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We successfully constructed a heterologous expression system for L-glutamate oxidase from the marine actinomycete Streptomyces lydicamycinicus NBRC 110027 (Sl-LGOX) in Escherichia coli BL21(DE3) as a host. This is the first example of L-glutamate oxidase from a marine microorganism. A chemically synthesized gene optimized for codon usage in E. coli was used as the inserted fragment, which was effective for enzyme expression. We expressed Sl-LGOX in the soluble fraction of E. coli BL21(DE3)/pET21b-Sl-lgox. We also succeeded in purifying recombinant Sl-LGOX (rSl-LGOX) to homogeneity from the cell-free extract of this clone via an Ni-NTA column. rSl-LGOX showed high specificity for L-Glu and was active and stable over a wide range of temperatures and pH values. In particular, it showed high specific activity and stability at an acidic pH. A variety of applications can take advantage of the unique enzymatic properties of rSl-LGOX., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

An 8-year-old boy developed serpiginous erythema on the soles of his feet and was diagnosed with cutaneous larva migrans (CLM). Following treatment with ivermectin, the erythema improved within 7 days, but it recurred 14 days later, requiring a second dose for complete resolution. Ultrasound and MRI did not reveal any parasites, but fluctuations in eosinophils, IgE and IgA levels were observed during treatment. This case highlights the importance of combining multiple diagnostic methods to evaluate treatment effectiveness., (© 2024 John Wiley & Sons Ltd.)

Purpose: Early surgery for infective endocarditis with intracranial hemorrhage can cause severe bleeding, which is correlated with an increased mortality. In 2005, we started using nafamostat mesilate and low-dose heparin as anticoagulants during cardiopulmonary bypass for early surgery. The outcomes of this strategy have been reviewed., Methods: All patients who underwent cardiac surgery for active infective endocarditis with intracranial hemorrhage between 2005 and 2023 were evaluated., Results: There were 23 consecutive patients (median age 62 years old). Ten patients (43%) had neurologic deficits. The indication for early surgery in most patients was the presence of mobile vegetation or existing embolic events (18 of 23, 78%). No complications were associated with cardiopulmonary bypass. The median interval between the diagnosis and surgery was two days. There was 1 early death (4%) due to sepsis. There was no exacerbation of intracranial hemorrhage. One patient had new ectopic microbleeds without deterioration of neurologic findings. One patient had a new-onset cerebral infarction with neurologic deficits. None of the patients exhibited neurologic deterioration. The median follow-up duration was 26 months. overall survival was 90.7% after 5 years., Conclusions: Our strategy of using nafamostat mesilate enabled us to safely perform early surgery in patients with intracranial hemorrhage without hemorrhage exacerbation., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest., (© 2024. The Author(s).)

Nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and its pathogenic mechanism is mediated by both loss-of-function and gain-of-toxicity of TDP-43. However, the role of TDP-43 gain-of-toxicity in oligodendrocytes remains unclear. To investigate the impact of excess TDP-43 on oligodendrocytes, we established transgenic mice overexpressing the ALS-linked mutant TDP-43 M337V in oligodendrocytes through crossbreeding with Mbp-Cre mice. Two-step crossbreeding of floxed TDP-43 M337V and Mbp-Cre mice resulted in the heterozygous low-level systemic expression of TDP-43 M337V with (Cre-positive) or without (Cre-negative) oligodendrocyte-specific overexpression of TDP-43 M337V . Although Cre-negative mice also exhibit subtle motor dysfunction, TDP-43 M337V overexpression in oligodendrocytes aggravated clasping signs and gait disturbance accompanied by myelin pallor in the corpus callosum and white matter of the lumbar spinal cord in Cre-positive mice. RNA sequencing analysis of oligodendrocyte lineage cells isolated from whole brains of 12-month-old transgenic mice revealed downregulation of myelinating oligodendrocyte marker genes and cholesterol-related genes crucial for myelination, along with marked upregulation of apoptotic pathway genes. Immunofluorescence staining showed cleaved caspase 3-positive apoptotic oligodendrocytes surrounded by activated microglia and astrocytes in aged transgenic mice. Collectively, our findings demonstrate that an excess amount of ALS-linked mutant TDP-43 expression in oligodendrocytes exacerbates motor dysfunction in mice, likely through oligodendrocyte dysfunction and neuroinflammation. Therefore, targeting oligodendrocyte protection, particularly through ameliorating TDP-43 pathology, could represent a potential therapeutic approach for ALS., Competing Interests: Declarations. Ethics approval and consent to participate: The experiments using genetically modified mice were approved by the Animal Care and Use Committee and the recombinant DNA experiment committee of Nagoya University (approval numbers RIEM240005, and #143, respectively). Consent for publication: Not applicable. Competing interests: The authors report no biomedical financial interests or potential conflicts of interest., (© 2024. The Author(s).)

Alzheimer's disease (AD) is the most common form of dementia and is characterized by the accumulation of amyloid β (Aβ) and phosphorylated tau. Neuroinflammation, mainly mediated by glial activation, plays an important role in AD progression. Although there is growing evidence for the anti-neuroinflammatory and neuroprotective effects of the cannabinoid system modulation, the detailed mechanism remains unclear. To address these issues, we analyzed the expression levels of cannabinoid receptor type II (Cnr2/Cb2) in App NL-G-F/NL-G-F mice and human AD precuneus, which is vulnerable to amyloid deposition in AD, and the effects of JWH 133, a selective CB2 agonist, on neuroinflammation in primary glial cells and neuroinflammation and cognitive impairment in App NL-G-F/NL-G-F mice. The levels of Cnr2/Cb2 were upregulated in microglia isolated from the cerebral cortex of App NL-G-F/NL-G-F mice. CNR2 expression was also increased in RNAs derived from human precuneus with advanced AD pathology. Chronic oral administration of JWH 133 significantly ameliorated the cognitive impairment of App NL-G-F/NL-G-F mice without neuropsychiatric side effects. Microglia and astrocyte mRNAs were directly isolated from the mouse cerebral cortex by magnetic-activated cell sorting, and the gene expression was determined by quantitative PCR. JWH 133 administration significantly decreased reactive astrocyte markers and microglial C1q, an inducer for the reactive astrocytes in App NL-G-F/NL-G-F mice. In addition, JWH133 administration inhibited the expression of p-STAT3 (signal transducer and activator of transcription 3) in astrocytes in App NL-G-F/NL-G-F mice. Furthermore, JWH 133 administration suppressed dystrophic presynaptic terminals surrounding amyloid plaques. In conclusion, stimulation of microglial CB2 ameliorates cognitive dysfunction in App NL-G-F/NL-G-F mice by controlling astrocyte activation and inducing beneficial neuroinflammation, and our study has implications that CB2 may represent an attractive therapeutic target for the treatment of AD and perhaps other neurodegenerative diseases involving neuroinflammation., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The experiments using human brains were approved by the Ethics Committees at Nagoya University (approval number #328) and Tokyo Metropolitan Institute (approval number # R21-145). Informed consent was obtained from their families. The experiments using genetically modified mice were approved by the Animal Care and Use Committee and the recombinant DNA experiment committee of Nagoya University (approval numbers R240025 and R240026, and #143, respectively). All procedures were conducted in accordance with the Declaration of Helsinki., (© 2024. The Author(s).)

