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Background: Antioxidants that can scavenge reactive oxygen in the brain and inhibit hyperactivity of the HPA axis are desirable., Aims: We investigated the cerebral translocation of the antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) and the effects of DHMBA administration on the hypothalamus-pituitary-adrenal (HPA) axis in stress-loaded rats., Methods: Experiment 1: Plasma and brain DHMBA concentrations were measured over time after oral DHMBA administration to male B6 mice. Experiment 2: Female Wistar Imamichi rats were used. The normal group was not subjected to stress. The stress, DHMBA, and vitamin E groups were subjected to individual and overcrowding stress. Brain and hippocampal 8-hydroxy-2'-deoxyguanosine levels, hippocampal glucocorticoid receptor-α levels, plasma corticosterone levels and RNA levels of glutathione peroxidase 4, catalase, and glutathione reductase in the hippocampus were measured., Results: In Experiment 1, DHMBA was not detected in the plasma or brain before DHMBA administration but was detected in both after administration. In Experiment 2, brain and hippocampal 8-hydroxy-2'-deoxyguanosine levels and plasma corticosterone levels were significantly lower in the DHMBA than in the stress group. Glucocorticoid receptor-α levels were higher in the DHMBA than in the stress group. DHMBA increased RNA levels of antioxidant enzymes in the hippocampus., Conclusion: DHMBA was translocated to the brain after administration. DHMBA administration decreased 8-hydroxy-2'-deoxyguanosine levels in the brain and hippocampus, increased hippocampal glucocorticoid receptor-α levels, and decreased the plasma corticosterone concentration, suggesting that DHMBA inhibits hyperactivity of the HPA axis. Nrf2 pathway activity induced by DHMBA resulted in increased antioxidant enzyme levels in the hippocampus., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Part of this study was entrusted by Watanabe Oyster Laboratory Co., Ltd. to Material Research Center Co., Ltd., and conducted by Material Research Center Co., Ltd. The authors belong to Watanabe Oyster Laboratory Co., Ltd., and they had role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Watanabe Mitsugu reports a relationship with Watanabe Oyster Laboratory Co., Ltd., that includes: board membership and equity or stocks. Emiko Miki, Kuroki Katsuya and Kenji Yoshiike report a relationship with Watanabe Oyster Laboratory Co., Ltd., that includes: employment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fracture-related infections (FRIs) are a challenging complication in orthopaedics. Standard of care management for FRIs typically involves prolonged antibiotic therapies, irrigation and debridement (I&D) of the fracture site, and retention of fracture-fixation implants with or without exchange. Unfortunately, this treatment regimen is associated with treatment failure rates of up to 38 %, such that improved preventive and therapeutic interventions are needed. To test and develop these interventions, clinically relevant preclinical animal models are required. The purpose of this study was to develop and validate a canine model for early onset (<2 weeks) FRI that replicates its clinical, radiographic, bacteriologic, and histologic features. In this model, bilateral proximal fibular 1-cm ostectomies were created to mimic an open fracture, which was then stabilized using a plate and screws pre-incubated in methicillin-resistant Staphylococcus aureus (MRSA). After 7 days, I&D was performed and twice-daily systemic antibiotics were administered until the 17-day endpoint. This model consistently resulted in clinical signs of local infection, compromised wound healing, radiographic evidence for delayed bone healing and implant loosening, and implant-associated biofilm formation. Importantly, MRSA was isolated from deep tissue cultures in all dogs, and histological assessments detected bacteria and bacterial biofilms associated with all fracture-fixation implants at the study endpoint. These clinical, radiographic, bacteriologic, and histologic outcomes in conjunction with the capabilities for standard of care interventions, such as antibiotic treatment and I&D, verify that this preclinical canine model for early onset FRI effectively replicated the pathology associated with this commonly encountered complication of orthopaedic trauma., Competing Interests: Declaration of competing interest • Aaron M. Stoker receives IP royalties from Musculoskeletal Transplant Foundation. • Cristi R. Cook receives IP royalties, is a paid consultant, paid presenter or speaker, and receives research support from Arthrex, Inc; receives IP royalties, is a paid consultant, paid presenter or speaker, and receives research support from Collagen Matrix Inc; receives IP royalties, is a paid consultant, paid presenter or speaker, and receives research support from Musculoskeletal Transplant Foundation. • James P Stannard is a paid consultant and receives research support from Arthrex, Inc; is a paid consultant for DePuy, A Johnson & Johnson Company; is on the editorial or governing board for the Journal of Knee Surgery; receives research support from National Institutes of Health (NIAMS & NICHD); is a paid consultant for Orthopedic Designs North America; is a paid consultant for Smith & Nephew; receives publishing royalties, financial or material support from Thieme; and receives research support from the U.S. Department of Defense. • James L. Cook receives research support from AANA; receives research support from AO Trauma; receives IP royalties, is a paid consultant and receives research support from Arthrex, Inc; is a paid consultant for Bioventus; is a paid consultant for Boehringer Ingelheim; is a paid consultant and receives research support from Collagen Matrix Inc; receives research support from GE Healthcare; is on the editorial or governing board for the Journal of Knee Surgery; is a board or committee member for Midwest Transplant Network; is a board or committee member, receives IP royalties and research support from Musculoskeletal Transplant Foundation; receives research support from the National Institutes of Health (NIAMS & NICHD); receives research support from OREF; receives research support from Orthopaedic Trauma Association; receives research support from PCORI; receives research support from Regenosine; receives research support from SITES Medical; receives publishing royalties, financial or material support from Thieme; is a paid consultant for Trupanion; and receives research support from U.S. Department of Defense. • Bryce W. Rigden, Chantelle C. Bozynski, Keiichi Kuroki, Tamara Gull have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this 12-month long, preclinical large animal study using a canine model, we report that engineered osteochondral grafts (comprised of allogeneic chondrocyte-seeded hydrogels with the capacity for sustained release of the corticosteroid dexamethasone [DEX], cultured to functional mechanical properties, and incorporated over porous titanium bases), can successfully repair damaged cartilage. DEX release from within engineered cartilage was hypothesized to improve initial cartilage repair by modulating the local inflammatory environment, which was also associated with suppressed degenerative changes exhibited by menisci and synovium. We note that not all histological and clinical outcomes at an intermediary time point of three months paralleled 12-month outcomes, which emphasizes the importance of in vivo studies in valid preclinical models that incorporate clinically relevant follow-up durations. Together, our study demonstrates that engineered cartilage fabricated under the conditions reported herein can repair full-thickness cartilage defects and promote synovial joint health and function.

