Protein S deficiency is an autosomal dominant disorder that results from mutations in the protein S gene (PROS1). Inherited deficiency of protein S constitutes a risk factor for venous thromboembolism. Protein S functions as a nonenzymatic cofactor for activated protein C in the proteolytic degradation of coagulation factors V a and Villa. The frequency of protein S deficiency seems to differ between populations. More than 200 rare mutations in PROS1 have been identified in patients with protein S deficiency. Among the prevalent mutations within PROS1, the S460P substitution (known as Heerlen polymorphism) detected in Caucasians and the K196E substitution (known as protein S Tokushima) found in Japanese have been intensively studied for their structures and potential functions in the disorder of protein S deficiency. Until now, causative mutations in PROS1 have been found in only approximately 50% of cases with protein S deficiency. Co-segregation analysis of microsatellite haplotypes with protein S deficiency in families with protein S deficiency suggests that the causative defects in the PROS1 mutation-negative patients are located in or close to the PROS 1 gene. Large PROS 1 gene deletions have been identified in 3 out of 9 PROS 1 mutation-negative Swedish VTE families with protein S deficiency and 1 out of 6 PROS1 mutation-negative Japanese patients with protein S deficiency. Intensive sequencing of the entire PROS 1 gene, including introns, may be needed to identify the cryptic mutations in those patients, and these efforts might uncover the pathogenesis of protein S deficiency.

Patients with focal hand dystonia demonstrate abnormally increased corticospinal excitability, which has been reported to be ameliorated, at least for a short term, with low frequency repetitive transcranial magnetic stimulation (rTMS). Transcranial direct current stimulation (tDCS), which is less costly and easier to apply than rTMS, is also known to modulate cortical excitability. Especially with cathodal tDCS, cortical excitability can be reduced. On the other hand, upper extremity splinting is also known to reduce dystonic symptoms by inhibiting abnormal movement. We therefore combined cathodal tDCS with finger splinting to treat focal hand dystonia in a 34-year-old man with traumatic brain injury who showed involuntary movement of his right fingers during writing and chopsticks use. After 5 days of cathodal tDCS sessions (1mA, 10min), he was encouraged to use interphalangeal joint splints for his thumb and index finger during these activities. We assessed computer-rated handwriting, reciprocal inhibition and intracortical inhibition before, 24 hours and 3 months after the 5-day tDCS sessions. Before the treatment, his flexor pollicis longus (FPL) and first dorsal interosseous (FDI) muscles showed 4Hz rhythmic hyperactivity during writing, and reciprocal inhibition at interstimulus intervals (ISI) of 20 and 100 ms were lost. Paired pulse TMS also revealed disinhibited short interval intracortical inhibition (SICI) at an ISI of 2 and 3 ms. The 5-day tDCS sessions reduced FPL and FDI EMG activities, and SICI and RI at 20 and 100 ms were also restored. Wearing the finger splints, these improvements were maintained at the 3-month follow-up. This case report is the first to demonstrate the possible long-term effects of tDCS combined with splinting for focal hand dystonia. It is supposed that splinting after tDCS plays an important role in making the tDCS aftereffects last longer.

We investigate the effects of training and detraining on the satellite cell activation in thoroughbred horse muscles after an exhaustive exercise. Six horses were subjected to conventional training for 18 weeks and detraining for 6 weeks. Before training (Pre), after 10-week and 18-week training (10Tr and 18Tr), and after 6-week detraining (DTr), an incremental exercise test (IET) was performed on inclined treadmill to measure VO₂max and the velocity at a plasma lactate of 4 mmol/l (VLA4). Biopsy samples from gluteus medius muscle was obtained before and at 1 minute (1min), 3 hour (3hr), 6 hour (6hr) and 1 day after each IET. Number of muscle satellite cell were counted in type identified muscle fibers by immuno-histochemical stain images. The levels of mRNA expressions were determined using real time RT-PCR system. The number of satellite cells in 10Tr was significantly higher in type IIa fibers (0.31±0.10) than Pre (0.15±0.06). As compared to each value before IET, IL-6 mRNA expression (fold change) increased remarkably at 6hr after IET in 10Tr (x 2290.2) and 18Tr (x 2304.2), but not in both Pre (x 260.0) and DTr (x 853.3). IGF-I and Myogenin mRNA expressions were significantly increased at 1 day after IET in 18Tr (x 6.6 and x 3.3), but not in both Pre and DTr. These results suggested that the increased reactivity of satellite cells by training for 18 weeks is almost disappeared after detraining for 6 week, as well as VO₂max and VLA4.

We report a rare case of severe aortic regurgitation after mitral valve replacement (MVR) and tricuspid annuloplasty (TAP). An 83-year-old woman underwent MVR and TAP for mitral regurgitation and secondary tricuspid regurgitation. The early postoperative course was not eventful until 6 days after surgery. However, 7 days after surgery, she suffered from acute heart failure and transthoracic echocardiography showed severe aortic regurgitation. We performed a second operation 13 days after the first surgery. Intraoperatively, we found the annulus suture of the TAP just under the NCC-RCC commissure of the aortic valve. We speculated that the suture pulled the aortic valve annulus, resulting in severe aortic regurgitation. We removed the suture and replaced the aortic valve with bioprosthetic artificial valve. Postoperative recovery was uneventful, and she was discharged 22 days after the second surgical procedure.

To ensure public trust in health professions, it is imperative for health professionals to understand the concept of conflict of interest (COI) in health professions education and manage it appropriately. However, there are not enough formal curricula on COI in health professions education in Japan. We propose an educational curriculum on COI in health professions education which focuses on relationship between physicians and for-profit corporations. We hope that this proposed curriculum stimulates educational activities on the ground while taking context into account. We also hope the proposed curriculum leads to the formal incorporation of COI in health professions education and educational policies nationwide.

The yips represent a disorder that makes it challenging for an individual to perform automatic and coordinated movements in sports activities. The cause of the yips is not sufficiently clarified, and limited information is available regarding throwing yips in baseball. Therefore, this study was designed to clarify the incidence and characteristics of the throwing yips among college baseball players. Total 107 players of the college baseball team participated in the study and completed the questionnaire by answering questions about their experience of the yips (loss of control to throw the ball accurately for more than 1 month), the symptom intensity, and changes observed in the symptoms in different situations. The 47.1% of players met the definition of throwing yips. The symptoms of the yips were more pronounced with short-distances and low intensity of throwing. Moreover, there were various subjective symptoms, such as the issue about co-contraction of the upper limb, sensory function, body ownership, and movement planning. Various physical symptoms associated with throwing yips suggest that the yips are not only a disorder of motor skills, but result from movement disorders. The present results show that the occurrence of the yips depends on the throwing condition; this finding provides useful insights into the mechanism and the treatment of the yips. Interdisciplinary studies that aim to elucidate the cause of the yips and develop effective intervention are necessary.