Search

BackgroundKnee osteoarthritis (OA) is a leading cause of disability in the elderly population. Chronic disabling pain is associated with maladaptive neuroplastic changes in brain networks, commonly associated with central sensitization. The main clinical features of nociplastic pain conditions include combined peripheral and central sensitization, and it is crucial to recognize this type of pain, as it responds to different therapies than nociceptive and neuropathic pain.ObjectiveTo report the effect of the Institute of Physical Medicine and Rehabilitation (IMREA) comprehensive rehabilitation program to reduce pain and to improve functioning in elderly people with knee OA, under the DEFINE cohort.MethodsThis is a retrospective observational cohort of 96 patients with knee OA, recruited from October 2018 to December 2019. All patients were evaluated by a trained multidisciplinary team using the Kellgren Lawrence classification, bilateral knee ultrasonography, the visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, rigidity and difficulty scores, the Timed Up and Go Test (TUG), 10-m and 6-min walking test (10 and 6 MWT), Berg Balance Scale, isokinetic dynamometry for knee extension and flexion strength, and pain pressure thresholds. The rehabilitation program included paraspinous lidocaine blocks, focal extracorporeal shockwaves combined with radial pressure waves and functional electrical stimulation according to individual needs. The baseline was compred with the treatment results with a paired t-test.ResultsThe study sample is composed of 96 participants, mostly females (n = 81, 84.38%), with bilateral osteoarthritis (n = 91, 94.79%), and a mean age of 68.89 (SD 9.73) years. Functional improvement was observed in TUG (p = 0.019), 6-mwt (p = 0.033), right knee flexion strength (p < 0.0001), WOMAC rigidity and difficulty domains (p < 0.0001). Pain was reduced from baseline as measured by WOMAC pain domain (p < 0.0001), VAS for both knees (p < 0.0001), and SF-36 pain domain (p < 0.0001). Pressure pain threshold was modified above the patella (p = 0.005 and p = 0.002 for right and left knees, respectively), at the patellar tendons (p = 0.015 and p = 0.010 for right and left patellar tendons, respectively), left S2 dermatome (p = 0.017), and L1-L2 (p = 0.008).ConclusionsThe IMREA comprehensive rehabilitation program improved functioning and reduced disabling pain in elderly people with knee OA. We highlight the relevance and discuss the implementation of our intervention protocol. Although this is an open cohort study, it is important to note the significant improvement with this clinical protocol.

Biologically active compounds are considered as powerful food factors that elicit profound effects on the maintenance of human health, and disease prevention. The research into how bioactive compounds work and their role in disease prevention in vitro and in vivo is rapidly expanding. Carotenoids are one among several classes of biologically active compounds that have been reported to possess greater antioxidant and anti-cancer activity. Today, this emerging class of nutrients is the driving force in the nutritional supplement industry, and serves as a new frontier in cancer and cardiovascular research. Cancer is one of the leading causes of death worldwide. It is the second most common disease responsible for maximum mortality with about 8.2 million deaths, and the global cancer burden rises to 14.1 million new cases in 2012. This review mainly focused to summarize the anti-cancer therapeutic targets of carotenoids by highlighting the important hallmarks of cancer in terms of (i) cell cycle arrest, (ii) resistance to apoptosis, (iii) metastasis and (iv) angiogenesis alongside the relation of carotenoids in cancer epidemiology.

An accelerator-driven system (ADS) has been investigated to transmute minor actinide (MA) included in high-level waste. In the neutronic design of the ADS, the accuracy of nuclear data for MA and lead bismuth (LBE) which is the candidate material for coolant and spallation target, is important. To know the current accuracy of nuclear data libraries, this study aims to compare representative nuclear data libraries, JENDL-4.0, 3.3, ENDF/B-VII.1 and VII.0 through the neutronic calculation of the ADS geometry proposed as the IAEA benchmark problem. The calculation results showed that about 1.1%dk, 0.7%dk and 2.7%dk differences were observed between JENDL-4.0 and ENDF/B-VII.1, ENDF/B-VII.0 and JENDL-3.3 at the beginning of cycle, respectively. These results mean that the current nuclear data libraries are still insufficient for the neutronic design of the ADS. The enhancement of nuclear data libraries by cross section measurement is required and, moreover, integral experiments with MA and LBE isotopes are essential

No abstract available.

The yeast cell walls of the budding yeast Saccharomyces cerevisiae are well studied and the results show the existence of a framework composed of β-1,3-glucan. It is reported that the cell wall of the fission yeast Schizosaccharomyces pombe has different components and our analysis by 13C-nuclear magnetic resonance (NMR) spectroscopy also showed there is α-1,3-glucan in its cell wall. To refine our understanding of the architecture of the yeast cell wall, we re-examined the cell wall glucans of S. pombe by NMR spectroscopy and prepared antibody against α-1,3-glucan, which is a characteristic component of this yeast. By the competitive enzyme-linked immunosorbent assay (ELISA) system, specificity of the antibody was restricted to α-1,3-glucan, which did not take a highly ordered structure. We analysed the localization of the cell wall glucans by immunoelectron microscopy. Transmission electron microscope (TEM) images showed that most of the α-1,3-glucan was along the cell membrane and appeared to enclose the cytoplasm, supporting previous reports that this glucan is synthesized on the cell membrane. [ABSTRACT FROM AUTHOR]

