Search

The current literature on the effects of clozapine on pregnancy is limited, and no cases of pregnant Japanese women have been reported. Decreased variability in the fetal heart rate due to clozapine exposure has been reported in countries other than Japan, but its association with serum concentrations of clozapine has not been documented. In this case, a 29-year-old Japanese primipara with treatment-resistant schizophrenia taking clozapine 250 mg/day experienced pregnancy. The pregnancy progressed without complications. At 40 weeks and 2 days of gestation, the patient developed premature rupture of membranes, and decreased variability in the fetal heart rate and variable deceleration were observed, leading to an emergency cesarean section. The neonate had no congenital malformations, metabolic disorders, seizures, floppy infant syndrome, leukopenia, or neutropenia. Serum concentrations of clozapine and norclozapine (N-desmethylclozapine), measured in the mother and in the neonate immediately after birth, suggested that clozapine and norclozapine were transported to the fetus during pregnancy. Based on these observations, the present case suggests that high fetal serum concentrations of clozapine and norclozapine may affect fetal heart rate. This case report concludes that, with careful monitoring, Japanese women taking clozapine can deliver successfully and emphasizes the importance of monitoring serum clozapine concentrations and fetal cardiac function throughout pregnancy, with particular attention to the later stages., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Aim: In March 2021, the Japanese Ministry of Health, Labour and Welfare revised the optimal gestational weight gain standards. In this study, we examined whether this revision affected gestational weight gain and low birth weight rates., Methods: We analyzed the records of singleton pregnant women who underwent checkups from their 1st trimester and delivered at our institute after 37 weeks between 2020 and 2021 (before the revision) and between 2022 and 2023 (after the revision). Pregnancy outcomes were assessed in the following four groups stratified by pre-pregnancy body mass index (BMI): underweight (BMI: <18.5 kg/m 2 ), normal-weight (BMI: 18.5-24.9 kg/m 2 ), overweight (BMI: 25-29.9 kg/m 2 ), and obese (BMI: ≥30 kg/m 2 ). Leaflets on the optimal gestational weight gain standards for each group were distributed to all pregnant women at the first prenatal checkup., Results: In each group, gestational weight gain did not change before and after the revision, with the corresponding values of 10.8 kg and 11.1 kg in the underweight (p = 0.94), 10.7 kg and 10.4 kg in the normal weight (p = 0.14), 9.7 kg and 9.2 kg in the overweight (p = 0.32), and 7.4 kg and 6.7 kg in the obese (p = 0.44) groups. Furthermore, the prevalence of low birth weight did not decrease in all groups., Conclusions: No significant differences in gestational weight gain or low birth weight were observed after the revision of the 2021 gestational weight gain recommendations. Merely distributing leaflets to pregnant women may not be sufficient to improve gestational weight gain or reduce low birth weight rates., (© 2024 Japan Society of Obstetrics and Gynecology.)

A seventh blind test of crystal structure prediction has been organized by the Cambridge Crystallographic Data Centre. The results are presented in two parts, with this second part focusing on methods for ranking crystal structures in order of stability. The exercise involved standardized sets of structures seeded from a range of structure generation methods. Participants from 22 groups applied several periodic DFT-D methods, machine learned potentials, force fields derived from empirical data or quantum chemical calculations, and various combinations of the above. In addition, one non-energy-based scoring function was used. Results showed that periodic DFT-D methods overall agreed with experimental data within expected error margins, while one machine learned model, applying system-specific AIMnet potentials, agreed with experiment in many cases demonstrating promise as an efficient alternative to DFT-based methods. For target XXXII, a consensus was reached across periodic DFT methods, with consistently high predicted energies of experimental forms relative to the global minimum (above 4 kJ mol -1 at both low and ambient temperatures) suggesting a more stable polymorph is likely not yet observed. The calculation of free energies at ambient temperatures offered improvement of predictions only in some cases (for targets XXVII and XXXI). Several avenues for future research have been suggested, highlighting the need for greater efficiency considering the vast amounts of resources utilized in many cases., (open access.)

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures., (open access.)

Purpose: The study aimed to explore and describe the lives of patients with persistent cloaca (PC) from childhood to adulthood., Methods: Semistructured interviews were conducted with nine adult patients with PC. Their experiences and thoughts regarding this disease were analyzed qualitatively and inductively., Results: After classifying the experiences and thoughts of patients with PC, 13 categories were extracted. The following five themes emerged from these categories. (1) Difficulties with excretion and vaginal management because of the disease. (2) The degree of understanding of those around them and society has a huge effect on their way of life. (3) The inferiority of a woman who is not a "normal woman." (4) A "never-ending disease" in which problems continue even after the transition period. (5) Differences in the central point of the narrative depending on the age group., Conclusions: In this study, qualitative and inductive analyses of data from semistructured interviews with patients with PC revealed their experiences and thoughts. The results will provide a guide for young patients and the medical professionals who treat them. Accordingly, monitoring their lives until adulthood is necessary., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Both mechanical and adhesion properties of cancer cells are complex and reciprocally related to migration, invasion, and metastasis with large cell deformation. Therefore, we evaluated these properties for human cervical cancer cells (HeLa) simultaneously using our previously developed micro tensile tester system. For efficient evaluation, we developed image analysis software to modify the system. The software can analyze the tensile force in real time. The modified system can evaluate the tensile stiffness of cells to which a large deformation is applied, also evaluate the adhesion strength of cancer cells that adhered to a culture substrate and were cultured for several days with their adhesion maturation. We used the modified system to simultaneously evaluate the stiffness of the cancer cells to which a large deformation was applied and their adhesion strength. The obtained results revealed that the middle phase of tensile stiffness and adhesion force of the microtubule-depolymerized group treated with colchicine (an anti-cancer drug) (stiffness, 13.4 ± 7.5 nN/%; adhesion force, 460.6 ± 258.2 nN) were over two times larger than those of the control group (stiffness, 5.0 ± 3.5 nN/%; adhesion force, 168.2 ± 98.0 nN). Additionally, the same trend was confirmed with the detailed evaluation of cell surface stiffness using an atomic force microscope. Confocal fluorescence microscope observations showed that the stress fibers (SFs) of colchicine-treated cells were aligned in the same direction, and focal adhesions (FAs) of the cells developed around both ends of the SFs and aligned parallel to the developed direction of the SFs. There was a possibility that the microtubule depolymerization by the colchicine treatment induced the development of SFs and FAs and subsequently caused an increment of cell stiffness and adhesion force. From the above results, we concluded the modified system would be applicable to cancer detection and anti-cancer drug efficacy tests., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

