Clinical Characteristics of Fragile X Syndrome Patients in Japan

[Background] Fragile X syndrome (FXS) is a well-known X-linked disorder clinically characterized by intellectual disability and autistic features. However, diagnosed Japanese FXS cases have been fewer than expected, and clinical features of Japanese FXS patients remain unknown. [Methods] We evaluated the clinical features of Japanese FXS patients using the results of a questionnaire-based survey. [Results] We presented the characteristics of seven patients aged 6 to 20 years. Long face and large ears were observed in five of seven patients. Macrocephaly was observed in four of five patients. The meaningful word was first seen at a certain time point between 18 and 72 months (median = 60 months). Developmental quotient or intellectual quotient ranged between 20 and 48 (median = 29). Behavioral disorders were seen in all patients (autistic spectrum disorder in six patients, hyperactivity in five patients). Five patients were diagnosed by polymerase chain reaction analysis, and two patients were diagnosed by the cytogenetic study. All physicians ordered FXS genetic testing for suspicious cases because of clinical manifestations. [Conclusion] In the present study, a long face, large ears, macrocephaly, autistic spectrum disorder, and hyperactivity were observed in almost cases, and these characteristics might be common features in Japanese FXS patients. Our finding indicated the importance of clinical manifestations to diagnosis FXS. However, the sample size of the present study is small, and these features are also seen to patients with other disorders. We consider that genetic testing for FXS should be performed on a wider range of intellectually disabled cases

Effects of transcutaneous electrical nerve stimulation on physical symptoms in advanced cancer patients receiving palliative care

Transcutaneous electrical nerve stimulation (TENS) is primarily used for pain, butmight be useful for various other physical symptoms, including nausea, fatigue,dyspnea, and constipation. However, few studies have used TENS for treating thephysical symptoms of patients with advanced cancer. In this crossover trial, we assessthe effects of TENS on pain and other physical symptoms in 20 in-patients withadvanced cancer receiving palliative care. For 5-day phases between wash out periodsof 5 days, patients received TENS or non-TENS. TENS was delivered at four points: thecenter of the back for mainly nausea and dyspnea, on the back at the same dermatomallevel as the origin of the pain (100 Hz), and on both ankle joints for constipation (10Hz). The intensity of pain and the total opioid dose used during phases were recorded.Physical symptoms were evaluated using the European Organization for Research andTreatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative Care(QLQ-C15-PAL). Hematological and biochemical data were recorded before and afterthe TENS phase. The average pain and total number of opioid rescue doses weresignificantly reduced by TENS. TENS tended to improve nausea and appetite loss, butnot constipation. There were no effects on hematological and biochemical parameters.Use of TENS could safely improve pain, nausea, and appetite loss in patients withadvanced cancer. Although it cannot be used as a substitute for opioids and otherpharmaceutical treatment, it may be useful to support palliative care

Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity

During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK). However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-ϐ-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein ϐ (C/EBPϐ) expression levels. The effect of C/EBPϐ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPϐ transgenic mice to investigate the relationship between C/EBPϐ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPϐ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPϐ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPϐ transgenic mice decreased C/EBPϐ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPϐ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure

Liver Parenchyma Perforation following Endoscopic Retrograde Cholangiopancreatography

Although endoscopic retrograde cholangiopancreatography (ERCP) is an effective modality for the diagnosis and treatment of biliary and pancreatic diseases, it is still related with several severe complications. We report on the case of a female patient who developed liver parenchyma perforation following ERCP. She underwent ERCP with sphincterotomy and extraction of a common bile duct stone. Shortly after ERCP, abdominal distension was identified. Abdominal computed tomography revealed intraabdominal air leakage and leakage of contrast dye penetrating the liver parenchyma into the space around the spleen. Since periampullary perforation related to sphincterotomy could not be denied, she was referred for immediate surgery. Obvious perforation could not be found at surgery. Cholecystectomy, insertion of a T tube into the common bile duct, placement of a duodenostomy tube and drainage of the retroperitoneum were performed. She did well postoperatively and was discharged home on postoperative day 28. In conclusion, as it is well recognized that perforation is one of the most serious complication related to ERCP, liver parenchyma perforation should be suspected as a cause

A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair.

When DNA replication is stalled at sites of DNA damage, a cascade of responses is activated in the cell to halt cell cycle progression and promote DNA repair. A pathway initiated by the kinase Ataxia teleangiectasia and Rad3 related (ATR) and its partner ATR interacting protein (ATRIP) plays an important role in this response. The Fanconi anemia (FA) pathway is also activated following genomic stress, and defects in this pathway cause a cancer-prone hematologic disorder in humans. Little is known about how these two pathways are coordinated. We report here that following cellular exposure to DNA cross-linking damage, the FA core complex enhances binding and localization of ATRIP within damaged chromatin. In cells lacking the core complex, ATR-mediated phosphorylation of two functional response targets, ATRIP and FANCI, is defective. We also provide evidence that the canonical ATR activation pathway involving RAD17 and TOPBP1 is largely dispensable for the FA pathway activation. Indeed DT40 mutant cells lacking both RAD17 and FANCD2 were synergistically more sensitive to cisplatin compared with either single mutant. Collectively, these data reveal new aspects of the interplay between regulation of ATR-ATRIP kinase and activation of the FA pathway

A Report on Overseas Teaching Practicum by Graduate Students in Elementary/Secondary Schools in the United States （XII）

This paper reports on the overseas teaching practicum in the U.S., which was supposed to be the 12th time this year. Eight students joined this year’s program and they prepared for the practicum in the U.S. They met regularly to discuss the lesson plans and deepen their understanding on how to create a lesson and what scaffolding steps they should prepare for conveying messages to American children who know little about Japanese culture and having different background from us. Unfortunately, just a few days before the departure, we had to give up our visit to the U.S. since there was a high chance of a hurricane hitting the area we were to visit. Though we could not make our visit in September, instead we held a forum in November and exchanged discussion on the impact of the program to the participants and the schools which accept us. The details of the lesson plans and the forum are reported in this paper

ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18

Toxoplasma virulence factor ROP18 targets endoplasmic reticulum–bound transcription factor ATF6β in the host cell, leading to the detrimental loss of ATF6β through proteasome-dependent degradation