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1. The objective of this study was to examine whether addition of plumping fluid (PF) to Lake's solution (LS) for storage of fowl spermatozoain vitroat 4°C can prolong survival and improve the quality of spermatozoa. 2. In experiment 1, aliquots of spermatozoa were storedin vitroin LS alone and LS containing 10%, 25%, 50% and 75% (v:v) PF for 0.5, 24, 48, 72, 96 and 120 h at 4°C. After the end of each storage period, spermatozoa were evaluated for their viability, mobility and penetrability. Viability was determined using SYBR-14 and propidium iodide (PI) staining. Mobility was assessed using an Accudenz assay. Penetrability was assessed using spermatozoa-inner perivitelline layer (IPL) interaction assay. 3. In experiment 2, aliquots of spermatozoa were storedin vitroin LS alone and LS containing 25% and 50% (v:v) PF for 0.5, 24, 48 and 72 h at 4°C, and then fertility of the spermatozoa was evaluated using intravaginal artificial insemination (AI) in hens. 4. Storage of spermatozoa in LS alone resulted in loss of viability, mobility, penetrability and fertility within 48 h. In contrast, no loss of viability and penetrability was observed for the spermatozoa stored for 48, 96, 72 and 48 h in LS containing 10%, 25%, 50% and 75% (v:v) PF, respectively. In particular, fertilising capacity was not lost for the spermatozoa stored in the presence of 25% or 50% PF in LS for 48 and 24 h, respectively. 5. In conclusion, these findings demonstrated thatin vitroexposure of fowl spermatozoa to PF during hypothermic storage in LS prolonged spermatozoa survival. A 25% (v:v) level of inclusion of PF in LS may be effective for the improvement of viability, penetrability and fertilising ability of the stored spermatozoa. [ABSTRACT FROM AUTHOR]

We report a rare case of solitary recurrence of ovarian cancer in the spleen which developed 4 years after initial treatment. Only six cases have been reported in the literature and all were serous carcinoma. Our patient had a splenectomy without any complications but developed a liver metastasis 10 months after splenectomy. [ABSTRACT FROM AUTHOR]

Flow around a vehicle running through a tornado was investigated experimentally. A tornado simulator was developed to generate a tornado-like swirl flow. PIV study confirmed that the simulator generates two-celled vortices which are observed in the natural tornadoes. A moving test rig was developed to run a 1/40 scaled train-shaped model vehicle under the tornado simulator. The car contained pressure sensors, a data logger with an AD converter to measure unsteady surface pressures during its run through the swirling flow. Aerodynamic forces acting on the vehicle were estimated from the pressure data. The results show that the aerodynamic forces change its magnitude and direction depending on the position of the car in the swirling flow. The asymmetry of the forces about the vortex centre suggests the vehicle itself may deform the flow field.

