Photoluminescent Layered Crystal Consisting of Anderson-Type Polyoxometalate and Surfactant toward a Potential Inorganic-Organic Hybrid Laser.

The hybridization of inorganic and organic components is a promising strategy to build functional materials. Among several functions, luminescence is an important function which should be considered for practical usage. Inorganic-organic hybrid luminescent materials have been investigated as phosphors, sensors, and lasers. Organic luminescent centers such as dye molecules have often been hybridized with inorganic matrices. Polyoxometalate anions (POMs) are effective inorganic luminescent centers due to their luminescent properties and structural designability. However, most luminescent POM components are limited to lanthanide-based POMs. In this report, a photoluminescent inorganic-organic hybrid crystal based on a non-lanthanide POM was successfully synthesized as a single crystal. Anderson-type hexamolybdochromate ([CrMo6O18(OH)6]3-, CrMo6) anion exhibiting emission derived from Cr3+ was utilized with n-dodecylammonium ([C12H25NH3]+, C12NH3) surfactant cation to obtain a photoluminescent hybrid crystal. The grown single crystal of C12NH3-CrMo6 comprised a distinct layered structure consisting of inorganic CrMo6 layers and interdigitated C12NH3 layers. In the CrMo6 layers, the CrMo6 anions were associated with water molecules by hydrogen bonding to form a densely packed two-dimensional network. Steady-state and time-resolved photoluminescence spectroscopy revealed that the C12NH3-CrMo6 hybrid crystal exhibited characteristic emission from the CrMo6 anion. Preliminary lasing properties were also observed for C12NH3-CrMo6, which shows the possibility of using the C12NH3-CrMo6 hybrid crystal as an inorganic-organic hybrid laser.

Reversible expansion of pancreatic islet progenitors derived from human induced pluripotent stem cells.

Transplantation of pancreatic islets is an effective therapy for severe type 1 diabetes. As donor shortage is a major problem for this therapy, attempts have been made to produce a large number of pancreatic islets from human pluripotent stem cells (hPSCs). However, as the differentiation of hPSCs to pancreatic islets requires multiple and lengthy processes using various expensive cytokines, the process is variable, low efficiency and costly. Therefore, it would be beneficial if islet progenitors could be expanded. Neurogenin3 (NGN3)-expressing pancreatic endocrine progenitor (EP) cells derived from hPSCs exhibited the ability to differentiate into pancreatic islets while their cell cycle was arrested. By using a lentivirus vector, we introduced several growth-promoting genes into NGN3-expressing EP cells. We found that SV40LT expression induced proliferation of the EP cells but reduced the expression of endocrine lineage-commitment factors, NGN3, NEUROD1 and NKX2.2, resulting in the suppression of islet differentiation. By using the Cre-loxP system, we removed SV40LT after the expansion, leading to re-expression of endocrine-lineage commitment genes and differentiation into functional pancreatic islets. Thus, our findings will pave a way to generate a large quantity of functional pancreatic islets through the expansion of EP cells from hPSCs.

STAT3 inhibitory activity of naphthoquinones isolated from Tabebuia avellanedae.

The extract of Tabebuia avellanedae has been used as a folk medicine, and the various biological activities of T. avellanedae have been extensively studied. However, few studies have reported which natural products play a role in their biological effects. In this study, we evaluated representative naphthoquinones isolated from T. avellanedae and found that furanonaphthoquinones were the key structures required to exhibit STAT3 phosphorylation inhibitory activities. Our SAR analysis indicated that removal of a hydroxyl group enhanced the STAT3 phosphorylation inhibitory activity. In addition, the combined results of a mobility shift assay, SH2 domain binding assay, and docking simulation by Autodock 4.2.6 suggested that (S)-5-hydroxy-2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione (1) could directly bind to the hinge region of STAT3.

[Effect of a Discharge Planning Educational Program in a University Hospital].

