The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells.

Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.

Relationship between evacuation after the Great East Japan Earthquake and new-onset hyperuricemia: A 7-year prospective longitudinal study of the Fukushima Health Management Survey.

INTRODUCTION: On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. However, the effect of evacuation on the new-onset of hyperuricemia have not been sufficiently elucidated. This study assessed the association between evacuation and new-onset hyperuricemia after the earthquake based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective. MATERIALS AND METHODS: This is a 7-year prospective longitudinal study included 18,140 residents (6,961 men and 11,179 women) with non-hyperuricemia who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between new-onset hyperuricemia and lifestyle- and disaster-related factors, including evacuation, were estimated using a Cox proportional hazards regression model analysis. Hyperuricemia was defined as uric acid levels > 7.0 mg/dL for men and > 6.0 mg/dL for women. RESULTS: During a median follow-up of 4.3 years, 2,996 participants (1,608 men, 23.1%, 1,388 women, 12.4%) newly developed hyperuricemia. Significant associations were observed between evacuation and onset of hyperuricemia in women (adjusted hazard ratio 1.18, 95% confidence interval, 1.05-1.32, p = 0.007), but not in men (adjusted hazard ratio 1.11, 95% confidence interval, 0.99-1.24, p = 0.067). DISCUSSION: Evacuation after a natural disaster is an independent risk factor for the new-onset of hyperuricemia in women. The possibility of hyperuricemia developing in response to natural disasters should be considered.

Facilitators and barriers in implementing the nurse practitioner role in Japan: A cross-sectional descriptive study.

AIM: To investigate the distribution of nurse practitioners (NPs) across Japan and their perceived facilitators and barriers to NP implementation in Japan. BACKGROUND: NP certification examinations have been conducted in Japan since 2011, and by 2020, there were 487 NPs in the country. The momentum of NP implementation is slower in Japan compared with other countries. METHODS: A cross-sectional descriptive study, following the STROBE guidelines, was conducted. Web-based survey questionnaires, developed by the authors, were administered to 248 NPs whose email addresses were maintained by the certification management body. RESULTS: Valid responses were obtained from 101 NPs (response rate: 40.7%), of which 34% were male. The respondents had more than 12 years of registered nurse experience on an average before enrolling in the graduate NP program. 53% were employed as NPs from the beginning, while 25% were initially employed as registered nurses and later advanced to NPs, and 11% still worked as RNs. A majority worked in hospitals with beds. Many NPs perceived the lack of NP national licensure and reimbursement benefits as barriers to NP implementation, whereas recognition from superiors and organizations was considered facilitators. CONCLUSIONS: Despite their small numbers in Japan, NPs take on crucial tasks and contribute to the appropriate distribution of medical resources. The NP licensure system and recognition from superiors and organizations may be necessary to promote NP roles in Japan. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Some certified NPs still work as registered nurses. Recognition from nursing and organization administrators is critical to implementing NPs. To this end, a reimbursement system benefiting the organizations and a legislation facilitating NP employment are required.

Unruptured cerebral aneurysms with the segmental duplicated middle cerebral artery formed a fenestrated structure at origin.

BACKGROUND: Middle cerebral artery (MCA) has a significantly lower incidence of anatomical variations than other intracranial arteries. We present an extremely rare case of unruptured aneurysms with the segmental duplicated MCA (d-MCA) formed a fenestrated structure at origin. CASE DESCRIPTION: A 55-year-old female underwent direct surgery for the unruptured aneurysms at the top of the right internal cerebral artery with d-MCA. The d-MCA branches separated at the right internal cerebral artery top and had comparable with that of the main MCA trunk. Moreover, there was an anastomosis between the d-MCA branches. We diagnosed this anastomosis as segmental d-MCA. Two aneurysmal domes were identified during surgery at the origin of the d-MCA, which the main dome protruding backward was wide necked and another small one was collapsed or thrombosed protruding forward. We used a fenestrated clip for the posterior projecting dome, and the aneurysms were successfully obliterated. CONCLUSION: Although cerebral aneurysms associated with d-MCA are rare, there are technical difficulties in the surgical management. A fenestrated clip might be most reasonable to obtain patency of the parent arteries for the posterior projecting aneurysms if the perforators can be avoided.

Preliminary evaluation of dual imaging plate intraoral radiography.