Objective: To evaluate hemostatic efficacy, complications, and subsequent pregnancy outcomes in women with placenta previa who underwent combined vertical compression sutures in the lower uterine segment and intrauterine balloon tamponade (Hot-Dog method) to achieve hemostasis after cesarean section., Methods: We retrospectively reviewed data for 117 women with singleton pregnancy diagnosed with placenta previa who underwent cesarean section between 29 and 38 weeks' gestation. Treatments were as follows: (1) conventional-intravenous oxytocin administration after placental detachment and suturing of bleeding points at the detachment site as needed (conventional group) (n = 47). (2) Intrauterine balloon tamponade alone (balloon group) (n = 41). (3) Vertical compression sutures + intrauterine balloon tamponade (Hot-Dog group) (n = 29)., Results: The placenta accreta spectrum prevalence was significantly higher in the balloon and Hot-Dog groups versus the conventional group. The prevalence of anteriorly located placenta was significantly higher in the Hot-Dog versus balloon groups. Intraoperative and total blood loss were significantly higher in the Hot-Dog versus conventional groups. Postoperative blood loss was significantly lower in the Hot-Dog versus balloon groups. Fewer additional procedures for managing postoperative hemorrhage were required in the Hot-Dog versus conventional and balloon groups. The number of subsequent pregnancies in the conventional, balloon, and Hot-Dog groups was 11 (23.4%), 8 (19.5%), and 4 (13.8%), respectively; all resulted in live births at term without serious obstetric complications., Conclusion: The Hot-Dog method is a straightforward and safe hemostasis technique for placenta previa that preserves fertility and controls severe bleeding., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Gamma-aminobutyric acid and glycine (GABA/Gly) are predominantly inhibitory neurotransmitters in the mature central nervous system; however, they mediate membrane potential depolarization during development. These differences in actions depend on intracellular Cl - concentrations ([Cl - ] i ), which are primarily regulated by potassium chloride cotransporter 2 (KCC2). After nerve injury, KCC2 expression markedly decreases and GABA/Gly mediate depolarization. Following nerve regeneration, KCC2 expression recovers and GABA/Gly become inhibitory, suggesting that KCC2 reduction and GABA/Gly excitation may be crucial for axonal regeneration. To directly clarify their involvement in regeneration, we analyzed recovery processes after tibial nerve severance and suturing between heterozygous KCC2 knockout mice (HT), whose KCC2 levels are halved, and their wild-type littermates (WT). Compared with WT mice, the sciatic functional index-indicating lower limb motor function-was significantly higher until 28 days after operation (D28) in HT mice. Furthermore, at D7, many neurofilament-positive fibers were elongated into the distal part of the sutured nerve in HT mice only, and myelinated axonal density was significantly higher at D21 and D28 in HT animals. Electron microscopy and galanin immunohistochemistry indicated a shorter nerve degeneration period in HT mice. Moreover, a less severe decrease in choline acetyltransferase was observed in HT mice. These results suggest that nerve degeneration and regeneration proceed more rapidly in HT mice, resulting in milder motor dysfunction. Via similar microglial activation, nerve surgery may reduce KCC2 levels more rapidly in HT mice, followed by earlier increased [Cl - ] i and longer-lasting GABA/Gly excitation. Taken together, reduced KCC2 may accelerate nerve regeneration via GABA/Gly excitation., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Introduction: The efficacy of second-line immune checkpoint inhibitor (ICI) therapy is limited in non-small cell lung cancer (NSCLC) patients with ≤ 49% PD-L1 expression. Although chemoimmunotherapy is a promising strategy, platinum-based chemotherapy followed by ICI monotherapy is often used to avoid synergistic adverse events. However, predictors of the efficacy of ICI monotherapy after platinum-based chemotherapy in NSCLC with ≤ 49% PD-L1 expression remain scarce., Methods: This multicenter retrospective study evaluated 54 advanced or recurrent NSCLC patients with ≤ 49% PD-L1 expression who were treated with second-line ICI monotherapy following disease progression on first-line platinum-based chemotherapy at nine hospitals in Japan. The impact of response to platinum-based chemotherapy on the efficacy of subsequent ICI monotherapy was investigated., Results: The response to first-line platinum-based chemotherapy was divided into two groups: the non-progressive disease (PD) group, which included patients who did not experience disease progression after four cycles of chemotherapy, and the PD group, which included patients who showed initial PD or could not maintain disease control during the four cycles of chemotherapy and switched to second-line ICI monotherapy. Among the 54 patients, 32 and 22 were classified into the non-PD and PD groups, respectively. The non-PD group showed better response rates (p = 0.038) and longer overall survival (OS) with ICI monotherapy (p = 0.023) than the PD group. Multivariate analysis identified that maintaining a non-PD status after four cycles of chemotherapy was an independent prognostic factor for ICI monotherapy (p = 0.046). Moreover, patients with a modified Glasgow Prognostic Score (mGPS) of 0 showed a tendency for longer OS with ICI monotherapy (p = 0.079), and there was a significant correlation between maintaining non-PD after four cycles of chemotherapy and an mGPS of 0 (p = 0.045)., Conclusion: Maintaining a non-PD status after four cycles of platinum-based chemotherapy was a predictor of OS after second-line ICI monotherapy. These findings will help physicians select the most suitable treatment option for NSCLC patients who were treated with platinum-based chemotherapy and switched to second-line treatment. Those who experienced early PD during platinum-based chemotherapy should not be treated with ICI monotherapy in the second-line setting., Competing Interests: HK has received personal fees from Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, and MSD. HY has received honoraria for lecture fees from Boehringer Ingelheim, Chugai Pharmaceutical, Nippon Kayaku, Taiho Pharmaceutical, Eli Lilly, Takeda Pharmaceutical, and Bristol Meyers Squibb. TY has received grants from Pfizer, Ono Pharmaceutical, Janssen Pharmaceutical, AstraZeneca, Takeda Pharmaceutical, and honoraria from Eli Lily. TK has received grants from AstraZeneca, MSD, Takeda Pharmaceutical, Janssen Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo Pharmaceutical, and honoraria for lectures from AstraZeneca, Eli Lilly, MSD, Ono Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, and Nippon Kayaku. KoT has received research grants from Chugai Pharmaceutical and Ono Pharmaceutical and personal fees from AstraZeneca, Chugai Pharmaceutical, MSD-Merck, Eli Lilly, Boehringer-Ingelheim, and Daiichi-Sankyo, outside the purview of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yoshimura, Takeda, Kataoka, Tanimura, Fukui, Chihara, Takei, Kawachi, Nakanishi, Yamanaka, Tamiya, Honda, Okura, Yamada, Uryu, Murai, Shiotsu, Yoshioka, Yamada, Kurata and Takayama.)

