Helicity Control of Circularly Polarized Luminescence from Aromatic Conjugated Copolymers and Their Mixture Using Reversibly Photoinvertible Chiral Liquid Crystals.

We synthesized cyclic chiral compounds [(R)/(S)-D2s] by linking a photoresponsive bisbenzothienylethene (BTE) moiety with an axially chiral binaphthyl moiety. Chiral nematic liquid crystals (N*-LCs) were prepared by adding chiral compounds as dopants to host N-LCs. These N*-LCs exhibited reversible chirality inversion upon photoisomerization between the open and closed forms of the BTE moiety. Here, the mechanism underlying chirality inversion in photoresponsive N*-LCs was investigated by comparing the helical twisting powers (HTPs) of (R)-D2s with those of analogous compounds. It was found that the helical inversion of N*-LCs containing (R)-D2s is governed by a delicate balance between two types of opposite helicity, i.e., the right-handed helicity of the inherently chiral binaphthyl moiety and the left-handed helicity of the BTE moiety bearing intramolecularly induced chirality. Namely, (R)-D2s induced chirality of the BTE moiety, which is attributed to intramolecular chirality transfer from the axially chiral binaphthyl moiety to the BTE moiety. Thus, (R)-D2s are chiral compounds with double chirality consisting of an intrinsically chiral moiety and an intramolecularly induced chiral moiety. Photocontrol of the helical senses and reversible photoinversion of the N*-LCs are achieved by utilizing UV and visible light irradiation and the steric effects of the substituents at the binaphthyl rings in (R)-D2s. In addition, photocontrol of the induced circularly polarized luminescence (CPL) was achieved using the photoinvertible N*-LC. The achiral aromatic conjugated copolymers that exhibited red, green, and blue fluorescence were dissolved and mixed in the present N*-LC, and they exhibited left- and right-handed white CPL with large dissymmetry factors (|glum|) ranging from 0.2 to 1.0. The CPLs were reversibly photoswitched due to photoisomerization between the open and PSS forms of the chiral compounds through UV and visible light irradiation.

[A Case of Pancreatic Cancer That Was Radically Resected after Chemotherapy and Radiation Therapy, but Recurred Early and Followed a Rapid Course].

A 71-year-old man presented to our hospital with abdominal pain. He was diagnosed with acute pancreatitis and pancreatic cancer. Peritoneal washing cytology(CY)was positive, and laparotomy findings revealed severe inflammatory changes of pancreatitis, suggesting a high likelihood of the need for combined resection of other organs. Therefore, following the exploratory laparotomy, mFOLFIRINOX was initiated as chemotherapy. After 24 courses of mFOLFIRINOX, he developed drug-induced pneumonia. Therefore, chemotherapy was interrupted, and a steroid was started. Radiotherapy was administered during steroid tapering. There was no evidence of local progression or distant metastasis. A radical resection that included pancreaticoduodenectomy and right hemicolectomy was performed 23 months after the exploratory laparotomy. CY was negative and R0 resection was achieved. However, 5 months after the operation, he developed liver abscesses and cholangitis and was suspected to have liver metastasis. He underwent PTAD and PTCD, but died due to liver failure 8 months postoperatively. The early recurrence of this case might have been caused by the lack of postoperative chemotherapy due to his frailty. Surgical indications should be carefully judged if there is a high risk of recurrence after NAC and a high possibility that ACT cannot be performed after radical surgery.

Cold agglutinin-induced hemolytic anemia during room temperature fluid resuscitation: a case report.

BACKGROUND: Cold agglutinin disease can cause the agglutination of red blood cells and hemolytic anemia due to cold temperature. Herein, we report a case of progressive hemolytic anemia due to cold agglutinin disease during fluid resuscitation and in the absence of exposure to cold. CASE PRESENTATION: A 71-year-old Japanese man was admitted to the emergency department with signs of hypotension and disturbed consciousness. He was diagnosed with diabetic ketoacidosis, and treatment with fluid resuscitation and insulin infusion was initiated. Laboratory test results obtained the following day indicated hemolytic anemia. On day 5 after admission, red blood cell agglutination was detected, and the patient was diagnosed with cold agglutinin disease. CONCLUSIONS: Cold agglutinin disease should be considered in the differential diagnosis of progressive hemolytic anemia during fluid resuscitation, even if the solution is at room temperature.

[Ischemic Colitis after Closure of Temporary Ileostomy for Low Anterior Resection of Rectal Cancer in a Dialysis Patient-A Case Report].

