Retroperitoneal leiomyosarcoma mimicking an ovarian tumor diagnosed using a negative ovarian pedicle sign.

Retroperitoneal leiomyosarcoma (RPLMS) is rare and usually presents as a large abdominal mass with poor clinical symptoms. Radiological findings of an RPLMS arising in the pelvis of a woman resemble those of adnexal tumors. Herein, we present a case of RPLMS mimicking an adnexal tumor which was differentiated from having an ovarian origin as the right ovarian vein was passing through the tumor but there was no direct vascular connection with the tumor. Therefore, it is important to identify the ovarian vein to distinguish between these tumors.

Prognostic outcome of cervical laser ablation using a holmium yttrium-aluminum-garnet (Ho:YAG) laser for the treatment of cervical intraepithelial neoplasia: A single-center retrospective study.

Objective: Although cervical conization is considered a standard treatment for cervical intraepithelial neoplasia (CIN) 2/3, laser ablation can compensate for the disadvantages of the former. CO2, semiconductor, and holmium yttrium-aluminum-garnet (Ho:YAG) lasers are applied in ablation, but no previous studies have shown the effectiveness of any of these techniques. Here, we retrospectively analyzed the application of the Ho:YAG laser in our hospital to verify its efficacy, and discussed the methods for optimal recurrence detection. Methods: We evaluated the recurrence rates of the pathological condition in patients who underwent laser ablation with a Ho:YAG laser for CIN2/3 at our institution from June 2012 to November 2021. We defined the recurrence as histologically confirmed CIN2 or more advanced stage. Age, preoperative diagnosis, human papillomavirus (HPV) genotype, and postoperative high-risk HPV status were recorded to establish their association with recurrence rates. Results: We performed surgery in 607 patients and the 2-year recurrence rate after interventions was 5.6%. Five patients were diagnosed with invasive cancer at the time of recurrence. Older age significantly correlated with higher risk of recurrence, but preoperative CIN grade and preoperative HPV 16/18 status did not significantly affect it. The postoperative high-risk HPV test was 100% sensitive for detecting recurrence. Conclusions: Laser ablation with the Ho:YAG laser yields promising results. Together with postinterventional management, high-risk HPV test after laser ablation should be conducted after diagnostic conization.This study received the approval from the Ethics Committee of the NHO Tokyo Medical Center (Ethics Committee approval number: R22-067).

Renal tubular necrosis associated with anagrelide administration: a case report.

A 62-year-old female patient with essential thrombocythemia experienced rapid renal dysfunction and was subsequently referred to our hospital. Further investigations did not reveal any significant abnormalities except for a slight increase in urinary ß2-microglobulin levels. A renal biopsy was performed to investigate the cause of her renal dysfunction, revealing acute tubular necrosis, interstitial edema, and arteriosclerosis. No significant glomerular lesions were observed. Immunofluorescence staining and electron microscopy showed no abnormalities. She had been using anagrelide for 4 years, and her dosage was increased from 2.0 to 3.0 mg/day 10 months before her initial admission. Her renal function began to deteriorate 2 months after the anagrelide dosage increase. Although 0.625 mg of bisoprolol was initiated for tachycardia 3 months after the anagrelide dosage adjustment, we suspected that the acute tubular necrosis was associated with anagrelide administration. After transitioning from anagrelide to hydroxyurea and discontinuing bisoprolol, her renal function improved. This case suggests the importance of considering anagrelide as a potential cause of renal dysfunction in patients using this medication. Therefore, renal biopsy, combined with a comprehensive medical history, is crucial for evaluating the etiology of renal injury in such cases.

Spontaneous complete regression of pancreaticoduodenal artery aneurysms with celiac artery occlusion after aorto-splenic bypass without additional treatment: a case report.