The purpose of this study was to investigate the effect of a discharge planning educational program on multidisciplinary team staff in a community. We provided training to nurses of a university hospital. The training covered an introduction to discharge planning, decision-making support, home care medicine and home nursing care, the medical social welfare system, and case review meetings. It was conducted every year from September through February between 2012 and 2015. Before and after the training, the awareness of nurses was evaluated by using self-administered questionnaires and the Discharge Planning scale for Ward Nurses(DPWN), and discharge planning satisfaction was measured using a visual analogue scale (VAS). The study process was reviewed and approved by the Ethics Committee of Tokyo Women's Medical University. The questionnaires were distributed to 96 nurses; of these, responses of 72 nurses(pre- and post-training)were analyzed(response rate: 75.0%). The average number of years of nursing experience was 8.5± 7.7. The total score of the DPWN and its subscales, as well as the VAS, with regard to satisfaction level significantly increased after the training(p<0.01), indicating that training improved nurses' awareness of discharge planning practices.

[Stereotactic radiotherapy for metastatic liver cancer].

Twenty cases (27 therapeutic sites/30 nodules) of metastatic liver cancer treated with stereotactic radiotherapy (SRT)were analyzed. The original sites of cancer were colorectal(8 cases), breast(4 cases), stomach(3 cases), esophagus(2 cases), and other organs (3 cases). SRT was performed with 52.8 Gy·4 fr·-1·wk-1. The response rate was 78%, including complete response (CR) at 8 sites, partial response (PR) at 10 sites, stable disease (SD) at 2 sites, progressive disease(PD) at 3 sites, and not detected(ND) at 4 sites, thus demonstrating a potent local therapeutic effect. Ten patients survived for more than 1 year, 8 patients survived for 2 years, and 4 died before 6 months. Clinical analysis suggests that the ideal indications for SRT are patients with a solitary nodule and without extrahepatic disease who have undergone systemic chemotherapy.

[Complications associated with the placement of subcutaneous central venous access port devices: reasons for removal and complications observed].

OBJECTIVE: To clarify the complications associated with subcutaneous central venous access port devices, we investigated the patients who underwent placement of central venous access port devices in our hospital. METHODS: Overall, 171 cancer patients who underwent placement of subcutaneous central venous access port devices (119 for chemotherapy and 52 for home parenteral nutrition) between February 2006 and December 2011 and who were followed up for 1 month, were retrospectively analyzed in this study. Univariate analysis was performed on complications related to clinical factors, including age, gender, insertion sites, intended purposes, duration of catheterization, surgeons, catheter materials, and use of bevacizumab. RESULTS: The mean follow-up time was 213 days (range, 31-1,873), and 35 patients (20.5%) required the port device to be extracted due to complications, including infection in 24(14.0%), wound dehiscence at the port site in 2 (1.2%), obstruction of the catheter in 6 (3.5%), catheter-induced venous thrombosis in 1 (0.6%), and catheter fracture in 2(1.2%). No statistically significant differences were observed between the frequency of complications and age, gender, insertion sites, intended purposes, duration of catheterization, surgeons, catheter materials, or use of bevacizumab. CONCLUSION: The incidences of complications related to implantation and management of these devices are relatively high and early. Patients should be followed carefully by chest radiography at regular intervals.

Total Synthesis of Paclitaxel.

The total synthesis of paclitaxel (Taxol) is described. Double Rubottom oxidation of the bis(silyl enol ether) derived from a tricarbocyclic diketone effectively installed a bridgehead olefin and C-5/C-13 hydroxy groups in a one-step operation. The novel Ag-promoted oxetane formation smoothly constructed the tetracyclic framework of paclitaxel.

Epstein-Barr virus-encoded Bcl-2 homologue functions as a survival factor in Wp-restricted Burkitt lymphoma cell line P3HR-1.

Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus (EBV). EBV-positive BL tumors display two latent forms of infection. One is referred to as latency I infection, in which EBV expresses the virus genome maintenance protein EBNA1 as the only viral protein. The other is referred to as Wp-restricted latency and was recently identified in a subset of BL tumors. In these tumors, EBV expresses EBNA1, EBNA3A, EBNA3B, EBNA3C, a truncated form of EBNA-LP, and the viral Bcl-2 homologue BHRF1, all of which are driven by the BamHI W promoter (Wp). To investigate the role of EBV in Wp-restricted BL, we conditionally expressed a dominant-negative EBNA1 (dnEBNA1) mutant which interrupts the virus genome maintenance function of EBNA1 in the P3HR-1 BL cell line. Induction of dnEBNA1 expression caused loss of the EBV genome and resulted in apoptosis of P3HR-1 cells in the absence of exogenous apoptosis inducers, indicating that P3HR-1 cells cannot survive without EBV. Stable transfection of the BHRF1 gene into P3HR-1 cells rescued the cells from the apoptosis induced by dnEBNA1 expression, whereas stable transfection of truncated EBNA-LP, EBNA3A, or EBNA3C did not. Moreover, knockdown of BHRF1 expression in P3HR-1 cells resulted in increased cell death. These results indicate that EBV is essential for the survival of P3HR-1 cells and that BHRF1 functions as a survival factor. Our finding implies a critical contribution of BHRF1 to the pathogenesis of Wp-restricted BLs.