Dialysis patients are at increased risk of ischemic colitis and are likely to develop irreversible ischemic colitis. We report a rare case of ischemic colitis after the closure of a temporary ileostomy for low anterior resection(LAR)of rectal cancer in a dialysis patient. A 77-year-old man undergoing maintenance dialysis was diagnosed as having colorectal cancer with a type 2 tumor at the anastomosis site of high anterior resection performed for sigmoid colon cancer 14 years ago. After undergoing excision which included the anastomosis site of the previous operation, LAR with anastomosis in the transverse colon and rectum and temporary ileostomy were performed. Seven months later, closure of the temporary ileostomy was performed, which resulted in ileus and septic shock. Computed tomography(CT)revealed inflammation in the colon on the oral side of the anastomosis, which was diagnosed as ischemic colitis. Ischemic colitis did not improve with conservative treatment, and fever reoccurred at each maintenance dialysis session. Therefore, ileostomy was performed again, but multiple organ failure due to disseminated intravascular coagulopathy(DIC)progressed and he died. It is considered that Hartmann's operation should be selected for dialysis patients with serious underlying diseases, and if ischemic colitis is observed after closure of the stoma temporary colostomy in such patients, the lesion site of ischemic colitis should be excised promptly and colostomy should be performed again.

Generation of four induced pluripotent stem cell lines (FHUi003-A, FHUi003-B, FHUi004-A and FHUi004-B) from two affected individuals of a familial neurohypophyseal diabetes insipidus family.

Four disease-specific induced pluripotent stem cell (iPSC) lines were respectively derived from peripheral blood mononuclear cells of two affected individuals in a family affected by familial neurohypophyseal diabetes insipidus carrying the c.314G>C mutation. The expression of pluripotency markers (NANOG, OCT4, and SOX2), maintenance of a normal karyotype, absence of episomal vectors used for iPSC generation, and presence of the original pathogenic mutation were confirmed for each iPSC line. The ability to differentiate into three germ layers was confirmed by a teratoma formation assay. These iPSC lines can help in disease recapitulation in vitro using organoids and elucidation of disease mechanisms.

Retrospective evaluations revealed pre-symptomatic citrulline concentrations measured by newborn screening were significantly low in late-onset ornithine transcarbamylase deficiency patients.

INTRODUCTION: Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder. Late-onset OTCD manifests after the neonatal period; therefore, if pre-symptomatic diagnosis and treatment are performed, it can improve the prognosis by preventing hyperammonemia. However, pre-symptomatic diagnosis is unreliable as the specific screening marker of OTCD has not been established yet. This retrospective study aimed to evaluate the pre-symptomatic blood citrulline levels in patients with late-onset OTCD. METHODS: Patients with late-onset OTCD who were born after the newborn screening based on tandem mass spectrometry (MS/MS-NBS) was started and were referred to Hyogo College of Medicine Hospital between 2014 and 2018 were included. Pre-symptomatic blood citrulline levels measured by MS/MS-NBS were retrospectively evaluated. RESULTS: Four patients were included in this study. The pre-symptomatic blood citrulline levels were 2.02, 4.50, 4.97, and 3.75 µmol/l, respectively. Compared with the citrulline levels in all newborns in Hyogo prefecture, these values were significantly low. CONCLUSIONS: These results suggest the possibility that hypocitrullinemia detected by the MS/MS-NBS can be used as a screening marker for some patients with late-onset OTCD. Further retrospective evaluation of pre-symptomatic citrulline levels in patients with late-onset OTCD, as well as prospective monitoring of hypocitrullinemia on the MS/MS-NBS should be conducted.

Generation of three induced pluripotent stem cell (iPSC) lines from a multiple endocrine neoplasia type 1 (MEN1) patient and three iPSC lines from an unaffected relative of the patient.

We generated three disease-specific iPSC lines from a Multiple endocrine neoplasia type 1 (MEN1) patient and three control iPSC lines from an unaffected blood relative of the patient using unutilized lymphoblastoid B cell lines (LCLs) as a cell resource. The expression of pluripotency markers, retaining of normal karyotype of chromosome, absence of episomal vectors used for generating the iPSCs and EBV used for generating LCLs, and the potential to differentiate into three germ layers, were confirmed for each iPSC line. These iPSC lines can be useful for construction of the disease models in vitro, and elucidation of the disease mechanisms.