Renal fibrosis occurs during renal failure progression and is exacerbated by oxidative stress. Oral silicon-based agents generate high intestinal hydrogen levels and reduce systemic oxidative stress. Therefore, in this study, we aimed to verify the efficacy of silicon-based agents against renal fibrosis and elucidate their underlying mechanisms in a unilateral ureteral obstruction mouse model. The mice were grouped based on the treatment provided. Comparisons between the groups were performed on postoperative days 1 and 14. On postoperative day 14, renal fibrosis, tubular cell apoptosis, and transforming growth factor-β and 4-hydroxy-2-nonenal expression were significantly reduced in the silicon-treated group (P < 0.05). Following RNA-sequencing on tissues extracted on postoperative day 14, pathway enrichment analysis was performed, revealing significant downregulation of various pathways associated with tissue fibrosis in mice in the silicon-treated group. Using tissues extracted on postoperative day 1, RNA sequencing and immunohistochemical analysis were performed. We found that complement component 3 expression was significantly reduced in mice treated with a silicon-based agent. Oxidative stress, tubular cell death, pro-fibrotic factors, and renal fibrosis were suppressed in our model following treatment with a silicon-based agent. Moreover, complement component 3 activity was inhibited during the early postoperative phase. Here, we showed that silicon-based agents represent potential novel therapeutic options against renal fibrosis., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Derivatization is essential for optimizing organic material properties. However, because functional groups are often introduced at an early stage of the synthesis, similar intermediates have to be repeatedly synthesized to produce derivatives, which amounts to a daunting and time-consuming task. Using thienobenzobisthiazole (TBTz) as a building unit of donor polymers for organic photovoltaics (OPVs), we demonstrate an efficient derivatization of a TBTz-based π-conjugated polymer by late-stage functionalization. In the developed synthetic route, functional groups are introduced at the last step of monomer synthesis, enabling us to easily synthesize several derivatives from a common intermediate. Ester and acyl groups are introduced into the polymer instead of the alkyl group, giving rise to deep HOMO energy levels and resulting in OPV cells with high open-circuit voltage even in the absence of halogen substituents that are typically introduced into the donor polymers. Notably, the ester-functionalized TBTz-based polymer shows a small nonradiative voltage loss (ΔV nr ) of 0.19 V and has one of the highest charge generation efficiencies among the halogen-free donor polymers with similar ΔV nr , improving the critical trade-off relationship between voltage loss and charge generation. Our results provide an important guideline for the efficient development of high-performance polymers for OPVs., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objective: Surgical intervention is commonly necessary for craniosynostosis. One of the preoperative concerns revolves around the cerebral venous drainage pattern and its potential involvement during surgery. Although there have been reports regarding venous drainage patterns in syndromic craniosynostosis, studies of nonsyndromic cases have been rare. In the present study, the aim was to study venous drainage patterns in nonsyndromic craniosynostosis., Methods: Nonsyndromic cases at a single institute were retrospectively reviewed, and cerebral venous drainage in the posterior (transverse sinus [TS]) and anterior (cavernous sinus [CS] and para-CS [ParaCS]) venous routes was systematically investigated. The occipital sinus (OS) and emissary veins were also evaluated., Results: A total of 89 nonsyndromic cases were evaluated, including 12 right coronal synostosis (RCS), 14 left coronal synostosis (LCS), 15 bilateral coronal synostosis (BCS), 36 sagittal synostosis, 6 metopic synostosis, and 6 combined metopic-sagittal synostosis cases. All venous studies were performed using MR venography. There was a significant difference among all six groups in TS dominance (p = 0.0108). In unilateral coronal synostosis (UCS; including RCS and LCS) cases, 76.9% had TS dominance on the opposite side of the synostotic suture (20 of 26 UCS, including 10 of 12 RCS and 10 of 14 LCS). There was a significant difference in the incidence of OS, with the highest incidence observed in the BCS group (33.3%, p = 0.027). CS/ParaCS venous drainage was observed in 94.4% of cases on the right side and 95.5% on the left side, showing no significant difference among the groups on both sides. No visible emissary vein was observed in any of the groups., Conclusions: A significantly higher predominance of left TS was found in RCS cases, in contrast with the typical right-side predominance seen in the normal population. In addition, the majority of UCS cases exhibited TS dominance on the opposite side of the synostotic suture. Furthermore, the present results showed a significant difference in the prevalence of OS, which was predominantly observed in BCS cases. These findings could be explained by the induction effect on venous sinuses by the compensatory growth of the skull according to Virchow's law, suggesting that synostotic sutures induce compensatory skull expansion in regions farthest (diagonally) from the affected sutures, thereby enlarging nearby venous sinuses.