PURPOSE: This study evaluated the contrast-to-noise ratio (CNR), spatial resolution, and subjective quality of dual imaging plates (DIP) intraoral radiography. METHODS: The DIP and conventional single IP (CSIP) methods both used YCR DT-1 imaging plates (Yoshida Co.). The DIP, comprising a front IP (FIP) and back IP (BIP), was constructed. DIP images were synthesized from the FIP and BIP images. An aluminum step phantom was used to measure the CNR. A line pair gauge was used to measure the spatial imaging resolution. A phantom comprising a porcine mandible embedded in acrylic resin was used for subjective evaluation. RESULTS: The CNR of the DIP image was 32% higher than that of the FIP image. The spatial resolution achieved using the FIP, DIP, and CSIP was highly comparable except above 4 line pairs/mm, where that of the CSIP was highest. In subjective evaluation, the noise in the DIP images was significantly lower than in those obtained using the FIP and CSIP. CONCLUSION: The CNR of the DIP was higher than that of the FIP. The decrease in spatial resolution of the DIP was limited. The subjective image quality of the DIP was higher than that of the FIP.

[Asymptomatic Aplastic or Twig-Like Middle Cerebral Artery Associated with Unruptured Cerebral Aneurysms at the Origin (A1) of a Collateral Artery and the Anterior Communicating Artery: A Case Report with Multiple Intracranial Atherosclerotic Stenoses].

We report a rare case of asymptomatic aplastic or twig-like middle cerebral artery (Ap/T-MCA) with small unruptured aneurysms at the origin (A1) of the anomalous collateral artery containing plexiform (twig-like) networks and in the anterior communicating artery. In Ap/T-MCA, other cerebrovascular systems are usually considered to exhibit normal findings not associated with atherosclerosis. At first admission, atherosclerotic M1 occlusion was suspected because of the patient's risk factors and multiple stenoses in major intracranial arteries. Cerebral blood flow (CBF) studies revealed reduction of resting CBF and vascular reserve in the ipsilateral MCA territory. After 5 years, a diagnosis of Ap/T-MCA was reached based on detailed image examination and intraoperative findings during aneurysm clipping in combination with extracranial-intracranial (EC-IC) bypass. It should be noted that atherosclerosis can coexist with Ap/T-MCA, which is considered a congenital anomaly in which bleeding often occurs due to a ruptured aneurysm within the fragile collateral vessels. In previous reports, A1 aneurysms at the origins of the collateral arteries ruptured even when they were small. Aggressive radical surgery using EC-IC bypass can be considered for the treatment of unruptured aneurysms associated with Ap/T-MCA, but further research is needed. (Received September 14, 2020; Accepted November 4, 2020; Published 1 April, 2021).

Carotid Endarterectomy Using Lone Star Retractor System.

Cervical carotid disease is typical atherosclerosis, which is responsible for ischemic stroke. The effectiveness of carotid endarterectomy (CEA) for advanced carotid stenosis has been established in many large studies, and CEA is the gold standard in surgical treatment. On the other hand, endovascular carotid artery stenting (CAS) has become increasingly popular recently. It is very important to avoid any complications to maintain the effectiveness of CEA. The retractor device is important for the exposure of carotid arteries and for the safe surgical manipulation. We have started to use lone star retractor system (LSRS) to deploy the surgical field. LSRS provides the usability to handle and a shallower surgical field without the disturbance of surgical manipulation. And it can facilitate exposure of the distal internal carotid artery because surgeon can retract freely in whole circumference by towing with moderate strength. LSRS may bring the smoother and easier surgical manipulations in CEA.

Evacuation after the Great East Japan Earthquake is an independent factor associated with hyperuricemia: The Fukushima Health Management Survey.

BACKGROUND AND AIMS: On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. This study assessed the association between evacuation and hyperuricemia based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective. METHODS AND RESULTS: This cross-sectional study included 22,812 residents (9391 men and 13,297 women) who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between hyperuricemia and lifestyle- and disaster-related factors including evacuation were estimated using a logistic and liner regression analysis. With hyperuricemia defined as uric acid levels >7.0 mg/dL for men and >6.0 mg/dL for women, significant associations were observed between evacuation and hyperuricemia in men (the multivariate-adjusted odds ratio 1.20, 95% confidence interval, 1.05-1.36, p = 0.005), but not in women. In the multivariate-adjusted multiple liner regression analysis, evacuation had significant and positive associations with uric acid levels both in men (ß = 0.084, p = 0.002) and women (ß = 0.060, p < 0.001). CONCLUSION: Evacuation after a natural disaster is an independent factor associated with hyperuricemia.

Morphological characteristics of interalveolar septum and mandible in BMAL1 gene knockout mice.

