ventricle (RV). However, there are no data regarding the accuracy of 3DE in patients with a dilated RV, as in shunt diseases. In this study, we evaluated the accuracy of 3DE and that of volumetric (Vol) cardiac magnetic resonance (CMR) for assessment of RV and left ventricular (LV) stroke volume (SV) and the pulmonary (Q p )/systemic (Q s ) blood flow ratio in patients with an atrial septal defect (ASD) using the two-dimensional phase contrast (2DPC) method as the gold standard., Methods: We retrospectively investigated 83 patients with ASD who underwent transcatheter closure and clinically indicated CMR and 3DE examinations. The ratio Q p /Q s was calculated using RV and LV SV measured by full-volume volumetric 3DE (Vol-3DE) and CMR (Vol-CMR) and by two-dimensional pulsed Doppler quantification (2D-Dop); the parameters were compared using 2DPC-CMR as the gold standard., Results: There was no significant difference in the Q p /Q s value between 2DPC-CMR and Vol-3DE (2.29 ± 0.70 vs 2.21 ± 0.63, P = .79) and 2D-Dop (vs 2.21 ± 0.65, P = 1.00); however, a significant difference was found between 2DPC-CMR and Vol-CMR (P < .001). The Q p /Q s value obtained using Vol-3DE showed the best correlation with 2DPC-CMR (r = 0.93, P < .001). The RV and LV SV values obtained by Vol-3DE showed the best correlation with 2DPC-CMR (RV SV, r = 0.82, P < .001; LV SV, r = 0.73, P < .001), although the absolute values were underestimated., Conclusion: Q p /Q s was more accurately evaluated by Vol-3DE than by Vol-CMR or 2D-Dop. Three-dimensional echocardiography assessment was feasible and reproducible even in a dilated RV., Competing Interests: Disclosures None., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: The structural and functional characteristics of the heart in patients with diabetes mellitus (DM) and without myocardial infarction (MI) are not fully understood., Methods: We retrospectively analysed the data of patients with left ventricular ejection fraction (LVEF) ≥ 40% who underwent contrast-enhanced cardiac magnetic resonance imaging (CMR), which was also used to exclude MI, at two hospitals. Volumetric data and extracellular volume fraction (ECVf) of the myocardium evaluated using CMR were compared between patients with and without DM, and their association with diastolic function was evaluated., Results: Among 322 analysed patients, 53 had DM. CMR revealed that the left ventricular mass index (LVMi) and ECVf were increased while LVEF was decreased in patients with DM after adjusting for patient characteristics (all P < 0.05). A stronger positive correlation was observed between LVMi and the early diastolic transmitral flow velocity to early diastolic mitral annular velocity ratio (E/e') in patients with DM than in those without DM (correlation coefficient [R] = 0.46, p = 0.001; R = 0.15, p = 0.021, respectively; p for interaction = 0.011). ECVf correlated with E/e' only in patients with DM (R = 0.61, p = 0.004)., Conclusions: Patients with DM have increased LVMi and ECVf. Importantly, there was a difference between patients with and without DM in the relationship between these structural changes and E/e', with a stronger relationship in patients with DM. Furthermore, DM is associated with mildly reduced LVEF even in the absence of MI., Competing Interests: Declaration of competing interest M.K. received research grants from KOWA company, Ltd. and FUJIREBIO Inc. Y.A. received scholarship grants from Abbott Medical Japan and Terumo. T.F. received a research grant from General Electric. Y.S. received an honorarium from Astra-Zeneca, Nippon Boehringer-Ingelheim Co., Ltd., Daiichi-Sankyo Company, and Novartis., (Copyright © 2024. Published by Elsevier B.V.)

This case report presents a rare case of infantile nystagmus syndrome (INS) in which the direction of infantile nystagmus (IN) was vertical. A 66-year-old woman was referred to our department for investigation of abnormal eye movements. She showed a disordered field of view with a homonymous hemianopia in the lower left quadrant and vertical gaze-evoked nystagmus, but there were no other abnormal neurological findings. She did not complain of an oscillopsia. Imaging revealed that the cause of hemianopia was atrophy and low cerebral blood flow in the right occipital lobe. The vertical nystagmus became strong when attempting to fixate to stationary targets. A reversed optokinetic nystagmus response was observed in the vertical optokinetic nystagmus test. From these eye movements, we diagnosed her nystagmus as vertical IN. Patients with INS see everything by saccades. IN consists of the alternate appearance of saccades and preceding slow eye movements. For these eye movements, a wide visual field is necessary. In this case, vertical IN was caused by the wider vertical than horizontal visual field resulting from homonymous hemianopia. Therefore, the direction of IN is horizontal in most patients with INS because their horizontal visual field is the widest field., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: The Epley maneuver (EM) shows immediate effect, wherein disappearance of positional nystagmus occurs soon after the EM. Our previous study showed that setting interval times during the EM reduced the immediate effect. The purpose of this study is to identify the head position for which interval time reduces the immediate effect., Methods: Fifty-one patients with posterior canal type of benign paroxysmal positional vertigo (BPPV) were randomly assigned to the following three groups: 10 min interval time set at the first head position of the EM in group A, at the third head position in group B, and at the fourth head position in group C. The primary outcome measure (POＭ) was the ratio of maximum slow-phase eye velocity of positional nystagmus soon after the EM, compared with that measured before the EM. A large ratio value indicates a poor immediate effect of the EM., Results: The POＭ in group A (0.07) was smallest (B: 0.36, C: 0.49) (p < 0.001)., Discussion: The interval times at the third and fourth head positions reduced the immediate effect of the EM. Our previous study showed that the effect of BPPV fatigue is continued by maintaining the first head position of the EM. BPPV fatigue constitutes fatigability of positional nystagmus with repeated performance of the Dix-Hallpike test. Our findings may be interpreted in accordance with the theory that the immediate effect of the EM is BPPV fatigue itself, because we observed that the effect of BPPV fatigue is strongest in group A., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report our findings in a 5-year-old Japanese girl with unilateral optic neuritis who was seropositive for anti-myelin-oligodendrocyte glycoprotein (MOG) antibody. Functional and microstructural changes were assessed longitudinally for 3.5 years by serial recordings of the pattern visual evoked potentials (pVEPs) and optical coherence tomography (OCT) during the acute and chronic phases. On the initial visit, the best-corrected visual acuity (BCVA) in the right eye was light perception. She was treated with 450 mg of intravenous methylprednisolone pulses followed by a gradual tapering of the oral prednisolone. The visual acuity decreased to no light perception, and plasmapheresis combined with high-dose intravenous immunoglobulin therapy was performed. The BCVA quickly improved to 1.0, and no recurrence was detected for approximately four years. The implicit times of N75, P100, and N145 of the pVEPs and peripapillary retinal nerve fiber (pRNFL) thickness in the OCT images were measured during the course of the disease process. The pRNFL thickness of the right eye decreased and was less than one-half of the baseline value at one year and then stabilized. In contrast, the optic pathway function assessed by pVEPs improved. The implicit times of the N75 and P100 components of the right eye were shortened and stabilized at approximately one year. However, the implicit times in the right eye were still longer than that of the left eye. Our findings documented the course of the function and structures of an eye with anti-MOG antibody-positive optic neuritis. This information should be helpful for the understanding of the pathology and prognosis of this disease entity. Further analysis of the pVEPs and structural changes in more cases is needed., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tachibana et al.)