The characteristic degradation mechanism of the cross-phase modulation (XPM) effect on multilevel amplitude and differentially phase-shift keying (APSK) signals in dense wavelength-division-multiplexing (DWDM) transmissions is analyzed and experimentally investigated, for the first time. Based on the results, we successfully demonstrate a 0.48-Tb/s (30-Gb/s/ch) 50-GHz-spaced 16-channel DWDM 160-km unrepeatered transmission of eight-level APSK signals suppressing the XPM-induced degradation. [ABSTRACT FROM PUBLISHER]

The axial merging method is one of the candidates to provide a center-solenoid-free start-up of high-beta spherical tokamak (ST) plasma. Two initially formed STs merge through magnetic reconnection in the presence of the guide (toroidal) magnetic field, which is perpendicular to the reconnection (poloidal) magnetic field. During ST merging start-up, electrons are effectively accelerated near the reconnection point where the reconnection electric field is almost parallel to the magnetic field. In order to evaluate the effectivity of this acceleration process on electron heating, the temporal and spatial distributions of generated energetic electrons are observed by a soft x-ray fast imaging system equipped on the UTST device. The energetic electrons were generated not only in the vicinity of the reconnection point but transiently in the inboard-side downstream region until the static electric field by charge separation grew to cancel the reconnection electric field component parallel to the magnetic field line. Adequate control of the downstream condition could enhance the generation of energetic electrons and provide a more effective conversion from the released magnetic energy to electron energy. [ABSTRACT FROM AUTHOR]

A centre-solenoid-free merging start-up scheme for spherical tokamak plasmas was developed in a University of Tokyo spherical tokamak (UTST) experiment by using outer poloidal field coils. Torus breakdown was initiated at null points and two spherical tokamak plasmas with a total current up to 80 kA were generated inductively. Their merging process provided substantial ion and electron heating by magnetic reconnection. The obtained dependence of heating on plasma current suggests that high-temperature and high-current plasma suitable for neutral beam injection is attainable under the realistic conditions in the merging start-up method. [ABSTRACT FROM AUTHOR]

A 46-year-old woman on low-dose estrogen-progestin (LEP) therapy for endometriosis developed a right-sided pneumothorax. Surgical findings included a pulmonary bulla in the right middle lung lobe and a small hole in the center tendon of the diaphragm, both of which were partially resected. Histopathology confirmed the presence of endometrial tissue, leading to a diagnosis of thoracic endometriosis. This case demonstrates that catamenial pneumothorax can occur despite LEP therapy, which is intended to suppress endogenous hormones. Clinicians should remain vigilant for this condition in patients with a history of endometriosis, even when hormonal treatment is in use., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. The Ethics Committee of Tohoku Medical and Pharmaceutical University issued approval 2024-4-060-0000. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ishibashi et al.)

Purpose: Middle-segment preserving pancreatectomy (MSPP) serves as an alternative to total pancreatectomy (TP) for preserving the pancreatic body in multifocal pancreatic neoplasms. Despite the potential benefits of TP, the detailed short- and long-term prognoses remain unclear. We evaluated the feasibility of MSPP by comparing the perioperative outcomes and postoperative endocrine and exocrine functions with those of TP., Methods: The study included 10 TP and 7 MSPP patients. Patients with pancreatic ductal adenocarcinoma and invasive intraductal papillary mucinous carcinoma were excluded., Results: MSPP was associated with a high incidence (57.1%) of postoperative pancreatic fistula (POPF); however, there were no cases of post-pancreatectomy hemorrhage or postoperative mortality in any group. The postoperative hospital stay and readmission rates were comparable between the groups. At 1 year postoperatively, MSPP reduced the risk of new-onset insulin-dependent diabetes mellitus, maintained good glycemic control with minimal hypoglycemic events, and preserved skeletal muscle, subcutaneous fat, and visceral fat. One patient in the MSPP group with a neuroendocrine tumor had postoperative recurrence in the para-aortic lymph node., Conclusions: Despite the high POPF rate and oncologic limitations, MSPP showed superior long-term outcomes in glycemic control and preservation of body composition. MSPP may be an acceptable treatment option for selected patients., Competing Interests: Declarations. Ethical approval: This study was approved by the Human Research Ethics Committee of the Tokyo Medical and Dental University (M2000-1080-06). Informed consent was obtained from all the participants included in this study. Conflict of interest: The authors declare no conflicts of interest in association with the present study., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Around 5-10 % of pancreatic cancer patients are non-expressors of carbohydrate antigen 19-9 (CA 19-9), which has an unknown impact on the aggressiveness and prognosis of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate the characteristics and the prognosis of PDAC patients who do not express CA 19-9., Methods: Patients with PDAC diagnosed between 2010 and 2018 were identified in the National Cancer Database. Clinical characteristics were compared according to CA 19-9 levels stratified in four different groups: non-expressors (≤1.0 U/mL), normal range (1.1-37.0 U/mL), mildly elevated (37.1-97.9 U/mL), and CA 19-9 ≥98.0 U/mL. The characteristics were analyzed in the whole cohort and overall survival (OS) was evaluated in a subgroup of upfront resected patients who had cT1-3 tumors without distant metastases., Results: In total, 88,749 patients were included, of which 4.5 % were CA 19-9 non-expressors. The non-expressors had a higher risk of having distant metastasis at diagnosis, compared to patients with normal-range or mildly elevated CA 19-9 levels. In resected patients (n = 4008), CA 19-9 non-expressors had shorted median OS compared to patients with normal-range CA 19-9 levels (29.3 vs 34.4 months, p = 0.024). This OS association remained in a multivariable Cox regression model (adjusted HR 1.22, 95 % CI 1.04-1.44)., Conclusions: CA 19-9 non-expression is associated with distant metastatic disease at diagnosis and with death in resected non-metastatic patients compared to normal-range CA 19-9 levels. This clinically relevant subgroup requires alternative biomarkers, and may need consideration of more extensive preoperative staging and intensive perioperative systemic therapy., Competing Interests: Declaration of competing interest Dr. Colborn reported receiving grants from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and Agency for Healthcare Research and Quality during the conduct of the study. Dr. Schulick reported being the inventor of a patent licensed to DynamiCure and receiving laboratory equipment from Haemonetics outside of the submitted work. Dr. Del Chiaro reported receiving grants from Haemonetics Inc. and research funding from Boston Scientific outside of the submitted work. No other disclosures were reported., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: The authors declare that they have no conflict of interest.