Background: Early cardiomyopathy diagnosis allows timely treatment and may help resolve problems that occur after cardiac implantable electronic device (CIED) implantation., Objective: This study aims to describe a novel technique for endomyocardial biopsy (EMB) using a 3-dimensional (3D) delivery sheath during CIED implantation. In addition, we investigated 3D delivery-sheath characteristics using sheath deflection during bioptome insertion., Methods: This study of 20 patients undergoing CIED implantation analyzed the EMB success rate and pathologic findings. Fluoroscopic images assessed 3D delivery sheath characteristics before and after bioptome insertion in 3 sheaths. CIEDs were implanted for sick sinus syndrome (n =3), atrioventricular conduction disorder (n = 16), and left ventricular dysfunction (n = 1). Fluoroscopic verification was performed using right anterior oblique (RAO) and left anterior oblique (LAO) views. EMB was performed with Selectra 3D (BIOTRONIK, Berlin, Germany), CSP Locator 3D (Abbott, Chicago, IL), and SSPC (Boston Scientific, Marlborough, MA) (12, 4, and 4 patients, respectively). The distance moved toward the right ventricular apex (RVA) in RAO was defined as Dis-RAO (mm) and that moved toward the RVA in LAO was defined as Dis-LAO (mm)., Results: Among the 3 sheaths, only the CSP Locator 3D and Selectra 3D showed significant differences in Dis-RAO (13.2 ± 2.0 mm vs 19.8 ± 3.8 mm, P < .01) and Dis-LAO (8.1 ± 1.3 mm vs 15.3 ± 3.9 mm, P < .01). A total of 77 EMB samples from 20 patients were collected without any complication, and 4 patients (20%) were diagnosed with cardiac amyloidosis (CA) based on pathologic findings., Conclusion: All 3D delivery sheaths were safe and effective for performing EMB from the RVS during CIED implantation, enabling early CA diagnosis in 20% of patients., Competing Interests: Disclosures Dr Kuroki has received grants from Medtronic Co, Ltd and Abbott Medical Japan LLC. He is a consultant of Abbott Medical Japan LLC, Microport CRM Japan Co, Ltd, and KANEKA CORPORATION. Dr Sato has received grants from Abbott Medical Japan LLC. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Osteochondral allograft transplantation (OCAT) can be a successful joint restoration treatment option for large post-traumatic articular defects but is still associated with significant revision and failure rates. Despite recent advances that have improved OCAT success, insufficient osteochondral allograft (OCA) osseointegration remains a major cause of failure. Deferoxamine (DFO) is an effective angiogenic and osteo-anabolic iron chelator that consistently promotes bone neovascularization and regeneration. This study was designed to investigate local delivery of DFO for augmenting OCA osseointegration using a preclinical canine model for OCAT in the knee and hip as commonly affected joints., Methods: On Institutional Animal Care and Use Committee (IACUC) approval, 12 purpose-bred dogs underwent OCAT of the femoral head or femoral condyles with DFO or DFO-free (controls) microspheres in recipient sites. OCA revascularization, cellular repopulation, and integration were evaluated based on functional, diagnostic imaging, microcomputed tomography, histology, and immunohistochemistry outcome measures., Results: Local delivery of DFO into OCAT recipient sites was associated with maintained or improved joint function, superior radiographic appearance, significantly greater trabecular thickness, higher bone volume, and new bone ingrowth compared with DFO-free controls., Conclusion: OCA osseointegration is dependent on cellular repopulation and neovascularization, resulting in new bone ingrowth through creeping substitution, and insufficient osseointegration with resorption and subsidence of the OCA remains a major cause of failure after transplantation. The results of this study suggest that local delivery of DFO using a controlled microsphere release system may reduce resorption and improve revascularization and cellular repopulation to increase new bone ingrowth, potentially expediting OCA osseointegration after transplantation., Competing Interests: J. L. Cook receives research support from AANA; receives research support from AO Trauma; receives IP royalties, is a paid consultant, and receives research support from Arthrex, Inc, Naples, FL; is a paid consultant for Bioventus; is a paid consultant for Boehringer Ingelheim; is a paid consultant and receives research support from Collagen Matrix Inc; receives research support from GE Healthcare; is on the editorial or governing board for the Journal of Knee Surgery; is a board or committee member for Midwest Transplant Network; is a board or committee member, receives IP royalties and research support for Musculoskeletal Transplant Foundation; receives research support from National Institutes of Health (NIAMS and NICHD); receives research support from OREF; receives research support from Orthopaedic Trauma Association; receives research support from PCORI; receives research support from Regenosine; receives research support from SITES Medical; receives publishing royalties, financial or material support from Thieme; is a paid consultant for Trupanion; and receives research support from US Department of Defense. A. M. Stoker receives IP royalties from Musculoskeletal Transplant Foundation. J. P. Stannard is a board or committee member for American Orthopaedic Association; is a board or committee member for AO Foundation; is a board or committee member for AO North America; is a paid consultant and research support from Arthrex, Inc; is a paid consultant for DePuy, A Johnson & Johnson Company; is on the editorial or governing board for Journal of Knee Surgery; is a board or committee member of Mid-America Orthopaedic Association; receives research support from National Institutes of Health (NIAMS and NICHD); is a paid consultant for Orthopedic Designs North America; is a paid consultant for Smith & Nephew; receives publishing royalties, financial or material support from Thieme; and receives research support from US Department of Defense. C. R. Cook receives IP royalties, is a paid consultant, paid presenter or speaker and receives research support from Arthrex, Inc; receives IP royalties, is a paid consultant, paid presenter or speaker, and receives research support from Collagen Matrix Inc; receives IP royalties, is a paid consultant, paid presenter or speaker and receives research support from Musculoskeletal Transplant Foundation. B. D. Crist is a board or committee member for AO Trauma North America; is a paid consultant for Curvafix; receives IP royalties for Globus Medical; is a board or committee member for International Geriatric Fracture Society; is on the editorial or governing board for the Journal of Hip Preservation; is on the editorial or governing board for the Journal of Orthopaedic Trauma; is a paid consultant, presenter or speaker for KCI; has stock or stock options for the Orthopaedic Implant Company; is a board or committee member for Orthopaedic Trauma Association; is an unpaid consultant for Osteocentric; has stock or stock options from RomTech; is on the editorial or governing board for SLACK Incorporated; is a paid consultant and receives research support from Synthes. The remaining authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Tongue-base cysts, which are occasionally categorized as vallecular cysts, are a rare yet potentially life-threatening cause of stridor in pediatric patients. Studies reporting the use of point-of-care ultrasound (POCUS) to identify tongue-base cysts are lacking. We present the case series of four infants in whom tongue-base cysts were detected using neck POCUS., Competing Interests: Conflicts of interest and source of funding: This research was supported by a grant from the National Center for Child Health and Development (2023C-22). Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Farmed cervids are of growing economic importance in the midwestern United States. Although diseases of wild and captive cervids have been examined in more northerly climates, little information exists on the health challenges of deer in the Midwest. We characterized and summarized the causes of mortality in farmed white-tailed deer ( Odocoileus virginianus ) submitted to the University of Missouri Veterinary Medical Diagnostic Laboratory (Columbia, MO, USA) over a 19-y period (2004-2023). Of 388 cases examined, 253 (65%) were carcasses submitted for autopsy, and 135 (35%) cases were tissue samples harvested by field veterinarians. Infectious disease was the most common cause of mortality ( n  = 335; 86.3%). Of infectious causes, primary pneumonia was most common ( n  = 140; 41.7%), followed by septicemia ( n  = 68; 20.1%), and primary enteritis ( n  = 64; 19.1%). Viruses were detected in 18% of pneumonia cases. The most common non-infectious diagnoses were emaciation and trauma (both 4 each; 1%). Thirteen animals (3.4%) died of unknown causes. Forty-nine percent of cases were juvenile deer <1-y-old. Most cases were received in the summer (212; 54.6%). Infectious diseases, particularly bacteria and viruses, pose a significant health challenge to farmed deer in the midwestern United States., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respects to the research, authorship, and/or publication of this article.