Background and Aim: The treatment strategy for patients with ulcerative colitis (UC) in clinical remission who have not achieved mucosal healing is unclear. This study aimed to determine the risk factors of relapse in patients in clinical remission with endoscopic activity., Methods: This retrospective, single-center study included patients with UC who underwent colonoscopy (CS) and were in clinical remission with endoscopic activity. Characteristics were compared between patients who relapsed within 2 years after CS and those who did not. A Cox proportional hazards regression model was used to identify risk factors contributing to clinical relapse. Recent worsening in bowel symptoms was defined as increase in bowel frequency and/or increase in abdominal pain within approximately 1 month based on the descriptions in the medical charts., Results: This study regarded 142 patients in clinical remission with an endoscopic activity of Mayo endoscopic subscore (MES) of ≥1 as eligible, and 33 (23%) patients relapsed during the observation period. Recent worsening of bowel symptoms was a significant risk factor for clinical relapse (hazard ratio [HR]: 3.02, 95% confidence interval [CI]: 1.34-6.84). This was particularly evident in patients with MES of 2 (HR: 5.16, 95% CI: 1.48-18.04), whereas no risk factors were identified in patients with MES of 1. The presence or absence of therapeutic intervention just after CS did not significantly affect clinical relapse., Conclusion: Recent worsening in bowel symptoms was a significant risk factor for clinical relapse in patients with UC who were in clinical remission with endoscopic activity., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Stem anteversion plays a crucial role in mitigating postoperative complications in total hip arthroplasty (THA). The application of the combined-anteversion theory in THA necessitates the intraoperative measurement of the stem anteversion angle (SAA). However, estimating SAA intraoperatively poses challenges for surgeons lacking a computer-assisted navigation system. In this study, we assessed the precision of intraoperative SAA measurements using a recently developed device, comparing them with 3-dimensional measurements obtained from postoperative computed tomography., Methods: We examined 127 hips in 127 patients who underwent unilateral THA at our institution. Employing our newly constructed device, attachable to rasping broach handles, we measured the SAA intraoperatively. This process involved incorporating the correction angle derived from the preoperative epicondylar view. We then compared the postoperative SAA with the intraoperative measurements, both with and without the correction angle, to ascertain the device's utility., Results: The device yielded an intraoperative SAA measurement of 17.93 ± 7.53°. In contrast, the true SAA measured on postoperative computed tomography was 26.40 ± 9.73°. The discrepancy between intraoperative and true SAA was 8.94 ± 5.44° (without the correction angle) and 4.93 ± 3.85° (with the correction angle). Accuracy within a discrepancy of <5° was achieved in 77 cases (60.6%), and <10° was achieved in 113 cases (89.0%). The accuracy remained consistent regardless of the stem-placement angle (varus/valgus, or flexion/extension) or the presence of ipsilateral knee osteoarthritis., Conclusions: The SAA-measuring device, attachable to various rasping handles, proves useful for straightforward, cost-effective, and noninvasive intraoperative SAA measurement during THA., (© 2024 The Authors.)

Objective : Current neuronal imaging methods mostly use bulky lenses that either impede animal behavior or prohibit multi-depth imaging. To overcome these limitations, we developed a lightweight lensless biophotonic system for neuronal imaging, enabling compact and simultaneous visualization of multiple brain layers. Approach : Our developed 'CIS-NAIST' device integrates a micro-CMOS image sensor, thin-film fluorescence filter, micro-LEDs, and a needle-shaped flexible printed circuit. With this device, we monitored neuronal calcium dynamics during seizures across the different layers of the hippocampus and employed machine learning techniques for seizure classification and prediction. Main results : The CIS-NAIST device revealed distinct calcium activity patterns across the CA1, molecular interlayer, and dentate gyrus. Our findings indicated an elevated calcium amplitude activity specifically in the dentate gyrus compared to other layers. Then, leveraging the multi-layer data obtained from the device, we successfully classified seizure calcium activity and predicted seizure behavior using Long Short-Term Memory and Hidden Markov models. Significance : Taken together, our 'CIS-NAIST' device offers an effective and minimally invasive method of seizure monitoring that can help elucidate the mechanisms of temporal lobe epilepsy., (Creative Commons Attribution license.)

Background and Aim: Endoscopic retrograde cholangiopancreatography (ERCP) may help detect cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC), but it may be associated with complications. This study was aimed at determining the prognostic impact of ERCP on patients with PSC without cholangitis., Methods: Patients with PSC without cholangitis were divided into two groups: those who underwent ERCP within three years after diagnosis (ERCP-performed group) and those who did not (non-ERCP group). These groups were compared in terms of clinical outcomes (liver-related death or liver transplantation, endoscopic treatment requirement and repeated cholangitis) and the composite outcome., Results: Of 99 patients with PSC with detailed medical history, 49 were included in the ERCP-performed group and 21 in the non-ERCP group. In Kaplan-Meier analysis, the non-ERCP group was less likely to achieve the three outcomes and the composite outcome, showing statistical significance (endoscopic treatment requirement; p = 0.017 and composite outcome; p = 0.014). A Cox proportional hazards model indicated that ERCP in the asymptomatic state was a significant predictor of endoscopic treatment requirement (hazard ratio [HR]: 4.37, 95% confidence interval [CI]: 1.03-18.59) and the composite outcome (HR: 4.54, 95% CI: 1.07-19.28)., Conclusion: ERCP in patients with PSC without cholangitis is likely to require further endoscopic treatment and may be associated with poor prognosis., (© 2024. The Author(s).)

