Brain-controlled cycling system for rehabilitation following paraplegia with delay-time prediction

Objective: Robotic rehabilitation systems have been investigated to assist with motor dysfunction recovery in patients with lower-extremity paralysis caused by central nervous system lesions. These systems are intended to provide appropriate sensory feedback associated with locomotion. Appropriate feedback is thought to cause synchronous neuron firing, resulting in the recovery of function. Approach: In this study, we designed and evaluated an ergometric cycling wheelchair, with a brain-machine interface (BMI), that can force the legs to move by including normal stepping speeds and quick responses. Experiments were conducted in five healthy subjects and one patient with spinal cord injury (SCI), who experienced the complete paralysis of the lower limbs. Event-related desynchronization (ERD) in the β band (18‐28 Hz) was used to detect lower-limb motor images. Main results: An ergometer-based BMI system was able to safely and easily force patients to perform leg movements, at a rate of approximately 1.6 seconds/step (19 rpm), with an online accuracy rate of 73.1% for the SCI participant. Mean detection time from the cue to pedaling onset was 0.83±0.31 s Significance: This system can easily and safely maintain a normal walking speed during the experiment and be designed to accommodate the expected delay between the intentional onset and physical movement, to achieve rehabilitation effects for each participant. Similar BMI systems, implemented with rehabilitation systems, may be applicable to a wide range of patients

Rattractor-Instant guidance of a rat into a virtual cage using the deep brain stimulation.

We developed "Rattractor" (rat attractor), a system to apply electrical stimuli to the deep brain of a rat as it stays in a specified region or a virtual cage to demonstrate an instant electrophysiological feedback guidance for animals. Two wire electrodes were implanted in the brains of nine rats. The electrodes targeted the medial forebrain bundle (MFB), which is a part of the reward system in the deep brain. Following the recovery period, the rats were placed in a plain field where they could move freely, but wired to a stimulation circuit. An image sensor installed over the field detected the subject's position, which triggered the stimulator such that the rat remained within the virtual cage. We conducted a behavioral experiment to evaluate the sojourn ratio of rats residing in the region. Thereafter, a histological analysis of the rat brain was performed to confirm the position of the stimulation sites in the brain. Seven rats survived the surgery and the recovery period without technical failures such as connector breaks. We observed that three of them tended to stay in the virtual cage during stimulation, and this effect was maintained for two weeks. Histological analysis revealed that the electrode tips were correctly placed in the MFB region of the rats. The other four subjects showed no apparent preference for the virtual cage. In these rats, we did not find electrode tips in the MFB, or could not determine their positions. Almost half of the rats tended to remain inside the virtual cage when position-related reward stimuli were triggered in the MFB region. Notably, our system did not require previous training or sequential interventions to affect the behavioral preferences of subjects. This process is similar to the situation in which sheep are chased by a shepherd dog in the desired direction

Cyclin D1 harboring the T286I mutation promotes oncogenic activation in endometrial cancer

金沢大学医薬保健研究域医学系Cyclin D1 is an important regulator of cell cycle progression. Phosphorylation of cyclin D1 at Thr286 by GSK3β triggers its nuclear export and cytoplasmic proteolysis via the 26S proteasome. Cyclin D1 overexpression is a common event in various types of human cancers; however, reports of mutations are extremely rare. We analyzed mutations of the cyclin D1 gene, CCND1, in 88 endometrial cancer tissue specimens and detected mutations in 2 cases (2.3%). Both were unreported mutations with substitution of threonine to isoleucine at codon 286 (T286I). These two tumors harbored coexisting mutations in K-ras, PIK3CA and/or PTEN and showed accumulation of cyclin D1 in the nucleus by immunohistochemistry. Furthermore, we analyzed the functions of mutant cyclin D1 (T286I) by luciferase assays, immunofluorescence, western blotting and clonogenic cell survival assays in HEK-293T cells. We found that exogenous mutant cyclin D1 (T286I) accumulated in the nuclei in HEK-293T cells, and that it inhibited the expression of pRb. Additionally, the number of colonies was increased by introduction of mutant cyclin D1 (T286I) compared to that of wild-type cyclin D1. In conclusion, we identified an unreported CCND1 mutation (T286I) in two endometrial cancers and revealed that the mutation was functional for inducing cell proliferation in human cells

