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Abstract Introduction In oral maxillofacial surgery, the nasal tracheal tube is mostly used to provide a better surgical field for oral, head and neck operations. Postoperative sore throat and hoarseness are common following tracheal intubation, with an incidence of 11–55%. Then, we previously reported advantage technique of fiberoptic scope to decrease the risk which the tip of the tube is visualized as the tube is advanced which helps avoid impingement of the tube. However, the extent to which this technique causes postoperative complications is unknown compared to traditional technique. The aim of this study was retrospectively to determine the effect of postoperative sore throat following nasotracheal intubation by tip of the tube is visualized by fiberoptic scope. Method Anesthesia records of the adult patients with nasotracheal intubation were checked. Patients underwent oral maxillofacial surgery from January 2021 until March 2023. Facilitated with rocuronium, nasotracheal intubation was performed using the traditional or observative method by fiberoptic scope with a 4.8 mm outer diameter. Intubation was performed with a cuffed 6.5–8.0 mm ID nasotracheal tube. The following variables were recorded: gender, age, height, weight, ASA classification, anesthesia time, duration of intubation, tube size, intubation attempts, fentanyl and remifentanil. The postoperative sore throat and the incidence of hoarseness were recorded at operative day and at the day after operative day, and the time to recovery. Result A total of 104 cases (traditional fiberoptic intubation n = 51, observative fiberoptic intubation n = 53) were enrolled in this retrospective study. There were no significant differences in clinical characteristics and anesthetic data. There was not significant difference in incidence of postoperative sore throat, hoarseness and recovery between the two groups (P = 0.61, 0.44, 0.90). For subjects reporting postoperative sore throat (n = 30), there was not a significant difference in VAS means at operative day and at the day after operative day between the two groups (P = 0.81, 0.91). Conclusion We found that postoperative sore throat and recovery were not influenced by observative fiberoptic scope for nasotracheal intubation.

The domestic silkworm, Bombyx mori, has been widely used in silk production for centuries. It is also used as a bioreactor by the textile and pharmaceutical industries to mass produce recombinant bioactive proteins containing silk-based materials. Furthermore, silkworms are well-known as a source of food and have also been orally administered to prevent and treat several human disorders. In this study, we aimed to investigate the inherent bio-physicochemical properties of edible silkworms to accurately evaluate their clinical and nutritional potential. We prepared raw powder from whole larvae of silkworm. The yield rate of the powder derived from dried larvae was almost 100% (98.1–99.1% in replicates). As “percentage yield” translates to “Budomari” in Japanese, this raw powder was named “B100rw.” We further prepared B100dn that was denatured through autoclaving. Thereafter, we examined whether B100rw sustained the original bio-physicochemical properties by comparing it with B100dn. There was no significant difference in nutritional content between B100rw and B100dn. B100rw contained proteins derived from silkworm larvae and mulberry leaves, whereas the proteins of B100dn were mostly degraded. On measuring the enzymatic activity of both powders using trehalase as an indicator enzyme, B100rw was found to maintain trehalase activity. B100rw also maintained a random coil conformation, similar to that of liquid silk. This suggested that B100rw sustained the unique bio-physicochemical properties of living larvae. These findings may facilitate the development of novel food products or orally administered vaccines.

Abstract The recruitment maneuver (RM) combined with PEEP to prevent atelectasis have beneficial effects. However, the change in tidal volume (VT) due to RM combined with PEEP in pediatric patients during the induction of general anesthesia is unknown. Therefore, we assessed the effects of RM combined with PEEP on VT. Pediatric patients were divided into three groups: infants, preschool children, and school children. The RM was performed by maintaining pressure control continuous mandatory ventilation (PC-CMV) with a 15 cmH2O and PEEP increase of 5 cmH2O. VT, respiratory function and hemodynamics were monitored before and after RM combined with PEEP. VT (mL) /ideal body weight (kg) before vs. after RM combined with PEEP were 9 vs 12 mL/kg (p