Tokyo Electric Power Company, TEPCO, has started tritiated water release into the Pacific Ocean. In order to reduce unreasonable rumor caused by tritium release, flounder, abalone, and sarggasum were exposed to tritium enriched seawater, and time dependent Tissues Free Water Tritium (TFWT) concentration was measured. Estimating the concentration of Organically Bound Tritium (OBT) is important to assess tritium impact because it has a longer biological half-life than TFWT. Current models estimate OBT concentrations using TFWT concentration. Understanding equilibration time is critical for making accurate TFWT concentration predictions. TFWT intake rate was analysed by the compartment model., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Pyoderma gangrenosum (PG) is a rapidly progressive disease characterized by deep ulcers, predominantly in the lower extremities. Adalimumab, a monoclonal antibody against tumor necrosis factor alpha, is the first drug approved for PG treatment in Japan, ahead of other countries. We conducted a multicenter, open-label, post-marketing observational study to evaluate the safety and effectiveness of adalimumab in Japanese patients with PG. Of 67 patients enrolled, 37 in the safety analysis set and 32 in the effectiveness analysis set were included in this interim analysis. (Nineteen patients whose case report forms were not collected and 11 whose data were not fixed by the data cut-off date were excluded from the study). In the safety analysis set, the mean age was 62.9 years and 86.5% of patients had comorbidities, including ulcerative colitis (21.6%), diabetes mellitus (18.9%), and hypertension (10.8%); subtypes of PG included ulcerative (n = 33), vegetative (n = 2), and pustular (n = 2). Mean exposure duration to adalimumab was 185.5 days. Systemic steroids were used before (70.3%) and during (56.8%) adalimumab treatment. The incidence proportion of overall adverse drug reactions was 18.9%. The incidence proportions of all infections and serious infections reported as adverse drug reactions were 13.5% and 10.8%, respectively. The proportion of patients with a Physician Global Assessment score (total lesions) of 0/1 at weeks 12, 26, and 52 was 42.9%, 36.8%, and 50.0%, respectively. This interim analysis revealed the characteristics of Japanese patients with PG treated with adalimumab in the actual clinical setting and the real-world safety and effectiveness of adalimumab. At the time of the interim analysis, adalimumab treatment was generally well tolerated, and no new safety concerns were detected. Further follow-up of this study will provide a more detailed understanding of the long-term safety and effectiveness of adalimumab in patients with PG refractory to conventional treatments., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Kidney transplantation is the most optimal treatment for patients with end-stage renal disease, offering significant improvements in patient outcomes over dialysis. However, the potential for immune rejection, where the recipient's immune system attacks the transplanted kidney, can compromise transplant success. The complement system, a key component of the immune response, plays a crucial role in both acute and chronic rejection, including T-cell- and antibody-mediated rejection. Understanding and controlling the complement system is essential for managing rejection and enhancing graft survival and overall success of kidney transplantation. In allogeneic transplantation, complement activation through various pathways contributes to graft damage and failure. Recent advancements in genetic engineering enable the development of transgenic pigs expressing human complement regulatory proteins, which display potential for reducing rejection in xenotransplantation. Despite these advances, the complex mechanisms of complement activation and regulation are not fully understood, necessitating further research. This review examines the role of the complement system in kidney transplantation, explores the latest developments in complement regulatory strategies, and discusses potential therapeutic approaches to improve transplant outcomes., 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. Published by Elsevier Inc.)

This study investigates backbone engineering and evaluates the thermoelectric properties of FeCl 3 -doped naphthobisthiadiazole (NTz)-based donor-acceptor (D-A) conjugated polymer films. The NTz acceptor unit is coupled with three distinct donor units, namely dialkylated terthiophene (3T), dialkylated quaterthiophene (4T), and dialkylated bisthienyl thienothiophene (2T-TT) to yield copolymers designated as PNTz3T, PNTz4T, and PNTzTT. The difference in donor units leads to diverse molecule stacking and electronic properties, which can be systematically discovered via the three polymers. The linear structure of PNTz4T enables an orderly arrangement of side chains, thereby promoting dopant intercalation for enhanced carrier concentration. Additionally, this linear structure leads to an edge-on stacking mode, thereby improving the in-plane carrier mobility. As a result, the doped PNTz4T exhibits the highest electrical conductivity (σ) of 88.3 S cm -1 along with a Seebeck coefficient (S) of 62.2 µV K -1 , thereby achieving the highest power factor (PF) of 34.2 µW m -1 K -2 . These results highlight the relationship between the molecular design, microstructure, and doping effects in manipulating the thermoelectric performance of doped NTz-based D-A polymers., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

An 86-year-old woman with residual left hemiplegia from a prior stroke, residing in a nursing facility, presented with swelling of the right side of her neck. Tuberculous lymphadenitis was diagnosed through polymerase chain reaction analysis and sputum culture, leading to treatment with isoniazid, rifampicin, and ethambutol. After 2 months, an abscess and ulcer formed; analysis of the bacterial flora of the ulcer revealed a Pseudomonas infection. Treatment with a topical iodine-containing ointment eradicated the Pseudomonas and led to increased diversity with the emergence of species from the Eukaryota and Archaea kingdoms. Subsequently, a loss of diversity occurred, ultimately resulting in a dominance of Escherichia-Shigella. We suggest that the bacterial flora of early ulcers may be dominated by multidrug-resistant Pseudomonas. Escherichia-Shigella may emerge during the ulcer healing process. We, therefore, strongly encourage recognition of the fact that individuals with tuberculosis are immunocompromised and emphasize the critical importance of early intervention in such infections., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients' quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine's impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ.

Myelin oligodendrocyte glycoprotein (MOG)-associated disorders are inflammatory demyelinating diseases of the CNS. Cerebral cortical encephalitis (CCE) is characterized by cortical fluid-attenuated inversion recovery hyperintensity with seizures and headaches. We report two cases of MOG antibody-associated CCE (MOG-CCE) evaluated using serial MRI sequences, including arterial spin labeling (ASL), pre- and posttreatment. In both patients, ASL demonstrated hyperperfusion correlating with disease activity, which normalized following steroid therapy. Our cases highlight the usefulness of ASL in early detection, monitoring, and assessment of treatment response in MOG-CCE., 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.

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of AREG in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC.

Introduction: Understanding of adverse reactions to coronavirus disease 2019 vaccines remains limited., Case Presentation: Case 1: A 52-year-old woman, post-kidney transplantation, experienced sudden vision loss in her left eye after receiving a second dose of coronavirus disease 2019 vaccine. She was diagnosed with ischemic optic neuropathy.Case 2: A 53-year-old woman, post-kidney transplantation, presented with worsening diplopia and left eye pain following the second dose of coronavirus disease 2019 vaccine. She was diagnosed with left abducens nerve palsy., Conclusion: Vigilance is essential for recognizing the potential for delayed cranial neuropathy in immunocompromised individuals after coronavirus disease 2019 vaccination., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Macrophages in the tumor microenvironment, termed tumor-associated macrophages (TAMs), promote the progression of various cancer types. However, many mechanisms related to tumor-stromal interactions in epithelial ovarian cancer (EOC) progression remain unclear. High-grade serous ovarian carcinoma (HGSOC) is the most malignant EOC subtype. Herein, immunohistochemistry was performed on 65 HGSOC tissue samples, revealing that patients with a higher infiltration of CD68 + , CD163 + , and CD204 + macrophages had a poorer prognosis. We subsequently established an indirect co-culture system between macrophages and EOC cells, including HGSOC cells. The co-cultured macrophages showed increased expression of the TAM markers CD163 and CD204, and the co-cultured EOC cells exhibited enhanced proliferation, migration, and invasion. Cytokine array analysis revealed higher YKL40 secretion in the indirect co-culture system. The addition of YKL40 increased proliferation, migration, and invasion via extracellular signal-regulated kinase (Erk) signaling in EOC cells. The knockdown of integrin β4, one of the YKL40 receptors, suppressed YKL40-induced proliferation, migration, and invasion, as well as Erk phosphorylation in some EOC cells. Database analysis showed that high-level expression of YKL40 and integrin β4 correlated with a poor prognosis in patients with serous ovarian carcinoma. Therefore, the YKL40/integrin β4 axis may play a role in ovarian cancer progression.

