The effect of early irregular cell division of human embryos on blastocyst euploidy: considerations from the subsequent development of the blastomeres by direct or reverse cleavage.

Objective: To investigate whether blastocysts that divide irregularly reduce subsequent blastocyst euploidy.

Design: Retrospective study.

Setting: Private clinic.

Evaluation of artificial intelligence using time-lapse images of IVF embryos to predict live birth.

Research Question: Can artificial intelligence (AI) improve the prediction of live births based on embryo images?

Design: The AI system was created by using the Attention Branch Network associated with deep learning to predict the probability of live birth from 141,444 images recorded by time-lapse imaging of 470 transferred embryos, of which 91 resulted in live birth and 379 resulted in non-live birth that included implantation failure, biochemical pregnancy and clinical miscarriage. The possibility that the calculated confidence scores of each embryo and the focused areas visualized in each embryo image can help predict subsequent live birth was examined.

Results: The AI system for the first time successfully visualized embryo features in focused areas that had potential to distinguish between live and non-live births.

Trends of fetal chromosome analysis by amniocentesis before and after beginning of noninvasive prenatal testing: A single-center experience in Japan.

Aim: This study is to investigate the role of amniocentesis for prenatal diagnosis before and after the beginning of noninvasive prenatal testing (NIPT) in Japan.

Methods: We performed a retrospective analysis of genetic amniocentesis at mid-trimester (15-20 gestational weeks) for fetal karyotype analysis at Nagoya City University between April 2006 and March 2020. The indications, test results, and the detection rate of fetal abnormal karyotype were compared before (phase 1, P1) and after (phase 2, P2) beginning of NIPT at April 2013.

Perspectives of Multidisciplinary Professional Teams during Assessment Processes for ATD Selection in the Japanese Public Provision System.

Selection of assistive technology devices (ATDs), which are imperative for persons with disabilities to improve their quality of life, requires collaboration of users and multidisciplinary professionals. However, it is still unknown how to design and implement an adequate collaborative work flow and a professional team. Under Japanese governmental ATD provision system, based on the application by clients, ATDs are mainly selected through collaborative processes with the clients and health professionals in public organizations, rehabilitation counseling centers (RCCs).

Assessment of driving skills of a mobility scooter using driving operation logs.

A mobility scooter is a major assistive technology that replaces human ambulatory functions for people with disabilities. A license is often not required for driving a mobility scooter; therefore, less skilled drivers might create safety concerns. An effective way of reducing these safety risks is by assessing the driving skills of users.

Study of Relationship Between Mode of Conception and Non-Specific Psychological Distress in Women Undergoing Noninvasive Prenatal Testing.

Background: Noninvasive prenatal testing (NIPT) has been performed worldwide to detect common fetal chromosomal aneuploidies.

Methods: Pregnant women (n=3743) with advanced maternal age who visited Nagoya University for NIPT were enrolled in this study. The K6 mental stress scores, that is non-specific psychological distress scores were obtained by questionnaires which were administered pre-NIPT and postpartum.

Effects of synchronised engine sound and vibration presentation on visually induced motion sickness.

Driving simulator usage is often accompanied by motion sickness, and techniques for its prevention are not yet established. To reduce visually induced motion sickness (VIMS), we investigated the effects of synchronised presentation of engine sounds and motorcycle vibration on VIMS. A total of 80 participants experienced a driving scene with a head-mounted display for 5 minutes with or without synchronised presentation of engine sound and vibration.

Novel Indirect AMP-Activated Protein Kinase Activators: Identification of a Second-Generation Clinical Candidate with Improved Physicochemical Properties and Reduced hERG Inhibitory Activity.

This study reports the synthesis and evaluation of novel indirect AMP-activated protein kinase (AMPK) activators. The series of compounds selectively inhibited cell growth in several human breast cancer cell lines by activating AMPK. We performed back-up medicinal chemistry synthetic research on ASP4132, a previously reported as a compound for clinical development that acts as an indirect AMPK activator.

Development of a potent and orally active activator of adenosine monophosphate-activated protein kinase (AMPK), ASP4132, as a clinical candidate for the treatment of human cancer.

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a key role in maintaining cellular metabolism. AMP or adenosine diphosphate (ADP) levels rise during metabolic stress, such as during nutrient starvation, hypoxia and muscle contraction, and bind to AMPK to induce activity. Recently, activation of AMPK has been considered an attractive therapeutic strategy in the field of human oncology.

Discovery of 3,5-Dimethylpyridin-4(1H)-one Derivatives as Activators of AMP-Activated Protein Kinase (AMPK).