Hemodialysis therapy is an extracorporeal circulation treatment that serves as a substitute for renal function. In Japan, patients receive this efficient four-hour treatment, three times per week, allowing them to maintain a social life nearly equivalent to that of healthy individuals. Before the treatment, two punctures are performed to establish extracorporeal circulation, and a high blood flow rate is essential to ensure efficient therapy. Specialized blood vessels created through arteriovenous fistula (AVF) surgery are utilized to achieve high blood flow rates. Although the AVF allows safe and efficient dialysis treatment, AVF stenosis leads to a serious problem in dialysis. To early detect this abnormal blood flow, auscultation and palpation methods are widely used in hospitals. However, these methods can only provide qualitative judgment of the AVF condition, so the results cannot be shared among other doctors and staff. Additionally, since the conventional methods require contact with the skin, some issues require consideration regarding infection and low reproducibility. In our previous study, we proposed an alternative method for auscultation using non-contact optical imaging technology. This study aims to construct a reliable AVF stenosis detection method using Thrill waveform analysis based on the developed non-contact device to solve the problem with the contact palpation method. This paper demonstrates the performance validation of the non-contact imaging in the normal AVF group (206 total data, 75 patients, mean age: 69.1 years) and in the treatable stenosis group (107 total data, 17 patients, mean age: 70.1 years). The experimental results of the Mann–Whitney U test showed a significant difference (p=0.0002) between the normal and abnormal groups, which indicated the effectiveness of the proposed method as a new possible alternative to palpation.

Abstract Background Nasal intubation using a fiberoptic scope is a useful technique. In clinical practice, we have experienced difficulty in advancing the endotracheal tube (ETT) over the fiberoptic scope because of resistance to the passage of the ETT against rotation in the nasal cavity, when it gets hung up on structures of the laryngeal inlet. Several maneuvers have been proposed to overcome this difficulty. The gap between the tip of the ETT and the fiberoptic scope can be reduced using a thicker fiberoptic scope and a thinner ETT. Moreover, simultaneous rotation of the fiberoptic scope and ETT could lead to successful intubation by reducing impingement on the ETT. However, the discrepancy between these rotation angles is unclear. This observational prospective study aimed to investigate the discrepancy in the rotation angle between the ETT and fiberoptic scope during nasal intubation. Methods The patients (aged 20–80 years) who underwent nasal intubation for oral and maxillofacial surgery participated in three sizes of preformed nasal ETT and were intubated using a fiberoptic scope. They were divided into three groups; the ETT internal diameter (ID) 6.5 mm (6.5 group), ID 7.0 mm (7.0 group), and ID 7.5 mm (7.5 group). The ETT was then inserted through the nasal cavity into the pharynx. After the fiberoptic scope was advanced through the ETT above the glottis, simultaneous rotation by both the proximal end of the fiberoptic scope and ETT was performed in 90° and 180° in both right (clockwise) and left (counterclockwise) directions, and the rotation angle at the distal end of the ETT was monitored using a video laryngoscope (Pentax-AWS). Results A total of 39 patients were included in the study. When both the proximal end of the fiberscope and ETT were simultaneously rotated by 90°, in the 6.5 group (n = 13), the distal end of the ETT rotated by 47.8 ± 1.5°. In the 7.0 °group (n = 13), the distal end of the ETT rotated by 45.5 ± 1.0°. In the 7.5 group (n = 13), the distal end of the ETT rotated by 39.9 ± 1.0°. When the proximal end of the fiberscope and ETT were rotated by 180°, in the 6.5 group, the distal end of the ETT rotated by 166.2 ± 2.5°. In the 7.0 group, the distal end of the ETT rotated by 145.7 ± 2.2°. In the 7.5 group, the distal end of the ETT rotated by 115.1 ± 2.0°. All rotation angles in the distal end of the ETT were significantly lower than those in both the proximal end of the fiberscope and ETT (p

