Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials.

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature.

Introduction: NGLY1-associated congenital disorder of deglycosylation (CDDG1: OMIM #615273) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive.

Case Presentation: A Japanese boy with delayed psychomotor development showed ataxic movements from age 5 years and myoclonic seizures from age 12 years.

Risk Factors for Frequent Infections in Patients With Extremely Severe Motor and Intellectual Disabilities.

Background: At our institution, patients of all ages with extremely severe motor and intellectual disabilities (ESMID) receive comprehensive management similar to intensive care for "extremely ill patients." Some patients with ESMID develop frequent infections that are difficult to manage. The purpose of this study was to identify risk factors for frequent infections in these patients.

Knowledge and Awareness of Human Papillomavirus Vaccination and Cervical Cancer among Men and Women in Japan: A Questionnaire Survey.

Background: In many advanced countries other than Japan, the incidence and mortality rates of cervical cancer, which is mainly caused by the human papillomavirus (HPV) infection, are decreasing probably due to the high rate of HPV vaccination and cervical cancer screening. In Japan, these rates are on the rise owing to the stagnation of vaccination and low screening rate. To improve these situations, active promotion of HPV vaccination and screening is required.

Recent topics and advanced therapies in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by the inability of phagocytes to produce reactive oxygen species (ROS) owing to a defect in any of the five components (CYBB/gp91phox, CYBA/p22phox, NCF1/p47phox, NCF2/p67phox, and NCF4/p40phox) and a concomitant regulatory component of Rac1/2 and CYBC1/Eros of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Patients with CGD are at an increased risk of life-threatening infections caused by catalase-positive bacteria and fungi and of inflammatory complications such as CGD colitis. Antimicrobial and azole antifungal prophylaxes have considerably reduced the incidence and severity of bacterial and improved fungal infections and overall survival.