Iqsec1 (IQ motif and Sec7 domain-containing protein 1), also known as BRAG2 (Brefeldin A-resistant Arf-GEF 2), is a guanine nucleotide exchange factor that regulates membrane trafficking, cytoskeletal organization, and signal transduction by activating class II and III ADP-ribosylation factors. To investigate the physiological role of Iqsec1 at the whole animal level, we generated Iqsec1-deficient mice using CRISPR/Cas9-mediated gene editing. Nearly all Iqsec1 -/- mice (99%) exhibited embryonic lethality with severe growth retardation. Electron microscopy revealed that Iqsec1 -/- embryos at embryonic day 8.5 lacked large apical vacuoles in visceral endoderm cells of the yolk sac, compared with controls. These findings suggest that Iqsec1 plays a critical role in embryogenesis, likely through regulation of membrane trafficking in visceral endoderm cells., (© 2024 Federation of European Biochemical Societies.)

Purpose: To gauge the value of low-vision-specific function and activities of daily living measures (LVFAM) in the assessment of Patient Reported Outcomes (PRO) of Retinitis Pigmentosa (RP)., Study Design: Prospective observation study., Methods: The May-July 2023 Visual activities of daily living (ADL) Survey of the low-vision-specific function and activities of daily living measure (LVFAM) was conducted on 15 RP patients attending our Ophthalmology outpatient clinic. We used the better corrected visual acuity, and the better Mean Deviation (MD) values of the central 10 degrees of Humphrey's visual field as macular sensitivity, and examined the total scores after Rasch Analysis for each of the low-vision-specific function of Daily Living (LVFDL) and the low-vision-specific activities of Daily Living (LVADL) among LVFAM, as well as the relationship between the items., Results: Age 26-78 (mean 60.8), 5 men and 10 women, corrected visual acuity of 0.01-1.0 (mean 0.45) in the better eye, macular sensitivity of 3.47-40.00 (mean 18.60) dB, mean 52.2 for LVFDL and 66.4 for LVADL. The correlations were positive for visual acuity and LVFDL and LVADL, and negative for macular sensitivity, LVFDL and LVADL. In addition, four items were scored 0 by at least 5 (33%) of the LVFDL respondents, and two items were scored 1 by at least 5 (33%) of the LVADL respondents, suggesting that the results differed by question items., Conclusion: The LVFAM was useful not only for the total score but also for each question item in the development strategy of PROs in RP with no treatment., Competing Interests: Declarations. Conflict of interest: T. Sugawara, None; K. Pak, None; G. Miura, None; T. Baba, None., (© 2024. The Author(s).)

Background: Peripheral primitive neuroectodermal tumors (pPNETs) are rare and aggressive small round cell tumors, tending to occur in the thoracic and paravertebral soft tissues in children and young adults. This report describes an exceptionally rare case of concurrent delayed recurrence of pPNET in the orbital and sellar/suprasellar regions in an older adult, with a discussion supported by a literature review., Case Presentation: We report an 82-year-old woman with a history of orbital pPNETs resection at age 62, followed by gamma knife radiosurgery for local recurrence at age 66. She presented left eye pain, left eye protrusion, decreased vision in the right eye, and right homonymous hemianopia. MRI revealed extensive lesions in the left orbital cavity and sellar/suprasellar region, contiguous through the optic canal. The recurrent tumor was treated through a two-stage resection via transcranial and transsphenoidal approaches, which resulted in symptom improvement and a pathologic diagnosis of pPNETs., Conclusion: This case highlights a highly rare instance of late-onset orbital pPNETs recurrence in an elderly patient, with evidence suggesting tumor progression into the sellar/suprasellar regions through the optic canal., 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.

Background: Assessment of individual tumor biology and response to systemic therapy in pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. The significance of anthropometric (body composition) changes during chemotherapy as a surrogate for tumor biology in the setting of localized PDAC is unknown., Methods: A retrospective, single-institution analysis of patients with PDAC who received neoadjuvant therapy (NAT) and pancreatectomy from 2017 to 2021 was performed. Radiologic anthropometric analysis used artificial intelligence-driven software to segment and compute total and sub-compartment muscle area, adipose tissue area, and attenuation values at the level of the L3 vertebra. Kaplan-Meier survival estimates, log-rank tests, and multivariable Cox regression models were used in survival analyses., Results: The inclusion criteria were met by 138 patients. Although decreases in muscle and adipose tissue areas during NAT were predominant, a subset of patients experienced an increase in these compartments. Increases in muscle greater than 5% (hazard ratio [HR], 0.352; 95% confidence interval [CI] 0.135-0.918; p = 0.033) and increases in adipose tissue greater than 15% (HR, 0.375; 95% CI 0.144-0.978; p = 0.045), were significantly associated with improved survival, whereas loss of visceral fat greater than 15% was detrimental (HR 1.853; CI 1.099-3.124; p = 0.021). No significant associations with single time-point anthropometrics were observed. Gains in total muscle and adipose mass were associated with improved pathologic response to systemic therapy and less advanced pathologic tumor stage., Conclusions: Dynamic anthropometric analysis during NAT for PDAC is a stronger prognostic indicator than measurements taken at a single point in time. Repeated anthropometric analysis during preoperative chemotherapy may serve as a biomarker for individual tumor biology and response to therapy., (© 2024. Society of Surgical Oncology.)