BACKGROUND: Pancreaticoduodenal artery aneurysm (PDAA) is a rare, but fatal disease. However, the association between aneurysm size and the risk of rupture remains unclear. There are many options for therapeutic strategies that should be discussed well because the treatment options are often complicated and highly invasive. However, it remains unclear whether additional endovascular therapy is essential for all patients undergoing bypass surgery. Here, we present a case of triple PDAAs with celiac axis occlusion and spontaneous complete regression of inferior PDAAs (IPDAA) after aneurysmectomy of superior PDAA (SPDAA) and aorto-splenic bypass. CASE PRESENTATION: A 68-year-old woman presented with one SPDAA and two IPDAAs caused by celiac axis occlusion. Aneurysmectomy for IPDAAs was difficult because of their anatomical location and shape. Therefore, we planned a two-stage hybrid therapy. The patient underwent aorto-splenic bypass and resection of the SPDAA. Follow-up CT was performed to evaluate the IPDAAs before planned endovascular embolization. Spontaneous regression of the IPDAAs and normalized PDA arcade decreased the blood flow in the PDA arcade. The patient is doing well without graft occlusion, and the IPDAAs have completely regressed 7 years after surgery. CONCLUSION: Normalization of hyperinflow to the PDA arcade can lead to the regression of PDAA. Potentially, additional endovascular therapy may not be required in all cases when dilation of the PDA improves. However, more cases must be accumulated to establish criteria for predicting the risks of short- and long-term PDAA ruptures.

Assessing Molecular Localization of Symbiont Microalgae in Coral Branches Through Mass Spectrometry Imaging.

Reef-building corals are a fundamental pillar of coral reef ecosystems in tropical and subtropical shallow environments. Corals harbor symbiotic dinoflagellates belonging to the family Symbiodiniaceae, commonly known as zooxanthellae. Extensive research has been conducted on this symbiotic relationship, yet the fundamental information about the distribution and localization of Symbiodiniaceae cells in corals is still limited. This information is crucial to understanding the mechanism underlying the metabolite exchange between corals and their algal symbionts, as well as the metabolic flow within holobionts. To examine the distribution of Symbiodiniaceae cells within corals, in this study, we used fluorescence imaging and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MS-Imaging) on branches of the Acropora tenuis coral. We successfully prepared frozen sections of the coral for molecular imaging without fixing or decalcifying the coral branches. By combining the results of MS-Imaging with that of the fluorescence imaging, we determined that the algal Symbiodiniaceae symbionts were not only localized in the tentacle and surface region of the coral branches but also inhabited the in inner parts. Therefore, the molecular imaging technique used in this study could be valuable to further investigate the molecular dynamics between corals and their symbionts.

Effects of high-dose betahistine on intractable dizziness in patients with uncompensated unilateral vestibulopathy.

OBJECTIVE: In the present study, we examined the effects of high-dose betahistine on dizziness handicap inventory (DHI) scores in patients with unilateral vestibulopathy. METHODS: An uncontrolled, open-label, multicenter clinical trial was conducted. Fifteen patients with unilateral vestibulopathy, such as vestibular neuritis, who complained of intractable dizziness for more than three months were enrolled. Initially, all patients were orally administered betahistine at a dose of 36 mg/day for four weeks, which is the standard dose and dosing period for the treatment of dizziness in Japan. The patients were then administered betahistine at a double dose of 72 mg/day for four weeks. Six patients who became aware of the benefits of high-dose betahistine were further administered betahistine at 72 mg/day for an additional 12 weeks (a total of 16 weeks). Perceived disability due to dizziness was assessed by DHI scores. RESULTS: In all 15 patients, short-term administration with high-dose (72 mg/day) betahistine for four weeks, but not low-dose betahistine (36 mg/day) for four weeks significantly decreased DHI scores. In particular, in six responding patients with self-reported benefits after short-term administration with high-dose betahistine, long-term administration with high-dose betahistine for 16 weeks further significantly decreased DHI scores. However, DHI scores of the remaining nine non-responding patients were not changed after short-term administration with high-dose betahistine for four weeks. CONCLUSION: Short-term administration with the standard dose and dosing period of betahistine did not improve DHI scores in the enrolled patients, indicating that they were not compensated for unilateral vestibulopathy with intractable dizziness. The present findings suggest that long-term administration with high-dose betahistine facilitates vestibular compensation to improve intractable dizziness in some, but not all patients with uncompensated unilateral vestibulopathy.

In Vitro Phagocytosis of Different Dinoflagellate Species by Coral Cells.