Background: We aimed to clarify the existence and pathological features of obesity cardiomyopathy (OCM) in Japan using our series of autopsy cases., Methods: In this retrospective autopsy study, OCM was defined as cardiac hypertrophy (≥ 400 g in men, ≥ 320 g in women) of unknown aetiology in individuals with obesity (body mass index [BMI] ≥ 25 kg/m 2 according to the Japanese definition of obesity). We compared cases of OCM with those with obesity without cardiac hypertrophy (OB) and normal weight without cardiac hypertrophy (normal control). Macroscopically, heart weight and cardiac parameters, including epicardial adipose tissue, were measured. Fibrosis, cardiomyocyte diameter, and adipose tissue infiltration were analysed microscopically., Results: Of the 294 cases, we identified 19 cases of OCM (6.5%) and compared them with the OB and normal control groups. Patients with OCM were slightly younger than non-OCM patients (p = 0.081). The median heart weight was significantly heavier in OCM cases than in OB cases (435 g, interquartile range [IQR] 408-515 g vs. 360 g, IQR 341-385 g). Macroscopically, OCM hearts had a "globoid" appearance with a thickened right ventricular outflow tract. Some OCM cases showed focal interstitial fibrosis in the left ventricle. Approximately half the OCM cases were diagnosed with sudden cardiac death (SCD), with significant differences., Conclusions: The prevalence of OCM may be higher than expected in Japan, and this may be a specific pathological finding. Given that approximately half the cases of OCM were due to SCD, OCM may cause SCD, emphasizing the need to recognise and diagnose OCM., (© 2024. The Author(s).)

Purpose: To describe the first report of third eyelid cartilage eversion in an adult American Quarter Horse mare., Case Presentation: A 22-year-old American Quarter Horse mare presented to the University of Missouri Veterinary Health Center Equine Hospital for a 2-week history of a third eyelid cartilage abnormality of the left eye with no known recent trauma. Complete ophthalmic examination revealed third eyelid cartilage eversion of the left nictitans. The abnormal scrolled cartilage was surgically excised using a handheld cautery unit and submitted for histopathologic evaluation., Results: Histopathologic findings displayed normal third eyelid cartilage, without evidence of neoplasia or inflammation. Mucosal hyperplasia and increased vascularity of the submucosa were observed. The horse healed well after electrocautery excision and normal third eyelid conformation was restored., Conclusion: To the authors' knowledge, this is the first report of an acquired, presumed spontaneous, third eyelid cartilage eversion in a horse., (© 2024 American College of Veterinary Ophthalmologists.)

Background: Psoriasis is an inflammatory skin condition where immune cells play a significant role. The importance of the cross-talk between keratinocytes and immune cells in the pathogenesis of psoriasis has recently been reaffirmed. Recent studies have found that several S1PR functional antagonists, other than S1PR2, are effective in improving psoriasis. This study aims to investigate the role of S1PR2 in psoriasis, that has not been investigated before., Methods: Spatial transcriptomics, RT-qPCR, and flow cytometry were used to map the immune cell landscape and its association with metabolic pathways in an imiquimod (IMQ)-induced psoriasis-like inflammation in S1pr2 fl/fl K14-Cre mice that could not sense sphingosine-1-phosphate (S1P) in the epidermis through the S1PR2 receptor., Results: Our analysis suggests that S1PR2 in keratinocytes plays a major role in psoriasis-like inflammation compared to other S1PRs. It acts as a down-regulator, inhibiting the recruitment of Th17 cells into the skin. In IMQ-induced psoriasis skin, both S1pr2 -/- and S1pr2 fl/fl K14-Cre mice showed higher expressions of proinflammatory cytokines such as TNF-α, IL-17A, and IL-1β together with higher expressions of MyD88/NF-κB pathway compared to the wild-type mice. Remarkably, in IMQ-treated mice, the deletion of S1pr2 in keratinocytes only resulted in a larger population of Th17 cells in skin-draining lymph nodes. Other S1PR modulators did not improve the worsening of psoriasis-like inflammation caused by S1PR2 deficiency in keratinocytes., Conclusion: This study reaches two main conclusions: signals from keratinocytes play a central role in creating an immune environment that promotes the development of psoriasis, and stimulating S1PR2, instead of suppressing it, represents a potential therapeutic approach for psoriasis., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could potentially create a conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Masuda-Kuroki, Alimohammadi, Lowry and Di Nardo.)

Bacillary hemoglobinuria (BH) is an infectious disease, mostly affecting cattle, caused by Clostridium haemolyticum ( C. novyi type D), with acute hepatic necrosis and intravascular hemolysis. Cattle are typically predisposed to BH by liver injury caused by Fasciola hepatica , although cases have been reported in cattle without evidence of this parasite. Here we describe a cluster of 14 BH cases from 7 counties in north-central to central Missouri submitted to a veterinary diagnostic laboratory between December 2020 and April 2023. Postmortem examination in all cases revealed hemoglobinuria and acute hepatic necrosis with large numbers of gram-positive bacilli with terminal-to-subterminal spores. Flukes, fluke ova, and/or fluke pigment consistent with Fascioloides magna were identified in 12 of 14 cases. Sequences of the nuclear ribosomal internal transcribed spacer 1 (ITS1) from one fluke had 100% identity to F. magna. C. novyi was detected by fluorescent antibody testing of liver impression smears (11 of 12 cases) and by immunohistochemistry of liver sections (7 of 7 cases). PCR on formalin-fixed, paraffin-embedded tissues amplified the C. haemolyticum beta toxin gene in each of the 7 cases tested. To our knowledge, a confirmed cluster of BH associated with F. magna has not been reported previously in cattle., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAF V600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%-60% of human melanomas, 30%-50% of human thyroid carcinomas and 10%-20% of human colorectal carcinomas. The orthologous BRAF V595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety-six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAF V597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAF T586T , was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology., (© 2024 John Wiley & Sons Ltd.)

We developed a novel hepatitis B virus (HBV) infection-monitoring system using a luminescent, 11-amino acid reporter (HiBiT). We performed high-throughput antiviral screening using this system to identify anti-HBV compounds. After the infection of primary human hepatocytes with the recombinant virus HiBiT-HBV, which contains HiBiT at its preS1, 1262 compounds were tested in a first screening using extracellular HiBiT activity as an indicator of viral infection. Following a second screening, we focused on the compound skimmianine, which showed a potent antiviral effect. When skimmianine was added at the same time as HiBiT-HBV infection, skimmianine inhibited HiBiT activity with EC 50 of 0.36 pM, CC 50 of 1.67 μM and a selectivity index (CC 50 :EC 50 ratio) of 5,100,000. When skimmianine was added 72 h after HiBiT-HBV infection, the EC 50 , CC 50 and selectivity index were 0.19 μM, 1.87 μM and 8.79, respectively. Time-lapse fluorescence imaging analysis using another recombinant virus, ReAsH-TC155HBV, with the insertion of tetra-cysteine within viral capsid, revealed that skimmianine inhibited the accumulation of the capsid into hepatocytes. Furthermore, skimmianine did not inhibit either attachment or internalization. These results imply that skimmianine inhibits the retrograde trafficking of the virus after internalization. This study demonstrates the usefulness of the recombinant virus, HiBiT-HBV, for high-throughput screening to identify anti-HBV compounds.

