Simple classification of carotid bifurcation: is it possible to predict twisted carotid artery during carotid endarterectomy?

Background: The internal carotid artery (ICA) usually runs posterolaterally to the external carotid artery (ECA), but occasionally we encounter the twisted carotid bifurcation, a variant in which the ICA courses medially to the ECA during carotid endarterectomy (CEA). Prediction of this anomaly in the preoperative evaluation is mandatory, although descriptions in the literature are limited. We reviewed the clinical features of patients who underwent CEA and analyzed preoperative cerebral angiography, especially the anteroposterior (AP) view to determine whether it could be a predictive modality. Methods: In 58 consecutive CEA cases, we simply classified them into three groups; type 1 (the ICA runs laterally and the ECA runs medially), type 2 (the ICA and ECA run to overlap each other), and type 3 (the ICA runs medially and the ECA runs laterally), based on the findings of AP view of cerebral angiography. We compared the clinical features and intraoperative findings of these groups. Results: Of 58 cases, types 1–3 were 24, 30, and four cases, respectively. Twisted carotid bifurcations were recognized in seven cases (12.4 %), including three cases in type 2 and four in type 3, and all twisted cases were found on the right side. Twisted carotids and right-sided lesion were significantly frequent in type 3, but no statistical differences of coexisting diseases were recognized among the three groups. CEAs of twisted carotid bifurcations were performed successfully with correction of the carotid position in three and as it was in four cases. Conclusions: Twisted carotid bifurcations were observed during operation in 10 % in type 2 and 100 % in type 3. CEA of twisted carotid bifurcations can be performed safely with or without correction of the carotid position. AP view of cerebral angiography could be useful for preoperative evaluation. © 2016 Springer-Verlag WienEmbargo Period 12 month

Transcriptome Analysis of the Hierarchical Response of Histone Deacetylase Proteins That Respond in an Antagonistic Manner to Salinity Stress

Acetylation in histone and non-histone proteins is balanced by histone acetyltransferase and histone deacetylase (HDAC) enzymatic activity, an essential aspect of fine-tuning plant response to environmental stresses. HDACs in Arabidopsis are composed of three families (RPD3-like, SIRT, and HD-tuins). A previous study indicated that class I (HDA19) and class II (HDA5/14/15/18) RPD3-like family HDACs control positive and negative responses to salinity stress, respectively. Furthermore, quintuple hda5/14/15/18/19 mutants (quint) exhibit salinity stress tolerance, suggesting that hda19 suppresses the sensitivity to salinity stress present in quadruple hda5/14/15/18 mutants (quad). In the present study, transcriptome analysis of the quint mutant was conducted to elucidate the hierarchical control of salinity stress response operated by RPD3-like family HDACs (HDA5/14/15/18/19). The analysis identified 4,832 salt-responsive genes in wild-type (Col-0), hda19-3, quad, and quint plants and revealed that 56.7% of the salt-responsive genes exhibited a similar expression pattern in both the hda19-3 and quint plants. These results indicate that deficiency in HDA19 has a bigger impact on salinity stress response than in class II HDACs. Furthermore, the expression pattern of genes encoding enzymes that metabolize phytohormones raises the possibility that a drastic change in the homeostasis of phytohormones, such as abscisic acid, brassinosteroid, and gibberellin, may contribute to increasing stress tolerance in hda19-3 and quint plants. Among these phytohormones, abscisic acid accumulation actually increased in hda19-3 and quint plants, and decreased in quad, compared with wild-type plants. Importantly, 7.8% of the salt-responsive genes in quint plants exhibited a similar expression pattern in quad plants, suggesting that some gene sets are regulated in an HDA5/14/15/18-dependent manner. The transcriptome analysis conducted in the present study revealed the hierarchical and independent regulation of salt stress response that is mediated through HDA19 and class II HDACs

Identification of the ultrahigh-risk subgroup in neuroblastoma cases through DNA methylation analysis and its treatment exploiting cancer metabolism

神経芽腫の新たな診断法と治療戦略を創出 --がん細胞の生存戦略「がん代謝」を逆用する--. 京都大学プレスリリース. 2022-11-02.Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed the DNA methylation and expression datasets of neuroblastomas, extracted a candidate gene characterizing the aggressive features, and conducted functional studies. Based on the DNA methylation data, we identified a subgroup of neuroblastoma cases with 11q loss of heterozygosity with extremely poor prognosis. PHGDH, a serine metabolism-related gene, was extracted as a candidate with strong expression and characteristic methylation in this subgroup as well as in cases with MYCN amplification. PHGDH inhibition suppressed neuroblastoma cell proliferation in vitro and in vivo, indicating that the inhibition of serine metabolism by PHGDH inhibitors is a therapeutic alternative for neuroblastoma. Inhibiting the arginine metabolism, which is closely related to serine metabolism using arginine deiminase, had a combination effect both in vitro and in vivo, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. Expression and metabolome analyses of post-dose cells confirmed the synergistic effects of treatments targeting serine and arginine indicated that xCT inhibitors that inhibit cystine uptake could be candidates for further combinatorial treatment. Our results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma

Functional characterization of the regulators of calcineurin in Candida glabrata

The serine-threonine-specific protein phosphatase calcineurin is a key mediator of various stress responses in fungi. Herein, we characterized functions of the endogenous regulators of calcineurin (RCNs), Rcn1 and Rcn2, in the pathogenic fungus Candida glabrata. Rcn1 exerted both inhibitory and stimulatory effects on calcineurin signaling, but Rcn2 displayed only inhibitory activity. Phenotypic analyses of C. glabrata strains lacking either RCNs, calcineurin, or both revealed that calcineurin requires Rcn1, but not Rcn2, for antifungal tolerance in C. glabrata

The glycosylphosphatidylinositol-linked aspartyl protease Yps1 is transcriptionally regulated by the calcineurin-Crz1 and Slt2 MAPK pathways in Candida glabrata.