Coral-dinoflagellate symbiosis is a unique biological phenomenon, in which animal cells engulf single-celled photosynthetic algae and maintain them in their cytoplasm mutualistically. Studies are needed to reveal the complex mechanisms involved in symbiotic processes, but it is difficult to answer these questions using intact corals. To tackle these issues, our previous studies established an in vitro system of symbiosis between cells of the scleractinian coral Acropora tenuis and the dinoflagellate Breviolum minutum, and showed that corals direct phagocytosis, while algae are likely engulfed by coral cells passively. Several genera of the family Symbiodiniaceae can establish symbioses with corals, but the symbiotic ratio differs depending on the dinoflagellate clades involved. To understand possible causes of these differences, this study examined whether cultured coral cells show phagocytotic activity with various dinoflagellate strains similar to those shown by intact A. tenuis. We found that (a) A. tenuis larvae incorporate Symbiodinium and Breviolum, but not Cladocopium, and very few Effrenium, (b) cultured coral cells engulfed all four species but the ratio of engulfment was significantly higher with Symbiodinium and Breviolum than Cladocopium and Effrenium, (c) cultured coral cells also phagocytosed inorganic latex beads differently than they do dinoflagellates . It is likely that cultured coral cells preferentially phagocytose Symbiodinium and Breviolum, suggesting that specific molecular mechanisms involved in initiation of symbiosis should be investigated in the future.

'Raisin bread sign' feature of pontine autosomal dominant microangiopathy and leukoencephalopathy.

Pontine autosomal dominant microangiopathy and leukoencephalopathy is one of hereditary cerebral small vessel diseases caused by pathogenic variants in COL4A1 3'UTR and characterized by multiple small infarctions in the pons. We attempted to establish radiological features of this disease. We performed whole exome sequencing and Sanger sequencing in one family with undetermined familial small vessel disease, followed by clinicoradiological assessment and a postmortem examination. We subsequently investigated clinicoradiological features of patients in a juvenile cerebral vessel disease cohort and searched for radiological features similar to those found in the aforementioned family. Sanger sequencing was performed in selected cohort patients in order to detect variants in the same gene. An identical variant in the COL4A1 3'UTR was observed in two patients with familial small vessel disease and the two selected patients, thereby confirming the pontine autosomal dominant microangiopathy and leukoencephalopathy diagnosis. Furthermore, postmortem examination showed that the distribution of thickened media tunica and hyalinized vessels was different from that in lacunar infarctions. The appearance of characteristic multiple oval small infarctions in the pons, which resemble raisin bread, enable us to make a diagnosis of pontine autosomal dominant microangiopathy and leukoencephalopathy. This feature, for which we coined the name 'raisin bread sign', was also correlated to the pathological changes.

Genes possibly related to symbiosis in early life stages of Acropora tenuis inoculated with Symbiodinium microadriaticum.

Due to the ecological importance of mutualism between reef-building corals and symbiotic algae (Family Symbiodiniaceae), various transcriptomic studies on coral-algal symbiosis have been performed; however, molecular mechanisms, especially genes essential to initiate and maintain these symbioses remain unknown. We investigated transcriptomic responses of Acropora tenuis to inoculation with the native algal symbiont, Symbiodinium microadriaticum, during early life stages, and identified possible symbiosis-related genes. Genes involved in immune regulation, protection against oxidative stress, and metabolic interactions between partners are particularly important for symbiosis during Acropora early life stages. In addition, molecular phylogenetic analysis revealed that some possible symbiosis-related genes originated by gene duplication in the Acropora lineage, suggesting that gene duplication may have been the driving force to establish stable mutualism in Acropora, and that symbiotic molecular mechanisms may vary among coral lineages.

Computational modeling of multiscale collateral blood supply in a whole-brain-scale arterial network.