[Complete remission of liver metastasis from gall bladder carcinoma after stereotactic radiotherapy-a case report].

A 75-year-old man was diagnosed as gall bladder carcinoma by postoperative histological examination following laparoscopic cholecystectomy. He underwent the second surgery of resection of liver bed and port sites with lymph node dissection. Isolated hepatic metastasis of 20 mm in diameter was found in S4/8 by MRI 18 months postoperatively, and stereotactic radiotherapy (52.8 Gy/4 Fr) was done for the metastatic lesion. The lesion could not be detected by CT 7 months after the radiotherapy, and thereafter no local recurrence has been observed for 24 months. However, lymph node metastasis of #9 was diagnosed 31 months postoperatively. Liniac radiotherapy (60 Gy/20 Fr)was performed and stable disease has been obtained for 9 months. The patient is alive at present of 43 months after surgery without any other site of the disease, and his quality of life is well maintained. Stereotactic radiotherapy showed an excellent local therapeutic effect without any serious complications, suggesting that this is a potent modality for isolated liver metastasis of gall bladder carcinoma.

[Re-resection for local recurrence in the remnant pancreas after pancreaticoduodenectomy for pancreatic cancer- a case report].

A 70-year-old female suffered from jaundice was admitted to our hospital for a tumor in the pancreas head. CA19-9 and DUPAN-2 levels were increased in laboratory test. Enhanced abdominal computed tomography (CT) scan revealed a low density area of pancreas head. Cytology of pancreatic juice was performed by ERCP, and malignant cells were detected. Pancreaticoduodenectomy was performed under a diagnosis of pancreatic cancer (T3N1M0, stage III). Despite of adjuvant chemotherapy (gemcitabine) after surgery, CT scan revealed a low density area in the cut end of remnant pancreas at 3 months, which was accompanied with elevation of and CA19-9 and DUPAN-2 levels. We diagnosed as a recurrent pancreatic cancer of remnant pancreas without any other side of recurrence and re-resection was performed. Because of chylous ascites and depression following a second surgery, postoperative adjuvant chemotherapy could not be started. Re-recurrence was detected at 3 months after the second surgery, and she died 6 months after the surgery. Remnant or repeated pancreatectomy for local recurrent pancreatic carcinomas is extremely rare with limited number of cases reported in the literature. We report our experience, and discuss the significance of re-resection for recurrence of remnant pancreas.

CD82 is a marker to isolate ß cell precursors from human iPS cells and plays a role for the maturation of ß cells.

Generation of pancreatic ß cells from pluripotent stem cells is a key technology to develop cell therapy for insulin-dependent diabetes and considerable efforts have been made to produce ß cells. However, due to multiple and lengthy differentiation steps, production of ß cells is often unstable. It is also desirable to eliminate undifferentiated cells to avoid potential risks of tumorigenesis. To isolate ß cell precursors from late stage pancreatic endocrine progenitor (EP) cells derived from iPS cells, we have identified CD82, a member of the tetraspanin family. CD82+ cells at the EP stage differentiated into endocrine cells more efficiently than CD82- EP stage cells. We also show that CD82+ cells in human islets secreted insulin more efficiently than CD82- cells. Furthermore, knockdown of CD82 expression by siRNA or inhibition of CD82 by monoclonal antibodies in NGN3+ cells suppressed the function of ß cells with glucose-stimulated insulin secretion, suggesting that CD82 plays a role in maturation of EP cells to ß cells.

[Evaluation of hepatic arterial infusion chemotherapy using removable W-spiral catheter].