The Japan Diabetes Society (JDS) adopted a sweeping decision to release consensus statements on relevant issues in diabetes management that require updating from time to time and launched a "JDS Committee on Consensus Statement Development." In March 2020, the committee's first consensus statement on "Medical Nutrition Therapy and Dietary Counseling for People with Diabetes" was published. In September 2022, a second consensus "algorithm for pharmacotherapy in people with type 2 diabetes" was proposed. In developing an algorithm for diabetes pharmacotherapy in people with type 2 diabetes, the working concept was that priority should be given to selecting such medications as would appropriately address the diabetes pathology in each patient while simultaneously weighing the available evidence for these medications and the prescribing patterns in clinical practice in Japan. These consensus statements are intended to present the committee's take on diabetes management in Japan, based on the evidence currently available for each of the issues addressed. It is thus hoped that practicing diabetologists will not fail to consult these statements to provide the best available practice in their respective clinical settings. Given that the persistent dual GIP/GLP-1 receptor agonist tirzepatide was approved in April 2023, these consensus statements have been revised 1) . In this revision, specifically, tirzepatide was added to the end of [likely involving insulin resistance] of "Obese patients" in Step 1: "Select medications to address the diabetes pathology involved" in Fig. 2. While the sentence, "Insulin insufficiency and resistance can be assessed by referring to the various indices listed in the JDS 'Guide to Diabetes Management.' was mentioned in the previous edition as well, "While insulin resistance is analogized based on BMI, abdominal obesity, and visceral fat accumulation, an assessment of indicators (e.g., HOMA-IR) is desirable" was added as information in order to more accurately recognize the pathology. Regarding Step 2: "Give due consideration to safety," "For renal excretion" was added to the "Rule of thumb 2: Avoid glinides in patients with renal impairment." The order of the medications in "rule of thumb 3: Avoid thiazolidinediones and biguanides in patients with heart failure (in whom they are contraindicated)." to thiazolidinediones then biguanides. In the description of the lowest part of Fig. 2, for each patient failing to achieve his/her HbA1c control goal, "while reverting to step 1" was changed to "while reverting to the opening" and "including reassessment if the patient is indicated for insulin therapy" was added. In the separate table, the column for tirzepatides was added, while the two items, "Characteristic side effects" and "Persistence of effect" were added to the area of interest. The revision also carried additional descriptions of the figure and table such as tirzepatides and "Characteristic side effects" in the statement, and while not mentioned in the proposed algorithm figure, nonalcoholic fatty liver disease (NAFLD) is covered from this revision for patients with comorbidities calling for medical attention. Moreover, detailed information was added to the relative/absolute indication for insulin therapy, the Kumamoto Declaration 2013 for glycemic targets, and glycemic targets for older people with diabetes. Again, in this revision, it is hoped that the algorithm presented here will not only contribute to improved diabetes management in Japan, but will continue to evolve into a better algorithm over time, reflecting new evidence as it becomes available., Competing Interests: Conflict of interestRyotaro Bouchi: Honoraria (Sumitomo Pharma; AstraZeneca; Novo Nordisk Pharma), and Research funding (Sumitomo Pharma) Yasuharu Ohta: Research funding (Manpei Suzuki Diabetes Foundation), and Subsidies or Donations (Sumitomo Pharma; Nippon Boehringer Ingelheim; Novo Nordisk Pharma). Daisuke Yabe: Honoraria (Novo Nordisk Pharma; Nippon Boehringer Ingelheim; Eli Lilly Japan; Sanofi; Kyowa Kirin; Sumitomo Pharma), and Research funding (Terumo Corporation; Nippon Boehringer Ingelheim), and Endowed departments by commercial entities (Novo Nordisk Pharma; Taisho Pharmaceutical; ARKRAY). Rimei Nishimura: Honoraria (Sanofi; Medtronic; Nippon Boehringer Ingelheim; KISSEI PHARMACEUTICAL; Eli Lilly Japan; Novo Nordisk Pharma; Astellas Pharma; Abbott Japan; Sumitomo Pharma; AstraZeneca; KOWA; ONO PHARMACEUTICAL; Taisho Pharmaceutical), and Research funding (Mitsubishi Electric), and Subsidies or Donations (Taisho Pharmaceutical; Nippon Boehringer Ingelheim; Abbott Japan; Sumitomo Pharma; Eli Lilly Japan; Arkley). Norio Harada: Research funding (Mitsubishi Tanabe Pharma; Eli Lilly Japan; Nippon Boehringer Ingelheim; ONO PHARMACEUTICAL). Hideki Kamiya: Honoraria (Novo Nordisk Pharma; Sanofi; Sumitomo Pharma; Eli Lilly Japan; Nippon Boehringer Ingelheim; DAIICHI SANKYO; AstraZeneca; ONO PHARMACEUTICAL; KISSEI PHARMACEUTICAL; Mitsubishi Tanabe Pharma; KOWA; Novartis Pharma; MSD; SANWA KAGAKU KENKYUSHO; Otsuka Pharmaceutical), and Research funding (ONO PHARMACEUTICAL; Eli Lilly Japan; KISSEI PHARMACEUTICAL), and Subsidies or Donations (ONO PHARMACEUTICAL; Taisho Pharmaceutical; Sumitomo Pharma; Takeda Pharmaceutical; Mitsubishi Tanabe Pharma; JAPAN TOBACCO; Novo Nordisk Pharma). Ryo Suzuki: Honoraria (Novo Nordisk Pharma; Sanofi; Sumitomo Pharma; Astellas Pharma; KOWA; MSD; Eli Lilly Japan; Mitsubishi Tanabe Pharma; TEIJIN PHARMA), and Research funding (Sumitomo Pharma), and Subsidies or Donations (Nippon Boehringer Ingelheim). Toshimasa Yamauchi: Honoraria (ONO PHARMACEUTICAL; Takeda Pharmaceutical; Sumitomo Pharma; TEIJIN PHARMA; Nippon Boehringer Ingelheim; Novo Nordisk Pharma), and Research funding (KOWA; Minophagen Pharmaceutical; NIPRO CORPORATION; Kyowa Kirin), and Subsidies or Donations (Novo Nordisk Pharma; Mitsubishi Tanabe Pharma; Kyowa Kirin; Takeda Pharmaceutical; ONO PHARMACEUTICAL; Sumitomo Pharma), and Endowed departments by commercial entities (ONO PHARMACEUTICAL; Mitsubishi Tanabe Pharma; Novo Nordisk Pharma; Nippon Boehringer Ingelheim; KOWA; NITTO BOSEKI; Asahi Mutual Life Insurance Company). Dr Daisuke Yabe, Dr Norio Harada, Dr Hideki Kamiya, Dr Toshimasa Yamauchi are Editorial Board members of Journal of Diabetes Investigation and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication., (© The Japan Diabetes Society 2024.)