Novel 3,5-dimethylpyridin-4(1H)-one scaffold compounds were synthesized and evaluated as AMP-activated protein kinase (AMPK) activators. Unlike direct AMPK activators, this series of compounds showed selective cell growth inhibitory activity against human breast cancer cell lines. By optimizing the lead compound (4a) from our library, 2-[({1'-[(4-fluorophenyl)methyl]-2-methyl-1',2',3',6'-tetrahydro[3,4'-bipyridin]-6-yl}oxy)methyl]-3,5-dimethylpyridin-4(1H)-one (25) was found to have potent AMPK activating activity.

Importance of mediastinal screening-based observation during endoscopic ultrasound to examine gastrointestinal pathologies.

In all endoscopic ultrasound (EUS) examinations performed at our hospital, the heart, vasculature, and mediastinal lymph nodes from the esophagus are observed after checking for gastrointestinal pathologies. Since the introduction of EUS using a convex linear-array echoendoscope at our hospital in April 2015, EUS examinations have been performed in 371 cases for examining pancreaticobiliary diseases, submucosal tumors, and other pathologies during the 3-year period, till March 2018. We diagnosed 2 patients with asymptomatic cardiovascular disease while observing the mediastinum during EUS examination to examine identified pancreaticobiliary disease.

Clinical utility of decorin in follicular fluid as a biomarker of oocyte potential.

This study investigated the concentration of decorin (DCN) in mature follicular fluid and the existence in the granulosa cells. It also investigated whether DCN is useful as a biomarker for outcomes of assisted reproductive technology (ART). A retrospective cohort study was performed involving 130 oocytes of 88 patients treated with ART because of unexplained infertility.

Combined effect of astaxanthin and squalene on oxidative stress in vivo.

Obesity and diabetes, risk factors for metabolic syndrome, are characterized by oxidative stress and inflammatory responses. Marine biofunctionals, astaxanthin (Ax) and squalene (SQ), were evaluated for their combined effect. Groups of male KK-A (y) mice were fed high fat/sucrose diet for 4 weeks, supplemented with either 0.

Immediate effect of spinal magnetic stimulation on camptocormia in Parkinson's disease.

Objectives: Spinal cord stimulation is a potential therapeutic option for the treatment of Parkinson's disease (PD)-associated symptoms. Repetitive trans-spinal magnetic stimulation (rTSMS) is a non-invasive and safe alternative for stimulation of spinal pathways that has not been studied for therapeutic efficacy in PD. We assessed the benefits of rTSMS on camptocormia, an often treatment-resistant postural abnormality observed in PD patients.

Regular ingestion of cinnamomi cortex pulveratus offers gastroprotective activity in mice.

The present study investigated the gastroprotective effects of a cinnamon diet using different gastric ulcer mouse models. Dose dependency and the effective dose period of administration of a cinnamon powder diet were established using the water immersion stress gastric ulcer model. A cinnamon powder diet significantly protected mice against ulceration by stress, ethanol, HCl and oral administration of aspirin, but not against ulceration by oral administration of indomethacin or subcutaneous administration of indomethacin or aspirin.

Coulombic aggregations of Mn(III) salen-type complexes and Keggin-type polyoxometalates: isolation of Mn2 single-molecule magnets.

The reaction of Mn(III) salen-type complexes with di- and tetraanionic α-Keggin-type polyoxometalates (POMs) was performed, and three types of Coulombic aggregations containing Mn(III) out-of-plane dimeric units (abbreviated as [Mn(2)](2+)) that are potentially single-molecule magnets (SMMs) with an S(T) = 4 ground state were synthesized: [Mn(2)(5-MeOsaltmen)(2)(acetone)(2)][SW(12)O(40)] (1), [Mn(2)(salen)(2)(H(2)O)(2)](2)[SiW(12)O(40)] (2), and [Mn(5-Brsaltmen)(H(2)O)(acetone)](2)[{Mn(2)(5-Brsaltmen)(2)}(SiW(12)O(40))] (3), where 5-Rsaltmen(2-) = N,N'-(1,1,2,2-tetramethylethylene)bis(5-R-salicylideneiminate) with R = MeO (methoxy), Br (bromo) and salen(2-) = N,N'-ethylenebis(salicylideneiminate). Compound 1 with a dianionic POM, [SW(12)O(40)](2-), is composed of a 1:1 aggregating set of [Mn(2)](2+)/POM, and 2, with a tetraanionic POM, [SiW(12)O(40)](4-), is a 2:1 set. Compound 3 with [SiW(12)O(40)](4-) forms a unique 1D coordinating chain with a [-{Mn(2)}-POM-](2-) repeating unit, for which a hydrogen-bonded dimeric unit ([Mn(5-Brsaltmen)(H(2)O)(acetone)](2)(2+)) is present as a countercation.

