Charge-Order Pattern of the Low-Temperature Phase of NaV2O5 Uniquely Determined by Resonant X-Ray Scattering from Monoclinic Single Domain

The present resonant x-ray scattering from each of monoclinically-split single domains of NaV2O5 has critically enhanced contrast between V4+ and V5+ ions strong enough to lead to unambiguous conclusion of the charge-order pattern of its low-temperature phase below Tc = 35 K. The zig-zag type charge-order patterns in the $ab$-plane previously confirmed have four kinds of configurations (A, A', B and B') and the stacking sequence along the c-axis is determined as the AAA'A' type by comparison with model calculations. By assigning the A and A' configurations to Ising spins, one can reasonably understand the previously discovered "devil's staircase"-type behavior with respect to the modulation of the layer-stacking sequences at high pressures and low temperatures, which very well resembles the global phase diagram theoretically predicted by the ANNNI model.Comment: 4 pages, 3 figure

Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model

BackgroundThe cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy.MethodsTwenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.ResultsAt 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05).ConclusionsThe combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure

Ultrafast isomerization-induced cooperative motions to higher molecular orientation in smectic liquid-crystalline azobenzene molecules

The photoisomerization of molecules is widely used to control the structure of soft matter in both natural and synthetic systems. However, the structural dynamics of the molecules during isomerization and their subsequent response are difficult to elucidate due to their complex and ultrafast nature. Herein, we describe the ultrafast formation of higherorientation of liquid-crystalline (LC) azobenzene molecules via linearly polarized ultraviolet light (UV) using ultrafast time-resolved electron diffraction. The ultrafast orientation is caused by the trans-to-cis isomerization of the azobenzene molecules. Our observations are consistent with simplified molecular dynamics calculations that revealed that the molecules are aligned with the laser polarization axis by their cooperative motion after photoisomerization. This insight advances the fundamental chemistry of photoresponsive molecules in soft matter as well as their ultrafast photomechanical applications

Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumors in vivo

<p>Abstract</p> <p>Background</p> <p>Boron neutron capture therapy (BNCT) is a cell-selective radiation therapy that uses the alpha particles and lithium nuclei produced by the boron neutron capture reaction. BNCT is a relatively safe tool for treating multiple or diffuse malignant tumors with little injury to normal tissue. The success or failure of BNCT depends upon the ¹⁰B compound accumulation within tumor cells and the proximity of the tumor cells to the body surface. To extend the therapeutic use of BNCT from surface tumors to visceral tumors will require ¹⁰B compounds that accumulate strongly in tumor cells without significant accumulation in normal cells, and an appropriate delivery method for deeper tissues.</p> <p>Hemagglutinating Virus of Japan Envelope (HVJ-E) is used as a vehicle for gene delivery because of its high ability to fuse with cells. However, its strong hemagglutination activity makes HVJ-E unsuitable for systemic administration.</p> <p>In this study, we developed a novel vector for ¹⁰B (sodium borocaptate: BSH) delivery using HVJ-E and cationized gelatin for treating multiple liver tumors with BNCT without severe adverse events.</p> <p>Methods</p> <p>We developed cationized gelatin conjugate HVJ-E combined with BSH (CG-HVJ-E-BSH), and evaluated its characteristics (toxicity, affinity for tumor cells, accumulation and retention in tumor cells, boron-carrying capacity to multiple liver tumors <it>in vivo</it>, and bio-distribution) and effectiveness in BNCT therapy in a murine model of multiple liver tumors.</p> <p>Results</p> <p>CG-HVJ-E reduced hemagglutination activity by half and was significantly less toxic in mice than HVJ-E. Higher ¹⁰B concentrations in murine osteosarcoma cells (LM8G5) were achieved with CG-HVJ-E-BSH than with BSH. When administered into mice bearing multiple LM8G5 liver tumors, the tumor/normal liver ratios of CG-HVJ-E-BSH were significantly higher than those of BSH for the first 48 hours (<it>p < 0.05</it>). In suppressing the spread of tumor cells in mice, BNCT treatment was as effective with CG-HVJ-E-BSH as with BSH containing a 35-fold higher ¹⁰B dose. Furthermore, CG-HVJ-E-BSH significantly increased the survival time of tumor-bearing mice compared to BSH at a comparable dosage of ¹⁰B.</p> <p>Conclusion</p> <p>CG-HVJ-E-BSH is a promising strategy for the BNCT treatment of visceral tumors without severe adverse events to surrounding normal tissues.</p

プロテインC カッセイ テイカ オ ハイケイ トシ オートマチックシャ エノ ヘンコウ オ ケイキ ニ ハイケッセン ソクセンショウ オ ハッショウ シタ タクシー ウンテンシュ ノ イチレイ