A 75-year-old woman presented with significant muscle weakness after statin use. A muscle biopsy revealed necrotizing myopathy, and the patient tested positive for serum anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, leading to a diagnosis of anti-HMGCR immune-mediated necrotizing myopathy (IMNM). Computed tomography revealed intraperitoneal lymphadenopathy, which was diagnosed as a diffuse large B-cell lymphoma. Immunostaining confirmed HMGCR expression in the lymphoma cells. The patient received chemotherapy and achieved complete remission of the lymphoma, along with nearly complete recovery from IMNM. Although the etiologies of IMNM and lymphoma remain unclear, HMGCR expression in lymphoma cells is likely to be associated with the development of IMNM.

Loss-of-function (LoF) variants in the TANK binding kinase 1 ( TBK1 ) gene are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we present the first familial cases of ALS and parkinsonism associated with a novel TBK1 variant. We describe two siblings: one diagnosed with classical ALS and the other with a unique syndrome overlapping ALS and parkinsonism. Comprehensive clinical and imaging evaluations supported these diagnoses. Genetic analysis through whole-genome sequencing revealed a previously unknown heterozygous splice site variant in TBK1 . Functional assessments demonstrated that this splice site variant leads to abnormal splicing and subsequent degradation of the mutated TBK1 allele by nonsense-mediated decay, confirming its pathogenic impact. Our findings suggest a broader involvement of TBK1 in neurodegenerative diseases and underscore the need for further research into TBK1's role, advocating for screening for TBK1 variants in similar familial cases.

Introduction: Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that can mimic progressive supranuclear palsy or corticobasal syndrome. Moreover, anti-IgLON5 disease can present with symptoms characteristic of multiple system atrophy (MSA), such as cerebellar ataxia and autonomic dysfunction. However, the clinical features of anti-IgLON5 disease resembling MSA have not been well established., Methods: We enrolled 35 patients with suspected MSA for whom anti-IgLON5 antibody tests were requested. We evaluated immunoglobulin G (IgG) against IgLON5 using cell-based assays. We also summarized the clinical characteristics of patients who were positive for anti-IgLON5 antibodies., Results: We identified serum and cerebrospinal fluid anti-IgLON5 antibodies in three patients. These patients had many clinical features characteristic of MSA, including parkinsonism, cerebellar ataxia, severe orthostatic hypotension, acute respiratory failure, sleep parasomnia, vocal cord paralysis, and pyramidal tract signs. Clinical features atypical for MSA were myorhythmia, horizontal eye movement restriction, fasciculations, and painful muscle cramps., Conclusion: Anti-IgLON5 disease may be an important differential diagnosis of MSA. A comprehensive physical examination, including assessments of eye movement, lower motor neuron signs, and atypical involuntary movements, is important to avoid misdiagnosis., 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.)

