Mtc6/Ehg2 is a novel endoplasmic reticulum-resident glycoprotein essential for high-pressure tolerance.

Hydrostatic pressure is a common mechanical stressor that modulates metabolism and reduces cell viability. Eukaryotic cells have genetic programs to cope with hydrostatic pressure stress and maintain intracellular homeostasis. However, the mechanism underlying hydrostatic pressure tolerance remains largely unknown. We have recently demonstrated that Maintenance of telomere capping protein 6 (Mtc6) plays a protective role in the survival of the budding yeast Saccharomyces cerevisiae under hydrostatic pressure stress by supporting the integrity of nutrient permeases. The current study demonstrate that Mtc6 acts as an endoplasmic reticulum (ER) membrane protein. Mtc6 comprises two transmembrane domains, a C-terminal cytoplasmic domain, and a luminal region with 12 Asn (N)-linked glycans attached to it. Serial mutational analyses showed that the cytoplasmic C-terminal amino acid residues GVPS are essential for Mtc6 activity. Multiple N-linked glycans in the luminal region are involved in the structural conformation of Mtc6. Moreover, deletion of MTC6 led to increased degradation of the leucine permease Bap2 under hydrostatic pressure, suggesting that Mtc6 facilitates proper folding of nutrient permeases in the ER under the stress condition. We propose a novel model of molecular function in which the glycosylated luminal domain and cytoplasmic GVPS sequences of Mtc6 cooperatively support the nutrient permease activity.

Feasibility and perceptions of a benzodiazepine deprescribing quality improvement initiative for primary care providers in Japan.

BACKGROUND: Quality improvement (QI) initiatives in primary care in Japan are rare. One crucial area for QI is the appropriate prescription of benzodiazepines due to the large and growing elderly population in the country. OBJECTIVE: This study aimed to determine the feasibility and other perceptions of a Benzodiazepine receptor agonist medications (BZRAs) deprescribing QI initiative for primary care providers (PCPs) in Japanese primary care clinics. DESIGN: A qualitative study within a QI initiative. PARTICIPANTS: We recruited 11 semi-public clinics and 13 providers in Japan to participate in a BZRAs deprescribing initiative from 2020 to 2021. After stratifying the clinics according to size, we randomly allocated implementation clinics to either an Audit only or an Audit plus Coaching group. INTERVENTIONS: For the Audit, we presented clinics with two BZRAs-related indicators. We provided monthly web-based meetings for the Coaching to support their QI activities. APPROACH: After the nine-month initiative, we conducted semi-structured interviews and used content analysis to identify themes. We organized the themes and assessed the key factors of implementation using the Consolidated Framework for Implementation Research (CFIR) framework. KEY RESULTS: Audit plus Coaching was perceived as more valuable than Audit only intervention. Participants expressed intellectual curiosity about the QI initiative from resources outside their clinic. However, adopting a team-based QI approach in a small clinic was perceived as challenging, and selecting the indicators was important for meaningful QI. CONCLUSION: The small size of the clinic could be a potential barrier, but enhancing academic curiosity may facilitate QI initiatives in primary care in Japan. Further implementation trials are needed to evaluate the possibility of QI with more various indicators and a more extended period of time.

Traumatic tumor hemorrhage of inflammatory myofibroblastic tumor of the lung.

A 23-year-old female with a history of idiopathic epilepsy was found to have a right chest cavity shadow in a school health checkup 5 years before. CT revealed a thin-walled cavity lesion in the right middle lobe containing a ball-like mass, showing air crescent sign. After falling due to a seizure, she was transported by ambulance and admitted. CT revealed diffuse ground-glass opacities throughout the right lung field. Bronchoscopy revealed bloody bronchial alveolar lavage fluid. Due to the tumor hemorrhage, an elective simple right middle lobe resection was performed without complications. The initial immunohistochemical staining was negative for ALK using ALK1 clone; however, subsequent staining of ALK by D5F3 and 5A4 clone was positive. Immunostaining findings led to a diagnosis of inflammatory myofibroblastic tumor. The patient remains under regular observation and has experienced no recurrence over the 6-year postoperative period. This case contains two different points: the first is that a cavity lesion of inflammatory myofibroblastic tumor may cause traumatic bleeding and should be treated with caution; the second is that attention should be paid to differences in stainability among clones when diagnosing inflammatory myofibroblastic tumor.