The authors analyzed the 62 patients who underwent hepatic arterial infusion (HAI) chemotherapy using W-spiral (WS) catheter. The catheter was successfully inserted into the hepatic artery without a coil fixation in 57 cases. After cessation of chemotherapy, the catheter was removed in 32 cases without difficulty, which resulted in improved patients' quality of life as well as preservation of patency of hepatic arteries. This catheter has a special shape-memory alloy in its tip, which allows preferable fixation without coils and removal of the catheter if desired. HAI using this catheter and subsequent removal of it is a reasonable strategy in the era with potent systemic chemotherapy.

[Adjuvant chemotherapy with FOLFOX4 regimen after curative resection of liver metastases from colorectal cancer].

Only a partial benefit of adjuvant chemotherapy administered after curative resection of colorectal cancer (CRC) metastases has been demonstrated. We report here our experience of 7 cases that were administered FOLFOX4 regimen as adjuvant chemotherapy after a curative resection of liver metastases from CRC. Five patients received 6 cycles of FOLFOX4 after prophylactic hepatic arterial infusion of 5-FU, and 2 remaining patients simply received 8 cycles of FOLFOX4. All patients completed the planned cycles of FOLFOX4 without any dose reduction of oxaliplatin. No patients developed a severe adverse effect greater than grade 2 except for grade 3 neutropenia observed in 4 cases. Although lung metastases occurred in 2 cases 28.1 and 21.3 months after liver resection, respectively, all patients are alive after a median follow up of 23.5 months. Our experience indicates that adjuvant chemotherapy with six to eight cycles of FOLFOX4 regimen is safe with a high dose intensity of oxaliplatin and expected to provide a survival benefit.

[A case of successfully treated lower rectal cancer with both inguinal lymph nodes by chemoradiotherapy].

We report a case of successfully treated lower rectal cancer with both inguinal lymph nodes by chemoradiotherapy. A 59-year-old man presented with anal pain. A colonoscopy revealed primary rectal cancer. The histological diagnosis was well to moderately differentiated adenocarcinoma. A computed tomography showed metastases to pararectal, both inguinal lymph nodes and right external iliac. After a ileostomy construction was done, he was treated with intensity modulated radiotherapy (a total 50.4 Gy) and chemotherapy with FOLFOX. The primary tumor had completely disappeared, and metastases to lymph nodes showed a remarkable shrinkage after the chemoradiotherapy. Nine months after radiation therapy, however, multiple lung and liver metastases were observed by a computed tomography, which were treated by systemic chemotherapy with FOLFOX and bevacizumab. The primary tumor and metastases to lymph nodes are still controlled well for 2 years after the initial chemoradiotherapy.

A typical case of giant cell arteritis with vision loss due to delayed diagnosis.

A 75-year-old woman lost vision because of delayed recognition of GCA. Early diagnosis and treatment of GCA are important for preventing visual complications. Physicians must remember to evaluate the entire body, not just a single organ/system.

Urinary Sodium-to-Potassium Ratio Tracks the Changes in Salt Intake during an Experimental Feeding Study Using Standardized Low-Salt and High-Salt Meals among Healthy Japanese Volunteers.

The Na/K ratio is considered to be a useful index, the monitoring of which allows an effective Na reduction and K increase, because practical methods (self-monitoring devices and reliable individual estimates from spot urine) are available for assessing these levels in individuals. An intervention trial for lowering the Na/K ratio has demonstrated that a reduction of the Na/K ratio mainly involved Na reduction, with only a small change in K. The present study aimed to clarify the relationship between dietary Na intake and the urinary Na/K molar ratio, using standardized low- and high-salt diets, with an equal dietary K intake, to determine the corresponding Na/K ratio. Fourteen healthy young adult volunteers ingested low-salt (3 g salt per day) and high-salt (20 g salt per day) meals for seven days each. Using a portable urinary Na/K meter, participants measured their spot urine at each voiding, and 24-h urine was collected on the last day of each diet period. On the last day of the unrestricted, low-salt, and high-salt diet periods, the group averages of the 24-h urine Na/K ratio were 4.2, 1.0, and 6.9, while the group averages of the daily mean spot urine Na/K ratio were 4.2, 1.1, and 6.6, respectively. The urinary Na/K ratio tracked changes in dietary salt intake, and reached a plateau approximately three days after each change in diet. Frequent monitoring of the spot urine Na/K ratio may help individuals adhere to an appropriate dietary Na intake.