Background: TactiFlex is a next-generation catheter that is being used increasingly in ablation-treatment strategies. The purpose of this study was to investigate the differences in ablation lesions when the ablation power, time, and perfusion flow are varied with TactiFlex and TactiCath catheters., Methods: The TactiFlex and TactiCath catheters were contacted perpendicularly/obliquely/parallel to the swine myocardium at varying powers (30, 40, and 50 W), time points (10, 15, 20, 25, 30, and 40 s), and forces (5, 10, 15, 20, and 30 g); the depth, width, and area of each lesion were measured, and the number of steam pops that occurred was counted., Results: A total of 672 (336 lesions for each catheter) radiofrequency (RF) energy applications were delivered and 648 lesions were analyzed, excluding steam pops. The surface area and volume increased significantly with an increasing contact force for the TactiCath. The TactiCath lesions were significantly deeper than those for TactiFlex in most groups with the same power and seconds. The surface area was significantly larger when the catheters were contacted obliquely/parallel to the myocardium than perpendicularly using TactiCath, whereas the difference was less significant in the case of TactiFlex. In a 10-g contact force ablation experiment, TactiFlex did not cause pops, but TactiCath caused pops in 9.8% of cases., Conclusion: The TactiFlex lesions were shallower than those of TactiCath. However, TactiFlex catheters reduced the steam pops during RF applications. Those data should help clinicians understand the characteristics of the catheters and develop adequate strategies., (© 2024. The Author(s).)

Patients with type 2 diabetes mellitus are frequently hospitalized for heart failure. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'), measured by echocardiography, is a simple and convenient indicator of diastolic dysfunction. Various large clinical trials have reported that sodium glucose transporter-2 inhibitor therapy reduced cardiovascular events and hospitalizations in heart failure patients. We examined the effect of tofogliflozin on various physiological and cardiac function. A retrospective analysis was performed on elderly patients aged 65 years or older with type 2 diabetes mellitus attending Himi Municipal Hospital who were taking oral tofogliflozin 20 mg/day. Measurement of physiological and hormonal variables, blood sampling, and echocardiographic evaluations at 0, 1, 3, and 6 months were performed on those with ejection fraction (EF) of 40% or greater at the time of treatment. Statistical analysis was performed using t-tests and mixed-effects models, with brain natriuretic peptide less than or not less than 100 pg/mL, estimated glomerular filtration rate (eGFR) less than or not less than 50 mL/min/1.73 m2, and diuretics administered or not. Hypoglycemic effects were observed at 0, 1, 3, and 6 months. At each time point, EF was retained and E/e' was significantly reduced. On the other hand, most physiological parameters and laboratory results showed no clinical abnormalities. Mixed-effects models showed time-dependent reduction of E/e' in high/low brain natriuretic peptide, high/low eGFR, with or without diuretics between baseline and at 6 months. The interaction with time was significant in high/low eGFR. Tofogliflozin was shown to improve E/e', a measure of diastolic function, while maintaining EF, with hypoglycemic effects and no clinical side effects., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: Despite the ongoing advancements in mechanical thrombectomy for large vessel occlusions causing acute ischemic stroke, successful recanalization is not achieved in all patients. One contributing factor is the presence of fibrin-rich hard clots. We proposed a new technique called the PREMIER technique, which aims to retrieve fibrin-rich clots. This study evaluated the efficacy of the PREMIER technique on fibrin-rich and erythrocyte-rich clots by comparing it with the simple use of EmboTrap III in an in vitro vessel model., Methods: The PREMIER technique involves partially resheathing a fully deployed EmboTrap III (CERENOVUS, Johnson & Johnson Medical Devices, Irvine, California, USA) using a microcatheter to capture and retrieve a hard clot between the inner channel and outer cages of EmboTrap III. We compared recanalization rate of the PREMIER technique with the simple use of EmboTrap III in an in vitro vessel model, occluding the M1 segment with fibrin-rich hard clots (0% erythrocyte composition) and erythrocyte-rich clots (50% erythrocyte composition)., Results: Among the 40 procedures (10 each for the PREMIER technique and the simple use of EmboTrap III for two different clots) for fibrin-rich clots, the PREMIER technique achieved successful recanalization in all 10 cases, with a significantly higher recanalization rate than the EmboTrap III (100% vs. 50%, p  = 0.03). For erythrocyte-rich clots, the recanalization rate was not significantly different in the PREMIER technique compared with the simple use of EmboTrap III (80% vs. 70%, p  = 1.00)., Conclusion: The PREMIER technique is a novel technique for acute large-vessel occlusions caused by fibrin-rich hard clots that hinders successful recanalization during mechanical thrombectomy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Namitome, Nagao, Shigehatake, Matsuo, Kawamoto, Kuroki, Hayashi, Nakajima, Terasaki, Ueda and Shindo.)

Canine distemper virus (CDV) belongs to morbillivirus, including measles virus (MeV) and rinderpest virus, which causes serious immunological and neurological disorders in carnivores, including dogs and rhesus monkeys, as recently reported, but their vaccines are highly effective. The attachment glycoprotein hemagglutinin (CDV-H) at the CDV surface utilizes signaling lymphocyte activation molecule (SLAM) and Nectin-4 (also called poliovirus-receptor-like-4; PVRL4) as entry receptors. Although fusion models have been proposed, the molecular mechanism of morbillivirus fusion entry is poorly understood. Here, we determined the crystal structure of the globular head domain of CDV-H vaccine strain at 3.2 Å resolution, revealing that CDV-H exhibits a highly tilted homodimeric form with a six-bladed β-propeller fold. While the predicted Nectin-4-binding site is well conserved with that of MeV-H, that of SLAM is similar but partially different, which is expected to contribute to host specificity. Five N -linked sugars covered a broad area of the CDV-H surface to expose receptor-binding sites only, supporting the effective production of neutralizing antibodies. These features are common to MeV-H, although the glycosylation sites are completely different. Furthermore, real-time observation using high-speed atomic force microscopy revealed highly mobile features of the CDV-H dimeric head via the connector region. These results suggest that sugar-shielded tilted homodimeric structure and dynamic conformational changes are common characteristics of morbilliviruses and ensure effective fusion entry and vaccination., Competing Interests: HF, KY, MS, MK, TO, MK, MY, SC, YI, ST, MM, JW, TH, JK, NM, CK, MT, KK, KM No competing interests declared, (© 2023, Fukuhara, Yumoto, Sako et al.)

Introduction. Maternal screening tests and prophylactic antibiotics are important to prevent neonatal and infant group B streptococcal (GBS) infections. Hypothesis/Gap Statement. The performance of enrichment broth media for GBS screening that are available in Japan is unclear. Whole-genome data of GBS isolates from pregnant women in Japan is lacking. Aim. The aim of this study was to compare the protocol performance of six enrichment broths and two subculture agar plates, which were all available in Japan, for GBS detection. In addition, we showed whole-genome data of GBS isolates from pregnant women in Japan. Methodology. We collected 133 vaginal-rectal swabs from pregnant women visiting clinics and hospitals in Nagasaki Prefecture, Japan, and compared the protocol performance of 6 enrichment broths and 2 subculture agar plates. All GBS isolates collected in this study were subjected to whole-genome sequencing analysis. Results. We obtained 133 vaginal-rectal swabs from pregnant women at 35-37 weeks of gestation from 8 private clinics and 2 local municipal hospitals within Nagasaki Prefecture, Japan. The detection rate of the protocol involving the six enrichment broths and subsequent subcultures varied between 95.5 and 100 %, depending on the specific choice of enrichment broth. The GBS carriage rate among pregnant women in this region was 18.8 %. All 25 isolates derived from the swabs were susceptible to penicillin, whereas 48 and 36 % of the isolates demonstrated resistance to erythromycin and clindamycin, respectively. The distribution of serotypes was highly diverse, encompassing seven distinct serotypes among the isolates, with the predominant serotype being serotype V ( n = 8). Serotype V isolates displayed a tendency towards increased resistance to erythromycin and clindamycin, with all resistant isolates containing the ermB gene. Conclusion. There was no difference in performance among the culture protocols evaluated in this study. GBS strains isolated from pregnant women appeared to have greater genomic diversity than GBS strains detected in neonates/infants with invasive GBS infections. To confirm this result, further studies with larger sample sizes are needed.