Background: Cerebral small vessel disease (CSVD) causes cognitive decline and perivascular space enlargement is one of the image markers for CSVD., Purpose: To search for clinical significance in the time-course augmentation of perivascular space in basal ganglia (BG-PVS) for cognitive decline., Material and Methods: This study population included 179 participants from a community-based cohort, aged 70 years at baseline. They had undergone magnetic resonance imaging (MRI) studies two or three times between 2000 and 2008. Based on the severity of BG-PVS or white matter hyperintensity lesions (WMHL) in 2000, the participants were divided into low-grade or high-grade groups, respectively. In addition, their time-course augmentation was evaluated, and we created a categorical BG-PVS WMHL change score based on their augmentation (1 = neither, 2 = BG-PVS augmentation only, 3 = WMHL augmentation only, 4 = both). Cognitive function was assessed based on the Mini-Mental State Examination (MMSE); the change was defined as the difference between scores in 2000 and 2008. We used simple or multiple regression analysis for MMSE score change according to MRI findings and clinical characteristics that were probably related to cognitive decline., Results: In univariate analysis, MMSE score change was negatively associated with BG-PVS high grade at baseline and BG-PVS WMHL change score 4; this remained significant in multivariate analysis. In the final model based on the Akaike Information Criterion, BG-PVS WMHL change score 4 was associated with a 3.3-point decline in subsequent MMSE score., Conclusions: This study suggested that augmentation in both BG-PVS and WMHL was associated with subsequent cognitive decline., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: This study examines the hepatic extracellular volume fraction (ECV) disparity between the left and right lobes (ECV&#95;left and ECV&#95;right) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its association with right heart catheterization (RHC) metrics, and with intolerance to increased pulmonary hypertension (PH)-targeted medication dosages., Methods: We retrospectively analyzed 72 CTEPH-diagnosed patients who underwent equilibrium-phase abdominal dual-energy CT (DECT) and RHC. Hepatic ECVs, derived from DECT's iodine maps using circular regions of interest in the liver and aorta, were correlated with RHC parameters via Spearman's rank correlation and lobe differences through the Wilcoxon signed-rank test. Logistic regression assessed cases with ECV&#95;left exceeding ECV&#95;right by > 0.05, while receiver operating characteristic curve analysis gauged ECVs' predictive power for medication intolerance., Results: Of the 72 patients (57 females; median age 69), ECV&#95;total (0.24, IQR 0.20-0.27) moderately correlated with RHC parameters (r s  = 0.28, -0.24, 0.3 for mean pulmonary arterial pressure, cardiac index [CI], and pulmonary vascular resistance index, respectively). ECV&#95;left significantly surpassed ECV&#95;right (0.25 vs. 0.22, p < 0.001), with a greater ECV&#95;left by > 0.05 indicating notably lower CI (p < 0.001). In 27 patients on PH medication, ECV&#95;left effectively predicted medication intolerance (AUC = 0.84)., Conclusion: In CTEPH patients, hepatic ECV correlated with RHC metrics, where elevated left lobe ECV suggested reduced CI and potential medication intolerance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: We examined whether time-course augmentation of perivascular space enlargement in the basal ganglia (BG-PVS) reflected cerebral small vessel disease (CSVD) severity by considering white matter hyperintensity lesion (WMHL) as an indicator for CSVD., Materials and Methods: This study population included 416 older participants from a community-based cohort. They participated in magnetic resonance imaging (MRI) studies more than once during the study period. The grades for BG-PVS and WMHL were evaluated by visual rating scales; BG-PVS time-course augmentation in 4-9 years was also evaluated. At baseline, the participants were asked about their smoking and drinking history, and medical history. They also underwent a blood examination and their office blood pressure (BP) examination. In addition, 24-h ambulatory BP monitoring was also performed within the study period., Results: Of the 416 participants, 48 participants (11.5%) had BG-PVS time-course augmentation. The participants with BG-PVS augmentation had significantly lower LDL levels, hyper-nighttime BP, and lower nighttime BP fall in univariate analysis (p = 0.03, p = 0.03, p = 0.003, respectively). In multivariate analysis, lower nighttime BP fall and male sex showed significance (p = 0.02, 0.03, respectively). Additionally, BG-PVS time-course augmentation was significantly associated with subsequent WMHL severity in univariate analysis (p < 0.001), which remained significant in multivariate analysis adjusted by imaging and demographic factors (p = 0.03). In multivariate analysis, additionally adjusted by the clinical factors, the significance disappeared (p = 0.07)., Conclusion: This study revealed that the lower nighttime BP fall in ambulatory blood pressure monitoring was a factor significantly associated with BG-PVS augmentation. Moreover, the BG-PVS time-course augmentation would be a notable finding that was associated with the subsequent WMHL., (© 2024. The Author(s).)

Background: This study aimed to investigate the relationship between 3-dimensional (3D) alignment and postoperative bone mineral density (BMD) changes with Accolade II tapered wedge stems, which have a different proximal shape from other tapered wedge stems, up to 5 years after primary total hip arthroplasty., Methods: We retrospectively analyzed the hips of 89 patients who underwent total hip arthroplasty using the second-generation proximally coated cementless stem (Accolade II; Stryker Orthopedics, Mahwah, NJ) at our institution from 2014 to 2018 over a 5-year follow-up. We evaluated the relationship between stem alignment, measured using 3D-templating software, and BMD changes in the 7 Gruen zones and compared the data with those from a former study using other short taper-wedge stems., Results: BMDs in zones 1 and 7 continued to decrease gradually every year after surgery, and BMD in zone 7 showed the largest decrease (21%) from baseline over 5 years. No correlation was found between stem alignment (varus/valgus, flexion/extension, and anteversion/retroversion) and changes in BMD in each zone over 5 years., Conclusions: Our data showed no correlation between 3D stem alignment and changes in BMD in each Gruen zone over 5 years. This suggests that the Accolade II stem may fit better into any shape of the proximal medullary canal because of its unique characteristics., (© 2024 The Authors.)

Background: Recently, the incidence of achalasia has been increasing, but its cause remains unknown. This study aimed to examine the initial symptoms and the course of symptoms and to find new insights into the cause and course of the disease., Methods: Altogether, 136 patients diagnosed with achalasia by high-resolution manometry (HRM) were enrolled. Questionnaires and chart reviews were conducted to investigate the initial symptoms, time from onset to diagnosis, and comorbidities, as well as the relationship between HRM results, time to diagnosis, and symptom severity., Results: In total, 67 of 136 patients responded to the questionnaire. The median ages of onset and diagnosis were 42 and 58 years, respectively. The median time from onset to diagnosis was 78.6 months, with 25 cases (37.3%) taking > 10 years to be diagnosed. The symptom onset was gradual and sudden in 52 (77.6%) and 11 (16.4%) patients, respectively. Of the 11 patients with acute onset, three (27.3%) developed anhidrosis at the same time. There was no correlation between the time from onset to diagnosis and esophageal dilatation, resting LES pressure, or mean integrated relaxation pressure (IRP). No correlation was also found between the degree of symptoms and resting LES pressure or IRP., Conclusion: Esophageal achalasia can have acute or insidious onsets. This finding may help to elucidate the cause of achalasia., (© 2024. The Author(s).)

Cadaverine is a bioactive substance derived from lysine degradation by lysine decarboxylase and has gained attention for its physiological effects. Studies in rodents have revealed its role as a cell growth regulator, particularly intestinal bacterial-produced cadaverine. However, the nutritional and physiological roles of cadaverine during the embryonic period remain unclear, especially considering the immature state of the gut microbiota and digestive functions during this stage. This study explored the potential functions of cadaverine as a nutritional and metabolic signal during chicken embryonic development. Experiments were conducted using an in ovo administration method to evaluate the effects of nutritional bioactive substances on developing chicken embryos. Although there were no observable changes in body or organ weights of newly hatched chicks following in ovo cadaverine administration to day 18 chick embryos, plasma tryptophan, N τ -methylhistidine, and N π -methylhistidine concentrations decreased and the gene expression of insulin/insulin-like growth factor 1 signaling in skeletal muscle was upregulated. These findings imply that cadaverine influences tryptophan metabolism and skeletal muscle catabolism during the embryonic period, suggesting its role as a bioactive factor contributing to energy metabolism signaling in skeletal muscle., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest., (2024 Japan Poultry Science Association.)