Spinal and bulbar muscular atrophy (SBMA) progressively impairs gait function, resulting in the need for patients to use a wheelchair approximately 20 years after onset. No reports have investigated the effects of long-term exercise training using the Hybrid Assisted Limb (HAL) in patients with multiple SBMA. This study investigated the effects of long-term exercise training using HAL in patients with SBMA and its effects on the quality of life (QoL). Six courses of HAL treatment were administered to three males with SBMA, and leuprorelin was administered to each patient. Each course had a 4-5 week duration, during which the treatment was performed nine times, with a rest period of at least 2 months between each course. A 2-minute walk test (2MWT) and a 10-m walk test (10MWT) were performed to measure gait ability, and a blood test to measure the serum creatine kinase (CK) and creatinine (CRE) levels was performed before and after each course of treatment. We evaluated QoL using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). The average 2MWT distance improved over 2 years (p = 0.038), and the 10MWT showed neither improvement nor decline. No increase or decrease in serum CK or CRE levels was observed. There were no significant changes in the SF-36 physical, mental, or social summary scores. In combination with leuprorelin therapy, robot-assisted training using HAL maintained gait ability and QoL in patients with SBMA for 2 years., 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. Published by Elsevier Ltd.)

The interleukin (IL)-1 superfamily upregulates immune responses and maintains homeostasis between the innate and adaptive immune systems. Within the IL-1 superfamily, IL-36 plays a pivotal role in both innate and adaptive immune responses. Of the four IL-36 isoforms, three have agonist activity (IL-36α, IL-36β, IL-36γ) and the fourth has antagonist activity (IL-36 receptor antagonist [IL-36Ra]). All IL-36 isoforms bind to the IL-36 receptor (IL-36R). Binding of IL-36α/β/γ to the IL-36R recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates downstream signalling pathways mediated by nuclear transcription factor kappa B and mitogen-activated protein kinase signalling pathways. Antagonist binding of IL-36Ra to IL-36R inhibits recruitment of IL-1RAcP, blocking downstream signalling pathways. Changes in the balance within the IL-36 cytokine family can lead to uncontrolled inflammatory responses throughout the body. As such, IL-36 has been implicated in numerous inflammatory diseases, notably a type of pustular psoriasis called generalized pustular psoriasis (GPP), a chronic, rare, potentially life-threatening, multisystemic skin disease characterised by recurrent fever and extensive sterile pustules. In GPP, IL-36 is central to disease pathogenesis, and the prevention of IL-36-mediated signalling can improve clinical outcomes. In this review, we summarize the literature describing the biological functions of the IL-36 pathway. We also consider the evidence for uncontrolled activation of the IL-36 pathway in a wide range of skin (e.g., plaque psoriasis, pustular psoriasis, hidradenitis suppurativa, acne, Netherton syndrome, atopic dermatitis and pyoderma gangrenosum), lung (e.g., idiopathic pulmonary fibrosis), gut (e.g., intestinal fibrosis, inflammatory bowel disease and Hirschsprung's disease), kidney (e.g., renal tubulointerstitial lesions) and infectious diseases caused by a variety of pathogens (e.g., COVID-19; Mycobacterium tuberculosis, Pseudomonas aeruginosa, Streptococcus pneumoniae infections), as well as in cancer. We also consider how targeting the IL-36 signalling pathway could be used in treating inflammatory disease states., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Hyponatremia is the most common clinical electrolyte disorder. Chronic hyponatremia has been recently reported to be associated with falls, fracture, osteoporosis, neurocognitive impairment, and mental manifestations. In the treatment of chronic hyponatremia, overly rapid correction of hyponatremia can cause osmotic demyelination syndrome (ODS), a central demyelinating disease that is also associated with neurological morbidity and mortality. Using a rat model, we have previously shown that microglia play a critical role in the pathogenesis of ODS. However, the direct effect of rapid correction of hyponatremia on microglia is unknown. Furthermore, the effect of chronic hyponatremia on microglia remains elusive. Using microglial cell lines BV-2 and 6-3, we show here that low extracellular sodium concentrations (36 mmol/L decrease; LS) suppress Nos2 mRNA expression and nitric oxide (NO) production of microglia. On rapid correction of low sodium concentrations, NO production was significantly increased in both cells, suggesting that acute correction of hyponatremia partly directly contributes to increased Nos2 mRNA expression and NO release in ODS pathophysiology. LS also suppressed expression and nuclear translocation of nuclear factor of activated T cells-5 (NFAT5), a transcription factor that regulates the expression of genes involved in osmotic stress. Furthermore, overexpression of NFAT5 significantly increased Nos2 mRNA expression and NO production in BV-2 cells. Expressions of Nos2 and Nfat5 mRNA were also modulated in microglia isolated from cerebral cortex in chronic hyponatremia model mice. These data indicate that LS modulates microglial NO production dependent on NFAT5 and suggest that microglia contribute to hyponatremia-induced neuronal dysfunctions., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Chronic stress can cause hypertension, whereas daily exercise promotes healthy well being through destressing. Although the nucleus of the solitary tract (NTS) is involved in the development of hypertension, the molecular and physiological mechanisms of stress and exercise remain unclear. In this study, we tested whether gene expression in the NTS is altered by stress and daily exercise and whether this is involved in cardiovascular regulation., Methods: We have performed RT 2 Profiler PCR arrays targeting a panel of neurotransmitter receptor genes in the NTS of Wistar rats subjected to chronic restraint stress (1 h a day over 3 weeks) with or without voluntary wheel exercise. We also performed immunohistochemistry to determine whether the identified molecules were expressed at the protein level. Additionally, microinjection studies in anesthetized rats were performed to examine whether validated molecules exhibit physiological roles in cardiovascular regulation of the NTS., Results: We observed that blood pressure was significantly increased by stress and the increase was suppressed by exercise. Using PCR analysis, we determined that the expression levels of four genes in the NTS, including the dopamine receptor D1 gene ( Drd1 ), were significantly affected by stress and suppressed by exercise. We also examined dopamine D1 receptor (D1R) expression in NTS neurons and found significantly greater expression in the stressed than nonstressed animals. Furthermore, the microinjection of a D1R agonist into the NTS in anesthetized rats induced hypotensive effects., Conclusion: These results suggest that NTS D1R plays a role in the counteracting processes of stress-induced hypertension., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: None disclosed.