PURPOSE: Circadian rhythm is associated with the pathogenesis of systemic disease and bone mineral metabolism. This study aimed to radiographically evaluate morphological characteristics of the interalveolar septum in circadian rhythm deficient animals. METHODS: Heads of 10 brain and muscle arnt-like protein-1 (BMAL1)-knockout (KO) mice and 10 wild-type mice sacrificed at 36 weeks were imaged using micro-computed tomography. The mean depth from the cementoenamel junction to the alveolar ridge (virtual bone sounding: VBS) of the interalveolar septum between the first and second molars, and the bone mineral density (BMD) of the interalveolar septum and the mandibular inferior cortex region were calculated. Tooth diameter was also measured. RESULTS: The VBS of the interalveolar septum in the BMAL1-KO mice was significantly deeper than that in wild-type mice. The BMD in the BMAL1-KO mice was significantly lower than in the wild-type mice in both regions. No significant difference was observed in tooth diameter between BMAL1-KO and wild-type mice. CONCLUSION: These results suggest that low BMD in the interalveolar septum accelerates bone resorption in the interalveolar septum in BMAL1-KO mice.

Evaluation of cone-beam computed tomography over a small field of view in a water bath based on the modulation transfer function with repeating-edge oversampling.

PURPOSE: The spatial resolution of cone-beam computed tomography (CBCT) in small fields of view (FOVs) is important for clinical applications. However, it is difficult to measure spatial resolution reliably due to error factors such as noise. The aim of this study was to obtain a modulation transfer function (MTF) more accurately. METHODS: A CBCT apparatus was used with small FOV. An aluminum pipe slightly tilted at an inclination ratio of 77/3 (25.7) was used as the measurement phantom. The MTF was calculated from the edge image of the phantom. The actual oversampling ratio was determined by regression analysis. The experiment was repeated 16 times and the edge-spread function (ESF) was approximated by the least-square method. Furthermore, a low-pass filter (LPF) was applied to eliminate the component at frequencies above the Nyquist frequency. Finally, the MTF was calculated from the pre-processed ESF. RESULTS: Results showed that pre-processing reduced the noise of the ESF. The MTFs at frequencies of 1.0 and 2.0 LP/mm were 0.59 and 0.18, respectively, in air and 0.52 and 0.16, respectively, in water. CONCLUSION: The repeating-edge oversampling method combined with ESF pre-processing improved the accuracy of the MTF under clinically relevant conditions with a phantom.

[Orbital Compartment Syndrome Perhaps Secondary to Intra-Orbital Fluid Retention and Orbital/Palpebral Emphysema Following Frontotemporal Craniotomy for an Unruptured Cerebral Aneurysm:A Case Report].

A 58-year-old woman underwent left frontotemporal craniotomy for clipping of an unruptured cerebral aneurysm. A small defect was accidentally created in the orbital roof intraoperatively. The patient developed left eyelid edema and ocular pain after recovery from anesthesia. The following day, the eyelid edema worsened, and she had difficulty opening her eyes. On the 9th postoperative day, she noticed diminished visual acuity and diplopia in her left eye when she was able to spontaneously open her eyes. Ophthalmological evaluation revealed mild left visual loss, decreased light reflex, ophthalmoplegia, ptosis, and chemosis. Computed tomography(CT)/magnetic resonance imaging revealed left proptosis, optic nerve stretching, intra-orbital fluid retention, and orbital/palpebral emphysema. She was diagnosed with orbital compartment syndrome(OCS)and received conservative treatment;however, her visual acuity did not improve. OCS observed after cerebral aneurysm surgery is rare;to date, only 24 cases have been reported in the available literature. Although the mechanism of OCS after craniotomy is unclear, it may be attributed to ocular compression by a muscle flap or increased intra-orbital pressure secondary to venous congestion. In the present case, the left superior ophthalmic vein and cavernous sinus were not clearly visualized on CT angiography. Therefore, we concluded that the right superior ophthalmic vein and superficial facial veins underwent dilatation and served as collateral circulation of the left orbital venous system. We speculate that OCS occurred secondary to increased intra-orbital pressure, possibly caused by inflow of cerebrospinal fluid with air into the orbit through a small bone defect that was accidentally created during craniotomy in a setting of orbital venous congestion.

[A Case of M2 Segment Dissection of the Middle Cerebral Artery Presenting with Deep White Matter Infarction Triggered by Minor Head Injury].

