Real-time identification of two substrate-binding intermediates for the light-driven sodium pump rhodopsin.

Membrane transport proteins undergo critical conformational changes during substrate uptake and release, as the substrate-binding site is believed to switch its accessibility from one side of the membrane to the other. Thus, at least two substrate-binding intermediates should appear during the process, that is, after uptake and before the release of the substrate. However, this view has not been verified for most transporters because of the difficulty in detecting short-lived intermediates. Here, we report real-time identification of these intermediates for the light-driven outward current-generating Na+-pump rhodopsin. We triggered the transport cycle of Na+-pump rhodopsin using a short laser pulse, and subsequent formation and decay of various intermediates was detected by time-resolved measurements of absorption changes. We used this method to analyze transport reactions and elucidated the sequential formation of the Na+-binding intermediates O1 and O2. Both intermediates exhibited red-shifted absorption spectra and generated transient equilibria with short-wavelength intermediates. The equilibria commonly shifted toward O1 and O2 with increasing Na+ concentration, indicating that Na+ is bound to these intermediates. However, these equilibria were formed independently; O1 reached equilibrium with preceding intermediates, indicating Na+ uptake on the cytoplasmic side. In contrast, O2 reached equilibrium with subsequent intermediates, indicating Na+ release on the extracellular side. Thus, there is an irreversible switch in "accessibility" during the O1 to O2 transition, which could represent one of the key processes governing unidirectional Na+ transport.

Comparative study of HO-1 expressing synovial lining cells between RA and OA.

OBJECTIVES: We aimed to clarify the characteristics of heme oxygenase (HO)-1 expressing cells in the synovium from rheumatoid arthritis (RA) and osteoarthritis (OA), and to investigate the co-expression of HO-1 and IgG-Fc/HLA-DR complex. METHODS: The characteristics of HO-1 expressing cells in the synovium were investigated by using immunohistochemistry. The co-expression of HO-1 and IgG-Fc/HLA-DR complex was examined by an in situ proximity ligation assay (PLA) with immunofluorescence. HO-1 mRNA was investigated by reverse transcription-polymerase chain reaction. RESULTS: The number of HO-1+ cells from the RA synovium is higher than that from OA synovium. The double positive cells of HO-1 and IgG-Fc/HLA-DR complex were detected by the in situ PLA with immunofluorescence in RA synovium. HO-1 mRNA was detected in both RA and OA synovium. CONCLUSION: A portion of HO-1+ cells with IgG-Fc/HLA-DR complex in lining layer of RA may be concluded as one of antigen presenting cells in RA and may be involved in production of RF.

New prognostic score for the survival of patients with esophageal squamous cell carcinoma.

PURPOSE: Recent studies have shown that the modified Glasgow Prognostic Score (mGPS), which is an inflammation-based prognostic score, is useful as a prognostic index for some cancer cases. The purpose of this study was to create a prognostic scoring system for patients with esophageal squamous cell carcinoma (ESCC) that was more independent and sensitive than the mGPS. METHODS: One hundred sixty-eight patients who had undergone esophagectomy for ESCC were included in the study. The new mGPS (NmGPS) was calculated based on the following cutoff values: CRP >0.75 mg/dL indicated NmGPS 1 or 2, depending on the absence or presence of hypoalbuminemia (<3.5 g/dL); and CRP ≤0.75 mg/dL indicated NmGPS 0. We also performed an analysis based on cutoff values of 0.5 and 0.25 mg/dL for CRP. RESULTS: Only the NmGPS with a cutoff CRP value of 0.5 mg/dL was able to divide into three independent patient groups in the survival curves. In the multivariate analyses, a NmGPS (CRP cutoff; 0.5 mg/dL) of 2 was a more significant independent prognostic factor (HR 4.437, 95 % CI 2.000-9.844, p = 0.0002) than a mGPS of 2 (HR 2.726, 95 % CI 1.021-7.112, p = 0.0449). CONCLUSIONS: The new prognostic score NmGPS (CRP cutoff; 0.5 mg/dL) was more independent and sensitive than the mGPS for patients with ESCC.

Limited Flexion of the Middle Finger Due to a Degenerative Partial Flexor Tendon Rupture Mimicking a Soft Tissue Tumor.

Atraumatic subcutaneous rupture of the finger flexor tendon of the hand and forearm is rare. Most sites of closed and subcutaneous ruptures of the finger flexor tendon are the tendon-bone insertion and musculotendinous junction, and an intratendinous lesion is unusual. We report the case of a 76-year-old female who presented to our department with a one-month history of a soft tissue mass and limited flexion of the left middle finger without trauma. Preoperative magnetic resonance imaging revealed a soft tissue mass that caused limited finger flexion. Intraoperative findings showed an intratendinous rupture of the flexor digitorum profundus tendon at the middle phalanx; the lesion was resected to obtain smooth grinding of the tendon. One year postoperatively, the soft tissue mass and limited flexion of the finger resolved without recurrence.