During surveillance of Staphylococcus aureus in lesions from patients with atopic dermatitis (AD), we isolated Staphylococcus argenteus , a species registered in 2011 as a new member of the genus Staphylococcus and previously considered a lineage of S. aureus . Genome sequence comparisons between S. argenteus isolates and representative S. aureus clinical isolates from various origins revealed that the S. argenteus genome from AD patients closely resembles that of S. aureus causing skin infections. We previously reported that 17%-22% of S. aureus isolated from skin infections produce staphylococcal enterotoxin Y (SEY), which predominantly induces T-cell proliferation via the T-cell receptor (TCR) Vα pathway. Complete genome sequencing of S. argenteus isolates revealed a gene encoding a protein similar to superantigen SEY, designated as SargEY, on its chromosome. Population structure analysis of S. argenteus revealed that these isolates are ST2250 lineage, which was the only lineage positive for the SEY-like gene among S. argenteus . Recombinant SargEY demonstrated immunological cross-reactivity with anti-SEY serum. SargEY could induce proliferation of human CD4 + and CD8 + T cells, as well as production of TNF-α and IFN-γ. SargEY showed emetic activity in a marmoset monkey model. S arg EY and SET (a phylogenetically close but uncharacterized SE) revealed their dependency on TCR Vα in inducing human T-cell proliferation. Additionally, TCR sequencing revealed other previously undescribed Vα repertoires induced by SEH. S arg EY and SEY may play roles in exacerbating the respective toxin-producing strains in AD., Importance: Staphylococcus aureus is frequently isolated from active lesions of atopic dermatitis (AD) patients. We reported that 17%-22% of S. aureus isolated from AD patients produced a novel superantigen staphylococcal enterotoxin Y (SEY). Unlike many S . aureus superantigens that activate T cells via T-cell receptor (TCR) Vß, SEY activates T cells via TCR Vα and stimulates cytokine secretion. Staphylococcus argenteus was isolated from AD patients during the surveillance for S. aureus . Phylogenetic comparison of the genome indicated that the isolate was very similar to S. aureus causing skin infections. The isolate encoded a SEY-like protein, designated SargEY, which, like SEY, activated T cells via the TCR Vα. ST2250 is the only lineage positive for SargEY gene. ST2250 S. argenteus harboring a superantigen SargEY gene may be a novel staphylococcal clone that infects human skin and is involved in the exacerbation of AD., Competing Interests: The authors declare no conflict of interest.

This study investigated the three-dimensional (3D) cellular interactions and tunneling nanotubes (TNTs) during fetal mouse skin regeneration on embryonic days 13 (E13) and 15 (E15). We aimed to understand spatial relationships among cell types involved in skin regeneration and assess the potential role of TNTs. Full-thickness skin incisions were performed in E13 and E15 embryos. Wound sites were collected, embedded in epoxy resin, processed for 3D reconstruction (1 μm thickness sections), and subjected to whole-mount immunostaining. We conducted in vitro co-culture experiments with fetal macrophages and fibroblasts to observe TNT formation. To assess the effect of TNTs on skin regeneration, an inhibiting agent (cytochalasin B) was administered to amniotic fluid. Results revealed that E13 epidermal keratinocytes interacted with dermal fibroblasts and macrophages, facilitating skin regrowth. TNT structures were observed at the E13-cell wound sites, among macrophages, and between macrophages and fibroblasts, confirmed through in vitro co-culture experiments. In vitro and utero cytochalasin B administration hindered those formation and inefficient skin texture regeneration at E13 wound sites. This emphasizes the necessity of 3D cellular interactions between epidermal and dermal cells during skin regeneration in mouse embryos at E13. The prevalence of TNT structures indicated their involvement in achieving complete skin texture restoration., (© 2024. The Author(s).)

Objective: This study aimed to clarify the maternal and neonatal outcomes based on the presence or absence of a Couvelaire uterus with placental abruption., Methods: This single-center retrospective study was conducted at a tertiary perinatal center in Japan, including patients diagnosed with acute placental abruption who delivered live births via cesarean section between 2016 and 2023. Patients were divided into two groups based on the presence or absence of a Couvelaire uterus during surgery: the Couvelaire and normal uterus groups. Maternal and neonatal outcomes were assessed., Results: This study included 76 patients: 24 in the Couvelaire group and 52 in the normal uterus group. No patients underwent hysterectomies. The Couvelaire group had significantly higher intraoperative blood loss (median 1152 vs 948 g, P = 0.010), blood transfusion rates (58% vs 31%, P = 0.022), fibrinogen administration rates (38% vs 13%, P = 0.038), intensive care unit/high care unit admission rates (29% vs 7.7%, P = 0.013), and disseminated intravascular coagulation complication rates (25% vs 7.7%, P = 0.038). There were no differences in birth weight, gestational age (median 2387 vs 2065 g, P = 0.082), Apgar score <4 at 5 min (4.2% vs 3.9%, P = 0.95), umbilical artery blood pH <7.1 (25% vs 22%, P = 0.82), and neonatal death (4.2% vs 1.9%, P = 0.57)., Conclusion: A Couvelaire uterus indicated adverse maternal outcomes but not neonatal ones. Its presence necessitates preparation for blood transfusions and/or intensive patient follow-up., (© 2024 International Federation of Gynecology and Obstetrics.)

Case: A 62-year-old woman receiving romosozumab for 3 months underwent extreme lateral interbody fusion (XLIF) for lumbar degenerative spondylolisthesis. From 1 week after surgery, she experienced gradually increasing pain from the right groin to the front of the thigh. Examination revealed ossifying myositis in bilateral psoas major muscles. Etidronate treatment was initiated, improving pain after 4 days. Computed tomography showed lesion disappearance by 3 months after surgery., Conclusion: We report a rare case of myositis ossificans in bilateral psoas major muscles following XLIF surgery, possibly influenced by intraoperative manipulation and romosozumab treatment. Etidronate administration may be effective, as with heterotopic ossification., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C372)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Introduction: Subclinical rejection (SCR) refers to the presence of acute rejection without accompanying kidney allograft dysfunction. The impact of SCR on long-term graft survival remains a subject of ongoing debate., Methods and Analysis: We will perform a systematic search of databases including MEDLINE, Embase and Cochrane Central, from January 1995 to November 2023. We will include English-language studies involving adult kidney transplant patients who investigated SCR. We will exclude studies focused on 'for-cause' biopsies. Both title, abstract screening and full-text screening will be performed by two or more reviewers. The primary outcome of this study will be death-censored allograft loss. The secondary outcome will include development of subsequent rejection. For time-dependent outcomes, we will prioritise HRs and the 95% CIs. In cases where HRs are unavailable, we will calculate risk ratios based on the recorded events. The risk of bias will be assessed using the Cochrane Collaboration's revised tool for assessing the risk of bias in randomised trials and the Newcastle-Ottawa scale for cohort studies. We will employ a random effects model. We will evaluate heterogeneity using the I 2 variable. We will assess publication bias by funnel plots, Begg and Mazumdar test, and Egger's test., Ethics and Dissemination: Ethics approval does not apply as no original data will be collected. The results will be disseminated through peer-reviewed publications and conference presentations., Prospero Registration Number: CRD42023463536., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hereditary forms of hemolytic uremic syndrome (HUS), formerly known as atypical HUS, typically involve mutations in genes encoding for components of the alternative pathway of complement, therefore they are often referred to as complement-mediated HUS (cHUS). This condition has a high risk of recurrence in the transplanted kidney, leading to accelerated graft loss. The availability of anti-complement component C5 antibody eculizumab has enabled successful transplantation with a notably reduced recurrence rate and improved prognosis. Open questions are related to the potential for complement inhibitor discontinuation, ideal timing of treatment withdrawal, and patient selection based on genetic abnormalities. Our review delves into the pathophysiology, classification, genetic predispositions, and management strategies for cHUS in the native and transplant kidneys., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Trans-sacral canal plasty (TSCP) is a minimally invasive lumbar spine surgery under local anaesthesia. TSCP is expected to be effective regardless of whether the patient has had previous surgery. However, there are cases in which open revision surgery is required after TSCP. This study aimed to identify risk factors for open revision surgery after TSCP in order to determine surgical indications and limitations. A retrospective case-control study was conducted in patients who underwent TSCP for lumbar spine disease. Data of 112 patients were analysed. During an observation period of 7-23 months, 34 patients (30.4%) required open revision surgery and 78 (69.6%) did not. The following patient background characteristics were investigated: age, sex, body mass index (BMI), diagnosis, history of spine surgery and the institution where the surgery was performed. Comorbidities were scored using the Elixhauser Comorbidity Index. Preoperative imaging parameters were investigated, including the lesion level (L4/5, L5/S1, other), presence of intervertebral instability, dural sac area, presence of bony stenosis and presence of epidural lipoma. Multivariate analysis revealed that intervertebral instability (odds ratio 2.56, confidence interval 1.00-6.51, p  = 0.046) and a narrow dural sac area (odds ratio 0.98, confidence interval 0.97-0.99, p  = 0.002) were significant risk factors for open revision surgery after TSCP., 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., (© 2024 Arimura, Shinohara, Katsumi, Obata, Ikegami, Sawada, Mori and Saito.)