The cerebral arterial network covering the brain cortex has multiscale anastomosis structures with sparse intermediate anastomoses (O[102] µm in diameter) and dense pial networks (O[101] µm in diameter). Recent studies indicate that collateral blood supply by cerebral arterial anastomoses has an essential role in the prognosis of acute ischemic stroke caused by large vessel occlusion. However, the physiological importance of these multiscale morphological properties-and especially of intermediate anastomoses-is poorly understood because of innate structural complexities. In this study, a computational model of multiscale anastomoses in whole-brain-scale cerebral arterial networks was developed and used to evaluate collateral blood supply by anastomoses during middle cerebral artery occlusion. Morphologically validated cerebral arterial networks were constructed by combining medical imaging data and mathematical modeling. Sparse intermediate anastomoses were assigned between adjacent main arterial branches; the pial arterial network was modeled as a dense network structure. Blood flow distributions in the arterial network during middle cerebral artery occlusion simulations were computed. Collateral blood supply by intermediate anastomoses increased sharply with increasing numbers of anastomoses and provided one-order-higher flow recoveries to the occluded region (15%-30%) compared with simulations using a pial network only, even with a small number of intermediate anastomoses (≤10). These findings demonstrate the importance of sparse intermediate anastomoses, which are generally considered redundant structures in cerebral infarction, and provide insights into the physiological significance of the multiscale properties of arterial anastomoses.

Protective effect of astaxanthin nanoemulsion on mammalian inner ear hair cells.

Background: Aminoglycoside antibiotics are used for treating certain acute infections. However, these drugs cause ototoxicity by inducing inner ear hair cell death. Aims/Objectives: We investigated the protective effect of a nanoemulsion of the carotenoid astaxanthin on mammalian inner ear hair cells against neomycin-induced ototoxicity. Material and Methods: Dose-response relationship, quantification of hair cell loss, and reactive oxygen species production were assayed in response to neomycin with and without astaxanthin in cultured utricles of CBA/N mice. In addition, auditory brain response (ABR) and hair cell loss after exposure to the nanoformulation and loud noise were examined in vivo in guinea pigs. Results: Astaxanthin suppressed neomycin-induced reduction of hair cells by reducing the production of hydroxy radicals. Furthermore, hair cell loss in the second rotation of the cochlea was significantly lower in the astaxanthin group than in the noise-only group. Conclusions and Significance: The blood-labyrinth barrier limits the successful delivery of drugs for inner ear complications. However, in the nanoemulsion form, astaxanthin can penetrate the round window (fenestra ovale) membrane, enabling topical administration. Thus, astaxanthin nanoemulsion could be useful in treating ototoxicity in individuals with inner ear complications.

Low-Rank Combinatorial Optimization and Statistical Learning by Spatial Photonic Ising Machine.

The spatial photonic Ising machine (SPIM) [13D. Pierangeli et al., Large-Scale Photonic Ising Machine by Spatial Light Modulation, Phys. Rev. Lett. 122, 213902 (2019).PRLTAO0031-900710.1103/PhysRevLett.122.213902] is a promising optical architecture utilizing spatial light modulation for solving large-scale combinatorial optimization problems efficiently. The primitive version of the SPIM, however, can accommodate Ising problems with only rank-one interaction matrices. In this Letter, we propose a new computing model for the SPIM that can accommodate any Ising problem without changing its optical implementation. The proposed model is particularly efficient for Ising problems with low-rank interaction matrices, such as knapsack problems. Moreover, it acquires the learning ability of Boltzmann machines. We demonstrate that learning, classification, and sampling of the MNIST handwritten digit images are achieved efficiently using the model with low-rank interactions. Thus, the proposed model exhibits higher practical applicability to various problems of combinatorial optimization and statistical learning, without losing the scalability inherent in the SPIM architecture.

Smart utilization of betaine lipids in the giant clam Tridacna crocea.

The giant clam Tridacna crocea thrives in poorly nourished coral reef water by forming a holobiont with zooxanthellae and utilizing photosynthetic products of the symbiont. However, detailed metabolic crosstalk between clams and symbionts is elusive. Here, we discovered that the nonphosphorous microalgal betaine lipid DGCC (diacylglycerylcarboxy-hydroxymethylcholine) and its deacylated derivative GCC are present in all tissues and organs, including algae-free sperm and eggs, and are metabolized. Colocalization of DGCC and PC (phosphatidylcholine) evidenced by MS imaging suggested that DGCC functions as a PC substitute. The high content of GCC in digestive diverticula (DD) suggests that the algal DGCC was digested in DD for further utilization. Lipidomics analysis showing the organ-specific distribution pattern of DGCC species suggests active utilization of DGCC as membrane lipids in the clam. Thus, the utilization of zooxanthellal DGCC in animal cells is a unique evolutionary outcome in phosphorous-deficient coral reef waters.

