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Abstract Background An aortoesophageal fistula can prove to be fatal. Salvage thoracic endovascular aortic repair as a bridging therapy and radical surgery with thoracotomy should be considered while treating aortoesophageal fistula without spontaneous closure. Moreover, it is essential to select a technique that reduces the risk of reinfection. Here we report a rare case of a ruptured thoracic aortic aneurysm related to esophageal perforation by a fish bone that led to massive hematemesis and shock, and the surgical treatment of an aortoesophageal fistula that developed after salvage thoracic endovascular aortic repair. Case presentation A 70-year-old Japanese female patient was admitted with hematemesis, thoracic pain, and shock related to esophageal perforation of a ruptured descending aortic aneurysm caused by fish bone aspiration and esophageal perforation 1 month previously. An emergency thoracic endovascular aortic repair was performed. Postoperatively, an aortoesophageal fistula that remained open and a food intake-related increase in the inflammatory response was noted. Radical blood-vessel prosthesis implantation and fistula closure were performed. The patient’s postoperative course was favorable and the patient was discharged 22 days after the blood vessel prosthesis implantation. Conclusion Such a case of rupture of a descending aortic aneurysm related to perforation by a fish bone and an aortoesophageal fistula is considerably rare. Thus, we report the therapeutic strategy of this particular case and review the relevant literature.

Abstract A 76‐year‐old woman with cT1bN2M1b stage IVA spindle cell carcinoma of the right lower lobe of the lung, no driver gene mutation, and programmed death ligand 1

To investigate the impact of matter mixing on the formation of molecules in the ejecta of SN 1987A, time-dependent rate equations for chemical reactions are solved for one-zone and one-dimensional (1D) ejecta models of SN 1987A. The latter models are based on the 1D profiles obtained by angle-averaging of the three-dimensional (3D) hydrodynamical models, which effectively reflect the 3D matter mixing; the impact is demonstrated, for the first time, based on 3D hydrodynamical models. The distributions of initial seed atoms and radioactive ^56 Ni influenced by the mixing could affect the formation of molecules. By comparing the calculations for spherical cases and for several specified directions in the bipolar-like explosions in the 3D hydrodynamical models, the impact is discussed. The decay of ^56 Ni, practically ^56 Co at later phases, could heat the gas and delay the molecule formation. Additionally, Compton electrons produced by the decay could ionize atoms and molecules and could destroy molecules. Several chemical reactions involved with ions such as H ^+ and He ^+ could also destroy molecules. The mixing of ^56 Ni plays a nonnegligible role in both the formation and destruction of molecules through the processes above. The destructive processes of carbon monoxide and silicon monoxide due to the decay of ^56 Ni generally reduce the amounts. However, if the molecule formation is sufficiently delayed under a certain condition, the decay of ^56 Ni could locally increase the amounts through a sequence of reactions.

In Arabidopsis thaliana (Arabidopsis), nonhost resistance (NHR) is influenced by both leaf age and the moment of inoculation. While the circadian clock and photoperiod have been linked to the time-dependent regulation of NHR in Arabidopsis, the mechanism underlying leaf age-dependent NHR remains unclear. In this study, we investigated leaf age-dependent NHR to Pyricularia oryzae in Arabidopsis. Our findings revealed that this NHR type is regulated by both miR156-dependent and miR156-independent pathways. To identify the key players, we utilized rice-FOX Arabidopsis lines and identified the rice HD-Zip I OsHOX6 gene. Notably, OsHOX6 expression confers robust NHR to P. oryzae and Colletotrichum nymphaeae in Arabidopsis, with its effect being contingent upon leaf age. Moreover, we explored the role of AtHB7 and AtHB12, the Arabidopsis closest homologues of OsHOX6, by studying mutants and overexpressors in Arabidopsis–C. higginsianum interaction. AtHB7 and AtHB12 were found to contribute to both penetration resistance and post-penetration resistance to C. higginsianum in a leaf age- and time-dependent manner. These findings highlight the involvement of HD-Zip I AtHB7 and AtHB12, well-known regulators of development and abiotic stress responses, in biotic stress responses in Arabidopsis.

The efficacy of quantum error correction of spins in a diamond nitrogen-vacancy that uses magnetic fields depends on spin’s location in the lattice. Here, an alternative, zero-field approach relying on geometric phase is demonstrated in a three-qubit system.