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory type 2 inflammation-based airway allergic disease that is prone to complications such as bronchial asthma. Pott's puffy tumor (PPT) is a rare clinical entity characterized by osteomyelitis of the frontal bone accompanied by a subperiosteal abscess. A 56-year-old female with a history of cranial surgery and bronchial asthma presented to an otolaryngology clinic with nasal obstruction and loss of smell, later developing swelling and redness on her forehead. She was diagnosed and treated for ECRS and was thought to have developed PPT during her course. Nasal endoscopy reveals bilateral polyp formation originating from the middle meatus. Paranasal computed tomography (CT) indicates substantial swelling extending from the opening of the frontal sinus to the adjacent subcutaneous tissue, accompanied by a defect in the frontal bone and osteolysis at the base of the frontal skull. Her management included conservative antibiotic therapy adjusted due to a drug eruption and, subsequently, endoscopic sinus surgery (ESS). The case was complicated by the patient's medical history and the absence of detailed surgical records, which limited the use of enhanced imaging techniques. This underscores the complexity of diagnosing and managing PPT in adults, particularly those with prior surgeries, emphasizing the need for a tailored diagnostic and therapeutic approach that integrates detailed patient history with current clinical indicators to effectively guide treatment. This case contributes to the limited literature on adult PPT and underscores the critical need for careful patient monitoring and detailed surgical history., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Tatsuki et al.)

Background: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes., Objective: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs)., Methods: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps., Results: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo., Conclusion: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To validate the effectiveness of Deflux® treatment for vesicoureteral reflux (VUR) following pediatric renal transplantation (RT), based on our single-institution experience., Method: A retrospective study was conducted using the medical records of pediatric patients who underwent Deflux® treatment for VUR after RT from April 2008 to March 2022., Results: Sixty-eight pediatric patients underwent RT. VUR was subsequently detected in 22 (32 %) of these patients. Seven of the 22 patients (32 %) underwent Deflux® treatment to avoid renal dysfunction due to urinary infection (UTI). The median age at the time of RT was 4 years (range:2-12). All 7 patients had urinary UTIs before Deflux® treatment. The median estimated glomerular filtration rate (eGFR) before Deflux® treatment was 67 ml/min/1.73 m 2  (range:42-138 ml/min/1.73 m 2 ). After Deflux® treatment, VUR was downgraded in three cases (43 %). Four patients (57 %) experienced postoperative UTI, two of who underwent a second Deflux® treatment, one underwent submuscular tunnel reconstruction, and the other one experienced UTI without VUR after 1st Deflux® treatment but did not reoccur. All seven patients continued prophylactic medication after Deflux® treatment, without any history of recurrent UTIs during the observation period after treatment (median 37 months [range 7-86 months]). Furthermore, the eGFRs did not significantly decrease after Deflux® treatment (median eGFR 58 ml/min/1.73 m 2  [range:33-99 ml/min/1.73 m 2 ], p > 0.1)., Conclusion: Deflux® treatment for VUR after RT is technically challenging because the new ureteral orifice is ventrally anastomosed at the bladder. We believe our results indicate the possibility of reducing the frequency of UTIs and contributing to preservation of the renal function after RT., Type of Study: Retrospective Study., Level of Evidence: Level III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To investigate the 5-year treatment outcomes of retinopathy of prematurity in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor therapies., Methods: A multicenter retrospective study comprised 24 eyes of 13 patients treated for Type 1 retinopathy of prematurity, followed for 5 years. Initial treatment was laser and anti-vascular endothelial growth factor in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, retinopathy of prematurity characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent, and astigmatism at 5 years posttreatment., Results: Median BCVA was 0.15 logarithm of the minimum angle of resolution (interquartile range, 0.0-0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median spherical equivalent was -2.37 (interquartile range, -6.1 to -0.1); 75% had myopia (≤-0.5 D), and 25% had high myopia (≤-6.0 D). Median astigmatism was 1.25 (interquartile range, 0.9-3.0); 46% had ≥1.5 D. Anti-vascular endothelial growth factor-treated eyes showed less myopia ( P < 0.009), with no BCVA or astigmatism difference ( P = 0.997, P = 0.271) compared with laser-treated eyes., Conclusion: One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of ≥20/20) 5 years after retinopathy of prematurity treatment. Refractive errors were common. Anti-vascular endothelial growth factor therapy may be superior to laser therapy in myopic refractive error.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Rendu-Weber syndrome, is a rare autosomal dominant disorder characterized by vascular malformations. This comprehensive review aimed to provide an overview and summarize various aspects of HHT, including the genetic abnormalities, complications associated with visceral arteriovenous malformations (AVMs), prognosis of HHT, quality of life (QOL), and treatment of epistaxis. In addition, this review highlights the challenges in diagnosing HHT and emphasizes the critical role of otolaryngologists in the early detection of HHT. Otolaryngologists can refer patients with refractory epistaxis for AVM screening to expedite intervention. Mutation of the genes involved in the transforming growth factor-β signaling pathway leads to the incidence of HHT, resulting in the formation of abnormal blood vessel formation. These vascular malformations commonly manifest as telangiectasia on the skin and mucous membranes; however, epistaxis remains the hallmark symptom of HHT. The impact of HHT goes beyond the visible symptoms and often includes the formation of life-threatening visceral AVMs in the lungs, liver, and brain. The prognosis of patients with HHT is closely related to the development of these complications, necessitating timely diagnosis and intervention. Refractory epistaxis diminishes the QOL of patients with HHT. The management of epistaxis ranges from conservative measures to advanced interventions such as prevention, conservative treatments, ablation, surgical procedures, and the administration of anti-angiogenic agents. However, effective management requires a multidisciplinary approach. The diagnosis of HHT remains challenging due to its variable presentation and lack of awareness among physicians. This review highlights the importance of reducing the duration between symptom onset and diagnosis. Otolaryngologists who are experienced in the management of refractory epistaxis can aid in identifying potential cases of HHT. They can facilitate the initiation of screening for visceral AVMs via prompt recognition of the signs and symptoms of HHT, contributing to improved patient outcomes. Early detection and intervention through screening can extend the life expectancy of patients with HHT to levels comparable with that of the general population. In conclusion, this review provides insight into various aspects of HHT and emphasizes the importance of timely diagnosis and intervention in the mitigation of the potentially life-threatening complications associated with this disorder. Otolaryngologists play a critical role in this process, serving as gatekeepers to the identification of cases of HHT and implementation of appropriate screening and management pathways, thereby improving the life expectancy and QOL of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The complement system is part of innate immunity and is pivotal in protecting the body against pathogens and maintaining host homeostasis. Activation of the complement system is triggered through multiple pathways, including antibody deposition, a mannan-binding lectin, or activated complement deposition. C3 glomerulopathy (C3G) is a rare glomerular disease driven by complement dysregulation with high post-transplantation recurrence rates. Its treatment is mainly based on immunosuppressive therapies, specifically mycophenolate mofetil and glucocorticoids. Recent years have seen significant progress in understanding complement biology and its role in C3G pathophysiology. New complement-tergeting treatments have been developed and initial trials have shown promising results. However, challenges persist in C3G, with recurrent post-transplantation cases leading to suboptimal outcomes. This review discusses the pathophysiology and management of C3G, with a focus on its recurrence after kidney transplantation., Competing Interests: Declaration of competing interest Paolo Cravedi reports financial support was provided by Chinook Therapeutics Inc. for consulting and research projects. Paolo Cravedi is associate Editor for Transplantation Reviews and American Journal of Transplantation. The other authors have no relevant conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Hypotaurine, a precursor to taurine, is known for its antioxidant properties and is prominently present in fetal plasma and the placenta. Our previous research revealed that ezrin-knockout mice experience fetal growth retardation, coinciding with reduced hypotaurine levels in fetal plasma. This study aims to elucidate the expression and role of hypotaurine transporters within the placenta., Methods: We employed quantitative RT-PCR to measure mRNA expression of GAT transporter family members in the placenta during mid-to-late gestation. LC/MS/MS was used to analyze the distribution of hypotaurine in different placental subregions. Immunohistochemistry was utilized to examine the localization of GAT2 in mice. Placental hypotaurine uptake from fetal circulation was studied via umbilical perfusion in rats., Results: Among hypotaurine transporters, GAT2 exhibited increased mRNA and protein expression in murine placenta during mid-to-late gestation. Notably, GAT2/Slc6a13 mRNA and hypotaurine were most concentrated in the labyrinth of murine placenta. In contrast, enzymes responsible for hypotaurine synthesis, such as cysteine dioxygenase, cysteine sulfinic acid decarboxylase, and 2-aminoethanethiol dioxygenase, showed minimal expression in the labyrinth. These findings suggest that GAT2 is a key determinant of hypotaurine levels in the placental labyrinth. Immunohistochemical examination unveiled that GAT2 was predominantly localized on the fetal-facing plasma membrane within syncytiotrophoblasts, which co-localized with ezrin. In rat umbilical perfusion experiments, the GAT2/3 and TauT inhibitor, SNAP-5114, significantly reduced hypotaurine extraction from fetal circulation to the placenta., Discussion: The results suggest that GAT2 plays a pivotal role in the concentrative uptake of hypotaurine from fetal plasma within syncytiotrophoblasts of the placenta., 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. 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.)