Abstract Background The surgical strategy for thoracic esophageal cancer that invades the lungs is controversial. In particular, invasion of the pulmonary vein is often regarded unresectable. We successfully applied bilateral video-assisted thoracic surgery (VATS) in esophagectomy for esophageal cancer with left inferior pulmonary vein invasion following induction chemoradiotherapy (CRT), with a favorable response. Case presentation A 64-year-old woman was diagnosed with squamous cell carcinoma of the lower third of the esophagus. Computed tomography (CT) revealed that the tumor was suspected to be invading the main trunk of the left lower pulmonary vein and left lower lung. We initiated induction CRT comprising 5-fluorouracil, cisplatin, and concurrent radiotherapy at 50.4 Gy/28Fr. CT revealed shrinkage of the tumor, and the main trunk of the left inferior pulmonary vein was released from the tumor invasion. We considered the tumor to be completely resectable. VATS esophagectomy is usually performed using a right-sided approach. However, the right-sided approach is inappropriate for evaluating tumors around the left inferior pulmonary vein. We started with left-sided VATS to determine tumor resectability and dissected between the esophagus and the main trunk of the left inferior pulmonary vein. We only needed to perform partial resection of the left lower lobe. We then performed a right-sided VATS esophagectomy and lymphadenectomy with partial en bloc resection of the left lower lobe. Following this, we performed hand-assisted laparoscopic proximal gastrectomy and reconstruction using the gastric remnant. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Histopathological examination of the surgical specimen revealed a complete pathological response without any remnant tumor or lymph node metastasis. There were no signs of recurrence or metastasis at the 1-year follow-up. Conclusions Curative resection for thoracic esophageal cancer that invades the pulmonary vein could be possible via the bilateral VATS approach following induction CRT with a favorable response.

Abstract Although several ribosomal protein paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-containing ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-containing ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide further insight into the mechanisms and physiological relevance of tissue-specific translational regulation.

Abstract Background Spontaneous retroperitoneal hematoma is defined as bleeding in the retroperitoneal space without any triggers such as trauma, invasive procedures, and abdominal aortic aneurysm. Case presentation A 48-year-old Japanese man who experienced sudden abdominal pain, severe hypotension, and decreased hemoglobin was diagnosed with spontaneous retroperitoneal hematoma. Contrast-enhanced computed tomography revealed massive left retroperitoneal hematoma; however, neither extravasation nor causative aneurysm was noted. Through conservative management with close monitoring, he was treated and discharged on the tenth hospital day without any morbidity. Conclusions Spontaneous retroperitoneal hematoma treatment comprises conservative management, transcatheter arterial embolization, and surgical intervention. The mortality rate of spontaneous retroperitoneal hematoma is so high that the optimal treatment timing needs to be carefully judged on the basis of detailed evaluation, and management algorithm with clear criteria.

Hereditary ATTR amyloidosis is caused by the point mutation in serum protein transthyretin (TTR) that destabilizes its tetrameric structure to dissociate into monomer. The monomers form amyloid fibrils, which are deposited in peripheral nerves and organs, resulting in dysfunction. Therefore, a drug that dissolves amyloid after it has formed, termed amyloid disruptor, is needed as a new therapeutic drug. Here, we first established a high throughput screening system to find TTR interactors from the LOPAC1280 compound library. Among the hit compounds, thioflavin T-based post-treatment assay determined lead compounds for TTR amyloid disruptors, NSC95397 and Gossypol, designated as B and R, respectively. Because these compounds have naphthoquinone-naphthalene structures, we tested 100 naphthoquinone derivatives, and found 10 candidate compounds that disrupted TTR amyloid. Furthermore, to determine whether these 10 compounds are selective for TTR amyloid, we evaluated them against beta-amyloid (Aβ1-42). We found two compounds that were selective for TTR and did not disrupt Aβ-derived amyloid. Therefore, we succeeded in identifying TTR-selective amyloid disruptors, and demonstrated that naphthoquinone compounds are useful structures as amyloid disruptors. These findings contribute to the on-going efforts to discover new therapeutic tools for TTR amyloidosis.