Trends in clinical trials for stroke by cell therapy: data mining ClinicalTrials.gov and the ICTRP portal site.

Definitive treatment of stroke constitutes an important thesis of regenerative medicine in the cerebrovascular field. However, to date, no cell therapy products for stroke are yet on the market. In this study, we examined the clinical research trends related to cell therapy products in the stroke field based on data obtained from the ClinicalTrials.gov website and International Clinical Trials Research Platform (ICTRP) portal site. These data do not offer results of clinical trials comprehensively but provide information regarding various attributes of planned clinical trials including work in progress. We selected 78 cell therapy studies related to the field of stroke treatment from ClinicalTrial.gov and ICTRP. These were analyzed according to, e.g., the reporting countries, origin (autologous or allogeneic), of cell used, cell types and source organs, the progress of translational phases, target phase of the disease (acute or chronic stroke), and route of administration. This analysis revealed a trend whereby in the acute phase, mesenchymal stem cells were administered intravenously at a relatively higher dose, whereas in the chronic phase a small number of cells were administered intracranially. Only two randomized controlled Phase III studies with over 100 patients are registered, but none of them has been completed. Thus, cell therapy against stroke appears to constitute a premature area compared with cartilage repair as assessed in our previous report. In addition, tracking by means of the ID number of each trial via PubMed revealed that 44% of clinical studies in this field have corresponding published results, which was also discussed.

Local dissemination of osteosarcoma observed after massage therapy: a case report.

BACKGROUND: Limited evidence is available regarding the dissemination of tumor tissues due to compression during massage therapy, a routine procedure in patients with various symptoms in Asian countries. CASE PRESENTATION: A 12-year-old male presented at a massage clinic with pain and swelling of his left knee, which worsened the same night. Consistent with conventional osteosarcoma, radiography revealed cortical bone destruction, osteoblastic changes, and periosteal reactions. Magnetic resonance imaging revealed a tumor in the distal femur, an extraskeletal mass, and an infiltrative lesion in the intramuscular and neurovascular areas surrounding the distal femur; this was considered as hemorrhage and dissemination of the tumor tissue. 18Fluorine-labelled fluorodeoxyglucose-positron emission tomography and computed tomography revealed multiple metastases in the spine, liver, and lung. Consistent with osteosarcoma, histopathological examination revealed tumor cell proliferation with extensive pleomorphism and mitoses. Despite undergoing chemotherapy, radiation therapy, and hip disarticulation, the patient died due to multiple metastases 13 months after the initial diagnosis. CONCLUSIONS: The present case suggests association of massage therapy with the local dissemination of tumor tissues, although influence of massage therapy on metastatic lesions remains unclear. Massage therapists should be aware of the possibility for dissemination of hidden malignancies due to the procedure.

Immunological Properties of Neural Crest Cells Derived from Human Induced Pluripotent Stem Cells.

Collecting sufficient quantities of primary neural crest cells (NCCs) for experiments is difficult, as NCCs are embryonic transient tissue that basically does not proliferate. We successfully induced NCCs from human induced pluripotent stem cells (iPSCs) in accordance with a previously described method with some modifications. The protocol used in this study efficiently produced large amounts of iPSC-derived NCCs (iPSC-NCCs). Many researchers have recently produced large amounts of iPSC-NCCs and used these to examine the physiological properties, such as migratory activity, and the potential for medical uses such as wound healing. Immunological properties of NCCs are yet to be reported. Therefore, the purpose of this study was to assess the immunological properties of human iPSC-NCCs. Our current study showed that iPSC-NCCs were hypoimmunogenic and had immunosuppressive properties in vitro. Expression of HLA class I molecules on iPSC-NCCs was lower than that observed for iPSCs, and there was no expression of HLA class II and costimulatory molecules on the cells. With regard to the immunosuppressive properties, iPSC-NCCs greatly inhibited T cell activation (cell proliferation and production of inflammatory cytokines) after stimulation. iPSC-NCCs constitutively expressed membrane-bound TGF-ß, and TGF-ß produced by iPSC-NCCs played a critical role in T cell suppression. Thus, cultured human NCCs can fully suppress T cell activation in vitro. This study may contribute to the realization of using stem cell-derived NCCs in cell-based medicine.

Late-onset ornithine transcarbamylase deficiency caused by a somatic mosaic mutation.