A ６２-year-old man, who was a taxi-driver, presented to our hospital for further examination and treatment of deep venous thrombosis（DVT）suspected in another clinic. Before ３ months of consultation, he had changed his taxi from manual transmission car to automatic transmission car. Around the same time, he had complained progressively worsening left pedal edema and pain. When he consulted our hospital, blood examination showed elevated D-dimer and deficiency of protein C. A venous ultrasound showed an occlusive DVT in left lower extremity through an external iliac vein. A contrast-enhanced computed tomography showed bilateral pulmonary embolism（PE） and extensive thrombus in the left lower extremity. Following hospitalization, an inferior vena cava （IVC）filter was placed in an infrarenal IVC position, and anticoagulant therapy was initiated with heparin and warfarin. His DVT and PE were managed successfully with anticoagulant therapy, and pedal edema was improved. Besides some risk factors of thrombogenicity such as age and deficiency of protein C, sitting position for long hours and decreased motion of left leg might have triggered off the thrombus formation in the left lower extremity. This report demonstrates the importance of careful follow-ups to long-distance drivers with risk factors of thrombus formation, especially about clutch operation

Trastuzumab タンザイ リョウホウ ガ チョコウ シタ セツジョ フノウ シンコウ イガン ノ 1レイ

Trastuzumab, a humanized monoclonal antibody directed against human epidermal growth factor receptor２ （HER２）, has been shown to be active against metastatic gastric cancer that overexpress HER２. A ７８-year-old man presented with an edema in the lower legs. He was diagnosed as having advanced gastric cancers with multiple liver metastases in our hospital. Immunohistochemistry of the tumor cells revealed HER２ overexpression with an intensity of ３＋. The patient was treated with DS-T chemotherapy （Docetaxel＋S‐１＋Trastuzumab） because of the presence of renal dysfunction. Due to the adverse effect appeared with his skin, DS-T chemotherapy has been canceled and trastuzumab chemotherapy was continued. After １１ months of trastuzumab monotherapy, metastatic liver tumors were diminished. There is very few report of a positive response to trastuzumab in a patient with HER２‐overexpressing metastatic gastric cancer

Chimeric anti-podoplanin antibody suppresses tumor metastasis through neutralization and antibody-dependent cellular cytotoxicity

Podoplanin is a platelet aggregation-inducing factor associated with tumor metastasis, malignant progression, and cancer stem cells. We produced a rat-human chimeric anti-podoplanin mAb, NZ-8, from rat anti-podoplanin mAb (NZ-1). Although both NZ-1 and NZ-8 possess high binding affinities and high neutralizing activities of platelet aggregation, the antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity of NZ-8 were much higher than NZ-1. Furthermore, both NZ-1 and NZ-8 inhibited the growth of podoplanin-expressing tumors in vivo. Both NZ-1 and NZ-8 also suppressed hematogenous metastasis of podoplanin-expressing tumors. These results suggest that antipodoplanin mAbs suppressed hematogenous metastasis by both neutralization and antibody-dependent cellular cytotoxicity/complement-dependent cytotoxicity activities. Targeting therapy to podoplanin-expressing tumors should be useful as a novel immunotherapy. (Cancer Sci, doi: 10.1111/j.1349-7006.2012.02385.x, 2012 P odoplanin is a platelet aggregation-inducing factor, and its expression has been reported in many tumors including malignant brain tumors, mesotheliomas, and squamous cell carcinoma. (1-10) Importantly, recent investigations have suggested that expression of podoplanin is associated with tumor metastasis, malignant progression, and epithelial-mesenchymal transition. (11-18) Podoplanin expression has also been reported to be associated with clinical outcome. (23) Because TICs are thought to be resistant to conventional therapies, and are responsible for relapse, targeting TICs could be a promising approach to cancer therapy. (24) Podoplanin has been reported to be a TIC marker; We previously produced an anti-podoplanin antibody, NZ-1. (5) NZ-1 should have not only high specificity and sensitivity but also high binding-affinity against podoplanin to be applied for radioimmunotherapy or immunotoxin therapy. Previous studies showed that NZ-1 is a suitable candidate for therapy against malignant gliomas because NZ-1 was highly internalized into glioma cell lines, and also well accumulated into tumors in vivo. (26) Moreover, NZ-1 inhibited tumor cellinduced platelet aggregation and tumor metastasis by its neutralizing activity. (12) However, it has not been clarified whether NZ-1 possesses antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) against podoplanin-expressing tumor cells. In this study, we produced rat-human chimeric anti-podoplanin antibody (NZ-8) from rat anti-podoplanin neutralizing antibody (NZ-1), and characterized NZ-8 activity in flow cytometry, Western blot, platelet aggregation, and ADCC/CDC analyses in vitro. Next, we investigated the antitumor and antimetastatic activities of the anti-podoplanin mAbs in vivo