The mode of cytokine receptor activation is diverse. Here, the authors find that the marine-sponge derived lectin ThC, a bivalent sugar binding protein, activates human cytokine receptor MPL. This mode of action resembles the pathogenic activation of MPL by mutant molecular chaperon calreticulin in hematologic malignancies.

The 70 kDa heat-shock proteins (Hsp70s) are ATP-dependent molecular chaperones that contain an N-terminal nucleotide-binding domain (NBD) and a C-terminal substrate-binding domain. Hsp70s bind to misfolded/unfolded proteins and thereby prevent their aggregation. The ATP hydrolysis reaction in the NBD plays a key role in allosteric control of the binding of substrate proteins. In the present study, the neutron crystal structure of the NBD of Hsp72, a heat-inducible Hsp70 family member, was solved in complex with ADP in order to study the structure–function relationship with a focus on hydrogens. ADP bound to Hsp72 was fully deprotonated, and the catalytically important residues, including Asp10, Asp199 and Asp206, are also deprotonated. Neutron analysis also enabled the characterization of the water clusters in the NBD. Enzymatic assays and X-ray crystallographic analysis revealed that the Y149A mutation exhibited a higher ATPase activity and caused disruption of the water cluster and incorporation of an additional magnesium ion. Tyr149 was suggested to contribute to the low intrinsic ATPase activity and to stabilize the water cluster. Collectively, these structural studies will help to elucidate the molecular basis of the function of Hsp72.

Abstract Anesthesiologists often compare intraoperative and preoperative electrocardiogram (ECG) waveforms in patients undergoing general anesthesia. In addition, many intraoperative ECG monitors have filters for removing electrocautery noise. In pediatric anesthesiology practice, we often note the appearance of elevated T waves—specifically, an increase in their height—with the use of such filters, even though no actual clinical change has occurred, which possibly leads to misdiagnosis. We investigated changes in R and T wave heights and in the T/R ratio according to the use of the strong (S) versus the diagnostic (D) filtering mode during pediatric anesthesiology. Primary outcomes were the dependence of the heights of the R and T waves on the filter mode and the correlation between rates of change in the R- and T-wave heights and heart rate (HR). In the S mode, the height of the R wave was lower (p = 0.013, η2 = 0.28) and the T/R ratio was higher than the corresponding values in the D mode (χ2 = 20.46, p

Abstract Objective The goal of this study was to compare the end-tidal sevoflurane concentration and time for intravenous cannulation at induction of anesthesia using sevoflurane with or without nitrous oxide in healthy children and in those with developmental disabilities. Methods Normal and developmentally disabled children were anesthetized by inhalation of sevoflurane with nitrous oxide or with nitrous oxide-free oxygen, and intravenous cannulae were introduced. Nitrous oxide was stopped after loss of consciousness. The following parameters were recorded for each patient: age, gender, height, weight, BMI, duration of intravenous cannulation, end-tidal concentration of sevoflurane at the completion of intravenous cannulation, and use of nitrous oxide. For each parameter except gender, p-value were calculated by one-way analysis of variance (ANOVA). For gender, p-value were calculated using the Fisher method. Two-way ANOVA was performed to evaluate the effect of patient health status and nitrous oxide use on the end-tidal concentrations of sevoflurane and the time required for intravenous cannulation. Results The end-tidal sevoflurane concentrations at the completion of the intravenous cannulation had received a significant main effect of the factor "the use of nitrous oxide" (F(1,166) = 25.8, p