The hepatitis B virus (HBV) infects many people worldwide. As HBV infection frequently leads to liver fibrosis and carcinogenesis, developing anti-HBV therapeutic drugs is urgent. Therapeutic drugs for preventing covalently closed circular DNA (cccDNA) production, which can eliminate HBV infection, are unavailable. The host factor dedicator of cytokinesis 11 (DOCK11) is involved in the synthesis and maintenance of HBV cccDNA in vitro . However, the effectiveness of DOCK11 as a target for the in vivo elimination of HBV cccDNA remains unclear. In this study, we assess whether DOCK11 inhibitors suppress HBV cccDNA production in mouse models of HBV infection. The tocopherol-conjugate hetero- gapmer, a DNA/RNA duplex of gapmer/complementary RNA targeting the DOCK11 sequence, partially reduces the expression of DOCK11 , but not that of HBV cccDNA, in the livers of HBV-infected human hepatocyte chimeric mice, along with weight loss and decreased serum human albumin levels. Lipid nanoparticle-encapsulated chemically modified siRNAs specific for DOCK11 suppress DOCK11 expression and decrease HBV cccDNA levels without adverse effects in the mice. Therefore, nucleic acid-based drugs targeting DOCK11 in hepatocytes are potentially effective anti-HBV therapeutics that can reduce HBV cccDNA levels in vivo ., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Aim: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection., Methods: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables., Results: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased., Conclusions: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576., (© 2024 Japan Geriatrics Society.)

Objective: To compare the bone healing effects of percutaneously delivered bone marrow aspirate concentrate (BMC) versus reamer irrigator aspirator (RIA) suspension in a validated preclinical canine ulnar nonunion model. We hypothesized that BMC would be superior to RIA in inducing bone formation across a nonunion site after percutaneous application. The null hypothesis was that BMC and RIA would be equivalent., Methods: A bilateral ulnar nonunion model (n= 6; 3 matched pairs) was created. Eight weeks after segmental ulnar ostectomy, RIA from the ipsilateral femur and BMC from the proximal humerus were harvested and percutaneously administered into either the left or right ulnar defect. The same volume (3 ml) of RIA suspension and BMC were applied on each side. Eight weeks after treatment, the dogs were euthanized, and the nonunions were evaluated using radiographic, biomechanical, and histologic assessments., Results: All dogs survived for the intended study duration, formed radiographic nonunions 8 weeks after segmental ulnar ostectomy, and underwent the assigned percutaneous treatment. Radiographic and macroscopic assessments of bone healing at the defect sites revealed superior bridging-callous formation in BMC-treated nonunions. Histologic analyses revealed greater amount of bony bridging and callous formation in the BMC group. Biomechanical testing of the treated nonunions did not reveal any significant differences., Conclusion: Bone marrow aspirate concentrate (BMC) had important advantages over Reamer Irrigator Aspirator (RIA) suspension for percutaneous augmentation of bone healing in a validated preclinical canine ulnar nonunion model based on clinically relevant radiographic and histologic measures of bone formation., Competing Interests: Declaration of competing interest Cristi R. Cook receives IP royalties, is a paid consultant, a paid presenter or speaker and receives research support from Arthrex, Inc; receives IP royalties, is a paid consultant, paid presenter or speaker and receives research support from Collagen Matrix Inc; receives IP royalties, is a paid consultant, is a paid presenter or speaker and receives research support from Musculoskeletal Transplant Foundation. Brett D. Crist is a board or committee member fromAO Trauma North America; receives other financial or material support from Arthrex, Inc; is a paid consultant, paid presenter or speaker from Curvafix; is a paid presenter or speaker for DePuy, A Johnson & Johnson Company; is a board or committee member for Fragility Fracture Network—USA; receives IP royalties from Globus Medical; is a board or committee member for International Geriatric Fracture Society; is on the editorial or governing board for the Journal of Hip Preservation; is on the editorial or governing board from Journal of Orthopaedic Trauma; is a paid consultant, paid presenter or speaker for KCI; is a board or committee member for Orthopaedic Trauma Association; is an unpaid consultant for Osteocentric; has stock or stock options for RomTech; is on the editorial or governing board for SLACK Incorporated; is a paid consultant or receives research support for Synthes; and is unpaid consultant for Urgo Medical. James L. Cook receives research support from AANA; receives research support from AO Trauma; receives IP royalties, is a paid consultant and receives research support from Arthrex, Inc; is a paid consultant from Bioventus; is a paid consultant for Boehringer Ingelheim; is a paid consultant and receives research support from Collagen Matrix Inc; receives research support from GE Healthcare; is on the editorial or governing board for the Journal of Knee Surgery; is a board or committee member for Midwest Transplant Network; is a board or committee member, receives IP royalties and research support from Musculoskeletal Transplant Foundation; receives research support from the National Institutes of Health (NIAMS & NICHD); receives research support from OREF; receives research support from Orthopaedic Trauma Association; receives research support from PCORI; receives research support from Regenosine; receives research support from SITES Medical; receives publishing royalties, financial or material support from Thieme; is a paid consultant for Trupanion; receives research support from the U.S. Department of Defense. Kenrick Lam, Chantelle Bozynski, Kei Kuroki and Will Bezold have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Commonly used isotonic arthroscopic irrigation fluids, such as normal saline or lactated Ringer's, were initially formulated for intravenous administration so they do not replicate the physiologic properties of healthy synovial fluid. Synovial fluid plays an important role in regulating joint homeostasis such that even transient disruptions in its composition and physiology can be detrimental. Previous studies suggest that hyperosmolar solutions may be a promising alternative to traditional isotonic fluids. This manuscript sought to systematically review and synthesize previously published basic science, translational, and clinical studies on the use of hyperosmolar arthroscopic irrigation fluids to delineate the optimal fluid for clinical use. A systematic literature search of MEDLINE/PubMed and Embase databases was performed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) guidelines. The search phrases were: ("cartilage" AND "hyperosmolar"); ("arthroscopy" OR "arthroscopic" AND "hyperosmolar"). The titles, abstracts, and full texts were screened for studies on hyperosmolar solutions and articular cartilage. Study quality was assessed, and relevant data were collected. A meta-analysis was not performed due to study heterogeneity. A risk of bias assessment was performed on the included translational and clinical studies. There were 10 basic science studies, 2 studies performed in translational animal models, and 2 clinical studies included in this review. Of the basic science studies, 7 utilized a mechanical injury model. The translational studies were carried out in the canine shoulder and equine stifle (knee) joint. Clinical studies were performed in the shoulder and knee. Multiple basic science, translational, and clinical studies highlight the short-term safety, cost-effectiveness, and potential benefits associated with use of hyperosmolar solutions for arthroscopic irrigation. Further work is needed to develop and validate the ideal formulation for a hyperosmolar irrigation solution with proven long-term benefits for patients undergoing arthroscopic surgeries., Competing Interests: J.L.C reports: Grants or contracts; AANA, Arthrex, Inc., GE Healthcare, National Institutes of Health (NIAMS & NICHD), Orthopaedic Trauma Association, Regenosine, AO Trauma, Collagen Matrix Inc., Musculoskeletal Transplant Foundation, OREF, PCORI, US Department of Defense.Royalties: Arthrex, Inc, Thieme, Musculoskeletal Transplant Foundation.Consulting fees: Arthrex, Collagen Matrix Inc., Bioventus, Trupanion.Leadership or fiduciary role: Journal of Knee Surgery, Midwest Transplant Network, Musculoskeletal Transplant Foundation.J.P.S reports: Grants or contracts: Arthrex, Inc, U.S. Department of Defense, National Institutes of Health (NIAMS & NICHD).Royalties: Thieme.Consulting fees: Arthrex, Inc, Orthopedic Designs North America, DePuy, A Johnson & Johnson Company, Smith & Nephew.Leadership or fiduciary role: American Orthopaedic Association, AO Foundation, AO North America, Journal of Knee Surgery, Mid-America Orthopaedic Association.A.M.S. Royalties from Musculoskeletal Transplant Foundation., (Thieme. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