Activation of CWI pathway through high hydrostatic pressure, enhancing glycerol efflux via the aquaglyceroporin Fps1 in Saccharomyces cerevisiae.

The fungal cell wall is the initial barrier for the fungi against diverse external stresses, such as osmolarity changes, harmful drugs, and mechanical injuries. This study explores the roles of osmoregulation and the cell-wall integrity (CWI) pathway in response to high hydrostatic pressure in the yeast Saccharomyces cerevisiae. We demonstrate the roles of the transmembrane mechanosensor Wsc1 and aquaglyceroporin Fps1 in a general mechanism to maintain cell growth under high-pressure regimes. The promotion of water influx into cells at 25 MPa, as evident by an increase in cell volume and a loss of the plasma membrane eisosome structure, activates the CWI pathway through the function of Wsc1. Phosphorylation of Slt2, the downstream mitogen-activated protein kinase, was increased at 25 MPa. Glycerol efflux increases via Fps1 phosphorylation, which is initiated by downstream components of the CWI pathway, and contributes to the reduction in intracellular osmolarity under high pressure. The elucidation of the mechanisms underlying adaptation to high pressure through the well-established CWI pathway could potentially translate to mammalian cells and provide novel insights into cellular mechanosensation.

Clinical outcome of ulcerative colitis with severe onset in children: a multicenter prospective cohort study.

BACKGROUND: As best practices for treating children with severe-onset ulcerative colitis remain controversial in the era of biologic agents, we prospectively investigated treatments and outcomes in a multicenter cohort. METHODS: Using a Web-based data registry maintained in Japan between October 2012 and March 2020, we compared management and treatment outcomes in an S1 group defined by a Pediatric Ulcerative Colitis Activity Index of 65 or more points at diagnosis with those in an S0 group defined by an index value below 65. RESULTS: Three hundred one children with ulcerative colitis treated at 21 institutions were included, with follow-up for 3.6 ± 1.9 years. Among them, 75 (25.0%) were in S1; their age at diagnosis was 12.3 ± 2.9 years, and 93% had pancolitis. Colectomy free rates in S1 were 89% after 1 year, 79% after 2, and 74% after 5, significantly lower than for S0 (P = 0.0003). Calcineurin inhibitors and biologic agents, respectively, were given to 53% and 56% of S1 patients, significantly more than for S0 patients (P < 0.0001). Among S1 patients treated with calcineurin inhibitors when steroids failed, 23% required neither biologic agents nor colectomy, similarly to the S0 group (P = 0.46). CONCLUSIONS: Children with severe ulcerative colitis are likely to require powerful agents such as calcineurin inhibitors and biologic agents; sometimes colectomy ultimately proves necessary. Need for biologic agents in steroid-resistant patients might be reduced to an extent by interposing a therapeutic trial of CI rather than turning to biologic agents or colectomy immediately.

Cerebral foreign body granulomas after mechanical thrombectomy: Two case reports and a review of the literature.

OBJECTIVES: A foreign body granuloma after an endovascular intervention is a rare complication. Some cases of foreign body granulomas, especially after coil embolization, have been reported. However, only four cases of foreign body granulomas after mechanical thrombectomy (MT) have previously been reported. The current study reports two cases of post-MT foreign body granulomas, including a biopsy-proven case. MATERIAL AND METHODS: Case 1: A 73-year-old woman presented with complete occlusion of the right middle cerebral artery. Cerebral angiography and MT were successfully performed with improvement in clinical symptoms. Left hemiparesis and a disturbance in attention appeared after discharge and progressed slowly. She was re-admitted to our hospital 120 days after cerebral infarction owing to foreign body granulomas diagnosed on biopsy. Case 2: A 78-year-old man presented with occlusion of the left cervical internal carotid artery and the left middle cerebral artery. Cerebral angiography, percutaneous transluminal angioplasty, and MT were successfully performed. On the 34th day, he experienced progressive consciousness disorder because of foreign body granulomas. Both cases were successfully treated with steroid therapy. RESULTS: MRI after steroid treatment showed the disappearance of most nodular lesions and improvement of the encephalopathy. CONCLUSIONS: The cause of the granuloma may be an allergic reaction to the hydrophilic polymers that peel from endovascular devices. Steroid therapy is an effective treatment; therefore, neurologists should consider this complication when neurological symptoms or signs on image appears or worsens. A reliable diagnosis is important for prompt treatment.