Background: Primary spontaneous pneumothorax (PSP) has been the subject of many studies, but its pathogenesis remains unclear. Most juvenile PSPs have a tall stature, thin build, and flat thorax, which is described as a "pneumothorax body shape." In this study, we compared the body shapes of spontaneous pneumothorax (SP) patients in their teens and 20s and examined the characteristics of SP patients., Methods: Among PSPs operated on in our hospital, we compared the body shapes of males in their teens and 20s. In addition to height, weight, and body mass index (BMI), we measured the size of the thorax using computed tomography (CT) and analyzed the relationship between the two groups and height., Results: A total of 77 cases of PSP in teens and 39 cases of PSP in 20s were entered into the study. Teenage PSPs had significantly lower BMI and were slimmer than those in their 20s. However, there were no differences in thorax size and height other than transverse diameter (TD). Furthermore, almost all thorax sizes of PSPs in their 20s were positively correlated with height, whereas those of PSPs in their teens were not correlated except for TD and vertical length., Conclusion: The study highlights significant differences in body shape characteristics between teenagers and individuals in their 20s at the onset of SP. These findings emphasize the need for age-specific considerations in the clinical approach to this condition. Further research is required to understand the underlying mechanisms and to optimize treatment strategies accordingly., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Clinical Research Review Committee, Tohoku Medical and Pharmaceutical University Hospital issued approval 2022-2-074. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nonomura et al.)

Background: Spontaneous pneumothorax (SP) is a frequently encountered respiratory condition. Despite advancements in treatment techniques, there is currently no standardized treatment protocol. The aim of this study was to standardize the management of SP by collecting long-term postoperative data through written surveys., Methods: Our study included 673 surgeries performed for SP at our institution between January 2011 and December 2019. We administered written surveys via mail to gather data on post-surgery recurrence rates and other related factors. The survey addressed key symptoms, medical consultations, and specific diagnoses of SP after surgery., Results: The effective response rate was 70.7%, with significant differences observed across age groups. Among teenagers, the recurrence rate peaked three years postoperatively, with an ipsilateral recurrence rate of 4.8% and a contralateral incidence rate of 11.8%, both of which were significantly higher than those in other age groups. Additionally, age, sex, postoperative contralateral pneumothorax, and the period before the survey were identified as factors influencing the survey results., Conclusion: This survey highlighted the need for long-term postoperative follow-up for teenagers. While written surveys have limitations, this study provided valuable data for understanding the outcomes of SP. Moving forward, it is advisable to conduct surveys using other effective tools or to continue follow-ups in outpatient clinics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nonomura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Reports of novel species of α-hemolytic Streptococcus have increased recently. However, limited information exists regarding the pathogenicity of these species, with the exception of Streptococcus pneumoniae and Streptococcus pseudopneumoniae . In this study, a quinolone-resistant α- Streptococcus strain, MTG105, was isolated from the sputum of a patient with pneumonia. This strain was first identified as S. pneumoniae at the hospital laboratory; however, it exhibited unique genetic features upon further analysis. Digital DNA-DNA hybridization and average nucleotide identity based on BLAST values from whole-genome sequencing revealed MTG105 to be a novel species closely related to S. pseudopneumoniae . Although MTG105 carried two copies of the pneumolysin gene, similar to S. pseudopneumoniae , this isolate exhibited susceptibility to optochin under both aerobic and 5% CO 2 conditions. Notably, no biochemical features could be used to definitively identify this species. In an infection assay using organotypic lung tissue models, MTG105 induced epithelial damage comparable to that of S. pneumoniae and S. pseudopneumoniae , possibly suggesting its potential as a pathogenic α- Streptococcus . The natural transformation abilities of Streptococcus species facilitate their exchange of genes within the same genus, resulting in the existence of species with increasingly more diverse genome structures. Therefore, the identification of this species highlights the importance of monitoring the emergence of novel species exhibiting virulence and/or multidrug resistance. This isolate was proposed as a novel species, designated Streptococcus nakanoensis sp. nov. The type strain was MTG 105 T (= JCM 35953 T = CCUG 76894 T )., Importance: The genus Streptococcus encompasses a wide range of bacteria with more than 60 species. Recently, there has been a notable increase in reports of novel species of α- Streptococcus based on genomic analysis data. However, limited information exists regarding the pathogenicity of these species. In this study, a quinolone-resistant α-hemolytic Streptococcus strain, MTG105, was isolated from a patient with pneumonia. Genetic analysis revealed that this species was a novel species closely related to S. pseudopneumoniae . In an infection assay using organotypic lung tissue models, MTG105 induced epithelial damage comparable to that caused by S. pneumoniae and S. pseudopneumoniae , strongly suggesting its potential as a pathogenic α- Streptococcus . The natural transformation abilities of Streptococcus species facilitate gene exchange within the same genus, leading to the emergence of species with increasingly diverse genome structures. Therefore, the identification of this species underscores the importance of monitoring the emergence of novel species exhibiting virulence and/or multidrug resistance., Competing Interests: The authors declare no conflict of interest.