Outbreaks caused by vancomycin-resistant enterococci that transcend jurisdictional boundaries are occurring worldwide. This study focused on a vancomycin-resistant enterococcus outbreak that occurred between 2018 and 2021 across two cities in Hiroshima, Japan. The study involved genetic and phylogenetic analyses using whole-genome sequencing of 103 isolates of vancomycin-resistant enterococci to identify the source and transmission routes of the outbreak. Phylogenetic analysis was performed using core genome multilocus sequence typing and core single-nucleotide polymorphisms; infection routes between hospitals were inferred using BadTrIP. The outbreak was caused by Enterococcus faecium sequence type (ST) 80 carrying the vanA plasmid, which was derived from strain A10290 isolated in India. Of the 103 isolates, 93 were E. faecium ST80 transmitted across hospitals. The circular vanA plasmid of the Hiroshima isolates was similar to the vanA plasmid of strain A10290 and transferred from E. faecium ST80 to other STs of E. faecium and other Enterococcus species by conjugation. The inferred transmission routes across hospitals suggest the existence of a central hospital serving as a hub, propagating vancomycin-resistant enterococci to multiple hospitals. Our study highlights the importance of early intervention at the key central hospital to prevent the spread of the infection to small medical facilities, such as nursing homes, with limited medical resources and a high number of vulnerable individuals., Competing Interests: The authors declare no conflict of interest.

Competing Interests: Conflict of interest: None declared.

An 8-year-old American Bulldog developed coalescing exophytic bulbous nodules that grew rapidly on the left pinna and a single cutaneous mass on the left flank. Histological examination of the pinnal biopsy by a diagnostic laboratory revealed a densely cellular neoplasm with haphazardly arranged round to spindle cells with high mitotic activity and epitheliotropism. The initial diagnosis was a poorly differentiated malignant neoplasm with differential diagnoses including melanoma, tumour of histiocytic origin and, less likely, a pleomorphic lymphoma. A panel of melanoma immunohistochemical markers and immunolabelling for CD18 were pursued. Neoplastic cells were immunopositive for CD18 but negative for Melan-A, PNL2, TRP-1 and TRP-2, suggestive of a histiocytic tumour or lymphoma. The left ear masses recurred, and more masses developed on the body. The pinnectomized ear was submitted to the University of Missouri Veterinary Medical Diagnostic Laboratory. Similar cells were seen and were immunolabelled for CD18 and CD3 but were immunonegative for SOX10, CD79a and CD20. PCR for antigen receptor rearrangements revealed a clonal rearrangement of T-cell receptor gamma. These findings enabled a final diagnosis of epitheliotropic T-cell lymphoma with spindle cell morphology. Lymphoma should be considered as a potential differential diagnosis for cutaneous nodules of spindle cell morphology and lymphocytic immunohistochemical markers should be included in diagnostic panels., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Kenji Kuroki and Akira Sato received research grants from Abbott Medical Japan, Inc. The remaining authors have no conflicts of interest to declare.

Inspired by a recent experiment showing that La&#95;{3}Ni&#95;{2}O&#95;{7} exhibits high T&#95;{c} superconductivity under high pressure, we theoretically revisit the possibility of superconductivity in this material. We find that superconductivity can take place, which is somewhat similar to that of the bilayer Hubbard model consisting of the Ni 3d&#95;{3z^{2}-r^{2}} orbitals. Although the coupling with the 3d&#95;{x^{2}-y^{2}} orbitals degrades superconductivity, T&#95;{c} can still be high enough to understand the experiment thanks to the very high T&#95;{c} reached in the bilayer Hubbard model.

Competing Interests: Conflict of interest: None declared.

Competing Interests: Conflict of interest: K.K. and A.S. have been granted research funding and honorarium by Biosense Webstar, Inc. M.Y. does not have a real or perceived conflict of interest.

The impact of long-term soy peptide consumption on mood-related behavior in adult male mice was studied under normal housing conditions. Male C57BL/6J mice were fed a modified AIN-93M diet containing 7% soy peptide for 70 d. Sucrose preference and tail suspension tests were conducted to evaluate anhedonia and despair, respectively. Mice fed soy peptide consumed more sucrose than those in the control group fed AIN-93M in the sucrose preference test. However, no significant difference was observed in the total immobility time between the two groups in the tail suspension test. These findings suggest that chronic soy peptide intake may attenuate anhedonia, a hallmark symptom of major depressive disorder characterized by decreased sensitivity to reward and pleasure.

Although guidelines recommend early aspirin administration after diagnosis of ST-elevation myocardial infarction (STEMI), the decision of pretransfer aspirin administration is at the discretion of the primary physicians. Therefore, this study aimed to determine whether pretransfer aspirin administration was associated with better angiographical outcomes in patients with STEMI. This study compared the angiographic findings of thrombolysis in myocardial infarction (TIMI) flow grade in the infarct-related artery before percutaneous coronary intervention (PCI) between patients who received pretransfer aspirin and those who did not. In total, 28 patients (11.2%) were administered aspirin before transfer and 219 (88.8%) were administered aspirin upon arrival at the hospital. Propensity score matching yielded 135 patients [27 patients (20%) who were administered aspirin before transfer and 108 patients (80%) who were administered aspirin upon arrival at the hospital]. Patients who received pretransfer aspirin had a higher rate of TIMI-3 flow before PCI compared to those who did not receive pretransfer aspirin [8 (28.6%) versus 15 (6.8%), P < 0.01, in all study patients; 8 (26.6%) versus 7 (6.5%), P < 0.01, in propensity-score-matched patients]. Multivariable logistic regression analysis revealed that pretransfer aspirin administration was significantly associated with the presence of TIMI-3 flow before PCI, independent of age, gender, transfer time, and statin use (OR: 5.43, 95% CI: 1.94-15.2, P < 0.01, in all study patients; OR: 6.17, 95% CI: 1.86-20.46, P < 0.01, in propensity-score-matched patients). Pretransfer aspirin administration could lead to the early restoration of coronary blood flow in patients with STEMI, supporting its active use in STEMI care.