Laparoscopic transabdominal preperitoneal approach for giant inguinal hernias

Summary: Background: Many surgical techniques have been developed to treat inguinal hernia. In recent years, the laparoscopic transabdominal preperitoneal (TAPP) approach has been widely performed to repair inguinal hernia. Giant inguinal hernia (GIH) is an extremely rare disease that is a challenge for general surgeons. GIH appears when patients neglect the treatment for many years and it is defined as an inguinal hernia that extends below the midpoint of inner thigh in standing position. According to previous publications, the Lichtenstein tension-free hernioplasty is recommended to repair GIH. In this article, we describe consecutive four cases of GIH repaired via the TAPP approach. Methods: From April 2015 to March 2017, 200 patients underwent hernioplasty against inguinal hernia at our hospital. Inguinal hernias were treated via the TAPP approach in principle. We performed hernioplasty via the TAPP approach in all 4 patients (2%) who met the definition of Type 1 GIH. Demographic information, maximum diameter of hernia sac, hernia orifice size, and surgical data were obtained. Results: The mean operative time was 135 min. No intraoperative complications were encountered. All patients could walk from postoperative day 1 and were discharged home early, but they all had scrotal seromas. Three patients did not need puncture or drainage, but one of them required puncture. All seromas disappeared within 6 months. There was no recurrence in the 8- to 24-month follow-up. Conclusion: The TAPP approach is a feasible, safe therapeutic option that may reduce wound size and pain following surgical treatment of Type 1 GIH. Keywords: Giant inguinal hernia, Scrotal hernia, TAPP, Transabdominal preperitoneal approac

Molecular epidemiology of pathogenic Leptospira spp. in the straw-colored fruit bat (Eidolon helvum) migrating to Zambia from the Democratic Republic of Congo

The role played by bats as a potential source of transmission of Leptospira spp. to humans is poorly understood, despite various pathogenic Leptospira spp. being identified in these mammals. Here, we investigated the prevalence and diversity of pathogenic Leptospira spp. that infect the straw-colored fruit bat (Eidolon helvum). We captured this bat species, which is widely distributed in Africa, in Zambia during 2008–2013. We detected the flagellin B gene (flaB) from pathogenic Leptospira spp. in kidney samples from 79 of 529 E. helvum (14.9%) bats. Phylogenetic analysis of 70 flaB fragments amplified from E. helvum samples and previously reported sequences, revealed that 12 of the fragments grouped with Leptospira borgpetersenii and Leptospira kirschneri; however, the remaining 58 flaB fragments appeared not to be associated with any reported species. Additionally, the 16S ribosomal RNA gene (rrs) amplified from 27 randomly chosen flaB-positive samples was compared with previously reported sequences, including bat-derived Leptospira spp. All 27 rrs fragments clustered into a pathogenic group. Eight fragments were located in unique branches, the other 19 fragments were closely related to Leptospira spp. detected in bats. These results show that rrs sequences in bats are genetically related to each other without regional variation, suggesting that Leptospira are evolutionarily well-adapted to bats and have uniquely evolved in the bat population. Our study indicates that pathogenic Leptospira spp. in E. helvum in Zambia have unique genotypes

Abnormal Blood Coagulation and Kidney Damage in Aged Hamsters Infected with Severe Acute Respiratory Syndrome Coronavirus 2

Systemic symptoms have often been observed in patients with coronavirus disease 2019 (COVID-19) in addition to pneumonia, however, the details are still unclear due to the lack of an appropriate animal model. In this study, we investigated and compared blood coagulation abnormalities and tissue damage between male Syrian hamsters of 9 (young) and over 36 (aged) weeks old after intranasal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite similar levels of viral replication and inflammatory responses in the lungs of both age groups, aged but not young hamsters showed significant prolongation of prothrombin time and prominent acute kidney damage. Moreover, aged hamsters demonstrated increased intravascular coagulation time-dependently in the lungs, suggesting that consumption of coagulation factors causes prothrombin time prolongation. Furthermore, proximal urinary tract damage and mesangial matrix expansion were observed in the kidneys of the aged hamsters at early and later disease stages, respectively. Given that the severity and mortality of COVID-19 are higher in elderly human patients, the effect of aging on pathogenesis needs to be understood and should be considered for the selection of animal models. We, thus, propose that the aged hamster is a good small animal model for COVID-19 research