Aim: In 2017, the American College of Cardiology (ACC) re-defined hypertension (HT) as follows: elevated blood pressure (EBP), systolic blood pressure (SBP) 120-129 mmHg and diastolic blood pressure (DBP) <80 mmHg; stage 1 HT, SBP 130-139 mmHg or DBP 80-89 mmHg; and stage 2 HT: SBP ≥140 mmHg or DBP ≥90 mmHg. It is well known that women with stage 2 HT are at higher risk of preeclampsia and have poorer pregnancy and delivery outcomes. While there are few reports on the risk in women with EBP and stage 1 HT, and none from Japan. This study aimed to determine whether women in Japan with EBP and stage 1 HT are at risk of preeclampsia., Methods: In this single-center retrospective study conducted in Japan, subjects were classified into stage 2 HT, stage 1 HT, EBP, and normal groups based on blood pressure measurements at the time of the first visit before 20 weeks of gestation. Women with a diagnosis of hypertension made before pregnancy were classified into the stage 2 HT group. We compared pregnancy and delivery outcomes, such as preeclampsia, between groups., Results: A total of 5129 cases (normal, n = 4283; EBP, n = 427; stage 1 HT, n = 303; stage 2 HT, n = 116) were included. Preeclampsia incidence rates were 2.7%, 5.6%, 10.6%, and 21.6%, respectively. The adjusted OR (95% CI) for preeclampsia incidence were 2.90 (1.81-4.66), 5.90 (3.87-9.20), and 13.80 (7.97-24.0), respectively., Conclusions: Women with EBP and stage 1 HT are at high risk of preeclampsia, similar to those with stage 2 HT., (© 2023 Japan Society of Obstetrics and Gynecology.)

Objective: The relationship between FMF and pregnancy outcomes remains unclear. This systematic review and meta-analysis aimed to clarify this association., Methods: Electronic databases-PubMed, Web of Science, Cochrane, and EMBASE-were searched on 20 December 2022, using specific search terms. Case-control, cohort, and randomized clinical trial studies comparing patients with FMF and healthy controls were considered eligible. We excluded systematic reviews, meta-analyses, case series with fewer than five cases, republished articles without new findings on pregnancy outcomes, studies targeting paternal FMF, and those not published in English. The results were summarized in the form of odds ratios (ORs) and 95% CIs, using a random-effects model. This study was registered in the University hospital Medical Information Network Clinical Trials Registry (Japan) as UMIN000049827., Results: The initial electronic search identified 611 records, of which 9 were included in this meta-analysis (177 735 pregnancies, 1242 with FMF, and 176 493 healthy controls). FMF was significantly associated with increased odds of preterm deliveries (OR, 1.67; 95% CI, 1.05-2.67; I2 = 22%) and insignificantly associated with increased odds of fetal growth restriction (OR, 1.45; 95% CI, 0.90-2.34; I2 = 0%) and hypertensive disorders during pregnancy (OR, 1.28; 95% CI, 0.87-1.87; I2 = 0%)., Conclusion: FMF was significantly associated with preterm delivery and insignificantly associated with fetal growth restriction and hypertensive disorders. All of the included studies were observational studies. Treatment characteristics were not fully collected from the articles, and further analysis of treatments for FMF in pregnancy is still warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: Cervical ripening is commonly performed before oxytocin administration during labor induction in pregnant women with an unfavorable cervix. In Japan, a controlled-release Dinoprostone vaginal insert (CR-DVI) was approved in 2020. Although many studies have compared the mechanical methods of ripening and prostaglandins, few have examined the impact of additional options for labor induction. This study aimed to assess the impact of CR-DVI as an additional option for labor induction in women with an unfavorable cervix., Methods: In this single-center retrospective study conducted in Japan, 265 participants were divided into two groups: before (January 2018 to May 2020) and after (June 2020 to November 2022) CR-DVI introduction. Before CR-DVI was introduced, hygroscopic dilators were used for all cases instead. On the other hand, after the introduction of CR-DVI, the first choice for cervical ripening was CR-DVI. The CR-DVI was retained vaginally for up to 12 hours after insertion. However, if hyper-stimulation or non-reassuring fetal status was suspected, or if a new membrane rupture occurred, it was removed immediately according to the removal criteria. Oxytocin infusions were used during both periods if needed. We compared delivery and neonatal outcomes between the groups., Results: The 265 participants were divided into two groups: before (n=116) and after (n=149) CR-DVI introduction. There were no significant differences in maternal characteristics except for the primiparous proportion. CR-DVI was used in 93% of cases after introduction. Hygroscopic dilators also continued to be used; however, their use decreased to about 34%. The vaginal delivery rate was significantly higher after the introduction of CR-DVI than before its introduction (50.9% vs. 66.4%; p=0.01). Multivariable analysis revealed a significantly higher rate of vaginal delivery after CR-DVI introduction. Of the 149 cases in which a CR-DVI was used, 111 (79.9%) were removed before 12 hours. There were no significant differences in neonatal outcomes., Conclusion: The rate of vaginal delivery was higher after CR-DVI introduction than before its introduction, and adverse pregnancy outcomes did not increase. Therefore, introducing CR-DVI as an option for labor induction may increase the probability of vaginal delivery. Safety can also be ensured by adhering to the removal criteria., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Shindo et al.)