Background: Kommerell's diverticulum with Stanford type A aortic dissection is a relatively rare condition. There is currently no standard treatment strategy for Kommerell's diverticulum. We herein report our surgical strategy with a review of literature for a case of Kommerell's diverticulum that developed acute aortic dissection. Case presentation: A 54-year-old woman was referred to our hospital after being diagnosed with Stanford type A acute aortic dissection at the hospital where she was admitted for chest and back pain. Contrast-enhanced computed tomography showed a right and left common carotid and left subclavian artery branching from the aortic arch; Kommerell's diverticulum and an aberrant right subclavian artery (RSCA) arising from it were noted in the distal arch. The contralateral aortic wall where Kommerell's diverticulum was located was the entry, resulting in aortic dissection, with retrograde dissection extending into the ascending aorta. Partial thrombosis was detected in the false lumen of the ascending aorta. The dissection extended from the ascending aorta to the common iliac artery. In addition, the thrombosed false lumen in the left common iliac artery was considered to have caused dynamic obstruction due to compression and narrowing of the true lumen. Based on these findings, total arch replacement with reconstruction of the 4-branched vessels in the arch, including an aberrant RSCA, the frozen elephant trunk technique, and femoro-femoral bypass for malperfusion of the left lower extremity were performed with deep hypothermic circulatory arrest. An artificial graft was anastomosed to the right axillary artery, which was used as the blood supply route for cardiopulmonary bypass. After cooling to hypothermia, the central portion of the aberrant right subclavian artery was clipped on the right side of the trachea. Thus, cerebral blood flow was maintained via the right vertebral artery, the aortic arch was opened, and cannulas for selective cerebral perfusion were inserted into the right common carotid artery, the left common carotid artery, and the left subclavian artery. After each vessel was reconstructed, the graft that had been anastomosed to the right axillary artery was anastomosed to the graft used for reconstruction of the right common carotid artery. The patient's postoperative course was generally good. Conclusion: The strategy used by us effectively created transient occlusion of the origin of Kommerell's diverticulum and the primary entry. Our results indicate that this method is feasible and effective for cases in which in situ reconstruction of the branch may be challenging.

Abstract Purpose To evaluate the efficacy of two progestins, levonorgestrel intrauterine system (LNG‐IUS) and dienogest (DNG), for adenomyosis. Methods This study enrolled 157 women with adenomyosis, randomized to either LNG‐IUS (n = 76) or DNG (n = 81) groups as a controlled clinical trial for 72 months. Participants were classified by three different localizations of adenomyosis: diffuse, focal, and extrinsic. VAS (Visual analog scale) score, days, and amount of uterine bleeding were assessed. Uterine volume or bone mineral density (BMD) were measured by three‐dimensional ultrasonography or dual‐energy X‐ray absorptiometry. Results LNG‐IUS and DNG comparably reduced pain scores in patients with adenomyosis. With regard to pain control, DNG offered greater efficacy than LNG‐IUS in 3 months of treatment. In all types of adenomyosis, the days of bleeding after 12 months with DNG were significantly decreased compared to those with LNG‐IUS. The decrease of whole uterine body was transient in any subtypes. A comparable decrease in BMD due to age‐related changes in both groups was observed. Conclusions LNG‐IUS and DNG could be useful for long‐term management of adenomyosis. In terms of durations of uterine bleeding, DNG was superior to LNG‐IUS for 6 years.

Abstract Background The main mechanism of body temperature decrease during cesarean delivery under spinal anesthesia is core-to-peripheral redistribution of body heat, attributable to vasodilation. Perfusion index (PI) obtained with a pulse oximeter helps to assess peripheral perfusion dynamics by detecting the change in peripheral vascular tone. This study aimed to examine whether preoperative toe PI could predict the decrease in core temperature induced by spinal anesthesia during cesarean delivery. Methods Parturients undergoing scheduled cesarean delivery under combined spinal-epidural anesthesia from September 2019 to March 2020 were enrolled in this single-center prospective cohort study. All parturients received 0.5% hyperbaric bupivacaine (10 mg) with fentanyl (15 μg) intrathecally. A pulse oximeter probe was placed on the left second toe for continuous PI measurement. The 3 M™ Bair Hugger™ Temperature Monitoring System placed over the right temporal region was used to record core temperature over time. We evaluated the association between the maximum core temperature decrease, which is the primary outcome, and the preoperative toe PI at operating room (OR) admission using a segmented regression model (SRM) and a generalized additive model (GAM). The maximum core temperature decrease was defined as the difference between core temperature at OR admission and minimum intraoperative core temperature. Results Forty-eight patients were evaluated. In the SRM, the slope for the association between the maximum core temperature decrease and the preoperative toe PI changed from 0.031 to 0.124 after PI = 2.4%. Likewise, with the GAM, there was a small core temperature decrease when preoperative toe PI was greater than 2.0 to 3.0%. Conclusions Low preoperative toe PI was associated with maternal core temperature decrease during cesarean delivery under spinal anesthesia. Preoperative toe PI is a simple, non-invasive, and effective tool for the early prediction of perioperative core temperature decrease during cesarean delivery. Trial registration UMIN Clinical Trials Registry (registry number: UMIN000037965 ).