Myoepithelial carcinoma of the breast with focal rhabdoid features.

Myoepithelial carcinoma of the breast is extremely rare and only 33 cases have been reported in the English literature. Herein, we report a case of myoepithelial carcinoma of the breast with focal rhabdoid features. The patient was a 67-year-old woman, who presented with a lump of the left breast that rapidly grew to 3 cm in diameter within 3 months. Lumpectomy revealed a solid and whitish colored tumor, which was composed mainly of elongated spindle-shaped cells with mild atypia, focal necrosis, and infiltrative margin. In a small area of the lesion, ovoid tumor cells exhibited eccentric nuclei with centrally located nucleoli and plump cytoplasm including round eosinophilic inclusions, resembling a rhabdoid tumor. Immunohistochemically, both types of tumor cells exhibited a myoepithelial phenotype. MIB-1 index was 30%. The cytoplasmic inclusion of the ovoid cells exhibited immunopositivity for both vimentin and cytokeratin. From these findings, this tumor was diagnosed as a myoepithelial carcinoma with focal rhabdoid features. Although rhabdoid features have been reported in some types of malignant and benign tumors, this is the first report of such features in myoepithelial carcinoma of the breast.

Autoimmune hepatitis complicated by adult-onset Still's disease during treatment with tocilizumab: A case report from acute onset to recurrence.

The characteristics of liver dysfunction due to adult-onset Still's disease are not specific. Differentiating from autoimmune hepatitis is important in deciding whether to continue corticosteroid therapy, and also in terms of management of cirrhosis and surveillance of hepatocellular carcinoma. Liver biopsy is thought to be the most important determinant for differential diagnosis.

An Autopsy Case of Post-COVID-19 Interstitial Lung Disease with Acute Exacerbation.

The prognosis of patients with post-coronavirus disease 2019 (COVID-19) interstitial lung disease remains unclear. We herein report an autopsy case in which serial progression after the onset of post-COVID-19 interstitial lung disease resulted in an acute exacerbation, leading to a fatal outcome. Autopsy findings included hyaline membrane formation/interstitial inflammatory cell infiltration, suggestive of acute lesions, and severe regional fibrosis, indicating a preexisting chronic condition. In the present case, we histopathologically confirmed the acute exacerbation of post-COVID-19 interstitial lung disease.

Novel lateral transfer assist robot decreases the difficulty of transfer in post-stroke hemiparesis patients: a pilot study.

PURPOSE: The purpose of this study was to clarify whether the novel lateral transfer assist robot facilitates easier transfers compared with a wheelchair in post-stroke hemiparesis patients. METHODS: This cross-sectional study enrolled 20 post-stroke hemiparesis patients, and the task difficulty of transfers was compared between a wheelchair and lateral transfer assist robot. All participants were asked to transfer from either wheelchair or lateral transfer assist robot to a platform table and back. The primary outcome was the transfer score of the Functional Independence Measure. The secondary outcome was the time required for transfer. RESULTS: The transfer score of the Functional Independence Measure was significantly higher with lateral transfer assist robot than with wheelchair (p < .001). The transfer times from these devices to a platform table and back showed no significant differences (to device from platform table: 7.8 s, lateral transfer assist robot vs 7.6 s, wheelchair, p > .05: device to platform table: 7.1 s, lateral transfer assist robot vs 8.0 s, wheelchair, p > .05). CONCLUSIONS: Transfer with a lateral transfer assist robot is easier than with wheelchair and facilitates independence in post-stroke hemiparesis patients.IMPLICATIONS FOR REHABILITATIONTransfer skill influences the functional independence and quality of life of a wheelchair userA novel structural mobility device-the lateral transfer assist robot (LTAR)-can facilitate transfersThe LTAR could improve the degree of independence for transfers than the wheelchair, without any time loss, in post-stroke hemiparesis patientsThe LTAR could potentially reduce the risk for falls in various medical and care facilities.

[Two cases of mixed infection following 2009 H1N1 influenza pneumonia].

Case 1 was a 73-year-old woman admitted to our hospital due to bilateral pneumonia with respiratory failure. Real-time reverse transcription polymerase chain reaction (RRT-PCR) analysis confirmed 2009 H1N1 influenza infection. Streptococcus pneumoniae was confirmed from sputum culture and a urine antigen test on admission. She was treated with antiviral drugs and antibiotics, and improved gradually. Case 2 was a 66-year-old woman admitted to our hospital due to suspected acute exacerbation of interstitial pneumonitis. RRT-PCR analysis confirmed 2009 H1N1 influenza infection, and methicillin-resistant Staphylococcus aureus was cultured from her sputum. Mixed pneumonia due to influenza virus, bacteria and fungus was suspected. Although she was treated with medicines for these pathogens, she died from respiratory failure. An autopsy confirmed primary viral pneumonia, Pseudomonas aeruginosa pneumonia and invasive pulmonary aspergillosis. Not only viral pneumonia, but also mixed infections due to bacteria or fungus, might influence the prognosis of 2009 H1N1 influenza infection. These cases indicate the importance of early identification of complicating pathogens and treatment in 2009 H1N1 influenza infection.