Background: The long overall survival (OS) observed among patients with non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression in chemoimmunotherapy (CIT) groups in previous phase III trials suggests the limited efficacy of CIT among the subgroup with ≤49% PD-L1 expression on tumor cells. Hence, sequential treatment with first-line platinum-based chemotherapy followed by second-line immune checkpoint inhibitor treatment (SEQ) is an option. This study examined whether first-line CIT would provide better outcomes than SEQ in patients with advanced NSCLC with ≤49% PD-L1 expression., Methods: This retrospective study evaluated patients with untreated NSCLC who received first-line CIT or SEQ at nine hospitals in Japan. OS, progression-free survival (PFS), PFS-2 (the time from first-line treatment to progression to second-line treatment or death), and other related outcomes were evaluated between the CIT and SEQ groups., Results: Among the 305 enrolled patients, 234 eligible patients were analyzed: 165 in the CIT group and 69 in the SEQ group. The COX proportional hazards model suggested a significant interaction between PD-L1 expression and OS ( p = 0.006). OS in the CIT group was significantly longer than that in the SEQ group in the 1-49% PD-L1 expression subgroup but not in the <1% PD-L1 expression subgroup. Among the subgroup with 1-49% PD-L1 expression, the CIT group exhibited longer median PFS than the SEQ group (CIT: 9.3 months (95% CI: 6.7-14.8) vs. SEQ:5.5 months (95% CI: 4.5-6.1); p < 0.001), while the median PFS in the CIT group was not statistically longer than the median PFS-2 in the SEQ group ( p = 0.586). There was no significant difference between the median PFS in the CIT and SEQ groups among the <1% PD-L1 expression subgroup ( p = 0.883); the median PFS-2 in the SEQ group was significantly longer than the median PFS in the CIT group (10.5 months (95% CI: 5.9-15.3) vs. 6.4 months (95% CI: 4.9-7.5); p = 0.024)., Conclusions: CIT is recommended for patients with NSCLC with 1-49% PD-L1 expression because it significantly improved OS and PFS compared to SEQ. CIT had limited benefits in patients with <1% PD-L1 expression, and the median PFS-2 in the SEQ group was significantly longer than the median PFS in the CIT group. These findings will help physicians select the most suitable treatment option for patients with NSCLC, considering PD-L1 expressions.