Background: Recently, reports of endoscopic approaches for neuroblastoma, ganglioneuroblastoma, and ganglioneuroma (peripheral neuroblastic tumor; PNTs) have been increasing. This study aimed to clarify the indications for endoscopic surgery for PNTs., Methods: Pediatric patients who underwent endoscopic surgery for PNTs at our institution were included in this study. Image-defined risk factors (IDRFs) were analyzed using preoperative computed tomography (CT)., Results: Twenty-four patients underwent endoscopic surgery for PNTs. The diagnoses included neuroblastoma (n = 11), ganglioneuroma (n = 10), and ganglioneuroblastoma (n = 3). Regarding the tumor site, there were 18 cases of adrenal tumors, five cases of mediastinal tumors, and one case of retroperitoneal tumors. Image-defined risk factors were positive in eight cases (contacted with a renal vessel, n = 6; compression of principal bronchi, n = 2). Complete resection was accomplished in 21 cases (14 of 16 IDRF-negative cases and seven of eight IDRF-positive cases). All patients survived without recurrence during the follow-up period., Conclusions: The CT findings of contact with renal vessels and compression of principal bronchi do not seem to be indicators of incomplete resection. An endoscopic approach to PNTs in pediatric patients is feasible with a good prognosis if patients are selected strictly., (© 2024 Japan Pediatric Society.)

Aim: This study aimed to clarify the perinatal prognosis of preeclampsia (PE) with fetal growth restriction (FGR) and determine appropriate medical interventions for these conditions., Methods: Singleton births delivered to mothers diagnosed with PE with FGR and hypertension at a tertiary center between January 2010 and June 2021 were included. Only patients with PE were included in the analysis, and patients with superimposed PE were excluded. The FGR-preceding group (group F) included patients who developed FGR first and had elevated blood pressure. The remaining cases were defined as the hypertension-preceding group (group H). The perinatal outcomes between the two groups were then compared. The primary outcome was pregnancy prolongation defined as the time from PE diagnosis to delivery. Secondary outcomes included mode of delivery, maternal outcomes, and neonatal outcomes., Results: The mean gestational age at the time of PE diagnosis was 34.7 (26-40.1) weeks for group F and 30.3 (22.6-39.4) weeks for group H (P=0.004). The median pregnancy prolongation from the time of PE diagnosis to delivery was eight (2-30) days in group F and 10.5 (2-43) days in group H, with no significant difference (P=0.52). The incidence of maternal critical complications was 10.4% in group F and 28.1% in group H (P=0.03; odds ratio 3.36; 95% confidence interval 1.13-10)., Conclusions: Among patients with PE, group H was more likely to develop serious maternal complications than group F, suggesting different pathogenesis between these types of PE. Both groups required cautious perinatal management, but more stringent maternal management was required for group H., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Iijima et al.)

Case: A 73-year-old woman, after spinal surgery, presented with symptomatic spinal subdural extra-arachnoid hygroma (SSEH) because of a fall on the third postoperative day. The hygroma was diagnosed by magnetic resonance imaging (MRI). Lumbar puncture was performed under local anesthesia, after which the leg pain disappeared immediately. MRI obtained immediately after puncture and 1 week later confirmed disappearance of the hygroma., Conclusion: Although dural transection is mentioned in most of the reports on treatment of symptomatic postoperative SSEH, we were able to treat this entity by epidural puncture. In the absence of paraplegia or cystorectal disturbance, puncture can be an effective and minimally invasive treatment option., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C252)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Objectives: To compare real-world, long-term outcomes of laser and anti-vascular endothelial growth factor (VEGF) therapies in patients with retinopathy of prematurity (ROP)., Methods: This was a multicentre retrospective study. We included 264 eyes of 139 patients treated for type 1 ROP or aggressive ROP (AROP) who were followed for at least 4 years. Laser treatment was initially performed in 187 eyes (the laser group), and anti-VEGF therapy was initially performed in 77 eyes (the anti-VEGF group). We collected data on sex, birth characteristics, zone, stage, and the presence of plus disease at the time of treatment and best-corrected visual acuity (BCVA), spherical equivalent (SE), and ocular complications (amblyopia and strabismus) in patients aged 4-6 years. We investigated the associations between treatment outcomes (BCVA, SE and the presence of amblyopia and strabismus) and influencing factors, including treatment procedure (anti-VEGF or laser therapy), sex, birth characteristics, zone, stage, and the presence of plus disease, using multivariable analysis and logistic regression analyses., Results: The initial treatment procedure was not associated with any specific treatment outcome. Subgroup analysis of patients with zone I ROP revealed that the anti-VEGF-treated eyes had significantly better BCVA and higher SE than laser-treated eyes (p = 0.004, p = 0.009, respectively). Female patients presented significantly better BCVA, less amblyopia and less strabismus than male patients (p < 0.001, p = 0.029, p = 0.008, respectively)., Conclusions: In zone I ROP, anti-VEGF therapy led to better visual acuity and less myopic refractive error than laser treatment., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Postpartum hemorrhage is the leading cause of maternal death and severe maternal morbidity worldwide. Previous studies have reported the importance of multidisciplinary treatment approaches for postpartum hemorrhage; however, only a few studies have shown a clear improvement in maternal outcomes. Therefore, this study aimed to investigate the efficacy of a call system for postpartum hemorrhage in a tertiary emergency facility for rapid multidisciplinary treatment and its effect on maternal outcomes., Methods: This single-center retrospective cohort study included patients transferred to our hospital due to postpartum hemorrhage between April 1, 2013, and March 31, 2019. The primary outcome was mortality, and the secondary outcomes were morbidity (duration of hospital stay, duration of intensive care unit stay, admission to the intensive care unit, respirator use, duration of ventilator support, acute kidney injury, transfusion-associated circulatory overload/transfusion-related acute lung injury, hysterectomy, composite adverse events, blood transfusion initiation time, blood transfusion volume, and treatment for postpartum hemorrhage). An in-hospital call system implementation commenced on April 1, 2016. The study outcomes were compared 3 years before and after implementing the call system., Results: The blood transfusion initiation time and duration of hospital stay were significantly shortened after implementing the call system for postpartum hemorrhage. No maternal deaths were observed after implementing the system., Conclusions: Implementing call systems specialized for postpartum hemorrhage in tertiary emergency facilities may improve maternal outcomes., (© 2023. The Author(s).)

Purpose: To evaluate the visual field after anti-vascular endothelial growth factor (VEGF) therapy and laser treatment for retinopathy of prematurity., Method: Retrospective cohort study. Infants with retinopathy of prematurity treated by anti-VEGF therapy or laser treatment were included in the study. Degrees of visual field in eight directions examined by Goldmann perimeter (intensity, 1000 apostilb; size, V4e = 64 mm 2 ) were compared between the anti-VEGF therapy and laser treatment groups. The visual acuity (VA) and spherical equivalent refraction were also compared between the two groups., Results: Nine eyes with anti-VEGF therapy and 12 eyes with laser treatment were enrolled in the analysis. The total, upper, nasal upper, nasal, nasal lower, temporal lower, and temporal upper visual fields were significantly wider in the eyes with anti-VEGF therapy than in those with laser treatment (496 vs 416, P = .002; 53 vs 45, P = .008; 56 vs 43, P = .003; 58 vs 39, P < .001; 55 vs 44, P = .01; 72 vs 65, P = .01; and 62 vs 56, P = .03, respectively). The logarithm of the minimum angle of resolution VA tended to be better in the eyes with anti-VEGF therapy than in those with laser treatment (0.01 vs 0.15, P = .06). Eyes with anti-VEGF therapy had significantly lower myopia than those with laser treatment (spherical equivalent refraction: -0.72 vs -5.7, P = .001)., Conclusion: Anti-VEGF therapy may provide a wider visual field, better VA, and less myopia compared with laser treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sacrococcygeal teratomas (SCTs) are known to cause urological complications, but urethrovaginal (UV) fistula as a complication of SCT is rare. We herein report a case of SCT with UV fistula and hydrocolpos., Case Presentation: A 1-day-old female neonate presented to our department with prominent swelling in the sacrococcygeal region. She was born at 37 gestational weeks via spontaneous vaginal delivery from a 39-year-old woman. The weight of the baby was 2965 g, and her Apgar scores were 4/10 (at 1 and 5 min). An MRI examination confirmed an 11 × 11 cm Altman classification typeII SCT associated with hydrocolpos, a dilated urinary bladder, and bilateral hydronephrosis. When she was 5 days, the SCT was excised totally and a coccygectomy was performed. After the operation, as her urinary output appeared unstable, a cystoscopic examination was performed on the third postoperative day. This revealed that the UV fistula was located approximately 1 cm from the urethral opening. In addition, the proximal urethra was unobstructed and connected to the bladder. The cystoscope allowed for the passage of a urinary catheter through the urethra. After 1 month of catheter placement, she was discharged from the hospital at 57 days of age. Follow-up was uneventful, with neither urinary infection nor retention., Conclusions: SCTs are associated with not only trouble with rectal function and lower extremity movement but also urinary complications. The pathogenesis of this UV fistula is thought to be the rapid growth of the SCT that developed in the fetal period, resulting in obstruction of the urethra by the tumor and the pubic bone, which in turn caused urinary retention and the formation of a fistula as an escape route for the pressure. Because SCTs can cause a variety of complications depending on the course of the disease, careful examination and follow-up are necessary., (© 2023. The Author(s).)