Objective: The extended outcomes of the KEYNOTE-024 study demonstrated a favorable 5-year overall survival (OS) rate of 31.9%. The present study investigated the outcomes of pembrolizumab monotherapy for advanced or recurrent non-small cell lung cancer (NSCLC) at our institution., Patient: The long-term outcomes of 102 patients with advanced or recurrent NSCLC treated with pembrolizumab monotherapy between March 2017 and December 2022 were retrospectively assessed., Results: This study included a total of 102 patients [mean age: 72 ± 9.6 years (range: 41-91 years), male/female=77/25; performance status (PS; 0, 1, 2, 3, 4)=49/38/15/0/0; smokers=91 (89%), non-squamous cell carcinoma/squamous cell carcinoma=66/36, PD-L1 tumor proportion score (TPS) ≥50%/1-49%=80/22, positive for EGFR mutation=5, advanced/postoperative recurrence=51/51, treatment line: first/second or later=81/21, treatment courses: median 8 (range: 1 - 39), objective response rate/disease control rate=44%/55%, immune-related adverse events (irAEs): 47, 5-year OS=34%]. On univariate analysis, PS, PD-L1 TPS, and irAEs were significant prognostic factors. On multivariate analysis, histology, PD-L1 TPS, and irAEs were significant prognostic factors., Conclusion: Pembrolizumab monotherapy demonstrated promising treatment outcomes for advanced or recurrent NSCLC, as evidenced by the significant association of PD-L1 TPS with irAEs and prognosis, suggesting its potential as a beneficial therapeutic option., Competing Interests: The authors declare no conflict of interest., (©2024 The Japanese Association of Rural Medicine.)

Melatonin plays a major role in regulating the sleep-wake cycle and enhancing testosterone production. We investigated the short-term effects of melatonin treatment for 14 consecutive days in the cryptorchidism model. We categorized experimental mice into Sham (S), Orchiopexy (O), Melatonin (Mel), and Orchiopexy + Melatonin (OMel) groups. Surgery involved inducing cryptorchidism in the left testis for seven days, followed by orchiopexy. The Mel group's testes did not descend, but they received melatonin injections after seven days of cryptorchidism. The OMel group underwent both orchiopexy and melatonin treatment. Both O and Mel groups exhibited decreased sperm and round-headed sperm in the epididymis. Significant increases were observed in the numbers of giant cells and negative Nectin-3 cells at p -value<0.05. The pattern of Cadm1 expression changed, and Nectin-2 and Nectin-3 co-expression was lacking in abnormal spermatids. Sertoli cell cytoplasm in both O and Mel groups exhibited autophagosomes and multivesicular bodies, which correlated with increased cyclooxygenase-2 expression. However, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cell numbers increased significantly in all treatment groups compared to the S group. Our study found that the combination of orchiopexy and melatonin positively influenced the expression of cell adhesion molecules (Cadm1, Nectin-2, and Nectin-3) involved in spermatogenesis, while reducing giant cells, autophagosomes, and apoptosis.

Background: Repeated exposure to ultraviolet A (UVA) irradiation, which can penetrate the epidermis and reach the dermis, is one of the major causes of skin photoaging. Photoaged skin is characterized clinically by generalized wrinkling, a dry and loose appearance, and seborrheic keratoses, along with skin barrier dysfunction. Fucoxanthin, a xanthophyll carotenoid with a specific allenic bond and 5,6-monoepoxide in its structure, has been found to serve various functions as a food supplement. In the present study, the protective effects of orally administered fucoxanthin at relatively low concentrations (0.001% and 0.01%) against UVA induced photoaging were evaluated in vivo using hairless mice., Results: Oral supplementation of 0.001% fucoxanthin was sufficient for its metabolites to accumulate in the skin, thereby inhibiting pathological changes induced by UVA irradiation, including impaired skin barrier function and accelerated wrinkle formation. Analysis of gene expression revealed that dietary fucoxanthin exerted antiphotoaging effects, possibly by modulating natural moisturizing factor (NMF) synthesis, desquamation, and ceramide composition in the epidermis, and by inhibiting the UVA induced degradation of collagen fibers and inflammation in the dermis., Conclusion: Taken together, our data indicate the potential application of dietary fucoxanthin as a novel ingredient in nutricosmetics for skin care against photoaging. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC., Methods: A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points., Results: The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months., Conclusions: Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC., (© 2024. Society of Surgical Oncology.)

This study aimed to evaluate the role of pathological features beyond tumor size in the risk of lymph node metastasis in appendiceal neuroendocrine tumors. Analyzing data from the national cancer database, we found that among 5353 cases, 18.8% had lymph node metastasis. Focusing on tumors smaller than 2 cm, a subject of considerable debate in treatment strategies, we identified lymphovascular invasion as one of the strongest predictors of lymph node disease. Interestingly, extension into the subserosa and beyond, a current factor in the staging system, was not a strong predictor. These findings suggest that careful interpretation of pathological features is needed when selecting therapeutic approaches using current staging systems.