An 18-month-old boy was diagnosed with late-onset ornithine transcarbamylase deficiency. Genetic analysis revealed a mosaic frameshift mutation (p.Q279fs) in the OTC gene. Despite the presence of a null mutation, he exhibited a milder phenotype, suggesting that the wild-type allele could rescue the function of OTC. The presence of mosaicism has great effects on the clinical phenotype and recurrence-risk assessment, which should be taken into consideration for genetic counseling.

Sensitivity improvement of dual-comb spectroscopy using mode-filtering technique.

In this study, we demonstrated an improvement in the detection sensitivity of dual-comb spectroscopy using the repetition rate multiplication of optical frequency combs. We compared the dual-comb signals in three dual-comb setups consisting of combinations of two combs with and without mode-filtering, and investigated how the repetition rate influences the signal-to-noise ratio (SNR) of dual-comb measurements. The dual-comb setups using high-repetition-rate combs enabled the absorption lines of HCN gas to be measured with a high SNR in a short averaging time, and real-time spectral data acquisition was realized using a low-sensitivity and low-resolution RF spectrum analyzer.

The Semaphorin 3A inhibitor SM-345431 preserves corneal nerve and epithelial integrity in a murine dry eye model.

Dry eye disease (DED) is a common disorder causing discomfort and ocular fatigue. Corneal nerves are compromised in DED, which may further cause loss of corneal sensation and decreased tear secretion. Semaphorin 3A (Sema3A) is expressed by the corneal epithelium under stress, and is known as an inhibitor of axonal regeneration. Using a murine dry eye model, we found that topical SM-345431, a selective Sema3A inhibitor, preserved corneal sensitivity (2.3 ± 0.3 mm versus 1.4 ± 0.1 mm in vehicle control, p = 0.004) and tear volume (1.1 ± 0.1 mm versus 0.3 ± 0.1 mm in vehicle control, p < 0.001). Fluorescein staining area of the cornea due to damage to barrier function was also reduced (4.1 ± 0.9% in SM-345431 group versus 12.9 ± 2.2% in vehicle control, p < 0.001). The incidence of corneal epithelial erosions was significantly suppressed by SM-345431 (none in SM-345431 group versus six (21%) in vehicle control, p = 0.01). Furthermore, sub-epithelial corneal nerve density and intraepithelial expression of transient receptor potential vanilloid receptor 1 (TRPV1) were significantly preserved with SM-345431. Our results suggest that inhibition of Sema3A may be an effective therapy for DED.

The Optimization of Short-Term Hepatocyte Preservation Before Transplantation.

BACKGROUND: No optimal methods for short-term hepatocyte preservation have been established. We have recently developed a prominent oxygen-permeable bag (Tohoku Device [TD]) for pancreatic islet culture and transplantation. In this study, we investigated whether TD is also effective for hepatocyte preservation and tried to optimize other conditions. METHODS: Hepatocytes were preserved in the following conditions, and their outcomes were observed. First, the effectiveness of TD was investigated. Second, hepatocyte medium (HM) and organ preservation solutions with or without fetal bovine serum (FBS) were compared. Third, as supplementations, FBS and human serum albumin (HSA) were compared. Fourth, low, room and high temperature were compared. And finally, hepatocytes preserved in various conditions were transplanted into the subrenal capsule space of nonalbumin rats and engrafted areas were assessed. RESULTS: The survival rate of hepatocytes preserved in TD tended to be higher and their viability and function were maintained significantly greater than those of non-TD group. Irrespective of FBS supplementation, the survival rate of HM group was significantly higher than those of organ preservation solution group while viabilities and plating efficiency were similar among them. Although survival rates of groups without FBS were extremely low, results of HSA supplemented group were not inferior to FBS supplemented group. Hepatocytes preserved at high temperature had the worst results. The engrafted area of TD group tended to be higher than those of other groups. CONCLUSIONS: TD is effective for short-term hepatocyte preservation. HSA is a useful substitute for FBS, and preserving in HM at low temperature is recommended.

Congenital dysfibrinogenemia in a Japanese family with fibrinogen Naples (BßAla68Thr) manifesting as superior sagittal sinus thrombosis.

: Congenital dysfibrinogenemia refers to the presence of a dysfunctional fibrinogen molecule, typically because of mutations in the fibrinogen gene. About 20% of fibrinogen gene mutations are responsible for thrombosis. Here, we described the case of a 17-year-old Japanese boy, who had a sudden stroke because of superior sagittal sinus thrombosis associated with dysfibrinogenemia. Genetic testing confirmed the presence of homozygous fibrinogen Naples (BßAla68Thr) mutation, which was previously reported as a causative mutation for thrombotic dysfibrinogenemia only in an Italian family. In this Japanese family, the patient's 12-year-old asymptomatic sister was also homozygous for this mutation. She, like her brother, was started on warfarin therapy. This report highlights the occurrence of fibrinogen Naples that has caused severe thrombotic complications in a young member of a Japanese family.