Background: Accurate preoperative evaluation of renal function in living kidney donor candidates (LKDCs) is crucial to prevent kidney failure after nephrectomy. We examined the performance of various estimated glomerular filtration rate (eGFR) equations, including the new chronic kidney disease epidemiology collaboration (CKD-EPI) equation in LKDCs., Methods: We analyzed 752 LKDCs who were assessed for measured GFR by inulin clearance as part of routine pretransplant examination from 2006 to 2020. CKD-EPI2012 from cystatin C (CKD-EPI12cys), CKD-EPI2021 from creatinine (CKD-EPI21cr), CKD-EPI21cr-cys, Japanese modified (JPN) eGFRcr, and JPN eGFRcys were compared in determining the suitability for LKDCs., Results: CKD-EPI12cys had the lowest absolute and relative biases, with higher P 30 and P 10 , followed by JPN eGFRcys, CKD-EPI21cr, and CKD-EPI21cr-cys. The root mean square error was least for CKD-EPI12cys, then JPN eGFRcys, CKD-EPI21cr-cys, CKD-EPI21cr, and JPN eGFRcr. CKD-EPI21cr, CKD-EPI12cys, and CKD-EPI21cr-cys estimated GFR higher, whereas JPN eGFRcr estimated GFR lower. At the threshold of 90 mL/min/1.73 m 2 , CKD-EPI21cr had the highest percentage of misclassification at 37.37%, whereas JPN eGFRcr had the lowest percentage of misclassification at 6.91%. Using the age-adapted approach, JPN eGFRcr had the lowest percentage of misclassification into overestimation at 7.31%. All eGFR had >5.0%, and CKD-EPI21cr had the highest percentage of misclassification at 21.94%. Conversely, CKD-EPI21cr-cys had the lowest percentage of misclassification into underestimation at 3.19%, both at the threshold of 90 mL/min/1.73 m 2 and the age-adapted approach. JPN eGFRcr had the highest percentage at 33.38% and 40.69%, respectively., Conclusions: In evaluating the renal function of Japanese LKDCs, the new CKD-EPI equation had a lower rate of underestimation but a relatively high rate of overestimation. New GFR estimation formulas are needed to be tailored to each ethnic group to enhance the accuracy and reliability of donor selection processes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objective: In the loop technique for mitral valve repair, the loop bundles are usually created during cardiac arrest after chordal length measurements, which seems time-consuming and less reproducible. To address this issue, we determined the loop length preoperatively using 4-dimensional computed tomography., Methods: The loop length was determined on the basis of the distance from the papillary muscle head to the free margin of nonprolapsing leaflet corresponding to the prolapsed leaflet, to which the loops would be secured. Measurements were made on the commissural and long-axis views created by a medical image post-processor in the late systolic phase. This technique was used in consecutive 45 patients undergoing mitral valve repair with the loop technique since April 2021., Results: A total of 55 loop bundles were created in 45 patients; in 10 cases loop bundles were fixed to both anterior and posterior papillary muscles. There were 31 posterior, 6 anterior, and 8 bileaflet prolapse. The loop length was set at 16 to 26 mm (median 19 mm). Mitral valve repair was successfully completed in all patients, and the loop bundles of predetermined length were used successfully in 42 patients (93.3%). Postoperative echocardiography revealed none/trace regurgitation in 41 and mild regurgitation in 4. There was no hospital mortality or major postoperative complication. During 4 to 35 months follow-up (median 10 months), no case required reintervention for the mitral valve., Conclusions: Preoperative measurements using 4-dimensional computed tomography can accurately and reproducibly predict the required loop length for mitral valve repair., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Since the approval of commercially manufactured stent grafts in Japan in 2008, thoracic endovascular aortic repair (TEVAR) has rapidly gained popularity as an alternative treatment for high-risk patients due to its advantage of not requiring a large thoracotomy or cardiopulmonary bypass. TEVAR has also been attempted for acute Stanford type B aortic dissections, leading to a paradigm shift in treatment strategies. To successfully perform TEVAR, meticulous preoperative preparation is essential, similar to open surgery. This paper aims to provide an overview of the practical aspects of TEVAR.

Bacteria produce polycationic homopoly(amino acid)s, which are characterized by isopeptide backbones. We previously demonstrated that two representative bacterial polycationic isopeptides, ε-poly-l-α-lysine consisting of 25-35 l-α-lysine residues (ε-PαL 25-35 ) and ε-poly-l-β-lysine consisting of l-β-lysine residues (ε-PβL 4-13 ), were internalized into mammalian cells by both energy-independent direct penetration and energy-dependent endocytosis/macropinocytosis, and then diffused throughout the cytosol. In this study, we investigated the cell-penetrating activity of an ε-PαL short-chain derivative consisting of 5-14 l-α-lysine residues (ε-PαL 5-14 ) to gain insight into the relationship between the isopeptide-chain length and the manner of cellular internalization. We prepared a conjugate of ε-PαL 5-14 and a fluorescent dye (FAM) by click chemistry, and incubated the resulting polymer, ε-PαL 5-14 -FAM, with HeLa cells. Unlike ε-PαL 25-35 -FAM, ε-PαL 5-14 -FAM was internalized into cells only by energy-dependent endocytosis/macropinocytosis. Furthermore, a high concentration (>50 μM) was required for the internalization events. ε-PαL 5-14 has a chain length almost equal to that of the membrane permeable ε-PβL 4-13 , which can enter cells at low concentrations. Considering that the basicity of the β-amino group is higher than that of α-amino acid at physiological pH, ε-PβL is expected to have a greater cell-penetrating capacity than ε-PαL, provided their isopeptide-chain lengths are similar, suggesting that a more extended chain derivative of ε-PβL would be more advantageous for cellular internalization of cargo proteins than ε-PαL 25-35 ., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of the study was to evaluate the efficacy and safety of pre-emptive transcatheter arterial embolization (P-TAE) of aortic side branches to prevent type II endoleak in patients with abdominal aortic aneurysm after endovascular abdominal aneurysm repair (EVAR)., Materials and Methods: This multicenter, prospective, single-arm trial enrolled 100 patients with abdominal aortic aneurysm from nine hospitals between 2018 and 2021. There were 85 men and 15 women, with a mean age of 79.6 ± 6.0 (standard deviation) years (range: 65-97 years). P-TAE was attempted for patent aortic side branches, including the inferior mesenteric artery, lumbar arteries, and other branches. The primary endpoint was late type II endoleak incidence at 6 months post-repair. Secondary endpoints included changes in aneurysmal sac diameter at 6- and 12 months, complications, re-intervention, and aneurysm-related mortality. Aneurysm sac changes at 6- and 12 months was compared between the late and no-late type II endoleak groups., Results: Coil embolization was successful in 80.9% (321/397) of patent aortic side branches, including 86.3% of the inferior mesenteric arteries, 80.3% of lumbar arteries, and 55.6% of other branches without severe adverse events. Late type II endoleak incidence at 6 months was 8.9% (8/90; 95% confidence interval: 3.9-16.8%). Aneurysm sac shrinkage > 5 mm was observed in 41.1% (37/90) and 55.3% (47/85) of the patients at 6- and 12-months post-EVAR, respectively. Patients with late type II endoleak had less aneurysm sac shrinkage than those without type II endoleak at 12 months (-0.2 mm vs. -6.0 mm; P = 0.040). No patients required re-intervention for type II endoleak, and no aneurysm-related mortalities occurred., Conclusion: P-TAE is safe and effective in preventing type II endoleak, leading to early sac shrinkage at 12 months following EVAR., Competing Interests: Declaration of competing interests The authors declare no actual or potential conflict of interest related to this study., (Copyright © 2024 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

A hydrophobic evaporable indano[60] fullerene ketone with low sublimation temperature (CF3-FIDO) was successfully synthesized, providing the fullerene mono-adduct derivative with the lowest sublimation temperature reported to date. The amorphous characteristic of the evaporated film was confirmed by grazing incidence X-ray diffraction (GIXRD) and atomic force microscopy (AFM). Perovskite solar cells using CF3-FIDO as the electron transport layer (ETL) achieved long-term device stability retaining 60% of their initial PCE after 500 h in air.