Practical applications like very thin stress-strain sensors require high strength, stretchability, and conductivity, simultaneously. One of the approaches is improving the toughness of the stress-strain sensing materials. Polymeric materials with movable cross-links in which the polymer chain penetrates the cavity of cyclodextrin (CD) demonstrate enhanced strength and stretchability, simultaneously. We designed two approaches that utilize elastomer nanocomposites with movable cross-links and carbon filler (ketjenblack, KB). One approach is mixing SC (a single movable cross-network material), a linear polymer (poly(ethyl acrylate), PEA), and KB to obtain their composite. The electrical resistance increases proportionally with tensile strain, leading to the application of this composite as a stress-strain sensor. The responses of this material are stable for over 100 loading and unloading cycles. The other approach is a composite made with KB and a movable cross-network elastomer for knitting dissimilar polymers (KP), where movable cross-links connect the CD-modified polystyrene (PSCD) and PEA. The obtained composite acts as a highly sensitive stress-strain sensor that exhibits an exponential increase in resistance with increasing tensile strain due to the polymer dethreading from the CD rings. The designed preparations of highly repeatable or highly responsive stress-strain sensors with good mechanical properties can help broaden their application in electrical devices., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Rosai-Dorfman disease is a very rare disease characterized by histiocytic accumulation in the head and neck region and lymph node enlargement. We report a rare pseudo-malignant paranasal extranodal Rosai-Dorfman disease. A 69-year-old-man presented nasal bleeding and nasal obstruction. Paranasal mass was detected in the left nasal cavity and computed tomography (CT) findings are the sphenoid sinus, maxillary sinus, and ethmoid sinus were involved with inconstant bone thickening, however, no bone destruction was detected. Magnetic resonance imaging scans show iso-intensity signal in T1-weighed image and T2-weighed image. Positron emission tomography/CT fluorodeoxyglucose (FDG) uptake in posterior ethmoid sinus and sphenoid sinus, bilateral cervical lymph node, clavicle, and sternum. Based on the above results, we considered malignant lymphoma and performed a biopsy. After pathological examination, a diagnosis of Rosai-Dorfman disease was established., 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.

Paranasal sinus tumors are a heterogeneous group of neoplasms (with paranasal schwannomas being a rare subtype) that are often present with non-specific symptoms, such as nasal obstruction and epistaxis. Thus, early diagnosis is crucial for optimal management. This study presents 2 cases of paranasal schwannomas, detailing their clinical presentation, diagnostic methods, and treatment approaches. Both patients underwent endoscopic sinus surgery with successful tumor excision and had no significant complications or recurrences during follow-up. Diagnosis was based on a combination of clinical examination, radiological imaging (computed tomography and magnetic resonance imaging), and histopathological confirmation with immunohistochemical staining. Treatment consisted primarily of endonasal resection, with consideration of frontal craniotomy if necessary. This study aims to contribute to the understanding of paranasal schwannomas and emphasizes the importance of early detection and treatment to improve patient outcomes., 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.

Atopic dermatitis (AD) shows frequent recurrence. Staphylococcus aureus is the primary microbial component in AD and is associated with disease activity. However, traditional typing methods have failed to characterize virulent AD isolates at the clone level. We conducted a comprehensive genomic characterization of S. aureus strains isolated from the skin of AD patients and healthy donors, comparing the whole-genome sequences of the 261 isolates with anatomical and lesional (AD-A)/nonlesional (AD-NL)/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. Sequence type (ST) diversity was lost with worsening disease activity; ST188 was the most frequently detected ST in AD-A and had the strongest correlation with AD according to the culture rate and proportion with worsening disease activity. ST188 and ST20 isolates inhabited all skin conditions, with significantly higher proportions in AD skin than in healthy skin. ST8, ST15, and ST5 proportions were equivalent for all skin conditions; ST30 was detected only in healthy skin; and ST12 was detected only in AD skin. ST97 detected in AD-A and healthy skin was clearly branched into two subclades, designated ST97 A and ST97 H . A comparison of two genomes led to the discovery that only ST97 A possessed the complete trp operon, enabling bacterial survival without exogenous tryptophan (Trp) on AD skin, where the Trp level was significantly reduced. Primary STs showing an AD skin inhabitation trend (ST188, ST97 A , ST20, and ST12) were all trp operon positive. The predominant clones (ST188 and ST97) possessed almost no enterotoxin genes, no mecA gene, and few other antimicrobial resistance genes, different from the trend observed in Europe/North America. IMPORTANCE While Staphylococcus aureus is a member of the normal human skin flora, its strong association with the onset of atopic dermatitis (AD) has been suggested. However, previous studies failed to assign specific clones relevant to disease activities. Enterotoxins produced by S. aureus have been suggested to aggravate and exacerbate the inflammation of AD skin, but their role remains ambiguous. We conducted a nuanced comprehensive characterization of isolates from AD patients and healthy donors, comparing the whole-genome sequences of the isolates with anatomical and lesional/nonlesional/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. We demonstrate that specific clones are associated with disease severity and clinical manifestations, and the dominant clones are devoid of enterotoxin genes and antimicrobial resistance genes. These findings undermine the established notion of the pathophysiological function of S. aureus associated with AD and introduce a new concept of S. aureus colonization in AD., Competing Interests: The authors declare no conflict of interest.

Japanese midwives are required to autonomously perform midwifery diagnosis and maternity care. However, education to promote the professional autonomy of midwives is inadequate, and previous studies have not been able to identify a measure for it. This study aimed to develop a professional autonomy scale for midwives, to be used for the education and career advancement of Japanese midwives. The Midwives Professional Autonomy Scale extracted items from the midwives' "autonomy" and "specialty" literature, and 10 professionals verified the surface and content validity of the scale. Overall, 695 Japanese midwives participated in a survey, of which a sample of 399 was recovered. Exploratory factor analysis was performed using the sample to confirm the validity of the construct and internal consistency of the scale (Cronbach's alpha value 0.95). Additionally, the validity of the criteria was confirmed using the self-efficacy scale, self-esteem scale, and job satisfaction, and the stability was confirmed by test-retest reliability. Consequently, the professional autonomy scale for Japanese midwives comprised 24 items and 5 factors. This scale can thus be used to evaluate the professional autonomy of Japanese midwives and for midwifery education., Competing Interests: There are no conflicts of interest to declare.