A novel micro-ECoG recording method for recording multisensory neural activity from the parietal to temporal cortices in mice

Abstract Characterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (μ)-electrocorticography (μECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped μECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current μECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel μECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the μECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the μECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our μECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques

Expression of DBC1 is associated with nuclear grade and HER2 expression in breast cancer

金沢大学医薬保健研究域医学系DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumor-suppressor gene cloned from breast cancer specimens and is reported to regulate p53-dependent apoptosis through its specific inhibition of SIRT1 deacetylase. Although SIRT1 plays a pivotal role in carcinogenesis by regulating cellular proliferation, survival and death, its role in breast cancer remains controversial. Therefore, we aimed to investigate the expression status and clinicopathological significance of DBC1 and SIRT1 in breast cancer tissues. We evaluated the expression of DBC1 and SIRT1 in breast core-needle biopsy specimens from 48 primary breast cancer patients between 2005 and 2008. These patients were treated with primary systemic chemotherapy and subsequent surgical resection of the lesions. Immunohistochemical expression scores of DBC1 and SIRT1 were evaluated, and the relationship between their expression levels and clinicopathological features of breast cancer was analyzed. The expression was observed exclusively in the nuclei of normal and neoplastic ductal cells. In breast biopsy specimens, positive expression of DBC1 and SIRT1 was noted in 85 and 98% of patients, respectively. Expression of DBC1 was significantly associated with the tumor nuclear grade (P=0.019). DBC1 and SIRT1 expression was inversely correlated with HER2 expression (P=0.026 and 0.003, respectively). Lower expression of DBC1 and SIRT1 indicated a tendency for a favorable pathological response to chemotherapy, although this was not statistically significant. Our results reveal that the expression of DBC1 and SIRT1 in breast tissues is associated with tumor characteristics. © 2011 Spandidos Publications Ltd

Putative tumor suppression function of SIRT6 in endometrial cancer

AbstractSIRT6, a member of the sirtuin family, has been identified as a candidate tumor suppressor. To pursue the role of SIRT6 in endometrial cancer, we investigated the anti-tumorigenic function of SIRT6. The expression of SIRT6 negatively affected the proliferation of AN3CA and KLE endometrial cancer cells. Increased expression of SIRT6 resulted in the induction of apoptosis by repressing the expression of the anti-apoptotic protein survivin. Consistent with this result, a survivin inhibitor YM155 efficiently inhibited cellular proliferation and induced apoptosis. These results revealed that SIRT6 might function as a tumor suppressor of endometrial cancer cells

Risk of endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia treated with total laparoscopic hysterectomy

Objective: Distinguishing atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) is often difficult, and patients with a preoperative diagnosis of AEH are sometimes diagnosed with EC after hysterectomy. In this study, we assessed the risk factors for EC in patients who underwent total laparoscopic hysterectomy (TLH) with a preoperative diagnosis of AEH. Patients and methods: We retrospectively analyzed 20 patients with a preoperative diagnosis of AEH using endometrial cytology, biopsy (fractional and total curettage), and hysteroscopic inspection. Results: Four of 20 (20%) patients were diagnosed with EC after TLH, all of whom had endometrioid adenocarcinoma Grade 1 and Stage IA without lymph node metastasis. Four of seven (57%) patients who were highly suspected of having EC by three diagnostic modalities (cytology, fractional curettage, and by hysteroscopy) were diagnosed with EC after TLH, whereas none of the 13 without any suspicious findings in these examinations were diagnosed with EC (p=0.007 by Fisher's exact test). Hysteroscopic findings were positive (suspicious of EC) in six of 11 patients tested, including all four EC patients. However, either endometrial cytology or fractional curettage alone failed to predict cancer in two EC patients. All four EC patients were also suspected of having EC by total curettage. Ovarian preservation was performed in 12 (60%) patients. Three of the four EC patients received subsequent surgery, including pelvic lymphadenectomy. Conclusion: Careful preoperative examinations, including hysteroscopy, might be useful to evaluate the risk of EC. Accordingly, we should be still careful about the possibility of overdiagnosis in patients with AEH