Formation of borabicyclo[3.2.0]heptadiene derivatives was achieved via boron-insertion into aromatic C-C bonds in the photo-promoted skeletal rearrangement reaction of triarylboranes bearing an ortho-phosphino substituent (ambiphilic phosphine-boranes). The borabicyclo[3.2.0]heptadiene derivatives were fully characterized by NMR and X-ray analyses. The dearomatized products were demonstrated to undergo the reverse reaction in the dark at room temperature, realizing photochemical and thermal interconversion between triarylboranes and boron-doped bicyclic systems. Experimental and theoretical studies revealed that sequential two electrocyclic reactions involving E/Z-isomerization of an alkene moiety proceed via a highly strained trans-borepin intermediate., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The thermoelectric performance of RbZn 4- x Cu x As 3 crystallized in the KCu 4 S 3 -type structure was investigated. Samples were synthesized via solid-state reactions, followed by hot pressing. Hole carriers were doped by substituting Zn with Cu until x = 0.02, resulting in an increase of the power factor from 0.049 to 0.52 mW/mK 2 at T = 797 K. The lattice thermal conductivity was substantially low, with a value of 1.61 W/mK at T = 312 K, independent of doping. This can be attributed to the large vibration of the Rb atoms, as demonstrated by the neutron diffraction analysis. The maximum dimensionless figure of merit, ZT, was 0.53 at T = 797 K, representing the highest value for the 143-Zintl compounds. The result indicated that the 143-Zintl compounds could be a new class of high-performance thermoelectric materials., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Bipolar radiofrequency catheter ablation (RFCA) is a novel strategy for refractory or recurrent ventricular arrhythmias (VAs) resistant to conventional ablation methods. Lesions created during bipolar RFCA are larger than those created during sequential unipolar ablation. We present a case of refractory LV summit VAs, which identified the origin using a 2.7-F over-the-wire microelectrodes catheter, and it was successfully treated with bipolar RFCA in the acute phase., Competing Interests: Kenji Kuroki and Akira Sato have received research grant and honoraria from Abbott Medical Japan, LLC. All other authors have no conflicts to disclose., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Mast cells (MCs) are tissue-resident immune cells of a hematopoietic origin that play vital roles in innate and adaptive immunity. Human MCs can be isolated and differentiated from various tissue sources, including cord blood, when supplemented with cytokines such as stem cell factor, interleukin 3, and interleukin 6. Our current research study has shown significant differences in the marker expressions of human cord blood-derived mast cells (hCBMCs) based on donor dependency and the type of medium used for culturing and differentiation. These findings are particularly relevant given the challenges of obtaining specialty media influencing MC phenotypic marker expressions. We found that hCBMCs cultured in StemSpanTM-XF medium had a moderate expression of mast/stem cell growth factor receptor Kit (c-KIT) (mRNA and protein), low expressions of FcεRI (mRNA) and TLR2 (mRNA and protein) but had high levels of MRGPRX2 (mRNA and protein) expressions. In contrast, hCBMCs cultured in Stem Line II medium expressed FcεRI and TLR2 (mRNA and protein) with higher c-KIT but had lower MRGPRX2 expressions compared to the hCBMCs cultured in the StemSpanTM-XF medium. These results suggest that it is crucial to consider both donor dependency and the medium when investigating MC functions and that further research is needed to fully understand the impact of these factors on the hCBMC marker expressions.

Background: During electrophysiological mapping of tachycardias, putative target sites are often only truly confirmed to be vital after observing the effect of ablation. This lack of mapping specificity potentiates inadvertent ablation of innocent cardiac tissue not relevant to the arrhythmia. But if myocardial excitability could be transiently suppressed at critical regions, their suitability as targets could be conclusively determined before delivering tissue-destructive ablation lesions. We studied whether reversible pulsed electric fields (PF REV ) could transiently suppress electrical conduction, thereby providing a means to dissect tachycardia circuits in vivo., Methods: PF REV energy was delivered from a 9-mm lattice-tip catheter to the atria of 12 swine and 9 patients, followed by serial electrogram assessments. The effects on electrical conduction were explored in 5 additional animals by applying PF REV to the atrioventricular node: 17 low-dose (PF REV-LOW ) and 10 high-dose (PF REV-HIGH ) applications. Finally, in 3 patients manifesting spontaneous tachycardias, PF REV was applied at putative critical sites., Results: In animals, the immediate post-PF REV electrogram amplitudes diminished by 74%, followed by 78% recovery by 5 minutes. Similarly, in patients, a 69.9% amplitude reduction was followed by 84% recovery by 3 minutes. Histology revealed only minimal to no focal, superficial fibrosis. PF REV-LOW at the atrioventricular node resulted in transient PR prolongation and transient AV block in 59% and 6%, while PF REV-HIGH caused transient PR prolongation and transient AV block in 30% and 50%, respectively. The 3 tachycardia patients had atypical atrial flutters (n=2) and atrioventricular nodal reentrant tachycardia. PF REV at putative critical sites reproducibly terminated the tachycardias; ablation rendered the tachycardias noninducible and without recurrence during 1-year follow-up., Conclusions: Reversible electroporation pulses can be applied to myocardial tissue to transiently block electrical conduction. This technique of pulsed field mapping may represent a novel electrophysiological tool to help identify the critical isthmus of tachycardia circuits., Competing Interests: Disclosures Dr Reddy: Affera-Medtronic: consultant, equity (stock); other disclosures not related to this article are detailed in the Supplemental Material. Dr Koruth: Affera-Medtronic: grant support, stock, consultant. Dr Neuzil: Affera-Medtronic: grant support.

Background & Aims: The current standard treatment modality for advanced head and neck squamous cell carcinoma (HNSCC), namely platinum-based (PB) concurrent chemoradiotherapy (CRT), is associated with frequent severe mucositis which is responsible for the multiple acute and late adverse events. So far, effective preventive methods for this CRT-induced mucositis are not identified. In the current study, we examined the prophylactic effects of beta-hydroxy-beta-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) (HMB/Arg/Gln) mixture., Methods: Patients with HNSCC who were subject to PBCRT were randomly assigned to HMB/Arg/Gln intervention (Group I) and non-intervention (Group NI) cohort. The incidences of ≧ grade 3 mucositis (primary endpoint), ≧ grade 2 mucositis, and opioid usage and the degree of body weight loss (secondary endpoints) were compared between Group I and Group NI., Results: A total of 75 patients were enrolled to this study and 38 patients were assigned to Group I, while 37 patients were to Group NI. After excluding patients who failed to complete CRT (3 in Group I and 2 in Group NI) or withdrew consents (11 in Group I and 1 in Group NI), 24 patients in Group I and 34 patients in Group NI were evaluated. HMB/Arg/Gln failed to reduce the incidences of ≧ grade 2 mucositis, but significantly (p = 0.0003) inhibited grade 3 mucositis in the late phase CRT, reducing the incidence from 64.6% (Group NI) to 25% (Group I) at 70Gy. The degree of body weight loss was significantly (p = 0.0038) lower in Group I (5.6%) compared to Group NI (8.9%), preventing the progression of PBCRT-induced cachexia., Conclusions: HMB/Arg/Gln administration demonstrated inhibitory effects on the progression of grade 3 mucositis and cancer cachexia in HNSCC patients treated with PBCRT. A larger scale phase III study is encouraged., Clinical Trial Registration: This study is registered to the UMIN Clinical Trial Registry: UMIN000050011., Competing Interests: Declaration of competing interest We have nothing to disclose., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Bamboo charcoal (BC) powder is prepared from thick bamboo stems via dry distillation and is often used for food coloring. Due to the unique structure of the micropores in bamboo stems, BC powder also serves as an indigestible carrier to prevent the absorption of toxic substances and nutrients from the digestive tract. This study evaluated the health-promoting function of BC, particularly its effects in decreasing visceral adipose tissue in a mouse model with high-fat diet (HFD)-induced obesity. Four-week-old male C57BL/6J mice were divided into three groups and fed either a low-fat (LF) diet (7% fat), HF diet (25% fat), or HF diet with 0.5% BC (HF-BC). After 80 days, the HF-BC diet was found to have decreased epididymal and mesenteric white adipose tissue weights compared to HFD. The inhibition of visceral fat accumulation by BC intake was partly due to enhanced fecal fatty acid excretion induced by its bile acid-binding and pancreatic lipase inhibition. Contrarily, the gut microbiota, known to influence systemic energy metabolism, did not change significantly between the HF and HF-BC groups. These results indicate that dietary BC inhibits visceral fat accumulation, which could reduce obesity development., Competing Interests: AUTHOR DISCLOSURE STATEMENT KK and ST are employees of Kandagiko Co., Ltd., which supplied the bamboo charcoal. The other authors declare no conflict of interest., (Copyright © 2023 by The Korean Society of Food Science and Nutrition.)