Background/Objectives: A highly porous titanium cup with a three-dimensional metal interface was recently introduced to improve biological fixation and survival. However, radiography has revealed concerns regarding these cups, despite their excellent short- and mid-term clinical outcomes. This study compared the clinical and radiographic results of a highly porous titanium cup with those of a hydroxyapatite-coated porous titanium cup after primary total hip arthroplasty (THA). Methods: Fifty-one primary THAs were investigated. A highly porous titanium cup was used in 17 hips, and a hydroxyapatite-coated porous titanium cup was used in 34 hips. No significant differences in preoperative patient demographic characteristics were observed between the two groups. The 2-year postoperative clinical and radiographic results were compared. Results: Radiolucent lines were observed in 13 (76%) of 17 hips with highly porous titanium cups and in none (0%) of 34 hips with hydroxyapatite-coated porous titanium cups ( p < 0.001). In the highly porous titanium cup group, radiolucent lines were observed in five hips (29%) in one zone, two hips (11%) in two zones, and six hips (35%) in three zones. No cup loosening was observed in either group. Conclusions: Radiolucent lines were significantly more frequent in highly porous titanium cups. This study suggests that, compared to the three-dimensional structure of porous titanium, the hydroxyapatite coating of porous titanium had a greater influence on bone ingrowth in the short term. The meaning of these findings in the long-term is unclear yet.

Introduction: The accuracy of acetabular cup placement using conventional portable imageless navigation systems in total hip arthroplasty (THA) in the lateral decubitus position remains challenging. Several novel portable imageless navigation systems have been developed recently to improve cup placement accuracy in THA. This study compared the accuracy of acetabular cup placement using a conventional accelerometer-based portable navigation (c-APN) system and a novel accelerometer-based portable navigation (n-APN) system during THA in the lateral decubitus position., Materials and Methods: This retrospective cohort study compared 45 THAs using the c-APN and 45 THAs using the n-APN system. The primary outcomes were the absolute errors between the intraoperative and postoperative values of acetabular cup radiographic inclination and anteversion angles and the percentage of cases with absolute errors within 5°. Intraoperative values were shown on navigation systems, and postoperative measurements were conducted using computed tomography images., Results: The median absolute errors of the cup inclination angles were significantly smaller in the n-APN group than in the c-APN group (3.9° [interquartile range 2.2°-6.0°] versus 2.2° [interquartile range 1.0°-3.3°]; P = 0.002). Additionally, the median absolute errors of the cup anteversion angles were significantly smaller in the n-APN group than in the c-APN group (4.4° [interquartile range 2.4°-6.5°] versus 1.9° [interquartile range 0.8°-2.7°]; P < 0.001). Significant differences were observed in the percentage of cases with absolute errors within 5° of inclination (c-APN group 67% versus n-APN group 84%; P = 0.049) and anteversion angles (c-APN group 62% versus n-APN group 91%; P = 0.001)., Conclusions: The n-APN system improved the accuracy of the cup placement compared to the c-APN system for THA in the lateral decubitus position., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Vonoprazan, a potassium-competitive acid blocker, demonstrates more potent acid inhibition than proton pump inhibitors (PPIs). This study aimed to evaluate the effect of vonoprazan in patients with unproven gastroesophageal reflux disease (GERD) by comparing patients with vonoprazan-refractory heartburn with those with PPI-refractory heartburn., Methods: This study included 104 consecutive patients with vonoprazan- or PPI-refractory heartburn (52 patients each), no erosive esophagitis on endoscopy and who underwent combined multichannel intraluminal impedance-pH (MII-pH) testing with vonoprazan/PPI discontinuation. Patients' backgrounds, symptom scores from four questionnaires, MII-pH results and high-resolution manometry results were compared between the two groups., Results: The vonoprazan group demonstrated significantly higher GERD symptoms and scores of abdominal pain and diarrhea on the Gastrointestinal Symptom Rating Scale questionnaire. MII-pH results revealed that the vonoprazan group demonstrated 40.4%, 17.3%, and 42.3% and the PPIs group exhibited 26.9%, 17.3%, and 55.8% of abnormal acid reflux [true non-erosive reflux disease (NERD)], reflux hypersensitivity and functional heartburn, respectively. The vonoprazan group demonstrated higher true NERD rates but with no significant difference (p = 0.307). Among the vonoprazan group, eight patients with true NERD underwent another MII-pH test on vonoprazan, and all cases demonstrated normal acid exposure times (0.0% [0.0-0.3])., Conclusion: Patients with unproven GERD with vonoprazan-refractory heartburn demonstrated more symptoms, including not only GERD symptoms but also functional dyspepsia and irritable bowel syndrome symptoms, than those with PPI-refractory heartburn., (© 2024. The Author(s).)

A 37-year-old woman developed severe colitis with diffuse mucosal erythema and ulcerations throughout the entire colon after the 3rd vaccination of COVID-19. Stool culture was negative, and the pathological findings showed increased lymphoplasmacytic and neutrophilic infiltration in the colonic lamina propria, which were consistent with ulcerative colitis. After the treatment with anti-tumor necrosis factor-α agent, the ulceration markedly improved with development of severe colonic stenosis, which was successfully dilated with endoscopic balloon dilation. In case of COVID-19 vaccination, it should be noted that vaccination could be a trigger for the onset of UC., (© 2024. The Author(s).)