Feasibility and acceptability of advance care planning facilitated by nonphysician clinicians in Japanese primary care: Implementation pilot study.

Background: Implementation of advance care planning (ACP) is urgently needed in Japan, which is one of the most aging countries. This study tested the feasibility and acceptability of ACP facilitated by nonphysician clinicians, and identified barriers and enablers to implementing ACP into Japanese primary care. Methods: We trained 10 nonphysician clinicians (seven registered nurses, two medical social workers, and one care manager) in four primary care clinics as ACP facilitators. From April to June 2019, the trained facilitators had 19 ACP conversations with their patients. We conducted semistructured interviews and surveys regarding satisfaction and appropriateness of the ACP with patients, family members, ACP facilitators, and primary care physicians (PCPs) regarding their perceptions about ACP facilitated by nonphysician clinicians. Survey data were analyzed using descriptive statistics, and interviews were analyzed using a qualitative content analysis approach. Results: Majority of patients (75%) and family members (71%) were satisfied with ACP facilitated by nonphysician clinicians. In 71%, ACP facilitators and PCPs thought their ACP facilitation was appropriate and acceptable. Patients stated that they felt comfortable having ACP conversations with nonphysician clinicians. Identified barriers and enablers for ACP included: time restraints, size and organization of the clinics, settings for ACP conversations (ACP at the patient's home), team collaboration, and use of existing system to trigger ACP. Conclusions: Advance care planning facilitated by nonphysician clinicians was feasible and acceptable in Japanese primary care. Further studies are needed to explore strategies to overcome the barriers and enhance the enablers identified in this study.

Scratching and Stretching the Shrunken Cranial Dura for Primary Closure.

BACKGROUND: At craniotomy, the dura shrinks due to the drying effect of illumination and air exposure, rendering its primary closure difficult. When the opening is narrow, it can be patched with autologous grafts. However, tissue harvesting and meticulous suturing take time. As the cost-effectiveness of using dural substitutes is poor, we developed a new technique that involves dural scratching for the primary closure of dural openings. METHODS: We applied our technique because in 53 adults who underwent supratentorial craniotomy we encountered difficulties with the primary closure of a dural opening 5 mm or less in width. With a scalpel, we placed several fine scratches parallel to the edge of the opening on the surface of the dura, taking care not to perforate the deep layer. This relieved dural tension and the tissue was stretched enough to permit closing with sutures. RESULTS: Our technique achieved primary dural closure in 46 of 53 patients (87%) who primarily had undergone narrow supratentorial craniotomies. The other 7 additionally required small autologous grafts to patch narrow residual openings at the intersection of the durotomy. There were no procedure-related complications such as cerebrospinal fluid leakage and persistent headache due to tension of the closed dura. CONCLUSIONS: Dural scratching is simple, safe, requires no special instrumentation, facilitates primary closure of the shrunken dura by stretching, and reduces the need for patch grafting.

Feasibility of Preoperative Magnetic Resonance Angiography/Black-Blood Magnetic Resonance Imaging/Computed Tomography Fusion Imaging Without Contrast Agent for Carotid Endarterectomy.