In the pathogenic fungus Candida glabrata, the YPS1 gene, which encodes a glycosylphosphatidylinositol-linked aspartyl protease, is required for cell wall integrity and virulence. Although the expression of YPS1 has been studied in Saccharomyces cerevisiae, the transcriptional regulation of this gene in C. glabrata is not well understood. Here, we report that C. glabrata Yps1 is required for cell growth at elevated temperatures, and that the heat-induced expression of YPS1 is regulated predominantly by the calcineurin-Crz1 pathway and partially by the Slt2 MAPK pathway. Although a total of 11 YPS genes are present in the C. glabrata genome, the loss of transcriptional induction in a calcineurin mutant was observed only for YPS1. The results of a YPS1 promoter-lacZ reporter assay using a series of constructs with mutated promoter elements indicated that the transcription factor Crz1 binds to multiple sites in the promoter region of YPS1. To date, as none of the putative Crz1 targets in C. glabrata have been characterized using a Δcrz1 mutant, monitoring the expression of YPS1 represents an effective method for measuring the activity of the calcineurin-Crz1 signaling pathway in this fungus

Surgical Outcomes of Pediatric Patients with Asymptomatic Tethered Cord Syndrome

Study Design: A retrospective cohort study. Purpose: To examine the validity of prophylactic surgery for children with tethered cord syndrome (TCS). Overview of Literature: Prophylactic surgery for pediatric patients with TCS remains controversial. Methods: We retrospectively analyzed the surgical outcomes of 14 children (nine boys and five girls) with asymptomatic TCS who were surgically treated at Hokkaido University Hospital between 1989 and 2015. Results: The median age at the time of initial surgery for asymptomatic TCS was 28.6 months (range, 0-66 months). The median final follow-up period was 142 months (range, 7-232 months). Of the 14 children with asymptomatic TCS, 12 had lumbosacral lipoma and two had meningocele. According to the classification of spinal lipoma, two children had dorsal type, four had caudal type, two had transitional type, and four had filar type. There were no children with lipomyelomeningocele. All children were free of neurological symptoms until 94 months after the initial surgery. Subsequently, one child exhibited delayed neurological deficits and underwent a second surgery because of motor and sensory disturbances; slight sensory disturbance was noted at the final follow-up examination. Another child later showed bowel and bladder dysfunction. However, a second surgery was not performed for this child because his motor and sensory functions were normal; hence, we chose to avoid nerve injury in the case of dissecting adhesion. Conclusions: All 14 children with asymptomatic TCS were free of neurological symptoms until 94 months after the initial surgery. However, two children exhibited delayed neurological deficits at 94 months and 177 months. We believe that prophylactic surgery for asymptomatic TCS is effective for a certain period. However, because the natural history of TCS is poorly understood, strict follow-up after surgery is necessary

Nonsuture dural repair using polyglycolic acid mesh and fibrin glue: clinical application to spinal surgery

Background: In spinal surgery, repair of the dura is difficult when it is torn, fragile, or is ossified as in cases with OPLL. We report our experience with a non-suture dural repair technique in patients undergoing spinal surgery; it employs a dura substitute composed of polyglycolic acid (PGA) mesh and fibrin glue. Here we report the efficacy and safety of non-suture duroplasty using PGA mesh and fibrin glue (PGA-fibrin sheet). Methods: The artificial dura mater is composed of a PGA-fibrin sheet. The dural defect is covered with a patch sprayed with fibrin glue without suturing to the dura mater. We first evaluated this technique in an experimental study by performing water leakage tests. Between May 2001 and January 2005 we used it in 160 spinal surgeries that required intraoperative dura repair. Results: Our preliminary tests showed that the threshold for water pressure without leakage was 161 ± 42 mmHg and 96.5 ± 32 mmHg when the unsprayed margin around the perimeter of the patch was 5 mm and 2 mm, respectively. Of the 160 operated patients, 10 (6.3%) experienced subcutaneous CSF leakage. Of these, 6 required a second operation, in the other 4 the CSF collection diminished spontaneously. There were no other complications such as allergic reaction, adhesion, or infection. Conclusion: In combination with CSF diversion, the PGA-fibrin sheet is a viable alternative method for dural repair in spinal surgery

Ad Creative Discontinuation Prediction with Multi-Modal Multi-Task Neural Survival Networks

Discontinuing ad creatives at an appropriate time is one of the most important ad operations that can have a significant impact on sales. Such operational support for ineffective ads has been less explored than that for effective ads. After pre-analyzing 1,000,000 real-world ad creatives, we found that there are two types of discontinuation: short-term (i.e., cut-out) and long-term (i.e., wear-out). In this paper, we propose a practical prediction framework for the discontinuation of ad creatives with a hazard function-based loss function inspired by survival analysis. Our framework predicts the discontinuations with a multi-modal deep neural network that takes as input the ad creative (e.g., text, categorical, image, numerical features). To improve the prediction performance for the two different types of discontinuations and for the ad creatives that contribute to sales, we introduce two new techniques: (1) a two-term estimation technique with multi-task learning and (2) a click-through rate-weighting technique for the loss function. We evaluated our framework using the large-scale ad creative dataset, including 10 billion scale impressions. In terms of the concordance index (short: 0.896, long: 0.939, and overall: 0.792), our framework achieved significantly better performance than the conventional method (0.531). Additionally, we confirmed that our framework (i) demonstrated the same degree of discontinuation effect as manual operations for short-term cases, and (ii) accurately predicted the ad discontinuation order, which is important for long-running ad creatives for long-term cases