Identification of 4-quinolone derivatives as inhibitors of reactive oxygen species production from human umbilical vein endothelial cells.

Oxidative stress is widely recognized as being associated with a number of disorders, including metabolic dysfunction and atherosclerosis. A series of substituted 4-quinolone derivatives were prepared and evaluated as inhibitors of reactive oxygen species (ROS) production from human umbilical vein endothelial cells (HUVECs). One compound in particular, 2-({[4-(3-hydroxy-3-methylbutoxy)pyridin-2-yl]oxy}methyl)-3-methylquinolin-4(1H)-one (25b), inhibited ROS production from HUVECs with an IC(50) of 140 nM.

Evaluation of the effects of mastication and swallowing on gastric motility using electrogastrography.

Objectives: The influence of mastication and swallowing on gastric motor function was evaluated by electrogastrography (EGG) and abdominal ultrasonography.

Methods: The subjects were 30 elderly patients with tubal feeding without mastication and swallowing (T group) and 30 elderly controls who processed food by mastication and swallowing (C group). Gastric motor function was percutaneously examined before and after the ingestion of 250 ml of a liquid diet using an electrogastrograph (NIPRO EGG, A and D, Tokyo, Japan).

Discovery of the first non-peptide full agonists for the human bradykinin B(2) receptor incorporating 4-(2-picolyloxy)quinoline and 1-(2-picolyl)benzimidazole frameworks.

In the course of our studies on non-peptide bradykinin (BK) B(2) receptor ligands, it was suggested that the 4-substituent of the quinoline ring may play a critical role in determining binding affinities for human and guinea pig B(2) receptors, as well as agonist/antagonist properties. We carried out an extensive investigation to elucidate the structure-activity relationships (SAR) for this key pharmacophore. Introduction of lower alkoxy groups to the 4-position of the quinoline ring of 3 led to the identification of 4-ethoxy derivative 22b as a unique partial agonist.

A new class of nonpeptide bradykinin B(2) receptor ligand, incorporating a 4-aminoquinoline framework. Identification of a key pharmacophore to determine species difference and agonist/antagonist profile.

Introduction of various aliphatic amino groups at the 4-position of the quinoline moiety of our nonpeptide bradykinin (BK) B(2) receptor antagonists afforded highly potent ligands for human B(2) receptor with various affinities for guinea pig B(2) receptor, indicating remarkable species difference. A representative 4-dimethyamino derivative 40a exhibited subnanomolar and nanomolar binding affinities for human and guinea pig B(2) receptors, respectively, and significantly inhibited BK-induced bronchoconstriction in guinea pigs at 10 microg/kg by intravenous administration. Further chemical modification led us to discover unique partial agonists for the human B(2) receptor that increase inositol phosphates (IPs) production by themselves in Chinese hamster ovary (CHO) cells expressing the cloned human B(2) receptor.

A new series of highly potent non-peptide bradykinin B2 receptor antagonists incorporating the 4-heteroarylquinoline framework. Improvement of aqueous solubility and new insights into species difference.

Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B(2) receptor antagonists resulted in enhancing binding affinities for the human B(2) receptor and reducing binding affinities for the guinea pig one, providing new structural insights into species difference. A CoMFA study focused on the diversity of the quinoline moiety afforded correlative and predictive QSAR models of binding for the human B(2) receptor but not for the guinea pig one. A series of 4-(1-imidazolyl)quinoline derivatives could be dissolved in a 5% aqueous solution of citric acid up to a concentration of 10 mg/mL.

Autonomic nervous dysfunction in patients with liver cirrhosis using 123I-metaiodobenzylguanidine myocardial scintigraphy and spectrum analysis of heart-rate variability.

Background: It has been reported that nitric oxide (NO) synthase is induced in patients with liver cirrhosis (LC), and that an excessive production of NO enhances sympathetic nervous function. The present report describes a study of the feasibility of evaluation of abnormalities of autonomic nervous function by 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and heart-rate variability in patients with LC.

Methods: Low-frequency (LF) power, high-frequency (HF) power, LF/HF, and 1/f fluctuations of heart rate variability were examined in 50 patients with LC (LC group), and 50 normal subjects (N group).