Background and Objectives: Blood neurofilament light chain (NfL) is a minimally invasive, but highly sensitive biomarker of neurological diseases. However, diseases and neurological damage associated with increased NfL remain unclear. Therefore, the present study investigated factors associated with increased plasma NfL levels in various neurological diseases, focal lesions and pathological processes., Methods: This was a retrospective cohort study on 410 participants with various neurological diseases and 17 healthy and cognitively unimpaired controls (HCU). Plasma samples were analyzed to measure NfL using ECL immunoassay. The focal lesions were classified as the cerebrum, cerebellum, brainstem, meninges, spinal cord, peripheral nerves, neuromuscular junction, and muscles based on medical records. A multiple regression analysis and receiver operating characteristic curve (ROC) analysis were performed to investigate whether plasma NfL levels predict specific diseases and focal lesions., Results: Plasma NfL levels discriminated between the HCU and all disease groups (area under the curve (AUC), 0.97), with a cut-off value of 63.4 pg/mL. A multiple regression analysis of focal lesions adjusted by pathogenic processes showed that brainstem and peripheral nerve involvement was associated with higher plasma NfL levels. A cut-off value of 53.8 pg/mL of NfL discriminated between the HCU and neurological disease group except for brainstem or peripheral disorders (AUC 0.962), while a cut-off value of 208.0 pg/mL distinguished this group from brainstem or peripheral nervous system disorders (AUC 0.716)., Discussion: These results demonstrate that plasma NfL has a potential to be a highly sensitive biomarker for neurological diseases and focal lesions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This case report shows unique aneurysm at the left ventricular apex associated with a double-chambered left ventricle (DCLV) in asymptomatic 69-year-old female. The aneurysm was located at the apex of an accessory chamber, which was formed by hypertrophied muscle band and the interventricular septum, along with a pronounced jet flow directed towards the apex aneurysm. These finding suggests that the obstruction at the base of the accessory chamber caused a pressure overload at the apex, ultimately leading to the development of the aneurysm. To best of our knowledge, this is the first case to prove the underlying cause of aneurysm formation in DCLV., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Peritoneal washing cytology (CY) in patients with pancreatic cancer is mainly used for staging; however, it may also be used to evaluate the intraperitoneal status to predict a more accurate prognosis. Here, we investigated the potential of deep learning of CY specimen images for predicting the 1-year prognosis of pancreatic cancer in CY-positive patients. CY specimens from 88 patients with prognostic information were retrospectively analyzed. CY specimens scanned by the whole slide imaging device were segmented and subjected to deep learning with a Vision Transformer (ViT) and a Convolutional Neural Network (CNN). The results indicated that ViT and CNN predicted the 1-year prognosis from scanned images with accuracies of 0.8056 and 0.8009 in the area under the curve of the receiver operating characteristic curves, respectively. Patients predicted to survive 1 year or more by ViT showed significantly longer survivals by Kaplan-Meier analyses. The cell nuclei found to have a negative prognostic impact by ViT appeared to be neutrophils. Our results indicate that AI-mediated analysis of CY specimens can successfully predict the 1-year prognosis of patients with pancreatic cancer positive for CY. Intraperitoneal neutrophils may be a novel prognostic marker and therapeutic target for CY-positive patients with pancreatic cancer., (© 2024. The Author(s).)

Background: Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting., Methods: This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup., Results: Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors., Conclusion: After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors., (© 2024. Society of Surgical Oncology.)

An 80-year-old man with a history of Bence-Jones potein (BJP) λ-type multiple myeloma (MM), which had been in remission for 16 years, was examined for shortness of breath and was found to have bilateral pleural and pericardial effusions. A pleural fluid test and a pleural biopsy under local anaesthesia performed by a previous physician failed to make the diagnosis. Despite diuretic therapy, his condition necessitated frequent thoracentesis. The patient was referred to our hospital and thoracoscopic pleural and pericardial biopsies performed under general anaesthesia revealed λ-type AL amyloidosis, indicating a relapse of MM. Despite drug therapy for MM, the patient died from aspiration pneumonia. The case underscores the importance of considering amyloidosis in differential diagnoses for refractory effusions, especially in patients with a history of MM, even after long-term remission., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

A 67-year-old man visited our hospital complaining of dark-colored urine and upper abdominal pain. Magnetic resonance cholangiopancreatography showed stricture of the distal bile duct, and contrast-enhanced computed tomography showed irregular thickening of the distal bile duct wall. However, no enlarged lymph nodes, pancreatic tumors, or other neoplastic lesions were apparent around the bile duct. Endoscopic ultrasonography and intraductal ultrasonography showed irregular thickening of the inner hypoechoic layer without the disappearance of the innermost thin hyperechoic layer. On the basis of these findings, we considered that the bile duct lesion was of non-epithelial origin. Thus, we repeatedly performed bile duct biopsies from the same site under fluoroscopy to obtain a sample of the submucosal tissue. The pathological diagnosis was diffuse large B-cell lymphoma, and the patient received systemic chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). After six courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, positron emission tomography-computed tomography showed the disappearance of 18-fluorodeoxyglucose uptake in the bile duct and endoscopic retrograde cholangiography showed improvement of the bile duct stricture. Endoscopic findings and repeated biopsies were useful in making the diagnosis of primary biliary diffuse large B-cell lymphoma., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The vertebral column is a characteristic structure of vertebrates. Genetic studies in mice have shown that Hox-mediated patterning plays a key role in specifying discrete anatomical regions of the vertebral column. Expression pattern analyses in several vertebrate embryos have provided correlative evidence that the anterior boundaries of Hox expression coincide with distinct anatomical vertebrae. However, because functional analyses have been limited to mice, it remains unclear which Hox genes actually function in vertebral patterning in other vertebrates. In this study, various zebrafish Hox mutants were generated for loss-of-function phenotypic analysis to functionally decipher the Hox code responsible for the zebrafish anterior vertebrae between the occipital and thoracic vertebrae. We found that Hox genes in HoxB- and HoxC-related clusters participate in regulating the morphology of the zebrafish anterior vertebrae. In addition, medaka hoxc6a was found to be responsible for anterior vertebral identity, as in zebrafish. Based on phenotypic similarities with Hoxc6 knockout mice, our results suggest that the Hox patterning system, including at least Hoxc6, may have been functionally established in the vertebral patterning of the common ancestor of ray-finned and lobe-finned fishes., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The treatment of nasal bone fractures involves closed reduction, in which the reduction position is generally evaluated indirectly by visual examination and palpation. While more direct evaluation methods using ultrasonography can improve treatment outcomes, ultrasonography of the nasal bones requires acoustic coupling materials to hold the entire ultrasonography probe in close contact with the nose. We report the use of the Glove Finger Pad, a homemade acoustic coupling material made from a medical glove. The Glove Finger Pad is easy to prepare and use and produces good images. We believe that the Glove Finger Pad will further enhance the usefulness of ultrasonography for the treatment of nasal fractures., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer., Methods: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes., Results: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%., Conclusions: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