It remains unclear whether the application of surgery to gastric cancer with peritoneal carcinomatosis prolongs survival. Twenty studies on conversion surgery were reviewed. Key points were the response to chemotherapy, complete resection, and a low tumor burden at the time of surgery. A bidirectional approach has been developed to increase the response rate. There are two different strategies in surgery. The outcomes of ongoing trials may clarify controversial issues., (© 2024 Wiley Periodicals LLC.)

Objective: This multicenter study aimed to analyze the risk factors for fluoroquinolone (FQ) resistance and to clarify the clinical characteristics of acute bacterial prostatitis (ABP) in Japan., Methods: A total of 124 patients clinically diagnosed with ABP at 13 medical institutions participating in the Japanese Research Group for Urinary Tract Infection between January and December 2017 were retrospectively reviewed., Results: Of the 124 patients included in this study, 37 were outpatients, and 87 were inpatients. The main underlying medical conditions before the onset of ABP were severe dysuria, urinary retention, transurethral manipulation, indwelling urinary catheter, and transrectal prostate biopsy (TRBx). The main symptoms were fever (≥37.5 °C), prostate tenderness, dysuria, micturition pain, urinary retention, and macrohematuria. Bacteremia was observed in 14 patients. Prostatic abscess was observed in three patients. Escherichia coli was the predominant organism, accounting for 48 % (51/106). FQ-resistant E. coli was detected in 33 % (17/51), and extended-spectrum beta-lactamase-producing E. coli in 12 % (6/51). TRBx (odds ratio [OR] = 48.60, 95 % confidence interval [CI]: 5.49-430.00, p < 0.001) and inpatient status (OR = 29.00, 95 % CI: 1.95-430.00, p = 0.014) were risk factors for the detection of FQ-resistant bacteria., Conclusions: The detection rate of FQ-resistant bacteria was significantly higher with TRBx ABP and inpatient status. These findings have important implications for the management of ABP and antimicrobial treatment, especially for TRBx ABP, which should be considered a separate category., Competing Interests: Declaration of Competing interest The authors declare no conflicts of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

This study introduces the α-rhamnose (Rham)-conjugated prodrug of SN-38 (Rham-SN-38) as a promising alternative to irinotecan. α-rhamnosidase, responsible for SN-38 release from Rham-SN-38, does not express in human cells, minimizing individual variability and side effects. The injection of the α-rhamnosidase into the tumor tissues makes it possible, for the first time, to activate the Rham-SN-38. Furthermore, α-rhamnosidase demonstrates significantly higher activity than carboxylesterase, the specific enzyme activating irinotecan. SN-38 release mediated by α-rhamnosidase completes within 2 h, with a k cat /K m value approximately 5.0 × 10 4 -fold higher than that of irinotecan. The 50% inhibition concentration (IC 50 ) of Rham-SN-38 against three types of cancer cells and one normal cell exceeds 4.5 × 10 3  nM. The addition of α-rhamnosidase significantly increases cytotoxicity, with IC 50 comparable to free SN-38. The QIC 50 , an index reflecting the difference in cytotoxicity with and without α-rhamnosidase, exceeds approximately 1.0 × 10 2 -fold. Rham-SN-38, synthesized in this study, demonstrates significant potential as a prodrug for cancer therapy., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

We aimed to investigate the clinical value of allograft biopsy performed long after renal transplantation. We retrospectively evaluated 99 allograft biopsies in recipients with transplantation vintages of 10 years or longer. Mixed-effects model showed that 1-year estimated glomerular filtration rate (eGFR) slopes after biopsy were significantly greater than those before biopsy [-3.13, -4.42 mL/min/1.73 m 2 /year, p = 0.01]. Renal biopsy changed the treatment strategies in more than half of the patients. Improvement in eGFR slopes was pronounced in 51 patients with treatment modification based on the biopsy results [2.27 (95% confidence interval (CI): 0.66, 3.89) mL/min/1.73 m 2 /year], whereas no improvement was observed in those without [0.33 (95% CI: -1.05, 1.71) mL/min/1.73 m 2 /year, P interaction = 0.001]. Among the treatment modifications, enhancement of immunosuppression (IS) led to the most remarkable improvement in eGFR slope. Patients with g scores ≥2 were more likely to receive IS enhancement than those with g scores = 0 [odds ratio; 15.0 (95% CI: 1.65, 136)]. Patients with active glomerulitis (g ≥ 1) without chronicity (cg ≤ 1) showed the most significant improvement in eGFR slope. Given the prevalence of active glomerulitis (g ≥ 1, 21%), which is responsive to treatment even long after transplantation, and the observed magnitude of eGFR slope improvement, renal biopsy can indeed improve allograft prognosis., 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 Namba-Hamano, Hamano, Doi, Hiraoka, Yonishi, Sakai, Takahashi, Mizui, Nakazawa, Yamanaka, Kakuta, Imamura, Nonomura and Isaka.)

Acquired osmotolerance induced by initial exposure to mild salt stress is widespread across Arabidopsis thaliana ecotypes, but the mechanism underlying it remains poorly understood. To clarify it, we isolated acquired osmotolerance-deficient 1 (aod1), a mutant highly sensitive to osmotic stress, from ion-beam-irradiated seeds of Zu-0, an ecotype known for its remarkably high osmotolerance. Aod1 showed growth inhibition with spotted necrotic lesions on the rosette leaves under normal growth conditions on soil. However, its tolerance to salt and oxidative stresses was similar to that of the wild type (WT). Genetic and genome sequencing analyses suggested that the gene causing aod1 is identical to CONSTITUTIVELY ACTIVATED CELL DEATH 1 (CAD1). Complementation with the WT CAD1 gene restored the growth and osmotolerance of aod1, indicating that mutated CAD1 is responsible for the observed phenotypes in aod1. Although CAD1 is known to act as a negative regulator of immune response, transcript levels in the WT increased in response to osmotic stress. Aod1 displayed enhanced immune response and cell death under normal growth conditions, whereas the expression profiles of osmotic response genes were comparable to those of the WT. These findings suggest that autoimmunity in aod1 is detrimental to osmotolerance. Overall, our results suggest that CAD1 negatively regulates immune responses under osmotic stress, contributing to osmotolerance in Arabidopsis., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