Heterozygous variants in the ATP1A3 gene are linked to well-known neurological phenotypes. There has been growing evidence for a separate phenotype associated with variants in residue Arg756—fever-induced paroxysmal weakness and encephalopathy (FIPWE) or relapsing encephalopathy with cerebellar ataxia (RECA). With only about 20 cases being reported, the clinical features associated with mutations at Arg756 have not been fully elucidated. We report a case of FIPWE with a p.Arg756Cys change in the ATP1A3 gene and a comparison of the clinical features, including electrophysiological examination, with previous cases. The 3-year-old male patient had normal psychomotor development, presenting with recurrent symptoms of generalized hypotonia with loss of gait, mutism, and dystonic movements only during febrile illnesses since 19 months of age. At 2.7 years of age, a third neurological decompensation episode occurred, during which electroencephalography (EEG) did not reveal high voltage slow waves or epileptiform discharge. Nerve conduction studies (NCS) also did not show latency delay or amplitude reduction. ATP1A3 exon sequencing showed a heterozygous p.Arg756Cys mutation. While the patient experienced repeated encephalopathy-like episodes, including severe hypotonia during febrile illness, EEG and NCS did not reveal any obvious abnormalities. These electrophysiological findings may represent an opportunity to suspect FIPWE and RECA.

Abstract Notch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing angiogenesis or arteriogenesis in a hindlimb ischemia model rat. In Sprague–Dawley rats, hindlimb ischemia was generated by femoral artery removal, then seven days after ischemic induction 1 × 105 SB623 cells or PBS was injected into the ischemic adductor muscle. As compared with the PBS group, tissue perfusion was significantly increased in the SB623 group. While capillary density did not vary between the groups, αSMA- and vWF-positive arterioles with a diameter > 15 μm were significantly increased in the SB623 group. Whole transcriptome analysis of endothelial cells co-cultured with SB623 cells showed upregulation of the Notch signaling pathway as well as several other pathways potentially leading to arteriogenesis. Furthermore, rat muscle treated with SB623 cells showed a trend for higher ephrin-B2 and significantly higher EphB4 expression, which are known as arteriogenic markers. In the hindlimb ischemia model, SB623 cells improved tissue perfusion by inducing arteriogenesis, suggesting a promising cell source for treatment of CLTI.

Gene or cell therapy is currently not fully efficacious for arteriosclerosis obliterans (ASO). In this study, we determined whether YS-1402, a slow-release synthetic prostacyclin agonist, promoted neovascularization and skeletal muscle regeneration in a mouse model of critical limb ischemia (CLI). We ligated the femoral artery and its branches to obtain the CLI mouse model, administered saline (S group) or YS-1402 (YS group) to the thigh adductor 1 week after femoral artery occlusion, and evaluated tissue blood flow after surgery. After treatment, the leg muscle was obtained for histological, gene expression, and protein analyses to assess angiogenesis and skeletal muscle regeneration. Tissue blood flow improved in the YS group compared with that in the S group, and the number of CD31+/α-smooth muscle actin (αSMA)+ arterioles increased in the YS group. Prostacyclin receptor (IPR), stromal cell-derived factor-1, hepatocyte growth factor, and neural cell adhesion molecule expression levels were higher in the YS than in the S group. Skeletal muscle regeneration was detected based on PAX7- and Ki-67-positive satellite cells in the YS group. Myogenin and MyoD expression was higher in the YS than in the S group. Therefore, YS-1402 promoted functional angiogenesis and skeletal muscle regeneration in the CLI mouse model, suggesting a new therapy for ASO.