The need for resection of the meningioma capsule has long been debated and remains controversial. Even the definition of a capsule does not seem to have been established. We described the histopathological findings of the so-called capsule and the necessity for resection, considering tumor cell invasion and recurrence, based on a literature review.

During human embryonic development, early cleavage-stage embryos are more susceptible to errors. Studies have shown that many problems occur during the first mitosis, such as direct cleavage, chromosome segregation errors, and multinucleation. However, the mechanisms whereby these errors occur during the first mitosis in human embryos remain unknown. To clarify this aspect, in the present study, we image discarded living human two-pronuclear stage zygotes using fluorescent labeling and confocal microscopy without microinjection of DNA or mRNA and investigate the association between spindle shape and nuclear abnormality during the first mitosis. We observe that the first mitotic spindles vary, and low-aspect-ratio-shaped spindles tend to lead to the formation of multiple nuclei at the 2-cell stage. Moreover, we observe defocusing poles in many of the first mitotic spindles, which are strongly associated with multinucleation. Additionally, we show that differences in the positions of the centrosomes cause spindle abnormality in the first mitosis. Furthermore, many multinuclei are modified to form mononuclei after the second mitosis because the occurrence of pole defocusing is firmly reduced. Our study will contribute markedly to research on the occurrence of mitotic errors during the early cleavage of human embryos., (© 2024. The Author(s).)

Pleomorphic adenomas occur primarily in the salivary glands, while the primary of the trachea is relatively rare. Depending on their location and size, they may elicit symptoms reminiscent of asthma and asphyxia. We performed a rigid bronchoscopic resection with a radiofrequency snare of a primary pleomorphic adenoma of the trachea with severe airway narrowing. In this case, the positive resection margins raised concerns about malignant transformation and local recurrence, but no recurrence has been observed seven years postoperatively. The low expression of Ki-67 on immunohistological examination may be one of the reasons for the absence of recurrence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

It has been reported that Mizoribine is an immunosuppressant used to suppress rejection in renal transplantation, nephrotic syndrome, lupus nephritis, and rheumatoid arthritis. The molecular chaperone HSP60 alone induces inflammatory cytokine IL-6 and the co-chaperone HSP10 alone inhibits IL-6 induction. HSP60 and HSP10 form a complex in the presence of ATP. We analyzed the effects of Mizoribine, which is structurally similar to ATP, on the structure and physiological functions of HSP60-HSP10 using Native/PAGE and transmission electron microscopy. At low concentrations of Mizoribine, no complex formation of HSP60-HSP10 was observed, nor was the expression of IL-6 affected. On the other hand, high concentrations of Mizoribine promoted HSP60-HSP10 complex formation and consequently suppressed IL-6 expression. Here, we propose a novel mechanism of immunosuppressive action of Mizoribine.

In patients presenting neck pain and hemiparesis, differentiation between cerebral infarction and cervical spinal epidural hematoma is vital yet challenging, particularly when magnetic resonance imaging (MRI) is not feasible. A 59-year-old woman presented with a sudden onset of left-sided hemiparesis and neck pain. MRI was contraindicated because the patient underwent embolization in childhood. Head computed tomography (CT) revealed no evidence of hemorrhage or early ischemic signs. Cervical CT revealed no evidence of hematoma within the spinal canal. Myelography and CT myelography revealed no significant cervical spine abnormalities. The diagnosis was cerebral infarction. Cervical spine MRI is the gold standard examination for diagnosing cervical spinal epidural hematoma, but cervical spine CT, myelography, and CT myelography may be useful when MRI is contraindicated., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tanaka et al.)

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking., Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy., Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months., Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection., Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively., Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89)., Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

The aryl hydrocarbon receptor (AhR) forms a complex with the HSP90-XAP2-p23 molecular chaperone when the cells are exposed to toxic compounds. Recently, 1,4-dihydroxy-2-naphthoic acid (DHNA) was reported to be an AhR ligand. Here, we investigated the components of the molecular chaperone complex when DHNA binds to AhR. Proteins eluted from the 3-Methylcolanthrene-affinity column were AhR-HSP90-XAP2-p23 complex. The AhR-molecular chaperone complex did not contain p23 in the eluents from the DHNA-affinity column. In 3-MC-treated cells, AhR formed a complex with HSP90-XAP2-p23 and nuclear translocation occurred within 30 min, while in DHNA-treated cells, AhR formed a complex with AhR-HSP90-XAP2, and translocation was slow from 60 min. Thus, the AhR activation mechanism may differ when DHNA is the ligand compared to toxic ligands., (© 2024 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