Aims: The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group)., Methods: The study included 36 patients with T-HA stems and 30 with N-HA stems. Dual-energy X-ray absorptiometry was used to measure the change in periprosthetic BMD, one and two years postoperatively. The 3D contact between the stem and femoral cortical bone was evaluated using a density-mapping system, and clinical assessment, including patient-reported outcome measurements, was recorded., Results: There were significantly larger contact areas in Gruen zones 3, 5, and 6 in the N-HA group than in the T-HA group. At two years postoperatively, there was a significant decrease in BMD around the proximal-medial femur (zone 6) in the N-HA group and a significant increase in the T-HA group. BMD changes in both groups correlated with BMI or preoperative lumbar BMD rather than with the extent of contact with the femoral cortical bone., Conclusion: The N-HA-coated stem showed a significantly larger contact area, indicating a distal fixation pattern, compared with the traditional fully HA-coated stem. The T-HA-coated stem showed better preservation of periprosthetic BMD, two years postoperatively. Surgeons should consider these patterns of fixation and differences in BMD when selecting fully HA-coated stems for THA, to improve the long-term outcomes., Competing Interests: Y. Minoda reports personal speaking payments from Aesculap/B. Braun, Zimmer Biomet, DePuy Synthes, Smith & Nephew, and Microport; institutional speaking payments from Microport, Zimmer Biomet, and Smith & Nephew; and institutional payments for manuscript preparation from Zimmer Biomet, DePuy Synthes, Microport, and Smith & Nephew, all unrelated to this study. R. Sugama reports an institutional speaking payment from Japan Medical Dynamic Marketing and Kyocera and personal speaking payments from Stryker, all unrelated to this study. H. Nakamura reports personal speaking payments from Daiichi Sankyo Co., Eli Lilly Japan K.K, Shionogi & Co., and Taisho Toyama Pharmaceutical Co., all unrelated to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Declining sequencing costs coupled with the increasing availability of easy-to-use kits for the isolation of DNA and RNA transcripts from single cells have driven a rapid proliferation of studies centered around genomic and transcriptomic data. Simultaneously, a wealth of new techniques have been developed that utilize single cell technologies to interrogate a broad range of cell-biological processes. One recently developed technique, transposase-accessible chromatin with sequencing (ATAC) with select antigen profiling by sequencing (ASAPseq), provides a combination of chromatin accessibility assessments with measurements of cell-surface marker expression levels. While software exists for the characterization of these datasets, there currently exists no tool explicitly designed to reformat ASAP surface marker FASTQ data into a count matrix which can then be used for these downstream analyses. To address this, we created CountASAP, an easy-to-use Python package purposefully designed to transform FASTQ files from ASAP experiments into count matrices compatible with commonly-used downstream bioinformatic analysis packages. CountASAP takes advantage of the independence of the relevant data structures to perform fully parallelized matches of each sequenced read to user-supplied input ASAP oligos and unique cell-identifier sequences., Competing Interests: Competing Interests The authors declare no competing interests.

Background and Aim: The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test., Methods: Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146)., Results: Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort., Conclusions: We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Previous human and rodent studies indicated that nociceptive stimuli activate many brain regions that is involved in the somatosensory and emotional sensation. Although these studies have identified several important brain regions involved in pain perception, it has been a challenge to observe neural activity directly and simultaneously in these multiple brain regions during pain perception. Using a transgenic mouse expressing G-CaMP7 in majority of astrocytes and a subpopulation of excitatory neurons, we recorded the brain activity in the mouse cerebral cortex during acute pain stimulation. Both of hind paw pinch and intraplantar administration of formalin caused strong transient increase of the fluorescence in several cortical regions, including primary somatosensory, motor and retrosplenial cortex. This increase of the fluorescence intensity was attenuated by the pretreatment with morphine. The present study provides important insight into the cortico-cortical network during pain perception., 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.)

Hearing loss is a pivotal risk factor for dementia. It has recently emerged that a disruption in the intercommunication between the cochlea and brain is a key process in the initiation and progression of this disease. However, whether the cochlear properties can be influenced by pathological signals associated with dementia remains unclear. In this study, using a mouse model of Alzheimer's disease (AD), we investigated the impacts of the AD-like amyloid β (Aβ) pathology in the brain on the cochlea. Despite little detectable change in the age-related shift of the hearing threshold, we observed quantitative and qualitative alterations in the protein profile in perilymph, an extracellular fluid that fills the path of sound waves in the cochlea. Our findings highlight the potential contribution of Aβ pathology in the brain to the disturbance of cochlear homeostasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fukuda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Macrophages are versatile cells of the innate immune system that work by altering their pro- or anti-inflammatory features. Their dysregulation leads to inflammatory disorders such as inflammatory bowel disease. We show that macrophage-specific upregulation of the clock output gene and transcription factor E4BP4 reduces the severity of colitis in mice. RNA-sequencing and single-cell analyses of macrophages revealed that increased expression of E4BP4 leads to an overall increase in expression of anti-inflammatory genes including Il4ra with a concomitant reduction in pro-inflammatory gene expression. In contrast, knockout of E4BP4 in macrophages leads to increased proinflammatory gene expression and decreased expression of anti-inflammatory genes. ChIP-seq and ATAC-seq analyses further identified Il4ra as a target of E4BP4, which drives anti-inflammatory polarization in macrophages. Together, these results reveal a critical role for E4BP4 in regulating macrophage inflammatory phenotypes and resolving inflammatory bowel diseases., (© 2024. The Author(s).)

Background: Although the effectiveness of BNT162b2 messenger RNA vaccines against the Omicron variant has been reported in several countries, data are limited in children living in Asian countries. Therefore, this study aimed to estimate the effectiveness of the pediatric primary two-dose monovalent mRNA vaccine series in preventing symptomatic novel coronavirus disease 2019 (COVID-19) in Japan., Methods: We conducted a test-negative case-control study (262 test-positive cases and 259 test-negative controls) in patients aged 5-11 years who presented with COVID-19-like symptoms during the Omicron BA.2- and BA.5-predominant periods. Vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, living environment, and PCR test results were obtained using parent-administered questionnaires and clinical records. Vaccine effectiveness (VE) against symptomatic COVID-19 was calculated using a multivariate logistic regression analysis., Results: Of the test-positive cases and test-negative controls, 9.2% (n = 24) and 12.7% (n = 33) received two vaccine doses, respectively. Having siblings and a BA.5-dominant period were significantly associated with symptomatic COVID-19. After adjusting for age, siblings, study period, and duration after the last vaccination, the overall VE of two-dose vaccination was 50.0% (95% confidence interval [CI], 5-74%). VE was 72% (95% CI, 24-89%) within 3 months after the two-dose vaccination, while it decreased to 24% (95% CI, -80% to 68%) after 3 months., Conclusion: Two BNT162b messenger RNA vaccine doses provided moderate protection against symptomatic COVID-19 during the Omicron variant period. A time-dependent decrease in VE was noted after the second dose; thus, a booster dose 3 months after the second dose is warranted.