Leptospira interrogans disseminates hematogenously to reach the target organs by disrupting epithelial adherens junctions (AJs), thus causing leptospirosis, which is a globally neglected zoonotic disease. L. interrogans induces E-cadherin (E-cad) endocytosis and cytoskeletal rearrangement during AJ disassembly, but the detailed mechanism remains unknown. Elucidation of AJ disassembly mechanisms will guide new approaches to developing vaccines and diagnostic methods. In this study, we combine proteomic and imaging analysis with chemical inhibition studies to demonstrate that disrupting the AJs of renal proximal tubule epithelial cells involves the degradation of two armadillo repeat-containing proteins, p0071 and p120-catenin, that stabilize E-cad at the plasma membrane. Combining proteasomal and lysosomal inhibitors substantially prevented p120-catenin degradation, and monolayer integrity destruction without preventing p0071 proteolysis. In contrast, the pan-caspase inhibitor Z-VAD-FMK inhibited p0071 proteolysis and displacement of both armadillo repeat-containing proteins from the cell-cell junctions. Our results show that L. interrogans induces p120-catenin and p0071 degradation, which mutually regulates E-cad stability by co-opting multiple cellular degradation pathways. This strategy may allow L. interrogans to disassemble AJs and disseminate through the body efficiently., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tokumon, Sebastián, Humbel, Okura, Yamanaka, Yamashiro and Toma.)

In June 2021, the Ministry of Health, Labor and Welfare approved Delytact Injection as a regenerative medical product for oncolytic virus therapy. The active substance of Delytact Injection is teserpaturev, a genetically engineered herpes simplex virus type 1 (strain F) in which the α47 gene and both copies of the γ34.5 gene have been deleted and the infected cell protein 6 (ICP6) gene has been inactivated by the insertion of the lacZ gene from Escherichia coli. Delytact Injection, when intratumorally administered to patients with malignant glioma, is expected to exert the following effects: (1) the mutant virus selectively replicates in tumor cells and destroys the infected cells through the replication process, exerting a cytocidal effect, and (2) the administration leads to induction of tumor-responsive T cells, which activates antitumor immunity and thus prolongs the survival of patients with malignant glioma. A Japanese phase II study (Study GD01) was conducted in patients with glioblastoma who had residual or recurrent tumors after radiotherapy with concomitant temozolomide. In Study GD01, however, stable disease continued for an extended period in some patients with glioblastoma. Hence, Delytact Injection is expected to be effective to a certain level. In line with this, Delytact Injection has been approved as an option for the treatment of malignant glioma, with one of the 3 approval conditions including conducting a use-results comparison survey and resubmission of the marketing authorization application within the granted time period of 7 years, under the conditional and time-limited approval scheme described in Article 23-26 of Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices., (© The Author(s) 2023. Published by Oxford University Press.)