We report two rare cases of cardiac tamponade after left upper lobectomy. Case 1:A 76-year-old man underwent thoracoscopic left upper lobectomy and lymph node dissection for lung cancer. The patient suddenly developed cardiac tamponade the day after surgery. Emergency surgery was performed to stop bleeding and confirm the source of bleeding, and dark red pericardial fluid and hematoma were observed in the pericardial sac. There was no postoperative recurrence of cardiac tamponade. He died 1 year and 2 months after the operation. Case 2:A 77-year-old woman underwent thoracoscopic left upper lobectomy and lymph node dissection for lung cancer. The patient did well until the 6th postoperative day. On the 7th postoperative day, she complained of sudden severe back pain, immediately after which she lost consciousness and went into cardiopulmonary arrest. The echocardiography revealed cardiac tamponade, and emergency pericardiocentesis was performed. The patient died without circulatory improvement despite drainage of approximately 200 ml of bloody pericardial fluid. The pathological findings of autopsy revealed penetrating atherosclerotic ulcer at the descending aorta. We speculated that severe back pain caused the afterload of left ventricle and the increase in left atrial pressure through mitral regurgitation, which might result in a bleeding from the staple-line of superior pulmonary vein in the pericardium.

•We herein present a case of chronic progressive autoimmune GFAP astrocytopathy.•Symmetrical high-intensity signals on FLAIR were observed in the white matter of the temporal and occipital lobes, lateral cerebral ventricle walls, hippocampus, amygdala, and occipital cortex, with extensive Gd enhancement in radial perivascular lesions and the ependyma in the choroid plexus.•Improvements were achieved by 4 courses of IVMP and one of IVIg., Competing Interests: None., (© 2024 The Authors.)

Endosomal trafficking of TrkA is a critical process for nerve growth factor (NGF)-dependent neuronal cell survival and differentiation. The small GTPase ADP-ribosylation factor 6 (Arf6) is implicated in NGF-dependent processes in PC12 cells through endosomal trafficking and actin cytoskeleton reorganization. However, the regulatory mechanism for Arf6 in NGF signaling is largely unknown. In this study, we demonstrated that EFA6A, an Arf6-specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF-dependent Arf6 activation, TrkA recycling from early endosomes to the cell surface, prolonged ERK1/2 phosphorylation, and neurite outgrowth. We also demonstrated that EFA6A forms a protein complex with TrkA through its N-terminal region, thereby enhancing its catalytic activity for Arf6. Similarly, we demonstrated that EFA6A forms a protein complex with TrkA in cultured dorsal root ganglion (DRG) neurons. Furthermore, cultured DRG neurons from EFA6A knockout mice exhibited disturbed NGF-dependent TrkA trafficking compared with wild-type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF-dependent TrkA trafficking and signaling., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In Japan, routine administration to one-year-old children of two-dose immunization for varicella was introduced in October 2014. Object The object of this study was to report outbreaks of varicella under routine immunization at a nursery school and in its surrounding area using data of surrounding areas from the (Nursery) School Absenteeism Surveillance System. Then, we measured the effectiveness of routine two-dose immunization for varicella to onset. We tentatively assessed its severity in a nursery school., Method: The study period extended from April 2017 through March 2018. The study area comprised Nursery school B and other nursery schools, and elementary and junior high schools in City A. Subjects in Nursery school B were 120 children. We analyzed vaccine effectiveness (VE) as an observational study and assessed severity using Fisher's exact test. We also assessed VE for severity using linear regression. Severity was defined as the length of nursery school absence attributable to varicella infection., Results: During the one month preceding a period of two weeks before the initial case at Nursery school B, there were 16 cases of varicella infection in nursery schools, 45 cases in elementary schools, and one case in junior high schools in City A. For children who had received one vaccine dose or more, VE was 48.1% for all ages and 49.2% among children three years old and older. No significant VE against infection was found. Vaccination using one dose or more can reduce severity significantly., Discussion and Conclusion: Because many nursery school children who had received two doses of vaccine were infected, VE was estimated as low in the nursery school and not significant. Although VE for severity with more than one dose was confirmed, a second dose might not reduce severity compared to one dose., 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.)

DNA circuits based on successive toehold-mediated DNA displacement reactions, particularly entropy-driven DNA circuit (EDC) systems, have attracted considerable attention as powerful enzyme-free tools for dynamic DNA nanotechnology. However, background leakage (noise signal) often occurs when the circuit is executed nonspecifically, even in the absence of the appropriate catalyst DNA (input). This study designed and developed a new latent toehold-mediated DNA circuit (LDC) system that relies on a bulge-loop structure as a latent toehold toward leakage reduction. Furthermore, the number (size) of nucleotides (nt) in the bulge-loop is found to play a significant role in the performance (i.e., leakage, signal, and kinetics) of LDC systems. In fact, the signal rate for the LDC systems increased as the number of nt in the bulge-loop increased from 4 to 8, whereas the leakage rate of the LDC systems with bulge-loops of 7 nt or less was low, but the leakage rate of the LDC system with a bulge-loop of 8 nt increased significantly. Note that the LDC system with the optimal bulge-loop (7 nt) was capable of not only reducing the leakage but also accelerating the circuit speed without any signal loss, unlike methods of reducing the leakage by reducing the signal reported previously for the conventional EDC systems. These facts indicate that the 7 nt bulge-loop acts as a "latent" toehold for the DNA circuit system. By using the amplification function of output signals with an accelerated circuit and reduced leakage, our LDC system with a 7 nt bulge-loop could be applied directly and successfully to signal-amplifying DNA logic gates such as OR and AND gates, and thus, sufficient output signals could be obtained even with a small amount of input. These findings reveal that our LDC systems with a bulge-loop structure can replace the conventional EDC system and have enormous potential in the field of DNA nanotechnology.