The prevalence and morphological types of non-carious cervical lesions (NCCL) in a contemporary sample of people.

Non-carious cervical lesions (NCCLs) were examined in 6541 extracted human teeth and classified based on the morphology of the lesions. As a result, NCCLs were found on 38.7% of teeth (41.6% on maxillary teeth and 36.0% on mandibular teeth), and were most frequent on canines and first premolars. According to the new method of classification, the morphology of NCCLs was classified both by the surface contour (SC) and by the cross-sectional contour (CC). Three types of NCCLs appeared to be dominant. The causes of these NCCLs were discussed based on their morphologies, positions where these NCCLs were frequently found, and the results of previous studies. NCCLs with a horizontal oval SC and a round CC (Type I), which were frequent on the labial surfaces of maxillary canines and buccal surfaces of maxillary first premolars, may be associated with wear by friction and chemical degradation. NCCLs with a vertical oval SC and a round CC (Type II), which were frequent on the lingual surfaces of mandibular incisors and canines, might be mainly related to chemical degradation. NCCLs with a horizontal oval SC and a wedge shape CC (Type III), which were extensively found on the buccal surfaces of maxillary premolars, had formed most probably due to wear by friction and microstructural loss by stress. This new method can classify the morphology of NCCLs more precisely and deduce the mechanisms of the formation of NCCLs more clearly than former methods.

Compartmentalized Spherical Collagen Microparticles for Anisotropic Cell Culture Microenvironments.

This paper describes a new fabrication method for obtaining anisotropic spherical hydrogel microparticles with different types of extracellular matrix (ECM) hemispheres for use in 3D cell culture. To fabricate the microparticles, a mixture of an ECM precursor solution and sodium alginate is ejected into a calcium chloride solution under large centrifugal acceleration by a centrifuge-based microfluidic device; the calcium alginate hydrogel plays a significant role as a "sacrificial gelation template" to maintain the ECM molecules in each hemisphere. This fabrication method enables gaining control of the hemispherical volume, density, and type of ECM. Using the microparticles, cells could be successfully encapsulated in each hemisphere selectively with high viability, which are then suitable for culture in the microparticles to form microtissues. It is believed that the proposed anisotropic ECM microparticles will facilitate the coculture of multiple cell types in different ECMs, which is similar to in vivo microenvironments, facilitating control of cell behavior in an anisotropic microenvironment for the benefit of large-scale and quantitative analyses in vitro.

Skin-Derived Precursors as a Source of Progenitors for Corneal Endothelial Regeneration.

Corneal blindness is the fourth leading cause of blindness in the world. Current treatment is allogenic corneal transplantation, which is limited by shortage of donors and immunological rejection. Skin-derived precursors (SKPs) are postnatal stem cells, which are self-renewing, multipotent precursors that can be isolated and expanded from the dermis. Facial skin may therefore be an accessible autologous source of neural crest derived cells. SKPs were isolated from facial skin of Wnt1-Cre/Floxed EGFP mouse. After inducing differentiation with medium containing retinoic acid and GSK 3-ß inhibitor, SKPs formed polygonal corneal endothelial-like cells (sTECE). Expression of major corneal endothelial markers were confirmed by Reverse transcription polymerase chain reaction (RT-PCR) and quantitative Real time polymerase chain reaction (qRT-PCR). Western blots confirmed the expression of Na, K-ATPase protein, the major functional marker of corneal endothelial cells. Immunohistochemistry revealed the expression of zonular occludens-1 and Na, K-ATPase in cell-cell junctions. In vitro functional analysis of Na, K-ATPase pump activity revealed that sTECE had significantly high pump function compared to SKPs or control 3T3 cells. Moreover, sTECE transplanted into a rabbit model of bullous keratopathy successfully maintained corneal thickness and transparency. Furthermore, we successfully induced corneal endothelial-like cells from human SKPs, and showed that transplanted corneas also maintained corneal transparency and thickness. Our findings suggest that SKPs may be used as a source of autologous cells for the treatment of corneal endothelial disease. Stem Cells Translational Medicine 2017;6:788-798.