Discovery of 2-(6-{[(1R,2R)-2-hydroxycyclohexyl]amino}-4,5-dimethylpyridazin-3-yl)-5-(trifluoromethyl)phenol (ASP0965): A potent, orally active and brain-penetrable NLRP3 inflammasome inhibitor with a novel scaffold for the treatment of α-synucleinopathy.

NLRP3 inflammasome inhibitor is a highly attractive drug target for the treatment of various inflammatory diseases. Here, we report the discovery of pyridazine derivatives as a new class of scaffold for NLRP3 inflammasome inhibitors. We optimized HTS hit 2a to improve both in vitro IL-1β inhibitory activity and the mean photo effect (MPE) value in the in vitro 3T3 neutral red uptake (NRU) phototoxicity test.

Agreement between 2D Visual- and 3D Motion Capture-based Assessment of Foot Strike Pattern.

Background: Foot strike patterns during running are typically categorized into two types: non-rearfoot strike (NRFS) and rearfoot strike (RFS), or as three distinct types: forefoot strike (FFS), midfoot strike (MFS), and RFS, based on which part of the foot lands first. Various methods, including two-dimensional (2D) visual-based methods and three-dimensional (3D) motion capture-based methods utilizing parameters such as the strike index (SI) or strike angle (SA), have been employed to assess these patterns. However, the consistency between the results obtained from each method remains debatable.

Differences in Lumbopelvic Alignment in Adolescent Male Soccer Players With Bilateral and Unilateral Lumbar Bone Stress Injuries: An MRI Evaluation.

Background: Differences in the physical characteristics of bilateral and unilateral lumbar bone stress injuries (BSIs) are unknown.

Purpose: To compare bilateral and unilateral lumbar BSIs in adolescent male soccer players, with a focus on lumbopelvic alignment.

Study Design: Cross-sectional study; Level of evidence, 3.

Long-time behavior of swimming in a heterogenous light environment.

The cell motion of in homogeneous and heterogeneous light environments was analyzed. Homogeneous and heterogeneous environments were prepared, with only a red color or with a red circle surrounded by brighter white regions, respectively. In a heterogeneous environment, the cells move into the red circle.

Development of a database for educating athletes in university sports.

[Purpose] The aim of this study was to investigate the development of a database and system for easily creating documents for educational guidance on a personal computer and to assess the efficacy of such a system. [Participants and Methods] Thirty-seven athletic trainers of students who belonged to an athletic department participated in the study. We used FileMaker Pro 17 Advanced for document creation, and data on independent exercises for athletic rehabilitation were used for database creation.

Benefits of Early Mobilization After Pediatric Liver Transplantation.

Objective: To evaluate the impact of early mobilization after pediatric liver transplantation in the PICU.

Design: A 70-month retrospective before-after study.

Setting: Medical and surgical PICU with 20 beds at a tertiary children's hospital.

Early Mobilization after Pediatric Liver Transplantation.

 This study aims to evaluate the impact of early mobilization (EM) after pediatric liver transplantation in the pediatric intensive care unit (PICU).  A 14-month prospective before and after study.  Multivalent PICU with 20 beds at a tertiary children's hospital.

[Summary of the Profiles of 22 Children with Traumatic Brain Injury Tacted with the Japanese Version of the WISC-IV].

The Japanese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) is often used to assess cognitive dysfunction in children with traumatic brain injury (TBI). To reveal the characteristics of cognitive impairment in pediatric TBI, we retrospectively analyzed the results of 22 children with TBI on the WISC-IV that was conducted at the Developmental Evaluation Center of the National Center for Child Health and Development over three years from July 2011 to July 2014. It has been hypothesized that the WISC-IV is limited for revealing neuropsychological dysfunction after traumatic brain injury.

[Case of long-term metamorphopsia caused by multiple cerebral infarction].

This report presents the case of a 79-year-old right-handed woman. One day on waking, she realized that the faces of her family members appeared distorted. She consulted an ophthalmologist at a nearby clinic in the vicinity and was diagnosed with left homonymous hemianopsia.

(+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6-(trifluoromethyl)pyridin-3- yl]piperazine-1-carboxamide (YM580) as an orally potent and peripherally selective nonsteroidal androgen receptor antagonist.

A novel series of trans-N-aryl-2,5-dimethylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic effects were evaluated. Pharmacological assays indicated that compound 33 was a potent AR antagonist, and subsequent optical resolution provided (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6-(trifluoromethyl)pyridin-3-yl]piperazine-1-carboxamide (33a, YM580) which exhibited the most potent antiandrogenic activity. Unlike bicalutamide, compound 33a decreased the weight of rat ventral prostate in a dose-dependent manner (ED(50) = 2.

[Lowered VIQ level following traumatic brain injury].