Abstract Background Air in the venous system may cause vascular air embolism, which is a potentially life-threatening event. The presence of air in venous system after basilar skull fracture is very rare. Case presentation A 77-year-old man fell from a truck bed and suffered head and neck trauma. On hospital arrival, his consciousness was clear and his vital signs were stable. His chief complaint was pain in the back of his head and neck. Head CT showed traumatic subarachnoid hemorrhage in the right frontal area and basilar skull fracture of the occipital bone. Whole body CT showed pneumocephalus and air in the jugular vein and right ventricle. The patient was placed in the supine position in a state of absolute rest to prevent vascular air embolism and was treated conservatively. On hospital day 3, CT was reperformed, revealing disappearance of air in the right ventricle and decreased air in the veins of the head and neck. On hospital day 4, the air in the veins disappeared completely on CT. He did not experience vascular air embolism after increasing of his activity level (e.g., raising his head on hospital day 3 and standing and walking alone on day 5). He was discharged 34 days after admission without sequelae. Conclusions Head trauma patients with basilar skull fracture might develop vascular air embolism if physicians fail to detect air in the venous system on hospital arrival. A high degree of suspicion regarding air in venous system or heart is required when patients present with such injuries.

Gingival tissue experiences an environment of nutrient shortage, such as low glucose conditions, after periodontal surgery. Our previous studies found that this low glucose condition inhibits normal gingival cell functions. However, the mechanism by which this glucose-deficient environment causes cellular damage to human gingival fibroblasts (HGnFs) remains unclear. This study aimed to investigate the biological effects of ROS induction on HGnFs under low glucose conditions. ROS levels and cellular anti-ROS ability of HGnFs under different glucose concentrations were evaluated by measuring ROS formation and the expression of superoxide dismutase and heme oxygenase 1. Changes in cellular viability were investigated using 5-bromo-2′-deoxyuridine assay and cell survival detection, and the cellular damage was evaluated by the expression of inflammatory cytokines and changes in the expression of autophagy-related protein. ROS formation was then blocked using N-acetyl-L-cysteine (NAC), and the effects of ROS on HGnFs under low glucose conditions were investigated. Low glucose conditions induced ROS accumulation, reduced cellular activity, and induced inflammation and autophagy. After NAC application, the anti-ROS capacity increased, cellular activity improved, and inflammation and autophagy were controlled. This can be effectively controlled by the application of antioxidants such as NAC.

Pink-eyed dilution castaneus (Oca2p-cas) is a mutant gene on mouse chromosome 7 that arose spontaneously in wild Mus musculus castaneus. Homozygotes for Oca2p-cas exhibit pink eyes and a light gray coat throughout life. In an ordinary mutant strain carrying Oca2p-cas, we previously discovered a novel spontaneous mutation that gradually increases melanin pigmentation in the eyes and coat with aging, and we developed a novel mutant strain that was fixed for the novel phenotype. The purpose of this study was to map major quantitative trait loci (QTLs) for the novel pigmentation phenotype and for expression levels of four important melanogenesis genes, microphthalmia-associated transcription factor (Mitf), tyrosinase (Tyr), tyrosinase-related protein-1 (Tyrp1) and dopachrome tautomerase (Dct). We developed 69 DNA markers and created 303 F2 mice from two reciprocal crosses between novel and ordinary mutant strains. The QTL analysis using a selective genotyping strategy revealed a significant QTL for eye pigmentation between 34 and 64 Mb on chromosome 13. This QTL explained approximately 20% of the phenotypic variance. The QTL allele derived from the novel strain increased pigmentation. Although eye pigmentation was positively correlated with Dct expression, no expression QTLs were found, suggesting that the pigmentation QTL on chromosome 13 may not be directly in the pathway of any of the four melanogenesis genes. This study is the first step toward identifying a causal gene for the novel spontaneous phenotype in mice and is expected to discover a new regulatory mechanism for complex melanin biosynthesis during aging.

Previous studies suggest that marathon running induces lower extremity muscle damage. This study aimed to examine inter- and intramuscular differences in hamstring muscle damage after a marathon using transverse relaxation time (T2)-weighted magnetic resonance images (MRI). 20 healthy collegiate marathon runners (15 males) were recruited for this study. T2-MRI was performed before (PRE) and at 1 (D1), 3 (D3), and 8 days (D8) after marathon, and the T2 values of each hamstring muscle at the distal, middle, and proximal sites were calculated. Results indicated that no significant intermuscular differences in T2 changes were observed and that, regardless of muscle, the T2 values of the distal and middle sites increased significantly at D1 and D3 and recovered at D8, although those values of the proximal site remained constant. T2 significantly increased at distal and middle sites of the biceps femoris long head on D1 (p = 0.030 and p = 0.004, respectively) and D3 (p = 0.007 and p = 0.041, respectively), distal biceps femoris short head on D1 (p = 0.036), distal semitendinosus on D1 (p = 0.047) and D3 (p = 0.010), middle semitendinosus on D1 (p = 0.005), and distal and middle sites of the semimembranosus on D1 (p = 0.008 and p = 0.040, respectively) and D3 (p = 0.002 and p = 0.018, respectively). These results suggest that the distal and middle sites of the hamstring muscles are more susceptible to damage induced by running a full marathon. Conditioning that focuses on the distal and middle sites of the hamstring muscles may be more useful in improving recovery strategies after prolonged running.