Psoriasis is a long-lasting skin condition characterized by redness and thick silver scales on the skin's surface. It involves various skin cells, including keratinocytes, dendritic cells, T lymphocytes, and neutrophils. The treatments for psoriasis range from topical to systemic therapies, but they only alleviate the symptoms and do not provide a fundamental cure. Moreover, systemic treatments have the disadvantage of suppressing the entire body's immune system. Therefore, a new treatment strategy with minimal impact on the immune system is required. Recent studies have shown that sphingolipid metabolites, particularly ceramide and sphingosine-1-phosphate (S1P), play a significant role in psoriasis. Specific S1P-S1P-receptor (S1PR) signaling pathways have been identified as crucial to psoriasis inflammation. Based on these findings, S1PR modulators have been investigated and have been found to improve psoriasis inflammation. This review will discuss the metabolic pathways of sphingolipids, the individual functions of these metabolites, and their potential as a new therapeutic approach to psoriasis.

Long-term field monitoring of leaf pigment content is informative for understanding plant responses to environments distinct from regulated chambers but is impractical by conventional destructive measurements. We developed PlantServation, a method incorporating robust image-acquisition hardware and deep learning-based software that extracts leaf color by detecting plant individuals automatically. As a case study, we applied PlantServation to examine environmental and genotypic effects on the pigment anthocyanin content estimated from leaf color. We processed >4 million images of small individuals of four Arabidopsis species in the field, where the plant shape, color, and background vary over months. Past radiation, coldness, and precipitation significantly affected the anthocyanin content. The synthetic allopolyploid A. kamchatica recapitulated the fluctuations of natural polyploids by integrating diploid responses. The data support a long-standing hypothesis stating that allopolyploids can inherit and combine the traits of progenitors. PlantServation facilitates the study of plant responses to complex environments termed "in natura"., (© 2023. Springer Nature Limited.)

Objectives: Linezolid is an antibiotic used to treat infectious diseases caused by vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Recently, Enterococcus Spp.-carrying mobile linezolid resistance genes were reported. Herein, we report the complete genome sequence of Enterococcus raffinosus JARB-HU0741, which was isolated from a bile sample of a patient in Japan on May 5, 2021, and carries a linezolid resistance gene, cfr(B). Nevertheless, this isolate was susceptible to linezolid., Methods: Whole-genome sequencing was performed using HiSeq X FIVE (Illumina) and GridION (Oxford Nanopore Technologies). The sequence reads were assembled using Unicycler v0.4.8, and the complete genome was annotated using DFAST v1.2.18. Antimicrobial resistance genes were detected with Abricate v1.0.1, using the ResFinder database. The minimum inhibitory concentrations (MICs) were determined using broth microdilution and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute., Results: E. raffinosus JARB-HU0741 contained a 3 248 808-bp chromosome and a 1 156 277-bp megaplasmid. cfr(B) was present in the Tn6218-like transposon, which was inserted into a gene encoding a PRD domain-containing protein present in the megaplasmid, but the isolate was susceptible to linezolid (MIC, 0.5 µg/mL). The Tn6218-like transposon was similar to the Tn6218 of Clostridioides difficile Ox3196 and the Tn6218-like transposon of Enterococcus faecium UW11733; however, three genes encoding a topoisomerase, an S-adenosylmethionine-dependent methyltransferase, and a TetR family transcriptional regulator were present in the previous Tn6218- or Tn6218-like transposon., Conclusion: This is the first report of the complete genome sequence of E. raffinosus carrying cfr(B). E. raffinosus carrying cfr(B) without linezolid resistance poses a threat, as it could serve as a reservoir for mobile linezolid resistance genes., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: HBV infection causes chronic liver disease and leads to the development of HCC. To identify host factors that support the HBV life cycle, we previously established the HC1 cell line that maintains HBV infection and identified host genes required for HBV persistence., Methods: The present study focused on endothelial lipase (LIPG), which binds to heparan sulfate proteoglycans (HSPGs) in the cell membrane., Results: We found HBV infection was impaired in humanized liver chimeric mouse-derived hepatocytes that were transduced with lentivirus expressing short hairpin RNA against LIPG. Long-term suppression of LIPG combined with entecavir further suppressed HBV replication. LIPG was shown to be involved in HBV attachment to the cell surface by using 2 sodium taurocholate cotransporting peptide (NTCP)-expressing cell lines, and the direct interaction of LIPG and HBV large surface protein was revealed. Heparin and heparinase almost completely suppressed the LIPG-induced increase of HBV attachment, indicating that LIPG accelerated HBV attachment to HSPGs followed by HBV entry through NTCP. Surprisingly, the attachment of a fluorescently labeled NTCP-binding preS1 probe to NTCP-expressing cells was not impaired by heparin, suggesting the HSPG-independent attachment of the preS1 probe to NTCP. Interestingly, attachment of the preS1 probe was severely impaired in LIPG knockdown or knockout cells. Inhibitors of the lipase activity of LIPG similarly impaired the attachment of the preS1 probe to NTCP-expressing cells., Conclusions: LIPG participates in HBV infection by upregulating HBV attachment to the cell membrane by means of 2 possible mechanisms: increasing HBV attachment to HSPGs or facilitating HSPG-dependent or HSPG-independent HBV attachment to NTCP by its lipase activity., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Recent studies have identified a subtype of the S1P-receptor family called sphingosine-1-phosphate receptor 2 (S1PR2), which plays a crucial role in maintaining the skin barrier. It has been observed that S1PR2 and Staphylococcus epidermidis ( S. epidermidis ) work together to regulate the skin barrier. However, the interaction between these two factors is still unclear. To investigate this, a study was conducted on healthy skin and allergic contact dermatitis (ACD) using 3,4-Dibutoxy-3-cyclobutene-1,2-dione (SADBE) on the ears of S1pr2 fl/f l and S1pr2 fl/f l K14-Cre mice and using 1 × 10 6 CFU of S. epidermidis to examine its effects on the skin. The results showed that in S. epidermidis -conditioned ACD, the ear thickness of S1pr2 fl/f l K14-Cre mice was lower than that of S1pr2 fl/f l mice, and mRNA expressions of Il-1β and Cxcl2 of S1pr2 fl/f l K14-Cre mice were lower than that of S1pr2 fl/f l mice in ACD with S. epidermidis . Furthermore, the gene expression of Claudin-1 and Occludin in S1pr2 fl/f l K14-Cre mice was higher than that of S1pr2 fl/f l mice in ACD with S. epidermidis . The study concludes that S. epidermidis colonization improves the skin barrier and prevents ACD even when S1P signaling malfunctions.