PsADH, an alcohol dehydrogenase originating in Pantoea sp. was characterized and found to convert a broad variety of fatty alcohols into their corresponding aldehydes, the substrates of alkane biosynthesis. By coupling PsADH with NpAD, a cyanobacterial aldehyde-deformylating oxygenase, and by optimizing the conditions of the enzyme-catalyzed reactions, we achieved a 52% conversion of 1-tetradecanol to tridecane. We further applied this system to generate alkanes ranging from C5-17. These alkanes can be used as biofuels, suggesting that introducing a suitable alcohol dehydrogenase is an effective strategy to utilize fatty alcohols for alkane production., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Purpose: The aim of this study was to clarify the appropriate management after birth for congenital biliary dilatation (CBD, choledochal cyst) patients with a prenatal diagnosis., Method: Thirteen patients with a prenatal diagnosis of CBD who underwent liver biopsy during excision surgery were divided into two groups and retrospectively analyzed: group A, with liver fibrosis above F1 and group B, without liver fibrosis., Results: Excision surgery was performed earlier in group A (F1-F2), at a median of 106 days old (p = 0.04). There were significant differences between the two groups in the presence symptoms and sludge, the cyst size, and the level of serum bilirubin and gamma glutamyl transpeptidase (GGT) before excision surgery (p < 0.05). Especially, in group A, prolonged serum GGT elevation and larger cysts were consistently observed from birth. The cut-off values of predictions for the presence of liver fibrosis in serum GGT and cyst size were 319 U/l and 45 mm. No significant differences were observed in the postoperative liver function or complications during the follow-up period., Conclusion: In patients with prenatally diagnosed CBD, the postnatal serial changes of serum GGT values and cyst size, in addition to symptoms, could help to prevent progressive liver fibrosis., Level of Evidence: Ⅲ., Type of Study: Treatment Study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effects of internal limiting membrane (ILM) peeling on retinal attachment after a single surgery, and on postoperative visual acuity (VA) at 6 months, in eyes with macula-off rhegmatogenous retinal detachment (RRD) complicated by proliferative vitreoretinopathy (PVR)., Study Design: Nationwide, multicenter retrospective cohort study., Methods: The Japan-RD Registry database was used for analysis of patients who had undergone vitrectomy for macula-off RRD complicated by PVR. Multivariate analysis was performed to detect prognostic factors for retinal attachment after a single surgery and for VA at 6 months postoperatively. Retinal attachment after a single surgery or VA at 6 months postoperatively was the objective variable; ILM peeling, preoperative VA, PVR grade, age, and intraocular pressure were explanatory variables., Results: Eighty-nine eyes met the inclusion criteria; ILM peeling was performed in 25 eyes (28%). Preoperative VA was significantly associated with retinal attachment, but ILM peeling did not (odds ratios = 2.1 and 1.3, respectively; p = 0.009 and 0.67, respectively). Poor preoperative VA and younger patient age were significantly associated with poor postoperative VA, but ILM peeling was not (β-values = 0.37, -0.008, and 0.15, respectively; p < 0.001, p = 0.02, and p = 0.15, respectively., Conclusions: Preoperative VA was a risk factor associated with retinal attachment. Preoperative VA and patient age were risk factors associated with postoperative poor VA. In eyes with macula-off RRD complicated by PVR, ILM peeling did not have a clear beneficial effect on anatomical and functional outcomes, suggesting that it may be unnecessary for eyes with this condition., (© 2023. Japanese Ophthalmological Society.)

Purpose: To investigate blood monocyte counts as a risk factor for retinopathy of prematurity (ROP) treatment., Design: Retrospective cohort study., Methods: Infants who underwent ROP screening at Shiga University of Medical Science Hospital between January, 2011 and July, 2021 were included in this study. Screening criteria were a gestational age (GA) < 32 weeks or birth weight (BW) < 1500 g. The week with the largest difference in monocyte counts between the infants with and without type 1 ROP determined based on the effect size. Multivariate logistic regression analysis was applied to investigate whether the monocyte counts constituted an independent risk factor for type 1 ROP. The objective variable was type 1 ROP, and the explanatory variables were GA, BW, infants' infection, and Apgar score at 1 min and monocyte counts in the week with the largest monocyte-counts difference between the with- and without type 1 ROP groups., Results: In total, 231 infants met the inclusion criteria. The monocyte counts in the fourth week after birth (4w MONO) exhibited the largest difference between infants with and without type 1 ROP. The analysis was performed on 198 infants, excluding 33 infants without 4w MONO data. Thirty-one infants had type 1 ROP, whereas 167 infants did not. BW and 4w MONO were significantly associated with type 1 ROP (odds ratio: 0.52 and 3.9, P < .001 and 0.004, respectively)., Conclusions: The 4w MONO was an independent risk factor for type 1 ROP and may be useful in follow-up of infants with ROP., (© 2023. Japanese Ophthalmological Society.)

Background: There is no standard timing for switching to surgical management for children with adhesive small bowel obstruction (ASBO) who initially receive conservative treatment. We hypothesized that an increased gastrointestinal drainage volume may indicate the need for surgical intervention., Methods: The study population included 150 episodes in the patients less than 20 years of age who received treatment for ASBO in our department from January 2008 to August 2019. Patients were divided into two groups: the successful conservative treatment group (CT) and the eventual surgical treatment group (ST). Following the analysis of all episodes (Study 1), we limited our analysis to only first ASBO episodes (Study 2). We retrospectively reviewed their medical records., Results: There were statistically significant differences in the volume on the 2nd day in both Study 1 (9.1 ml/kg vs. 18.7 ml/kg; p < 0.01) and study 2 (8.1 ml/kg vs. 19.7 ml/kg; p < 0.01). The cut-off value was the same for both Study 1 and Study 2 (11.7 ml/kg)., Conclusions: The gastrointestinal drainage volume on the 2nd day in ST was significantly larger than that in CT. Accordingly, we considered that the drainage volume may predict eventual surgical intervention for children with ASBO who initially receive conservative treatment., Level of Evidence: Level IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Surgical treatment of spinal metastases has been associated with high morbidity and mortality in patients with sarcopenia based on low skeletal muscle mass. We assessed physical performance using the Eastern Cooperative Oncology Group performance status scale and the Barthel Index on the 30th day after palliative surgery for spinal metastases and investigated the effectiveness of surgery according to sarcopenia assessed by skeletal muscle mass., Methods: We retrospectively analyzed 78 consecutive patients with thoracic and lumbar spinal metastases who underwent palliative surgery. The value of the area of the psoas major muscle at the L3 level normalized by the vertebral area was divided into first, middle, and third tertiles. Clinical variables were compared by tertile. Variables affecting the 30-day good performance status were investigated with univariate and multivariate analyses., Results: The 30-day morbidity rates were 50%, 38.5%, and 15.4% by tertile. The 30-day mortality rate was 2%; all were in the first tertile. Good preoperative performance status scores were seen in 15.4% of first and 50% of third tertile patients. Postoperatively, the performance status improved in all groups, with 30.8%, 65.4%, and 92.3% by tertile. Multivariate regression analysis revealed that a good preoperative performance status (OR: 15.50, 95% CI: 1.610-149.00, P < 0.05) and the value of the area of the psoas major muscle at the L3 level normalized by the vertebral area not in the first tertile (OR: 0.22, 95% CI: 0.06-0.82, P < 0.05) were significant predictors of a good postoperative 30-day performance status., Conclusions: A good preoperative performance status and exclusion from the first tertile were clinical factors predicting a good postoperative 30-day performance status. In patients with large psoas muscle mass (third tertile), a good 30-day performance status can be expected after surgery, suggesting that surgery in this population should be pursued aggressively., Competing Interests: Conflicts of Interest The authors declare there are no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Recently, hand skeletal maturity systems such as the Simplified Skeletal Maturity Scale (SSMS) or Thumb Ossification Composite Index (TOCI) have been introduced to attempt to prospectively predict the occurrence of peak height velocity (PHV) in adolescents. This study aims to compare the frequency of the mismatch in estimation of HV between Risser sign (RS) and SSMS/TOCI stages in adolescent idiopathic scoliosis (AIS) patients., Methods: One hundred thirty-three female patients with AIS were included. The mean age of the patients was 13.1 years. A whole spine and hand X-rays were obtained to establish skeletal maturity stage according to RS, SSMS, and TOCI systems. A mismatch resulting in overestimation (MOE) with RS compared to SSMS/TOCI was defined as the combination of RS 3-4/SSMS 3-5 or RS 3-4/TOCI 4-6, whereas a mismatch resulting in underestimation (MUE) with RS and SSMS/TOCI was defined as RS 0-1/SSMS 6-8 or RS 0-1/TOCI 7-8. Height velocity (HV) was compared between MOE/non-MOE and MUE/non-MUE groups., Results: Between RS and SSMS, the rates of the MOE and MUE groups were 4.3% and 1.7%, respectively. Between RS and TOCI, rates were 2.8% and 1.7%, respectively. With the combination of RS and SSMS stages, an estimate of HV of 5.6 cm/year in the MOE group was significantly larger than that of 2.7 cm/year in the non-MOE group, and 3.7 cm/year in the MUE group was significantly smaller than 6.9 cm/year in the non-MUE group. Likewise, with the combination of RS and TOCI stages, an estimate of HV of 5.8 cm/year in the MOE group was significantly greater that of 2.7 cm/year in the non-MOE group, and 3.7 cm/year in the MUE group was significantly smaller than 6.9 cm/year in the non-MUE group., Conclusions: These findings support the use of SSMS/TOCI as the standard for assessing HV and skeletal maturity in patients with AIS., (© 2023. The Author(s), under exclusive licence to Scoliosis Research Society.)