Bombyx mori densovirus 1 (BmDV1) is a pathogen that causes flacherie disease in mulberry silkworms (B. mori). The absolute resistance (non-susceptibility) to BmDV1 of certain silkworm strains is determined independently by two genes, nsd-1 and Nid-1. Previously, we investigated the expression of viral transcript in virus-inoculated silkworms carrying different nsd-1 and Nid-1 genotypes, and observed that nsd-1 and Nid-1 expression blocked the early and late steps of BmDV1 infection, respectively. In addition, we found that nsd-1 encoded a Bombyx-specific mucin-like membrane protein only present on the surface of the midgut, where BmDV1 could infect. In this study, we dissected the resistance mechanism by Nid-1 against BmDV1 infection by investigating the sequential changes in the accumulation of viral DNA, transcripts, and proteins derived from BmDV1 in susceptible strain (pxj) and Nid-1-carrying resistant strain (No. 908) after inoculation with BmDV1. Genomic PCR results showed that the BmDV1 DNA was detected immediately after the infection in both strains but rapidly decreased in the Nid-1-carrying strain No. 908 compared with the susceptible strain pxj. RT-PCR results also showed that the BmDV1 transcripts of Nid-1-carrying strain No. 908 were rapidly decreased after the infection. Moreover, BmDV1-derived proteins were not detected in No. 908 throughout the infection. These results suggest that Nid-1 expression might inhibit the accumulation of viral DNA and transcripts. As Nid-1 has not been molecularly characterized, its identification will contribute to the elucidation of the interactions between the silkworm and BmDV1.

Introduction: When performing cardiopulmonary resuscitation (CPR) on a patient who has suffered a cardiopulmonary arrest during dental treatment, few dental chairs have sufficient stability to perform effective chest compressions. We previously proposed a method of stabilizing the backrest of a dental chair using a support stool. As a result, we confirmed that the vertical displacement of the backrest could be significantly reduced. In the present study, we verified the effectiveness of the stool stabilization method using several dental chairs (flat and curved) with significantly different backrest shapes. Methods: Vertical displacement of the backrests of dental chairs was recorded. Data were obtained at three different stool positions (without a stool, under the chest at the level that participants were performing manual chest compressions, and under the shoulders). Reduction displacement ratios were calculated to evaluate the effectiveness of the stool positions. Results: The method significantly reduced the vertical displacement of the backrest for all types. When the curvature of the backrest was large, the reduction in vertical displacement was 40% when the stool was placed under the chest at the level of manual chest compressions and 65% when placed underneath the shoulder. In the case of a flat dental chair, this reduction was 90% when using a stool in either position, compared to no stool. Conclusion: When we need to perform CPR on a patient in the dental chair, placing a stool under the shoulders allows effective manual chest compression by firmly supporting the backrest of a dental chair of any shape.

Abstract The bivoltine strain of the domestic silkworm, Bombyx mori, has two generations per year. It shows a facultative diapause phenotype determined by environmental conditions, including photoperiod and temperature, and nutrient conditions during embryonic and larval development of the mother. However, it remains unclear how the environmental signals received during development are selectively utilized as cues to determine alternative diapause phenotypes. We performed a comparative analysis between the Kosetsu strain of B. mori and a Japanese population of the wild mulberry silkworm B. mandarina concerning the hierarchical molecular mechanisms in diapause induction. Our results showed that for the Kosetsu, temperature signals during the mother’s embryonic development predominantly affected diapause determination through the thermosensitive transient receptor potential ankyrin 1 (TRPA1) and diapause hormone (DH) signaling pathways. However, embryonic diapause in B. mandarina was photoperiod-dependent, although the DH signaling pathway and thermal sensitivity of TRPA1 were conserved within both species. Based on these findings, we hypothesize that TRPA1-activated signals are strongly linked to the signaling pathway participating in diapause induction in Kosetsu to selectively utilize the temperature information as the cue because temperature-dependent induction was replaced by photoperiodic induction in the TRPA1 knockout mutant.