BACKGROUND: Preoperative identification of the carotid bifurcation (CB) location and plaque and stenosis distal end of the cervical internal carotid artery in relation to bony structures is essential for carotid endarterectomy (CEA). However, for patients with contrast contraindications, cervical 3-dimensional computed tomography angiography (3D-CTA) is unavailable. In this study, we created fusion images of magnetic resonance angiography (MRA), black-blood (BB) magnetic resonance imaging (MRI), and CT to determine if these noncontrast agent images are superior to 3D-CTA for preoperative CEA planning. METHODS: The fusion images showed vascular structures obtained by MRA, plaque observed by BB-MRI, and bone structures shown by CT. Spatial localization accuracy was verified by directly overlaying contrast-enhanced 3D-CTA images on the fusion images. We validated this technique in 50 patients with unilateral ICA stenosis, 28 of whom underwent CEA. The 2D-distance CB MRA-CTA (the 2D distance difference between CB MRA and CB CTA perpendicular to the long axis of the carotid artery) was measured. We also compared the findings of the fusion image regarding the CB location and plaque distal end with the operative findings. RESULTS: The median 2D distance CB MRA-CTA was 1 mm. CB MRA was located distal and proximal to CB CTA in 21and 29 patients, respectively. The CB location and fusion-image plaque were consistent with the intraoperative findings in all CEA patients. CONCLUSIONS: Fusion images created from MRA, BB-MRI, and noncontrast CT were feasible as an alternative to 3D-CTA for patients with contrast contraindications.

Pull-Force Generated by the Revolving High-speed Drill Shaft Results in Unexpected Tissue Wrapping Around the Shaft.

BACKGROUND: Despite holding soft tissue away from high-speed drills during surgery, tissue can unexpectedly wrap around the drill shaft. We performed experiments to examine what precipitates such mishaps. METHODS: In a windless environment, a Signature Drill System (Stryker) featuring a 4-mm diameter coarse diamond or cutting bit was placed parallel to a suspended strip of polypropylene. The distance between the end of the strip and the drill shaft or bits was 4 or 8 mm. In another experiment, we placed the drill horizontally 10 mm above the top of dry-ice fog. The maximum drill speed was 75,000 rpm, and the horizontal motion of the polypropylene strip and the vertical motion of the dry-ice fog were recorded by a video camera. RESULTS: In the experiments, the strip parallel to the vertical shaft and the dry-ice fog were pulled toward the shaft; the higher the revolving drill speed, the faster its motion. On the other hand, in experiments where the end of the strip was next to either bit, no such motion was observed. CONCLUSIONS: The pulling force generated by revolving high-speed drill shafts may result in tissue wraparound even when soft tissue is held away from the shaft.

Using a Carpenter's Square to Localize Narrow or Multilayered Chronic Subdural Hematomas Diagnosed on Computed Tomography.

BACKGROUND: Chronic subdural hematomas (CSDHs) with narrow or multilayered hematomas must be accurately localized for burr hole drainage. We present a simple alternative localization method using conventional computed tomography (CT) scans acquired for the initial diagnosis and a commercially available carpenter's square (CS). METHODS: Using our novel method, we localized 77 narrow or multilayered CSDHs. A single burr hole site on the thickest portion of narrow hematomas or on the site allowing access to both the isolated superficial layer and the deep layer of multilayered hematomas was identified on axial CT images; the image was parallel to the orbitomeatal line (OML). On the target CT slice, the level from the OML and from the surface of the forehead to the intended burr hole (sagittal distance) was measured. The OML and the level of the CT target slice were marked using the CS. Then, the CS was placed at the marked target level; the 2 edges of the CS were situated on the frontal and temporal scalp and parallel to the OML and the sagittal line. The sagittal distance was then marked. RESULTS: All burr holes reached the CSDHs. The mean deviation of the burr holes was 4.7 mm inferior and 1.4 mm anterior to the intended site. In 65 instances (84.4%), a deviation within 10 mm was observed in both the superoinferior and the anteroposterior directions. CONCLUSIONS: Our simple and inexpensive method can localize narrow or multilayered CSDHs with acceptable accuracy and increases the efficiency of routine clinical work.

Substrate-induced differential degradation and partitioning of the two tryptophan permeases Tat1 and Tat2 into eisosomes in Saccharomyces cerevisiae.