Oncolytic virotherapy with human telomerase reverse transcriptase promoter regulation enhances cytotoxic effects against gastric cancer.

Currently, gastric cancer is the third most common cause of cancer-associated mortality worldwide. Oncolytic virotherapy using herpes simplex virus (HSV) has emerged as a novel therapeutic strategy against cancer. Telomerase is activated in >90of malignant tumors, including gastric cancer, and human telomerase reverse transcriptase (hTERT) is one of the major components of telomerase enzyme. Therefore, in oncolytic HSV, placing the essential genes under the regulation of the hTERT promoter may enhance its antitumor efficacy. The present study examined the antitumor effect of fourth-generation oncolytic HSVs, which contain the ICP6 gene under the regulation of the hTERT promoter (T-hTERT). To examine the association between hTERT expression and prognosis in patients with gastric cancer, immunohistochemical analysis of resected tumor specimens was performed. The enhanced efficacy of T-hTERT was determined in human gastric cancer cell lines in vitro and in human gastric adenocarcinoma specimens in vivo. In in vitro experiments, enhanced cytotoxicity of T-hTERT was observed in MKN1, MKN28 and MKN45 cells compared with that of a third-generation oncolytic HSV, T-null. In particular, the cytotoxicity of T-hTERT was markedly enhanced in MKN45 cells. Furthermore, in vivo experiments demonstrated that 36.7 and 54.9% of cells were found to be lysed 48 h after infection with T-null or T-hTERT viruses at 0.01 pfu/cell, respectively. The T-hTERT-treated group exhibited considerably lower cell viability than the control [phosphate-buffered saline (-)] group. Therefore, employing oncolytic HSVs that contain the ICP6 gene under the regulation of the hTERT promoter may be an effective therapeutic strategy for gastric cancer. To the best of our knowledge, the present study was the first to describe the effect of an oncolytic HSV with ICP6 expression regulated by the hTERT promoter on gastric cancer cells.

Effect of ankle joint fixation on tibialis anterior muscle activity during split-belt treadmill walking in healthy subjects: A pilot study.

OBJECTIVES: This study aims to examine the characteristics of muscle activity change of the tibialis anterior (TA) muscle in healthy adults while they walked on a split-belt treadmill with one fixed ankle. PATIENTS AND METHODS: This randomized controlled trial was conducted between November 2017 and July 2018. Fourteen healthy male individuals (mean age 31.4 years; range, 23 to 50 years) were divided into two groups: right ankle joint fixed by ankle-foot orthosis (fixation group) and no orthosis (control group). Both groups were asked to walk on a treadmill with the same belt speed. After familiarizing with walking on both belts at 5.0 km/h, they walked for 6 min with the right belt slower (2.5 km/h) and the left faster (5.0 km/h). For analysis, the 6 min were divided equally among three time periods. The TA muscle activity was calculated at first and last time periods. We compared muscle activities in time periods (early and late phase) and in groups (fixation and control) using two-way mixed analysis of variance. RESULTS: The TA muscle activity decreased in the late phase regardless of ankle joint fixation, and also decreased in the fixation group regardless of the time periods. There was an interaction between these factors. CONCLUSION: These data show that changes in the TA muscle activity were smaller in the fixation group, suggesting that the ankle joint fixation reduces the adaptation.

Oncolytic virotherapy with human telomerase reverse transcriptase promoter regulation enhances cytotoxic effects against gastric cancer.

[This retracts the article DOI: 10.3892/ol.2021.12751.].

Oncolytic virotherapy with SOCS3 enhances viral replicative potency and oncolysis for gastric cancer.

Oncolytic virotherapy is an encouraging treatment using herpes simplex virus (HSV) for gastric cancer patients. To treat gastric cancer, we generated and evaluated the efficacy of an attractive type of oncolytic HSV expressing the suppressor of cytokine signaling 3 (SOCS3). We constructed a third-generation type of oncolytic HSV (T-SOCS3) arming with SOCS3 by a bacterial artificial chromosome (BAC) system. We examined the viral replicative intensification and oncolysis of T-SOCS3 for human gastric cancer cell lines ex vivo. T-SOCS3 enhanced its replication and potentiated its cell-killing effect for MKN1 human gastric cancer cell lines, which are resistant to a non-armed third-generation type of oncolytic HSV (T-01) ex vivo. T-SOCS3 also induced the destruction within human gastric cancer specimens. Armed oncolytic HSVs expressing SOCS3 may be an efficacious therapeutic agent for gastric cancer treatment.

