Knockdown of vps54 aggravates tamoxifen-induced cytotoxicity in fission yeast

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)‒positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) ‘biological process’ terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including ‘cell cycle’ (cdc2, rik1, pas1, and leo1), ‘signaling’ (sck2, oga1, and cki3), and ‘vesicle-mediated transport’ (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the ‘signaling’ GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

Neurodevelopmental Problems in Non-Syndromic Craniosynostosis

Craniosynostosis is the premature fusion of calvarial sutures, resulting in deformed craniofacial appearance. Hence, for a long time, it has been considered an aesthetic disorder. Fused sutures restrict growth adjacent to the suture, but compensatory skull growth occurs to accommodate the growing brain. The primary goal for the management of this craniofacial deformity has been to release the constricted skull and reform the distorted shape of the skull vault. However, the intellectual and behavioral prognosis of affected children has also been taken into consideration since the beginning of the modern era of surgical management of craniosynostosis. A growing body of literature indicates that extensive surgery, such as the whole-vault cranioplasty approach, would result in better outcomes. In addition, the age at treatment is becoming a major concern for optimal outcome in terms of cosmetic results as well as neurodevelopment. This review will discuss major concerns regarding neurodevelopmental issues and related factors.

Multiple Spontaneous Intracerebral Hematoma without Presenting Risk Factors

The incidence of intracerebral hemorrhage in those aged 45–84 years is 0.3-0.5%. In people over 80 years of age, this incidence increases 25-fold compared with that of the total population. The most common causes of spontaneous intracerebral hemorrhage in the younger population are vascular malformation, aneurysm, and overuse of drugs. In contrast, common causes in the elderly include hypertension, tumors, and coagulation disorders. Here, we present a case involving a 72-year-old male patient who, without any of these predisposing conditions, was admitted to the hospital with spontaneous intracerebral hemorrhage and showed signs of multifocal intracerebral hemorrhage during his stay. We conclude that spontaneous intracerebral hemorrhage can occur without any predisposing factors, and can lead to a patient's death. Therefore, the possibility of recurrent spontaneous intracerebral hemorrhage must be considered in patients with primary spontaneous intracerebral hemorrhage.

Cognitive Outcome of Pediatric Moyamoya Disease

Quality of life is the current trend and issue for the most of human diseases. In moyamoya disease (MMD), surgical revascularization has been recognized as the possible assistance to reduce the neurological insult. However, the progressive nature of the disease has been invincible so far. To improve the quality of life of MMD patients not only the protection from the neurological insult but also the maintenance or improvement of cognitive function is inevitable. For pediatric MMD patients, younger age or longer duration of disease is the key factor among the prognostic factors for bad neurological outcomes. Hence, 'the earlier, the better' is the most precious rule for treatment. Protection from neurological insult is very critical and foremost important to improve cognitive outcome. Clinicians need to know the neuropsychological profile of MMD patients for the care of whole person and make an effort to protect the patients from neurological insults to maintain or improve it.

Immediate Revision Surgery due to Post-Anterior Cervical Discectomy and Fusion (ACDF) Spinal Epidural Hematoma

Anterior cervical discectomy and fusion(ACDF) is a surgical treatment for cervical radiculopathy and myelopathy. Though this is a common surgery, spinal epidural hematomas occur rarely and an immediate treatment decision and surgical decompression are required in this situation. In this report, we discuss the proper treatment of spinal epidural hematoma after ACDF.

Immediate Revision Surgery due to Post-Anterior Cervical Discectomy and Fusion (ACDF) Spinal Epidural Hematoma

Anterior cervical discectomy and fusion(ACDF) is a surgical treatment for cervical radiculopathy and myelopathy. Though this is a common surgery, spinal epidural hematomas occur rarely and an immediate treatment decision and surgical decompression are required in this situation. In this report, we discuss the proper treatment of spinal epidural hematoma after ACDF.

Correction of Coronal Imbalance in Degenerative Lumbar Spine Disease Following Direct Lateral Interbody Fusion (DLIF)

OBJECTIVE: The authors have recently been using a surgical technique of minimally invasive direct lateral interbody fusion (DLIF) for correcting of coronal imbalance. The purpose of this study was to evaluate the surgical outcome and complication of DLIF. METHODS: We undertook retrospective analysis of a consecutive series of 8 DLIF procedures in Degenerative lumbar spine disease since May 2011. Four patients underwent DLIF only, and the others underwent combined DLIF and posterior fixation. Data on intra- and postoperative complications were collected. The pre- and postoperative X-rays were reviewed. We investigated coronal deformity, Cobb's angle, and apical vertebral translation (AVT). The mean follow-up period was months with a range of 2 to 8 months. RESULTS: A mean preoperative coronal Cobb's angle was 21.8degrees (range 11.5-32.4degrees). Following after DLIF, the mean Cobb's angle was decreased to 13.0degrees (range 2.9-21.5degrees). Following additional posterior screw fixation, mean Cobb's angle was further decreased to 7.4degrees (range 2.9-13.2degrees). A mean preoperative AVT was 2.0 cm(range 0.6-3.5 cm), and improved to 1.4 cm(range 0.3-2.4 cm) and 0.8 cm(range 0.2-1.8 cm) postoperatively (DLIF and, posterior fixation respectively). One patient (12.5%) showed cage migration during follow-up period. Two patients (25%) developed motor weakness, and 4 patients (50%) experienced postoperative thigh paresthesias or dysesthesias. During follow up period, motor weakness had resolved in 1 patient. Sensory symptoms were improved in all patients at the last follow-up. CONCLUSION: Degenerative lumbar disease can be effectively corrected by DLIF with acceptable complications.