Purpose: This study aimed to compare bone mineral density (BMD) changes around the femoral component after total hip arthroplasty (THA) in a fully hydroxyapatite-coated stem (CORAIL) and in a tapered-wedge stem (Taperloc complete) and identify predictors of BMD changes., Methods: This retrospective study compared 43 hips in the CORAIL group and 40 hips in the Taperloc group. The relative changes in BMD at 2 years after THA measured using dual-energy X-ray absorptiometry and the three-dimensional quantified contact states of the stem with the femoral cortical bone were assessed. Predictors of the relative change in the BMD around the proximal part of the stem were examined using multiple regression analysis., Results: The decrease in BMD in Gruen zone 7 was significantly less in the CORAIL group than in the Taperloc group (P = 0.02). In the CORAIL group, the contact area in any zone was not a significant predictor of the relative changes in BMD. The contact area between the Taperloc stem and the femoral cortical bone in zones 2 and 6 was a positive predictor of the relative changes in BMD in zones 1 (P = 0.02 and P = 0.04, respectively) and 2 (P = 0.008 and P = 0.004, respectively)., Conclusion: The CORAIL stem suppressed the postoperative BMD loss around the stem, irrespective of the contact state. The Taperloc complete stem required contact with the proximal femoral metaphysis to suppress the postoperative BMD loss around the stem., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Introduction: Factors affecting mucosal permeability (MP) in ulcerative colitis (UC) are largely unknown. We aimed to investigate the difference in MP among patients with UC classified according to the colonic locations and to evaluate the correlations between local MP and endoscopic or histological activity of UC., Methods: The transepithelial electrical resistance (TER), which is inversely proportional to permeability, of tissue samples from the mucosa of the ascending colon, descending colon, and rectum of patients with UC and healthy individuals (HIs) was measured by using the Ussing chamber. TERs were compared between patients with UC and HIs and evaluated according to colonic locations and disease activity of UC., Results: Thirty-eight patients with UC and 12 HIs were included in this study. Both in HIs and patients with UC, MP tends to be higher in the anal side. TER in the ascending colon was significantly lower in patients with UC than in HIs (45.3 ± 9.0 Ω × cm 2 vs 53.5 ± 9.7 Ω × cm 2 , P = 0.01). The increased permeability in UC was observed also in the descending colon, only when the inflammation involved the location. A significant correlation between TER and endoscopic activity was found in the rectum only ( r = -0.49, P = 0.002). There were no significant correlations between TERs and UC histology., Discussion: The MP in the colon differs according to the colonic location. The ascending colon among patients with UC showed disease-specific changes in MP, whereas the MP is increased in proportion to the endoscopic activity in the rectum., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: There is no consensus on the effectiveness of prophylactic clipping after colonic cold snare polypectomy (CSP). This study aimed to evaluate the utility of prophylactic clipping in preventing delayed bleeding (DB) after colorectal CSP in patients on antithrombotic agents., Methods: We retrospectively recruited consecutive patients on antithrombotic agents who underwent colorectal CSP in Chiba University Hospital. The DB rate was compared between patients with and without prophylactic clipping., Results: The study included 133 patients (422 polyps) requiring prophylactic clipping and 85 patients (282 polyps) not requiring prophylactic clipping. There were no significant differences in DB and hematochezia rates between the groups. By weighted logistic regression analysis, the odds ratio of hematochezia was 0.557 (95% confidence interval, 0.225-1.378; P = .205) in patients without clipping compared to those with clipping., Conclusions: Prophylactic clipping may not be necessary to prevent DB after colorectal CSP in patients on antithrombotic agents., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The self-monitoring of physical activity is an effective strategy for promoting active lifestyles. However, accurately assessing physical activity remains challenging in certain situations. This study evaluates a novel floor-vibration monitoring system to quantify housework-related physical activity., Objective: This study aims to assess the validity of step-count and physical behavior intensity predictions of a novel floor-vibration monitoring system in comparison with the actual number of steps and indirect calorimetry measurements. The accuracy of the predictions is also compared with that of research-grade devices (ActiGraph GT9X)., Methods: The Ocha-House, located in Tokyo, serves as an independent experimental facility equipped with high-sensitivity accelerometers installed on the floor to monitor vibrations. Dedicated data processing software was developed to analyze floor-vibration signals and calculate 3 quantitative indices: floor-vibration quantity, step count, and moving distance. In total, 10 participants performed 4 different housework-related activities, wearing ActiGraph GT9X monitors on both the waist and wrist for 6 minutes each. Concurrently, floor-vibration data were collected, and the energy expenditure was measured using the Douglas bag method to determine the actual intensity of activities., Results: Significant correlations (P<.001) were found between the quantity of floor vibrations, the estimated step count, the estimated moving distance, and the actual activity intensities. The step-count parameter extracted from the floor-vibration signal emerged as the most robust predictor (r 2 =0.82; P<.001). Multiple regression models incorporating several floor-vibration-extracted parameters showed a strong association with actual activity intensities (r 2 =0.88; P<.001). Both the step-count and intensity predictions made by the floor-vibration monitoring system exhibited greater accuracy than those of the ActiGraph monitor., Conclusions: Floor-vibration monitoring systems seem able to produce valid quantitative assessments of physical activity for selected housework-related activities. In the future, connected smart home systems that integrate this type of technology could be used to perform continuous and accurate evaluations of physical behaviors throughout the day., (©Yuki Nakajima, Asami Kitayama, Yuji Ohta, Nobuhisa Motooka, Mayumi Kuno-Mizumura, Motohiko Miyachi, Shigeho Tanaka, Kazuko Ishikawa-Takata, Julien Tripette. Originally published in JMIR Formative Research (https://formative.jmir.org), 25.04.2024.)

Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1β (IL-1β), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1α), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1β production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1β production, indicating that IRE1α is required for CT- or CTB-induced IL-1β production in RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)