Herein, we report a rare case of a dissecting aneurysm of the M2 segment of the middle cerebral artery(MCA), presenting with a deep white matter infarction triggered by minor head injury. A 31-year-old woman was admitted to our hospital with headache and vomiting 3 hours after a mild head impact. A magnetic resonance angiogram obtained 10 months earlier, when the patient had complained of sudden headache, showed mild fusiform dilatation of the left M2 segment. On admission, computed tomography angiography(CTA)revealed irregular fusiform dilatation of the superior trunk of the left M2. Magnetic resonance imaging showed an intramural hematoma on the wall of the left M2 and acute infarction in the left deep white matter. Eight days after admission, CTA revealed further dilation of the aneurysm, and it was diagnosed as a dissecting aneurysm. The patient was successfully treated with proximal clipping and superficial temporal artery(STA)-MCA(M4)bypass on day 15. Bypass to a cortical M4 recipient was performed after the efferent M4 was identified using indocyanine green videoangiography. Four weeks postoperatively, the patient was discharged without any neurological deficits. The M2 dissecting aneurysm gradually regressed, and the bypass remained patent for 10 months postoperatively. To our knowledge, this is the first case of a dissecting M2 aneurysm treated by proximal clipping and STA-MCA bypass. This procedure seems a feasible option when the distal portion of the dissected MCA is difficult to expose.

[Early Development of a Symptomatic Expanding Porencephalic Cyst in the Hematoma Cavity after Subcortical Hematoma Removal in an Adult:A Case Report].

A 69-year-old woman presented on an emergency basis, with headache and left hemiparesis. Initial head CT at the time of admission revealed a large subcortical hematoma with perihematomal edema extending from the right parietal to the occipital lobe. A small part of the hematoma extended toward the trigone of the right lateral ventricle. CT angiography revealed no vascular abnormalities. Emergency craniotomy was erformed, and the patient's initial postoperative course was unremarkable. However, the patient's neurological symptoms worsened 10 days postoperatively, and CT revealed a new low-density cystic lesion with perifocal edema at the site of hematoma removal, in addition to severe cerebral compression. We performed a reoperation, and intraoperatively we observed hematoma fluid mixed with cerebrospinal fluid without any abnormal blood vessels or neoplastic lesions in the hematoma cavity. We identified the choroid plexus deep within the surgical field, and slight leakage of cerebrospinal fluid was detected from the ventricular aspect, indicating the formation of a small passage between the hematoma cavity and the ventricle. After the second operation, her postoperative course was uneventful without recurrent cyst formation. An early symptomatic expanding porencephalic cyst in the hematoma cavity after removal of an intracerebral hematoma is rare, and only a few cases have been reported in the literature. Based on literature review and considering the likely mechanism of cyst development, we speculated that progressive cyst expansion could be attributed to a check valve mechanism between the ventricle and the cavity from which the hematoma was removed, as observed in the present case.

[Ruptured Cerebral Aneurysm Associated with Arachnoid Cyst].

Cerebral aneurysms and arachnoid cysts are relatively common cerebral malformations and the use of recent modalities has increased their detection rates. However, cerebral aneurysms associated with arachnoid cysts are unusual. We describe two cases of ruptured cerebral aneurysms associated with arachnoid cysts. According to previous reports, clinical presentation may sometimes be unusual, as cysts can prevent subarachnoid hemorrhage. Moreover, in some cases, CT may reveal typical arachnoid cysts without subarachnoid hemorrhage, without intracystic hematoma, or with subdural hematoma alone. These clinical presentations and radiologic findings can lead to delayed diagnosis of subarachnoid hemorrhage. Therefore, we should consider the coexistence of arachnoid cyst in case of a warning sign of aneurysm rupture.

[Task-shifting Carried out by an Emergency Department's Stroke Hotline and Medical Care Support Conducted by Nurse Practitioners].