Central nervous system manifestations, a variety of benign and malignant tumors as well as non-neoplastic abnormalities, are found in over 70% of neurofibromatosis type 1 (NF1) patients. Herein, we report hitherto undescribed space-occupying lesions in the setting of NF1. We aimed to clarify their characteristics, especially whether they represent neoplastic or non-neoplastic (hyperplastic) lesions. All 3 cases were preoperatively assessed as non-neoplastic; 2 and 1 cases were suspected to be arachnoid cysts and dilation of subarachnoid space, respectively. However, all lesions were revealed to be whitish jelly-like masses by operation, and the histology composed of spindle cells resembling arachnoid trabecular cells with moderate cellularity and cellular uniformity gave an impression that these lesions may be neoplastic. In contrast, electron microscopic analysis showed that the characteristics of these cells were compatible with those of normal arachnoid trabecular cells. Furthermore, whole-exome sequencing and array comparative genomic hybridization did not show any obvious alterations suggestive of their neoplastic nature. DNA methylation analysis demonstrated that these lesions were epigenetically distinct not only from meningiomas but also from normal healthy meninges. In conclusion, considering the clinicopathologic aspects of the present lesions and the results of the molecular analysis that failed to suggest their neoplastic nature, they may represent previously unrecognized rare hyperplasia of arachnoid trabecular cells, which may be associated with NF1., Competing Interests: Conflicts of Interest and Source of Funding: Partially supported by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, through the University Reform Action Plan “Gunma University Initiative for Advanced Research (GIAR).” The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Renal pelvis rupture during pregnancy is rare. Although the most common cause is urolithiasis, no cases of pregnant women with ureterorenal stones have been reported. We report on a 33-year-old pregnant woman with renal pelvis rupture and a stone at the ureteropelvic junction with an abrupt onset of severe flank pain at 37 weeks' gestation. Transabdominal ultrasonography revealed bilateral hydroureters with right predominance and an anechoic space around the right kidney. Computed tomography (CT) revealed a renal stone at the ureteropelvic junction of the right kidney, a low-density area around the kidney on the same side, and bilateral hydronephrosis, which led to the diagnosis of pelvis rupture, urolithiasis, and perirenal urinary extravasation of the right kidney. Although there are potential adverse effects from radiation on fetuses and neonates, CT can be a useful diagnostic modality especially in such cases of acute abdominal pain from non-obstetric causes during pregnancy.

In Phlebobranchiata ascidians, oocytes and spermatozoa are stored in the oviduct and spermiduct, respectively, until spawning occurs. Gametes in the gonoducts are mature and fertilizable; however, it was found that the gametes of the ascidians Phallusia philippinensis and Ciona intestinalis could not undergo fertilization in the gonoductal fluids. The body fluids of the ascidians, especially in the gonoducts, were much more acidic (pH 5.5-6.8) than seawater (pH 8.2), and the fertilization rate was low under such acidic conditions. Hence, we examined the effect of pH on gametes. Pre-incubation of gonoductal eggs at pH 8.2 prior to insemination increased fertilization rates, even when insemination was performed under low pH conditions. Furthermore, an increase in ambient pH induced an increase in the intracellular pH of the eggs. It was also found that an increase in ambient pH triggered the release of sperm attractants from the egg and is therefore necessary for sperm chemotaxis. Hence, acidic conditions in the gonoductal fluids keep the gametes, especially eggs, infertile, and the release of eggs into seawater upon spawning induces an increase in ambient pH, which enables egg fertilization.

Purpose: We performed a new ultrasonographic risk assessment of uterine scar dehiscence, which is a potential risk factor for uterine rupture, in pregnancy after cesarean section. We attempted to shed light on the natural course of the change in the lower uterine segment by means of a longitudinal investigation through quantitative and qualitative evaluations., Methods: This retrospective single-center study involved 31 women with a normal singleton pregnancy delivered by elective cesarean section between 2020 and 2021, with all women showing a "niche" in the lower uterine segments. The lower uterine segments were assessed qualitatively and quantitatively using transvaginal ultrasonography at 16-21, 22-27, and 28-33 weeks of gestation, and subjects were divided into two groups: those with uterine dehiscence (12 women) and those without uterine dehiscence (19 women), depending on the gross findings of the lower uterine segments at cesarean section. Analyses were performed using Wilcoxon's rank-sum and Mann-Whitney U test with a significance level of P < 0.05., Results: The lower uterine segments changed from V-shaped to U-shaped to thin as gestation progressed and was more prominent in the uterine dehiscence group, occurring mostly at 22-27 weeks. At 22-27 weeks, the median myometrial thickness in the uterine dehiscence group was lower than in the group without uterine dehiscence (P = 0.0030). Thinning of the lower uterine segments had moved the cephalad at 22-27 and 28-33 weeks in cases with and without uterine dehiscence., Conclusion: A model of morphological changes in the niche was constructed based on qualitative and quantitative assessments. The morphological changes and actual thinning of the lower uterine segments were prominent in the second trimester in women considered to have uterine scar dehiscence., (© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)