Buildings with brittle columns are in danger of gravity load collapse and may be hazardous in the event of future earthquakes. To plan for building evacuation, the time required for such buildings to collapse must be known. This study thus uses dynamic analysis to examine the collapse time of reinforced-concrete (RC) buildings designed according to old Japanese codes. Model lateral load vs interstory drift relations are represented based on previous collapse tests of brittle columns. The results reveal that (1) in most cases, the time between shear failure and collapse is very short for individuals to safely evacuate a building, and (2) the collapse time can be long for earthquakes with long durations.

Abstract A 64-year-old female patient with spinocerebellar ataxia type 6 was referred to our department for pancreatic cancer and anesthetized with volatile anesthesia combined with epidural anesthesia for pancreaticoduodenectomy. No complications arose during surgery. On postoperative day 4, a head tremor was noticed at the time of mobilization. The tremor was a postural and “no-no” tremor rather than an intention or resting tremor. The head tremor caused difficulty in eating and in other activities of daily living. No abnormal results were obtained by magnetic resonance imaging of the brain. The tremor was resistant to drugs, including anti-Parkinson drugs and benzodiazepines, and was therefore difficult to treat.

Ehlers-Danlos syndrome (EDS) comprises a series of rare hereditary connective tissue diseases characterized by musculoskeletal, skin, and cardiovascular involvements. EDS may be associated with physical as well as psychological pain that can lead to psychiatric problems. EDS imposes substantial psychological burden on patients, and recent large-scale studies have suggested that patients with EDS have a higher risk of mood disorders than the general population. To the best of our knowledge, we describe, for the first time, the cases of two Japanese patients with EDS complicated with mood disorders who secondarily developed transvestism that was judged strongly related to early stressful situations through childhood and adolescence. The first case was of a man in his mid-30s and the second of a woman in her late 20s. We report on detailed psychosocial data to further discuss the medical management and genetic counseling of such infrequent but challenging conditions. Physicians are advised to be aware of various potential psychological and psychiatric issues that may accompany EDS.

Objective. Joint torque differences between healthy and rehabilitated legs are often measured as a clinical index of recovery from muscle strain injury. Unfortunately, it should be noted that this is a questionable evaluation measure of the muscle after injury because it is a composite value including related cooperating muscles. Meanwhile, the use of ultrasound elastography for the measurement of individual muscle mechanical properties (i.e., muscle hardness) has recently expanded. The purpose of this study was to examine, using ultrasound elastography, the differences in the linear relationship between muscle contraction intensity and muscle hardness during knee extension in athletes who had recovered from grade II rectus femoris muscle strain injury through comparison of the healthy and rehabilitated legs. Methods. Six athletes participated. Rectus femoris muscle hardness, determined during isometric contraction at 10%, 20%, 30%, and 40% of maximum voluntary contraction, was evaluated using ultrasound strain elastography. Results and Conclusion. The results indicated that for the healthy legs, the strain ratios, as indicated by muscle hardness, decreased linearly (became harder) with contraction intensity, but the strain ratios for the rehabilitated legs decreased nonlinearly. These results show the danger of judging the recovery period using only the difference between healthy and rehabilitated muscle strengths and the importance of evaluating individual muscles.

Cancer tissues are composed of cancer cells and the surrounding stromal cells (e.g., fibroblasts, vascular endothelial cells, and immune cells), in addition to the extracellular matrix. Most studies investigating carcinogenesis and the progression, invasion, metastasis, and angiogenesis of cancer have focused on alterations in cancer cells, including genetic and epigenetic changes. Recently, interactions between cancer cells and the stroma have attracted considerable attention, and increasing evidence has accumulated on this. Several researchers have gradually clarified the origins, features, and roles of cancer-associated fibroblasts (CAFs), a major component of the cancer stroma. CAFs function in a similar manner to myofibroblasts during wound healing. We previously reported the relationship between CAFs and angiogenesis. Interleukin-6 (IL-6), a multifunctional cytokine, plays a central role in regulating inflammatory and immune responses, and important roles in the progression, including proliferation, migration, and angiogenesis, of several cancers. We showed that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions. Furthermore, CAFs contribute to drug-resistance acquisition in cancer cells. The interaction between cancer cells and the stroma could be a potential target for anti-cancer therapy.