Achievement of Target Glycemic Goal with Simple Basal Insulin Regimen in Women with Gestational Diabetes: A Prospective Cohort Study.

There is little evidence concerning the need to treat gestational diabetes (GDM) in the same way as pregestational diabetes. We evaluated the efficacy of the simple insulin injection (SII) regimen for achieving the target glucose goal without increasing adverse perinatal outcomes in singleton pregnant women with GDM. All subjects underwent self-monitoring of blood glucose (SMBG), and insulin therapy was indicated according to the SMBG profile. Insulin was initially started with the SII regimen, in which one daily injection of NPH insulin before breakfast was used, and another NPH injection was added at bedtime, if necessary. We used the target glucose as <95 mg/dL at fasting and <120 mg/dL postprandial and accepted <130 mg/dL for the latter. If the target glucose did not reach with the regimen, we switched to the multiple daily injection (MDI) with additional prandial insulin aspart. We compared the SMBG profile before delivery as well as the perinatal outcomes between the SII and MDI groups. Among 361 women (age 33.7 years, nullipara 41%, prepregnancy body mass index 23.2 kg/m2) with GDM, 59%, 18%, and 23% were in the diet-alone, SII, and MDI groups, respectively. Consequently, regarding women requiring insulin therapy, 43% were treated with the SII regimen throughout pregnancy. The severity of baseline hyperglycemia according to the SMBG data at baseline was the MDI>the SII>the diet group. The rate of achieving target glucose levels before delivery in the SII group at fasting, postprandial < 120 mg/dL and <130 mg/dL were 93%, 54% and 87%, respectively, which were similar to that in the MDI group (93%, 57%, and 93%, respectively), with no significant differences in perinatal outcomes. In conclusion, more than 40% of women with GDM requiring insulin therapy achieved the target glucose goal with this simple insulin regimen without any increase in adverse effects.

Bioconvection pattern of Euglena under periodical illumination.

Microorganisms respond to environmental conditions and often spontaneously form highly ordered convection patterns. This mechanism has been well-studied from the viewpoint of self-organization. However, environmental conditions in nature are usually dynamic. Naturally, biological systems respond to temporal changes in environmental condition. To elucidate the response mechanisms in such a dynamic environment, we observed the bioconvection pattern of Euglena under periodical changes in illumination. It is known that Euglena shows localized bioconvection patterns under constant homogeneous illumination from the bottom. Periodical changes in light intensity induced two different types of spatiotemporal patterns: alternation of formation and decomposition over a long period and complicated transition of pattern over a short period. Our observations suggest that pattern formation in a periodically changing environment is of fundamental importance to the behavior of biological systems.

The pathogenic role of the BRCA2 c.7847C>T (p.Ser2616Phe) variant in breast and ovarian cancer predisposition.

Substantial numbers of variants of unknown significance (VUSs) have been identified in BRCA1/2 through genetic testing, which poses a significant clinical challenge because the contribution of these VUSs to cancer predisposition has not yet been determined. Here, we report 10 Japanese patients from seven families with breast or ovarian cancer harboring the BRCA2 c.7847C>T (p.Ser2616Phe) variant that was interpreted as a VUS. This variant recurs only in families from Japan and has not been reported in the global general population databases. A Japanese patient with Fanconi anemia with compound heterozygous variants c.7847C>T (p.Ser2616Phe) and c.475+1G>A in BRCA2 was reported. In silico predictions and quantitative cosegregation analysis suggest a high probability of pathogenicity. The clinical features of the variant carriers were not specific to, but were consistent with, those of patients with hereditary breast and ovarian cancer. A validated functional assay, called the mixed-all-nominated-in-one-BRCA (MANO-B) method and the accurate BRCA companion diagnostic (ABCD) test, demonstrated the deleterious effects of the variant. Altogether, following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, this variant satisfied the "PS3," "PM2," "PM3," and "PP3" criteria. We thus conclude that the BRCA2 c.7847C>T (p.Ser2616Phe) variant is a "likely pathogenic" variant that is specifically observed in the Japanese population, leading to a breast and ovarian cancer predisposition.