A patient with traumatic brain injury (TBI) is often associated with incidence of cognitive dysfunction as a sequela. We have conducted WAIS-R to 237 patients who were diagnosed as TBI at the Kanagawa Rehabilitation Hospital in order to assess their intellectual function. Twelve patients, whose VIQ being marked significantly lower than PIQ, were retrospectively analyzed in terms of their Functional Independence Measure (FIM), neuropsychological test results and lesions found in diagnostic images.

[Cognitive dysfunction in 32 diffuse axonal injury cases].

In acute stage of traumatic brain injury, it is not easy to diagnose diffuse axonal injury (DAI) by computer imaging. Even in chronic stage, DAIs occasionally show no remarkable abnormality by ordinal CT or MRI images. We retrospectively studied 32 DAI cases by the Functional Independence Measure (FIM), a battery of neuropsychological tests and CT or MRI films of acute and chronic phase.

Dynamic postural control in patients with hemiparesis.

Objective: Decreased postural stability is a common problem associated with hemiparesis secondary to stroke. The purpose of this study was to evaluate dynamic postural control in patients with hemiparesis and in normal subjects matched for age.

Design: Quantitative posturography (EquiTest System) was performed to assess the response of subjects to sudden perturbations.

[A case of falcotentorial meningioma with visual allesthesia].

Visual allesthesia, in which visual images are transposed from one homonymous half-field of visual field to another, is a rare phenomenon. Palinopsia is the persistence or recurrence of visual images after the exciting stimulus object has been removed. Some authors have reported these phenomena, but these pathophysiology has not been understood.

Enantio- and diastereocontrolled synthesis of (-)-iridolactone and (+)-pedicularis-lactone.

[structure: see text]. Two iridoid lactones, (-)-iridolactone and (+)-pedicularis-lactone, have been synthesized in an enantio- and diastereocontrolled manner starting from a tricyclic chiral building block serving as a synthetic equivalent of chiral 3-(hydroxymethyl)cyclopenta-2,4-dien-1-ol.

[Two cases of an intracranial large hemangiopericytoma associated with brain swelling in the early operative stage].

Intracranial hemangiopericytomas are hypervascular tumors. Consequently, resection of these tumors must occasionally be stopped owing to profuse bleeding. We report two cases of large intracranial hemangiopericytoma whose resection had to be stopped owing not to bleeding but to brain swelling.

[Unruptured aneurysm of the right sinus of Valsalva: a case report].

A previously healthy and asymptomatic 45-year-old woman was referred for evaluation of a heart murmur and an unusual dilatation in the aortic root. Transthoracic and transesophageal echocardiography, computed tomography, magnetic resonance imaging, and cardiac catheterization revealed an aneurysm with a maximum diameter of 6.0 cm in the right sinus of Valsalva.

Changes in proteasome activity following transient ischemia.

Succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide (Suc-LLVY-MCA) hydrolyzing activities of the 20S and 26S proteasomes in the gerbil cortex following transient forebrain ischemia were examined. Using extraction solutions without ATP, only 20S proteasome activity was noted after separation with glycerol gradient centrifugation. When these extracts were incubated with ATP and an ATP-regenerating system prior to glycerol gradient separation, both 20S and 26S proteasome activities were detected.

Lack of effect of transient ischemia on ubiquitin conjugation.

Ubiquitin-conjugating activities in the soluble fractions of gerbil cortex and hippocampus following transient ischemia were examined in vitro. Ten minutes of ischemia did not affect the ubiquitination of heat-denatured lysozyme both in the cortex and in the hippocampus. No reduction of the conjugating activities following ischemia was also confirmed using the partially purified ubiquitin conjugating enzymes from the cortex.

Increase in ubiquitin conjugates dependent on ischemic damage.

Insoluble ubiquitin conjugates (UC) in the mitochondrial fraction of the gerbil cortex were analyzed following transient forebrain ischemia. At 1 h of reperfusion after 2-10 min of ischemia, UC increased as the duration of ischemia was prolonged. Pre-treatment with pentobarbital, rather than post-treatment immediately after recirculation, reduced the increase of UC at 1 h of reperfusion following 5 min of ischemia.

[A case of visual allesthesia].

A case of visual allesthesia is reported. A thirty-year-old right-handed man with a right temporo-occipital arteriovenous malformation underwent the surgery for extirpation of the lesion. Postoperatively he had left homonymous hemianopsia.

[A case of pseudo-TSH.PRL-producing pituitary adenoma with secondary hypothyroidism].

A 24-year-old housewife presented with weight gain of about 30 kg, constipation and pitting edema of extremity nine years after having a thyroidectomy. Hormonal examination revealed low levels of serum T3 and T4 and high levels of serum TSH and PRL. She also had enlarged pituitary gland (pituitary hyperplasia) with suprasellar extension on CT and MRI image.