Tryptophan is a relatively rare amino acid whose influx is strictly controlled to meet cellular demands. The yeast Saccharomyces cerevisiae has two tryptophan permeases, namely Tat1 (low-affinity type) and Tat2 (high-affinity type). These permeases are differentially regulated through ubiquitination based on inducible conditions and dependence on arrestin-related trafficking adaptors, although the physiological significance of their degradation remain unclear. Here, we demonstrated that Tat2 was rapidly degraded in an Rsp5-Bul1-dependent manner upon the addition of tryptophan, phenylalanine, or tyrosine, whereas Tat1 was unaffected. The expression of the ubiquitination-deficient variant Tat25K>R led to a reduction in cell yield at 4 µg/mL tryptophan, suggesting the occurrence of an uncontrolled, excessive consumption of tryptophan at low tryptophan concentrations. Eisosomes are membrane furrows that are thought to be storage compartments for some nutrient permeases. Tryptophan addition caused rapid Tat2 dissociation from eisosomes, whereas Tat1 distribution was unaffected. The 5 K > R mutation had no marked effect on Tat2 dissociation, suggesting that dissociation is independent of ubiquitination. Interestingly, the D74R mutation, which was created within the N-terminal acidic patch, stabilized Tat2 while reducing the degree of partitioning into eisosomes. Moreover, the hyperactive I285V mutation in Tat2, which increases Vmax/Km for tryptophan import by 2-fold, reduced the degree of segregation into eisosomes. Our findings illustrate the coordinated activity of Tat1 and Tat2 in the regulation of tryptophan transport at various tryptophan concentrations and suggest the positive role of substrates in inducing a conformational transition in Tat2, resulting in its dissociation from eisosomes and subsequent ubiquitination-dependent degradation.

Laboratory-size x-ray microscope using Wolter mirror optics and an electron-impact x-ray source.

We developed a laboratory-size three-dimensional water-window x-ray microscope using condenser and objective grazing incidence Wolter type I mirrors, an electron-impact-type x-ray source, and a back-illuminated CCD. The imaging system was improved for practical applications in life science research fields. Using a new objective mirror with reduced figure errors, a resolution limit of 3.1 line pairs/µm was achieved for two-dimensional transmission images and sub-micrometer-scale three-dimensional structures were resolved. Incorporating a cryogenic stage into the x-ray microscope, we observed biological samples embedded in ice to evaluate the usefulness of observation in the water-window region and multi-energy observation was demonstrated using an x-ray source with multiple x-ray tubes.

The Boy:Girl Ratio of Children Diagnosed with Growth Hormone Deficiency-Induced Short Stature Is Associated with the Boy:Girl Ratio of Children Visiting Short Stature Clinics.

BACKGROUND: About twice as many boys as girls undergo growth hormone (GH) therapy in GH deficiency (GHD). However, this sex difference may not correctly reflect a real incidence. OBJECTIVES: We analyzed the evidence of a selection bias whereby more boys seek treatment at short stature clinics. SUBJECTS AND METHODS: The present study included 3,902 children who visited 17 short stature clinics with a height SD score of -2 SD or less. The percentage of children who underwent the GH stimulation test was compared between boys and girls, as was the percentage of children ultimately diagnosed with GHD. RESULTS: The children comprised 2,390 boys (61.3%) and 1,512 girls (38.7%), with a boy:girl ratio of 1.58:1. The percentage of children who underwent the GH stimulation test did not differ between boys (45.7%) and girls (49.8%). Among the children who underwent the GH stimulation test, the percentage diagnosed with GHD did not differ significantly between boys (22.0%) and girls (20.1%). The boy:girl ratio of children diagnosed with GHD was 1.59:1. CONCLUSIONS: The boy:girl ratio of children with short stature (1.58:1) did not differ significantly from that of children diagnosed with GHD (1.59:1). These results indicate that the predominance of boys in GHD does not reflect a real incidence, but rather a selection bias whereby a higher proportion of boys with short stature seek treatment at clinics. This difference arises because parents are more concerned about boys' height, and because boys reach adult height at an older age.

[Anterior Interosseous Nerve Palsy with Isolated Flexion Palsy of the Thumb or Index Finger as an Initial Symptom:Two Case Reports].