Long-time behavior of swimming Euglena gracilis in a heterogenous light environment.

The cell motion of Euglena gracilis in homogeneous and heterogeneous light environments was analyzed. Homogeneous and heterogeneous environments were prepared, with only a red color or with a red circle surrounded by brighter white regions, respectively. In a heterogeneous environment, the cells move into the red circle. Swimming orbits at 1/25 s intervals for 120 s were analyzed. The speed distribution of the 1 s-averaged cell orbits in a homogeneous environment was different from that in a heterogeneous environment, where the faster swimming fraction was enhanced. The relationship between speed and curvature radius was analyzed using a joint histogram. Histograms for short timescale motion, constructed by 1 s-averaged orbits, suggest that the cell swimming curves are not biased, while those for long timescale motion, constructed by 10 s-averaged orbits, suggest that the cell swimming curves are biased in the clockwise direction. Furthermore, the curvature radius determines the speed, which does not seem to depend on the light environment. The mean squared displacement in a heterogeneous environment is larger than that in a homogeneous environment on a 1 s timescale. These results will be the basis for constructing a model for the long-time behavior of photomovement for light differences.

Prevention of progressive hearing loss in a mouse model of diabetes by oral intake of eicosapentaenoic acid ethyl ester.

BACKGROUND: The prevalence of hearing impairment in patients with diabetes was significantly higher, and the development of preventive methods is desirable. AIMS/OBJECTIVES: This study examined the effects of eicosapentaenoic acid (EPA) administration on the prevention of early hearing loss in diabetic mice. MATERIALS AND METHODS: Tsumura, Suzuki, Obese Diabetes (TSOD) mice were used as a model of diabetes and Tsumura, Suzuki, Non Obesity (TSNO) mice were used as controls. The animals were divided into three groups: the TSNO group and the TSOD (EPA-) group (provided sunflower oil), and the TSOD (EPA+) group (provided EPA). Auditory brainstem responses (ABRs) were measured and the cochlea was evaluated histologically. RESULTS: The TSOD (EPA+) group showed a lower tendency to increase thresholds than the TSOD (EPA-) group. The TSOD (EPA+) group had a significantly lower ABR threshold than the TSOD (EPA-) group from 11 to 14 months of age at 4 kHz. Narrowing of the capillary lumens in the stria vascularis and thickening of the vessel wall in the modiolus were observed in the TSOD (EPA-) group. CONCLUSIONS AND SIGNIFICANCE: It was suggested that the suppression of cochlear vascular atherosclerosis by EPA administration in TSOD mice suppressed early age-related hearing loss.

Antiproliferative Effect of N-Heterocyclo-Coumarin Derivatives against Multidrug-Resistant Cells.

Chemotherapy refers principally to the use of small molecules to treat cancer, and natural product derivatives have been main sources of clinically using anticancer drugs. While the coumarin skeleton does not inhibit cell growth, its derivatives are often active, and numerous coumarins have been examined for antiproliferative activity against human cancer cell lines. In this study, 16 novel coumarin derivatives (1, 1a-5a, 1b, 2b, 6b, 7b, 8-13) with attached N-heterocycles, including aminopyrrolidine, aminopiperidine, aminoazepane, and indoline, were prepared and ultimately esterified or amidated with alcohols or amines, respectively. All synthesized N-heterocycles containing coumarin derivatives with alcohols, amines, and carboxylic acids were assessed for antiproliferative activity against several human cancer cell lines, containing triple-negative breast cancer (TNBC) as well as a P-glycoprotein (P-gp) overexpressing multidrug-resistant (MDR) KB subline KB-VIN. Five coumarin derivatives (3a-5a, 12, 13) showed no effect (IC50 >40 µM) against all tested cell lines. In contrast, derivative 1a showed broad-spectrum activity against four cell lines, while 1b and 10 were nearly twice as selective for KB-VIN cells as the parent KB. The coumarin derivatives 1a, 1b, and 10 were optimal for antiproliferative activity in this study and could provide a new avenue for overcoming MDR tumors. Derivatives 1a, 1b, and 10 showed MDR cell-selective antiproliferative activity, indicating that N-heterocycle-coumarins exert previously unexplored bioactivity with selective action on MDR cancer cells.