A Patient with Lung Adenocarcinoma Accompanied by Whole Right Lung Torsion Induced by the Accumulation of a Large Amount of Pleural Effusion.

A 68-year-old man visited a physician with a chief complaint of difficulty breathing. Right pleural effusion was noted, and he was referred to our department for a close examination and treatment. Thoracoscopy was performed under local anesthesia, and pleural dissemination of lung adenocarcinoma was noted, so a chest drain was placed. Since poor right lung inflation persisted and whole right lung torsion was observed on computed tomography, thoracoscopy-assisted thoracotomic reduction of lung torsion was performed. In this patient, the right middle lobe and anterior chest wall were adhered, suggesting that whole right lung torsion occurred when atelectasis was formed due to pleural effusion.

Pleomorphic Carcinoma with Exophthalmos and a Subsequent Diagnosis of Paraneoplastic Syndrome.

The patient was a 75-year-old man who developed polyopia and exophthalmos. Chest computed tomography (CT) revealed a mass in the left upper lobe. A CT-guided biopsy suggested lung adenocarcinoma. He was treated by neoadjuvant chemotherapy followed by left upper lobectomy. He was diagnosed with stage IIB pleomorphic carcinoma postoperatively. Preoperative head magnetic resonance imaging revealed exophthalmos and bilateral swelling of the extraocular muscles. The thyroid function of the patient was within the normal range, and he tested negative for autoantibodies. As his symptoms and swelling of the extraocular muscles improved postoperatively, he was diagnosed with paraneoplastic syndrome.

Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.

Background: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function. Case Presentation: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation. Conclusion: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.

Lateral Transfer Assist Robot (LTAR): Development of a proof-of-concept prototype.

BACKGROUND: Falls during transfer to and from a wheelchair are associated with numerous problems. Factors responsible for difficulty in transferring include horizontal/vertical gaps between surfaces; obstacles, such as armrests; and complicated brake/footrests configurations before transferring. Moreover, controlling a wheelchair sufficiently close to the transfer surface within the confined home space is difficult. OBJECTIVE: We described the design of the novel Lateral Transfer Assist Robot (LTAR) for solving problems during transfer. Furthermore, the effectiveness and usability of the robot were preliminary examined in healthy adults. METHOD: The transfer problems and basic designs were organized. The effectiveness of the prototype was measured by three-dimensional motion analysis and questionnaire. RESULTS: The prototype LTAR was developed. With just a push on a button, the footplate lowers to the floor and the seat and armrest lowers to the height of the seating surface to fill the gap between the surfaces. Using these features, users can transfer by simply shifting their buttocks sideways. Additionally, LTAR has omnidirectional wheels that help move it within a narrow space. The LTAR was confirmed to reduce the physical and subjective burden, except for maneuverability. CONCLUSION: The LTAR was found to be effective for home use and reducing burden of transfer.

Conversion Surgery for Gastric Cancer with Peritoneal Metastasis Based on the Diagnosis of Second-Look Staging Laparoscopy.

BACKGROUND: Patients with positive peritoneal cytology (CY1) or peritoneal dissemination (P1) have significantly poor prognosis. We performed pre-therapeutic staging laparoscopy (SL) to diagnose peritoneal metastasis for patients with advanced gastric cancer. When peritoneal metastasis disappears by chemotherapy for patients with CY1 or P1, we have intention to perform conversion surgery (CS). This study aims to clarify the clinical significance of CS for such patients. METHODS: We retrospectively analyzed clinical outcomes of 115 patients with advanced gastric cancer (large type 3, type 4, serosa-invasion) who underwent SL between 2005 and 2014. Disappearance of peritoneal metastasis was confirmed by second-look SL. RESULTS: CY0P0, CY1P0, and P1 were found in 56, 26, and 33 patients, respectively. In patients with CY1P0, 12 patients (66.7%) underwent CS (R0) as peritoneal cytology turned negative. All cases received S-1-based regimens, with median five treatment courses. The survival of patients with CS was significantly longer than those without CS (median survival time (MST); 41 vs. 11 months, respectively, P < 0.001). We observed no difference in overall survival between patients who underwent CS and patients with CY0P0 at the first SL (P = 0.913). All patients with P1 received chemotherapy. As peritoneal metastasis of five patients (15.2%) disappeared by chemotherapy, those patients underwent the CS (R0). The survival of patients who underwent CS was significantly longer than those who did not (MST; 31 vs. 10 months, respectively, P = 0.034). CONCLUSION: This study suggests that conversion surgery contributes to improvement in survival of patients with peritoneal metastasis.