Case 1: A 73-year-old man who had undergone neurolysis for right cubital tunnel syndrome complained of difficulty using chopsticks. Froment's sign test showed that the interphalangeal(IP)joint of the right thumb that had flexed preoperatively was extended. This finding was considered to indicate recovery from ulnar neuropathy, and the patient was closely followed up. One year later, the patient was unable to push a camera shutter button and was unable to flex the IP joint of the thumb and the distal interphalangeal(DIP)joint of the index finger, a characteristic symptom of anterior interosseous nerve(AIN)palsy. Therefore, the patient underwent AIN neurolysis and subsequently reported slight improvement in his condition. Case 2: A 60-year-old woman reported difficulty performing computer mouse clicks with her right hand. As flexing the index finger DIP joint was difficult, a local lesion was suspected, and the patient was closely followed up. One year later, the patient was unable to push the button of a ballpoint pen with her thumb. Extension of the thumb and index finger indicated AIN palsy. The patient refused treatment and was only followed up. The following year, the patient reported that the weakness improved. Simultaneous flexion palsy of the thumb and index finger can lead to a diagnosis of AIN palsy. However, flexion palsy of a single finger in incomplete AIN palsy, as reported here, is often overlooked because of its similarity to the flexor tendon rupture. Awareness regarding this incomplete form of AIN palsy is needed for early and correct diagnosis.

Aneurysms Arising from Persistent Arteries in the Vertebrobasilar Paramedian Longitudinal Axis: Two Case Reports.

A 50-year-old man and a 69-year-old woman with consciousness disturbance were diagnosed to have suffered from subarachnoid hemorrhage (SAH) involving the posterior fossa. In both cases, the initial 3D CT angiogram failed to reveal the SAH source in the vertebrobasilar system. Delayed 3D rotational angiography revealed aneurysms on unfamiliar aberrant arteries. One was a dissecting aneurysm located between the proximal part of the posterior inferior cerebellar artery and the distal part of the intracranial vertebral artery. It was trapped and resected; the patient subsequently presented with lateral medullary symptoms. The other aneurysm was between the distal posterior and the distal anterior inferior cerebellar artery. It was successfully embolized; there were no complications. We think that the aberrant aneurysm-harboring vessels encountered in these two patients were primitive arteries on or adjacent to the vertebrobasilar paramedian longitudinal axis and that they persisted past the embryologic stage. Such aneurysms arising from unfamiliar persistent arteries beside the brainstem are extremely rare but must be considered when the SAH source is not detected in the trunk of the vertebrobasilar system.

Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry.

BACKGROUND/AIMS: There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children. METHODS: This was a cross-sectional multicenter registry study of newly diagnosed Japanese pediatric IBD patients. The Paris classification was used to categorize IBD features, and results were compared with published EUROKIDS data. RESULTS: A total of 265 pediatric IBD patients were initially registered, with 22 later excluded for having incomplete demographic data. For the analysis, 91 Crohn's disease (CD), 146 ulcerative colitis (UC), and 6 IBD-unclassified cases were eligible. For age at diagnosis, 20.9% of CD, 21.9% of UC, and 83.3% of IBD-unclassified cases were diagnosed before age 10 years. For CD location, 18.7%, 13.2%, 64.8%, 47.3%, and 20.9% were classified as involving L1 (ileocecum), L2 (colon), L3 (ileocolon), L4a (esophagus/stomach/duodenum), and L4b (jejunum/proximal ileum), respectively. For UC extent, 76% were classified as E4 (pancolitis). For CD behavior, B1 (non-stricturing/non-penetrating), B2 (stricturing), B3 (penetrating), and B2B3 were seen in 83.5%, 11.0%, 3.3%, and 2.2%, respectively. A comparison between Japanese and European children showed less L2 involvement (13.2% vs. 27.3%, P< 0.01) but more L4a (47.3% vs. 29.6%, P< 0.01) and L3 (64.8% vs. 52.7%, P< 0.05) involvement in Japanese CD children. Pediatric perianal CD was more prevalent in Japanese children (34.1% vs. 9.7%, P< 0.01). CONCLUSIONS: Upper gastrointestinal and perianal CD lesions are more common in Japanese children than in European children.