Our hospital serves as the main hub for eight remote island hospitals(RIHs)in Nagasaki Prefecture, Japan. The shortage of stroke physicians, which has led to overwork, is a major concern. Several "task-shifting" systems were adopted to avoid physician burnout. First, the emergency department established a hotline system for receiving emergency calls regarding a stroke, and which managed initial care until the stroke physicians arrived(called the Nagasaki Medical Center stroke hotline system: N-SHOT)in 2014. The rt-PA administration rate increased from 3.3% in the Pre-N-SHOT group to 6.7% in the N-SHOT group. Second, the 'isolated islands stroke hotline system(I-SHOT)', with which physicians in RIHs participate in cooperation with N-SHOT, was started in 2017. After I-SHOT was introduced, the number of patients treated with the drip and ship method using teleradiology and 24-h helicopter transportation increased from 20(2010-2016)to 29 cases in 2017-2018. Additionally, new information and communication technology(ICT)using smart devices was introduced into the teleradiology system for task support. Third, on behalf of stroke physicians, nurse practitioners(NP)helped bedridden patients who had been delivered from RIHs and who had received acute treatment, and returned to their islands by helicopter or airplane as transitions of care. N-SHOT is smoothly operated by each hospital department without reducing the quality of the stroke hotline. It has contributed to an increase in rt-PA and mechanical thrombectomy cases; I-SHOT has had the same effect. Task-shifting and task support with N- & I-SHOT, the smooth transfer system by NP, and the new ICT are considered to be useful for reducing the overall burden of stroke physicians.

[A Case of Radiation-induced Glioblastoma 29 Years after Treatments for Germinoma].

Intracranial germinomas are considered one of the most radiosensitive tumors and are curable by radiotherapy alone. Although patients can expect long-term survival, the adverse effects of radiotherapy and late sequelae in survivors are a major concern. Radiation-induced secondary neoplasms are one of those sequelae and are a serious concern because they are often connected directly with life prognosis. We describe a case of radiation-induced glioblastoma after radiotherapy for germinoma. An 11-year-old boy with basal ganglia germinoma was successfully treated with postoperative cranial irradiation. At the age of 40 years, he was admitted to our hospital for aphasia and memory disturbance. CT and MRI revealed a tumor in the left parietal lobe with dissemination. The tumor of the parietal lobe was removed surgically, and pathohistologically, it was diagnosed as glioblastoma. Long-term survivors who receive radiotherapy for germinomas in childhood are at risk for late complications, including radiation-induced neoplasms. Therefore, careful follow-up neurological examinations are recommended in these patients, even 20-30 years after radiotherapy.

[A Rare Case of Communicating Hydrocephalus with Intraparenchymal Pericatheter Cyst and Surrounding Edema in an Adult due to Accidental Change in the Pressure Setting of the Programmable Shunt System].

A 59-year-old woman suffering from memory impairment visited our hospital. She was discharged nine years ago without complications after undergoing neck clipping surgery for intracranial aneurysm rupture and a right ventricular peritoneal shunt using the CODMAN® HAKIM® programmable valve system(CHPV)for hydrocephalus. Initial CT/MRI revealed a cystic lesion with surrounding edema in the right frontal lobe around the proximal catheter, and a left frontal subacute subdural hematoma. The right ventricle was shown as a slit as before. The cystic portion presented with an MRI signal of the same intensity as the cerebrospinal fluid(CSF), and no enhancement effect was observed. It was thought to be a CSF cyst around the shunt catheter with interstitial CSF edema. Skull radiographs showed an accidental change in the CHPV pressure setting(100 to 190mmH2O), possibly due to head impact. We concluded that the newly set valve pressure caused sudden shunt dysfunction, resulting in CSF cyst formation and surrounding edema. Image findings and her symptoms were immediately improved on adjusting the shunt valve. This complication in adults associated with shunt dysfunction is very rare and only 10 cases have been reported to date. This is the first report of this complication due to an accidental reset of CHPV. To prevent the risk of misdiagnosing this condition as a tumor or abscess and performing unnecessary surgery, it is always necessary to suspect the possibility of this complication. For that purpose, detailed images, including diffusion-weighted images and contrast-enhanced MRI, should be done early in clinical practice.

Use of experimental phantoms to determine the accuracy and reliability of mandibular cortical width measurements by panoramic radiography and cone-beam computed tomography.

The present study used an aluminum phantom to calculate accurate vertical magnification values around the mental foramen on panoramic radiography (PR) and compared corrected PR (Cor-PR) thickness measurements of the aluminum phantom and mandibular cortical width (MCW) of the human head with cone-beam computed tomography (CBCT) measurements at two fields of view (FOVs). The calculated vertical magnification value for PR around the mental foramen was 1.37. Measurements of the aluminum phantom significantly differed between Cor-PR and CBCT with an FOV of 100 mm and between CBCT with FOVs of 40 and 100 mm; however, MCW measurements did not significantly differ among the three methods. There was a very strong correlation between Cor-PR and CBCT with an FOV of 40 mm and between CBCT with FOVs of 40 mm and 100 mm, and intraobserver and interobserver agreement was good-to-excellent for all methods. These results suggest that Cor-PR and CBCT with small and large FOVs are acceptable for measuring MCW.