Practical synthesis of the C-ring precursor of paclitaxel from 3-methoxytoluene.

The practical synthesis of the C-ring precursor of paclitaxel starting from 3-methoxytoluene is described. Lipase-catalyzed kinetic resolution of a substituted cyclohexane-1,2-diol, derived from 3-methoxytoluene in three steps, successfully afforded a desired enantiomer with >99% ee, which was transformed to a cyclohexenone. 1,4-Addition of a vinyl metal species, followed by Mukaiyama aldol reaction with formalin in the presence of a Lewis acid provided the known C-ring precursor of paclitaxel in a 10 g scale.

Crystal structure of (±)-(7RS,8SR)-7-methyl-1,4-dioxa-spiro-[4.5]decane-7,8-diol.

In the title compound, C9H16O4, the five-membered dioxolane ring adopts a twist conformation; two adjacent C atoms deviate alternately from the mean plane of other atoms by -0.297 (4) and 0.288 (4) Å. The spiro-fused cyclo-hexane ring shows a chair form. The hy-droxy group substituted in an axial position makes an intra-molecular O-H⋯O hydrogen bond with one of the O atoms in the cyclic ether, forming an S(6) ring motif. In the crystal, the O-H⋯O hydrogen bond involving the equatorial hy-droxy group connects the mol-ecules into a zigzag chain with a C(5) motif running along the c axis.

Crystal structures of (±)-(1SR,5SR,6SR,7SR,10SR,11SR,13RS,14SR)-13-hy-droxy-7-meth-oxy-meth-oxy-11,15,18,18-tetra-methyl-3-oxo-2,4-dioxa-tetra-cyclo-[12.3.1.0(1,5).0(6,11)]octa-dec-15-en-10-yl benzoate, its 13-epimer and 13-one derivative.

The title compounds, C29H38O8·0.25C5H12, (A), C29H38O8, (B), and C29H36O8, (C), are tetra-cyclic benzoates possessing a taxane skeleton with a fused dioxolane ring as the core structure. In the asymmetric unit of (A), there are two independent benzoate mol-ecules (A and A') and a half mol-ecule of solvent pentane disordered about an inversion center. The mol-ecular conformations of (A), (B) and (C) are similar except for the flexible meth-oxy-meth-oxy group. The cyclo-hexane, cyclo-hexene and central cyclo-octane rings adopt chair, half-chair and chair-chair (extended crown) forms, respectively. The dioxolane rings are essentially planar, while the dioxolane ring of A' is slightly twisted from the mean plane. In the crystal of (A), inter-molecular O-H⋯O, C-H⋯O and C-H⋯π inter-actions link the independent benzoates alternately, forming a chain structure. In the crystals of (B) and (C), mol-ecules are linked through O-H⋯O and C-H⋯π inter-actions, and C-H⋯O hydrogen bonds, respectively, into similar chains. Further, weak inter-molecular C-H⋯O inter-actions connect the chains into a three-dimensional network in (A) and a sheet in (B), whereas no other interactions are observed for (C).

Crystal structure of (±)-(1SR,5SR,6SR,7SR,10SR,11SR,13SR)-13-benz-yloxy-7-meth-oxy-meth-oxy-11,15,18,18-tetra-methyl-3-oxo-2,4-dioxa-tetra-cyclo-[12.3.1.0(1,5).0(6,11)]octa-deca-14,16-dien-10-yl benzoate.

In the title compound, C36H42O8, the dioxolane ring adopts a twist conformation; the two adjacent C atoms deviate alternately from the mean plane of other atoms by -0.287 (5) and 0.174 (5) Å. The cyclo-hexane, cyclo-hexa-diene and central cyclo-octane rings show chair, half-chair and boat-chair forms, respectively. As a result of the strained ring system, the tetra-subsituted olefin in the cyclo-hexa-diene is skewed from an ideal planar structure. In the crystal, C-H⋯O hydrogen bonds connect the mol-ecules into a sheet parallel to (100). The sheets are further linked by other weak C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.