The surgical outcomes of aortic root replacement for Stanford type A acute aortic dissection( AAAD) remain unacceptable with a 30-day mortality rate of 20%. Additionally, in young patients requiring aortic root replacement for AAAD, the preservation of native valve is desirable, yet challenging to achieve in emergent surgery with poor preoperative status. Ideally, we aim to avoid aortic root replacement whenever possible, opting instead for partial remodeling even in cases necessitating incision into the aortic root. We present our surgical outcomes in the strategy for aortic root pathology due to AAAD. We conducted an analysis of 517 cases of AAAD surgery from 2002 to 2023, wherein 499 cases( 96%) underwent aortic root preservation, 10 cases( 1.9%) underwent partial remodeling, and 8 cases( 1.5%)necessitated emergent aortic root replacement. Of these, 13 cases underwent aortic root replacement after AAAD repair( 8 David procedures and 5 Bentall procedures), all demonstrating favorable surgical outcomes, including long-term results. We believe that this strategy for aortic root pathology holds significant merit, particularly in AAAD in young patients with enlarged aortic root.

Background: Although endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) is widely used worldwide, the fact that it is associated with increased rates of reintervention has been considered a problem. This study aimed to analyze the outcomes of primary open AAA repair and open conversion with explantation of stent grafts after EVAR., Methods: In this retrospective study, we enrolled 1,120 patients (open repair, n = 664; EVAR, n = 456) who underwent AAA repair at Kobe University from 1999 to 2019. Of the 664 patients who underwent open repair, 121 (patients who underwent primary open repair (POR) as a concomitant procedure and patients with ruptured AAA) were excluded from the study. The outcomes of POR were compared with those of open conversion with explantation of stent grafts., Results: Of the 543 patients who underwent open repair, 513 underwent POR and 30 underwent open conversion with explantation of stent grafts. The operation time for POR was significantly less than that for open conversion with explantation. During surgery, patients who underwent open conversion with explantation required significantly more transfusions of red cell concentrate, fresh frozen plasma, and platelet concentrate than those who underwent POR. Overall, 30 patients who underwent open conversion with explantation required a total of 48 reinterventions before surgery. Hospital mortality rates were 0.7% and 0% in the POR and open conversion with explantation groups, respectively (P = 0.62). Although overall survival at 5 years in the POR group was significantly better than that in the open conversion with explantation group (89.3 ± 1.7% vs. 79.5 ± 9.6%; P = 0.01), there were no significant differences between the 2 groups regarding the freedom from aortic event (hospital death, reintervention, and aortic death). According to the multivariate analysis, open conversion with explantation was not an independent risk factor for late death. There were 20 patients who were hesitant to undergo OCE, although we recommended OCE. In a subgroup analysis, the overall mean cost borne by patients who underwent EVAR was approximately 2.3 times higher compared with that borne by patients who underwent POR., Conclusions: Although demanding, both early and long-term outcomes of OCE have been favorable in our present study. OCE is highly recommended in patients with persistent sac enlargement after EVAR., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Focal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers., Objective: To ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them., Methods: A multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6 months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated., Results: Out of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7 years before diagnosis, and the next most common, MPD dilatation, 1.1 years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1 year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis., Conclusion: This large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

There is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify the new therapeutic targets associated with inflammatory cells. We characterized the specific distribution of myeloid cells of both human type A AAD samples and a murine AAD model generated using angiotensin II (ANGII) and β-aminopropionitrile (BAPN) by single-cell RNA sequencing (scRNA-seq). We also examined the effect of an anti-interleukin-1β (IL-1β) antibody in the murine AAD model. IL1B + inflammatory macrophages and classical monocytes were increased in human AAD samples. Trajectory analysis demonstrated that IL1B + inflammatory macrophages differentiated from S100A8/9/12 + classical monocytes uniquely observed in the aorta of AAD. We found increased infiltration of neutrophils and monocytes with the expression of inflammatory cytokines in the aorta and accumulation of inflammatory macrophages before the onset of macroscopic AAD in the murine AAD model. In blocking experiments using an anti-IL-1β antibody, it improved survival of murine AAD model by preventing elastin degradation. We observed the accumulation of inflammatory macrophages expressing IL-1β in both human AAD samples and in a murine AAD model. Anti-IL-1β antibody could improve the mortality rate in mice, suggesting that it may be a treatment option for AAD., (© 2024. The Author(s).)

MYH9-related disorders are a group of autosomal dominant disorders caused by mutations in MYH9, and are characterized by thrombocytopenia, sensorineural hearing loss, cataracts, and renal failure. Here, we report a case of chronic renal failure due to MYH9-related disorder with renal symptoms in a patient who underwent living-donor renal transplantation. The patient was diagnosed with proteinuria during a health checkup at the age of 12 years. Her renal function gradually deteriorated, and hemodialysis was initiated at 34 years of age. No definitive diagnosis of renal disease was made through renal biopsy. At the age of 35, she underwent living-donor renal transplantation from her mother as the donor. Six years after transplantation, her renal function remained stable, and no evidence of recurrent nephritis was found during renal biopsies. The family history revealed that her father, uncle, and younger brother had end-stage kidney disease. Genetic testing revealed a mutation (p.E1653D) related to the MYH9 gene. As her father had a history of renal biopsy and was diagnosed with focal segmental glomerulosclerosis (FSGS), we diagnosed chronic renal failure due to FSGS associated with MYH9 disorder. There were no findings suggestive of hearing loss, cataracts, or thrombocytopenia in the recipient or their family members with renal failure, and no symptoms other than renal failure were noted., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

The use of fibrin glue for inguinal hernia mesh fixation has been suggested to be effective in preventing hematomas and reducing postoperative pain compared to tacks and sutures.. The effect of fibrin glue can vary significantly based on the device used. This study assessed the efficacy of fibrin glue based on the type of devices used in an ex vivo system. The rabbit's abdominal wall was trimmed to a size of 3.0 × 6.0 cm and was secured at the edges with metal fixtures. To measure the maximum tensile strength at the point of adhesion failure, the hernia mesh was fixed to the rabbit's abdominal wall using fibrin glue in a 2 cm square area, left for 3 min, and then pulled at a speed of 50 cm/min. The test was conducted 10 times for each group. The median (minimum-maximum) tensile strength values using the spraying, two-liquid mixing, and sequential layering methods were 3.58 (1.99-4.95), 0.51 (0.27-1.89), and 1.32 (0.63-1.66) N, respectively. The spraying method had predominantly higher tensile strength values than the two-liquid mixing and sequential layering methods (P < 0.01). In conclusion, in hernia mesh fixation, the spraying method can be adopted to achieve appropriate adhesive effects., (© 2024. The Author(s).)