The defining biology that distinguishes neutrophil extracellular traps (NETs) from other forms of cell death is unresolved, and techniques which unambiguously identify NETs remain elusive. Raman scattering measurement provides a holistic overview of cell molecular composition based on characteristic bond vibrations in components such as lipids and proteins. We collected Raman spectra from NETs and freeze/thaw necrotic cells using a custom built high-throughput platform which is able to rapidly measure spectra from single cells. Principal component analysis of Raman spectra from NETs clearly distinguished them from necrotic cells despite their similar morphology, demonstrating their fundamental molecular differences. In contrast, classical techniques used for NET analysis, immunofluorescence microscopy, extracellular DNA, and ELISA, could not differentiate these cells. Additionally, machine learning analysis of Raman spectra indicated subtle differences in lipopolysaccharide (LPS)-induced as opposed to phorbol myristate acetate (PMA)-induced NETs, demonstrating the molecular composition of NETs varies depending on the stimulant used. This study demonstrates the benefits of Raman microscopy in discriminating NETs from other types of cell death and by their pathway of induction., (© 2023. The Author(s).)

Introduction: To verify the effectiveness of intervention in early pregnancy for women with early-onset gestational diabetes mellitus (GDM)., Research Design and Methods: This study included women with a singleton pregnancy who were diagnosed with early-onset GDM by 20 weeks of gestation according to the International Association of Diabetes and Pregnancy Study Group (IADPSG) threshold. We retrospectively evaluated the pregnancy outcomes in pregnant women with early-onset GDM. In the treatment from early pregnancy group (n=286), patients were diagnosed with early-onset GDM at the Yokohama City University Medical Center (YCU-MC) in 2015-2017 and were treated for GDM from early pregnancy. Concerning the treatment from mid-pregnancy group (n=248), participants were diagnosed with early-onset GDM at five sites, including the YCU-MC in 2018-2019, and were followed up without treatment until the second 75 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Treatment for GDM was given only if the GDM pattern was still present in the second OGTT., Results: There were no significant differences in maternal backgrounds, including GDM risk factors and gestational weight gain, between the groups. Among the treatment from mid-pregnancy group, the false-positive early GDM was 124/248 (50%). Regarding pregnancy outcome, the rate of large for gestational age (LGA) was 8.8% in the treatment from early pregnancy group and 10% in the treatment from mid-pregnancy group, with no significant difference, whereas small for gestational age (SGA) was significantly higher in the treatment from early pregnancy group (9.4%) than in the treatment from mid-pregnancy group (4.8%) (p=0.046). There were no significant differences in maternal adverse events and neonatal outcomes between the groups. In a subanalysis limited to body mass index >25 kg/m 2 , LGA was significantly lower in the treatment from early pregnancy group than in the treatment from mid-pregnancy group., Conclusions: The strategy for diagnosing GDM by IADPSG thresholds in early pregnancy and providing treatment to all patients from early pregnancy did not improve the pregnancy outcomes, but rather increased the SGA rate., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Radioactive isotope (RI) metals are a new type of tracer for positron emission tomography generated from the target metal by proton irradiation using a cyclotron. The generated metal RIs need to be separated from the target metal rapidly and effectively. In the present study, we developed a 3D-printed flow device to separate metal RIs from target metals. The separation was performed with selective formation of ethylenediaminetetraacetic acid (EDTA) complex based on the difference in formation constants. The RI metal selectively formed a EDTA complex, thus changing its ionic charge in solution. The solution was then introduced into a cation exchange column for selective adsorption of the target metal. The solution with added chelator and controlled pH was introduced into the developed system and automatically separated metal RI from target metals within 14 min. The separation method was applied to separate RI 67 Ga from target metal Zn using a mixture of 107 pg L -1 67 Ga in 250 mg L -1 Zn 2+ . The recoveries of 67 Ga and Zn were 97% and 100%, respectively. Furthermore, an ultraviolet (UV) radiation reactor was integrated into the system to decompose the EDTA complex and recover the Ga 3+ ion. Ga 3+ recovery by UV radiation was effective, 87%. The developed system was also successfully applied to the separation of Zr and Y. Therefore, the method and system can be applied to separate other metal RIs from target metals., (© 2023. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Aims: Diabetes mellitus (DM) is the leading cause of chronic kidney disease. Albuminuria is associated with an increased risk of cardiovascular mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) and mineralocorticoid receptor antagonists (MRAs) protect against albuminuria; however, their combined effects on albuminuria are unclear. We performed a network meta-analysis to investigate the effects of SGLT2-Is, MRAs and their combination on albuminuria in type 2 DM., Methods: We systematically searched PubMed, Medline, EMBASE and the Cochrane Library from inception up to 20 November 2022. We selected randomized control and crossover trials that compared MRAs, SGLT2-Is, MRAs + SGLT2-Is, or a placebo in patients with type 2 DM with a urinary albumin-creatinine ratio (UACR) ≥30 mg/g creatinine. The primary outcome was the change in the UACR., Results: This meta-analysis analysed 17 studies with 34 412 patients. The use of combination treatment with SGLT2-Is and MRAs was associated with lower albuminuria compared with the use of SGLT2-Is, MRAs, or the placebo alone [mean difference (95% CI): -34.19 (-27.30; -41.08), -32.25 (-24.53; -39.97) and -65.22 (-57.97; -72.47), respectively]. Treatment with SGLT2-Is or MRAs alone caused a significant reduction in UACR compared with the placebo [mean difference (95% CI): -31.03 (-28.35; -33.72) and -32.97 (-29.68; -36.27), respectively]. The effects of MRAs on the UACR are comparable with those of SGLT2-Is. Sensitivity analyses showed similar results., Conclusion: Combination therapy with SGLT2-Is and MRAs was associated with lower albuminuria in patients with type 2 DM compared with monotherapy with SGLT2-Is or MRAs alone., (© 2023 John Wiley & Sons Ltd.)