Amino acid homeostatic control by TORC1 in Saccharomyces cerevisiae under high hydrostatic pressure.

Mechanical stresses, including high hydrostatic pressure, elicit diverse physiological effects on organisms. Gtr1, Gtr2, Ego1 (also known as Meh1) and Ego3 (also known as Slm4), central regulators of the TOR complex 1 (TORC1) nutrient signaling pathway, are required for the growth of Saccharomyces cerevisiae cells under high pressure. Here, we showed that a pressure of 25 MPa (∼250 kg/cm2) stimulates TORC1 to promote phosphorylation of Sch9, which depends on the EGO complex (EGOC) and Pib2. Incubation of cells at this pressure aberrantly increased glutamine and alanine levels in the ego1Δ, gtr1Δ, tor1Δ and pib2Δ mutants, whereas the polysome profiles were unaffected. Moreover, we found that glutamine levels were reduced by combined deletions of EGO1, GTR1, TOR1 and PIB2 with GLN3 These results suggest that high pressure leads to the intracellular accumulation of amino acids. Subsequently, Pib2 loaded with glutamine stimulates the EGOC-TORC1 complex to inactivate Gln3, downregulating glutamine synthesis. Our findings illustrate the regulatory circuit that maintains intracellular amino acid homeostasis and suggest critical roles for the EGOC-TORC1 and Pib2-TORC1 complexes in the growth of yeast under high hydrostatic pressure.

[Lymphorrhea at the Site of Repeated Fascia Lata Harvesting:A Case Report].

This 74-year-old man had undergone a third re-operation for anaplastic meningioma in the convexity six weeks before he was referred to us. He presented with a bulge on the lateral aspect of the left thigh. We observed a fresh fascia lata harvesting scar that extended peripherally from an old proximal scar. The bulge was colorless. The aspirated subcutaneous fluid(more than 200mL)was watery and yellowish;there was no evidence of abscess or hematoma. Although the bulge shrank after aspiration and the placement of a compression bandage, it recurred in three days. Surgery-associated lymphorrhea was the diagnosis given. Goreisan, a herbal medicine for hydrostatic modulation, was administered. One week later, the bulge diminished in size. Harvesting of the fascia lata in the lateral aspect of the thigh is usually safe. However, additional dissection and peripheral extension due to repeated harvesting risks damaging the superficial lymphatic pathways because of scar formation after earlier surgeries and the hyperdense distribution of the lymphatic pathways in the peripheral part. When subcutaneous fluid collection after fascia lata harvesting is refractory, lymphorrhea must be considered in the differential diagnosis.

[Successful unrelated cord blood transplantation for extensive meningeal juvenile xanthogranuloma developing after treatment of Langerhans cell histiocytosis in a child].

A 2-year and 4-month-old boy developed Langerhans cell histiocytosis (LCH) at the left parietal region of the skull. After treatment with chemotherapy, the patient achieved remission but experienced three relapses. After 3 years, he complained of headache, blurred vision, and lethargy. Brain magnetic resonance imaging revealed multiple dura-based meningeal masses. Biopsy was performed, and the patient was then diagnosed with juvenile xanthogranuloma (JXG). The analysis of both LCH/JXG tissues revealed BRAF V600E mutation. The JXG masses were not responsive to prednisolone, which was injected locally, radiotherapy (24 Gy), and chemotherapy (2-chlorodeoxy-adenosine). In addition, since the patient developed macrophage activation syndrome associated with systemic JXG progression, he received unrelated cord blood transplantation (u-CBT) at the age of 10 years and 11 months. Engraftment was performed at day 42, and significant GVHD was not observed. Four months after CBT, the patient was treated with infliximab (Remicade®) and dexamethasone palmitate (Limethasone®). The size of the intracranial JXG masses gradually decreased after u-CBT and disappeared after 4 years. Currently, the patient is doing well at the age of 25 years and is receiving androgen replacement therapy.