Purpose: To evaluate the effectiveness and safety of pre-emptive transcatheter arterial embolization (P-TAE) for aortic side branches (ASBs) to prevent Type 2 endoleaks (EL2) before endovascular aneurysm repair (EVAR) using the Excluder stent-graft system (Excluder)., Materials and Methods: In this prospective, multicenter study, 80 patients (mean age, 79.1 years [SD ± 6.7]; 85.0% were men; mean aneurysmal sac diameter, 48.4 mm [SD ± 7.4]) meeting the eligibility criteria were prospectively enrolled from 9 hospitals. Before EVAR, P-TAE was performed to embolize the patent ASBs originating from the abdominal aortic aneurysm. Contrast-enhanced computed tomography (CT) was performed at 1 month and 6 months after EVAR. The primary endpoint was EL2 incidence at 6 months, and the secondary endpoints were aneurysmal sac diameter changes at 6 and 12 months, P-TAE outcomes, adverse events related to P-TAE, reintervention, and aneurysm-related mortality., Results: All patients successfully underwent P-TAE without serious. Coil embolization was successful in 81.6% of ASBs. EL2 incidence at 6 months was identified in 18 of 70 (25.7%) patients. Aneurysmal sac diameter shrinkage (≥5 mm) was observed in 30.0% of patients at 6 months and in 40.9% at 12 months. Only 1 patient required reintervention for EL2 within 1 year of EVAR; aneurysm-related deaths were not observed., Conclusions: P-TAE for ASBs before EVAR using Excluder is a safe and effective strategy. It aids in achieving early aneurysmal sac shrinkage and reduces EL2 reintervention at 1 year after EVAR., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

A 52-week postmarketing surveillance study was initiated to evaluate the safety and effectiveness of guselkumab, a human anti-interleukin 23 subunit p19 monoclonal antibody, in Japanese patients with psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis in real-world practice. Here, we report results of the 20-week interim analysis of the ongoing postmarketing surveillance study. Patients who received guselkumab between May 2018 (the date of commercial launch in Japan) and October 2020 were registered in this study. In total, 411 and 245 patients were included in the safety and effectiveness analysis sets, respectively. Adverse drug reactions (ADRs) occurred in 6.6% (27 of 411) and serious ADRs in 2.2% (nine of 411) of patients. The most frequent ADRs by System Organ Class were "Infections and infestations" (2.4%), with nasopharyngitis being the most frequently observed ADR (0.7%). The mean Psoriasis Area Severity Index score decreased from 11.6 at baseline to 6.5 at week 4 and 2.2 at week 20, with improvements achieving statistical significance at each time point. Clinical Global Impression, Dermatology Life Quality Index, and Nail Psoriasis Severity Index outcomesalso showed substantial improvements. Our findings demonstrate that guselkumab is well tolerated and effective in Japanese patients with psoriasis through 20 weeks of treatment in real-world clinical practice, showing significant effectiveness observed as early as 4 weeks. The study was officially registered with the University Hospital Medical Information Network Clinical Trials Registry with the identifier UMIN000032969., (© 2024 Janssen Pharmaceutical K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Oculomotor nerve schwannoma in children not associated with neurofibromatosis is a rare disease, with 26 pediatric cases reported so far. There is no established treatment plan. A 7-year-old girl presented with oculomotor nerve palsy. Surgical reduction of the tumor combined with postoperative gamma knife surgery preserved the oculomotor nerve, improved oculomotor nerve function, and achieved tumor control during the observation period of 20 months. The combination of partial surgical resection and gamma knife surgery as a treatment strategy for oculomotor nerve schwannoma resulted in a good outcome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Evaporable indano[60]fullerene ketone (FIDO) was converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron-withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives (FIDO, FIDS, C 60 ) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C 60 ., (Copyright © 2024, Zhai et al.)

Amyotrophic lateral sclerosis (ALS) selectively affects motor neurons. SOD1 is the first causative gene to be identified for ALS and accounts for at least 20% of the familial (fALS) and up to 4% of sporadic (sALS) cases globally with some geographical variability. The destabilisation of the SOD1 dimer is a key driving force in fALS and sALS. Protein aggregation resulting from the destabilised SOD1 is arrested by the clinical drug ebselen and its analogues (MR6-8-2 and MR6-26-2) by redeeming the stability of the SOD1 dimer. The in vitro target engagement of these compounds is demonstrated using the bimolecular fluorescence complementation assay with protein-ligand binding directly visualised by co-crystallography in G93A SOD1. MR6-26-2 offers neuroprotection slowing disease onset of SOD1 G93A mice by approximately 15 days. It also protected neuromuscular junction from muscle denervation in SOD1 G93A mice clearly indicating functional improvement., (© 2024. The Author(s).)

We succeeded in homogeneously expressing and purifying L-asparaginase from Latilactobacillus sakei LK-145 (Ls-Asn1) and its mutated enzymes C196S, C264S, C290S, C196S/C264S, C196S/C290S, C264S/C290S, and C196S/C264S/C290S-Ls-Asn1. Enzymological studies using purified enzymes revealed that all cysteine residues of Ls-Asn1 were found to affect the catalytic activity of Ls-Asn1 to varying degrees. The mutation of Cys196 did not affect the specific activity, but the mutation of Cys264, even a single mutation, significantly decreased the specific activity. Furthermore, C264S/C290S- and C196S/C264S/C290S-Ls-Asn1 almost completely lost their activity, suggesting that C290 cooperates with C264 to influence the catalytic activity of Ls-Asn1. The detailed enzymatic properties of three single-mutated enzymes (C196S, C264S, and C290S-Ls-Asn1) were investigated for comparison with Ls-Asn1. We found that only C196S-Ls-Asn1 has almost the same enzymatic properties as that of Ls-Asn1 except for its increased stability for thermal, pH, and the metals NaCl, KCl, CaCl 2 , and FeCl 2 . We measured the growth inhibitory effect of Ls-Asn1 and C196S-Ls-Asn1 on Jurkat cells, a human T-cell acute lymphoblastic leukemia cell line, using L-asparaginase from Escherichia coli K-12 as a reference. Only C196S-Ls-Asn1 effectively and selectively inhibited the growth of Jurkat T-cell leukemia, which suggested that it exhibited antileukemic activity. Furthermore, based on alignment, phylogenetic tree analysis, and structural modeling, we also proposed that Ls-Asn1 is a so-called "Type IIb" novel type of asparaginase that is distinct from previously reported type I or type II asparaginases. Based on the above results, Ls-Asn1 is expected to be useful as a new leukemia therapeutic agent., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)