Abstract Antibodies have been widely used for cancer therapy owing to their ability to distinguish cancer cells by recognizing cancer-specific antigens. Epidermal growth factor receptor (EGFR) is a promising target for the cancer therapeutics, against which several antibody clones have been developed and brought into therapeutic use. Another antibody clone, 528, is an antagonistic anti-EGFR antibody, which has been the focus of our antibody engineering studies to develop cancer drugs. In this study, we explored the interaction of 528 with the extracellular region of EGFR (sEGFR) via binding analyses and structural studies. Dot blotting experiments with heat treated sEGFR and surface plasmon resonance binding experiments revealed that 528 recognizes the tertiary structure of sEGFR and exhibits competitive binding to sEGFR with EGF and cetuximab. Single particle analysis of the sEGFR–528 Fab complex via electron microscopy clearly showed the binding of 528 to domain III of sEGFR, the domain to which EGF and cetuximab bind, explaining its antagonistic activity. Comparison between the two-dimensional class average and the cetuximab/sEGFR crystal structure revealed that 528 binds to a site that is shifted from, rather than identical to, the cetuximab epitope, and may exclude known drug-resistant EGFR mutations.

Death-associated protein kinase 1 (DAPK1) is a large multidomain protein with an N-terminal serine/threonine protein kinase domain. DAPK1 is considered to be a promising molecular target for the treatment of Alzheimer's disease (AD). In the present study, the inhibitory potency of resveratrol (RSV), a dietary polyphenol found in red wine, against the catalytic activity of DAPK1 was investigated. Kinetic and fluorescent probe competitive binding analyses revealed that RSV directly inhibited the catalytic activity of DAPK1 by binding to the ATP-binding site. Crystallographic analysis of DAPK1 in complex with RSV revealed that the A-ring of RSV occupied the nucleobase-binding position. Determination of the binding mode provided a structural basis for the design of more potent DAPK1 inhibitors. In conclusion, the data here clearly show that RSV is an ATP-competitive inhibitor of DAPK1, encouraging speculation that RSV may be useful for the development of AD inhibitors.

Background: Tracheobronchomalacia (TBM) is a severe life-threatening perioperative complication. It is a rare condition caused by congenital and developmental anomalies of the trachea and/or the bronchus. It is often difficult to diagnose TBM before surgery as this congenital disease presents very few symptoms preoperatively and most often appears postoperatively. Case presentation and Review: The study describes a case of cleft-lip-plate (CL/P) in a 7-month-old Japanese female with TBM and Tetralogy of Fallot syndrome. Before undergoing cleft-lip surgery, her TBM was not fully elucidated by preoperative examinations, and the operation was completed uneventfully. After the surgery, however, she started showing severe respiratory distress and developed hypoxia and bradycardia in the operating room. CPR was performed successfully, but a bronchoscopy revealed a severely collapsed airway, and the pathological condition was diagnosed as TBM occurred postoperatively. Eight months later, she died of sudden respiratory failure similar to that of the postoperative event caused by TBM. A literature review was conducted on the complications of CL/P from 1990 to 2017 in Japan. Conclusions: It was hypothesized that CL/P with congenital heart disease (CHD) and TBM with CHD may crossover in relatively high rates. Currently, there are very few solutions available to treat severe airway obstruction related to TBM. This highlights the need for preoperative diagnosis of TBM as an important step in overcoming severe airway complications.

Abstract Background Total hemoglobin (tHb) measurement is indispensable for determining the patient’s condition (hemorrhagic vs. ischemic) and need for blood transfusion. Conductivity- and absorbance-based measurement methods are used for blood gas analysis of tHb. For conductivity-based measurement, tHb is calculated after converting blood conductivity into a hematocrit value, whereas absorbance measurement is based on light absorbance after red blood cell hemolysis. Due to changes in plasma electrolytes and hemolysis, there is a possibility that conductivity- and absorbance-based measurement methods may cause a difference in tHb. Methods In this study, test samples with controlled electrolyte changes and hemolysis were created by adding sodium chloride, distilled water or hemolytic blood to blood samples collected from healthy volunteers, and tHb values were compared between both methods. Results Conductivity-based measurement revealed reduced tHb value (from 15.49 to 13.05 g/dl) following the addition of 10% sodium chloride, which was also reduced by the addition of hemolysate. Conversely, the addition of distilled water significantly increased tHb value than the expected value. In the absorbance method, there was no significant change in tHb value due to electrolyte change or hemolysis. Conclusions We have to recognize unexpected conductivity changes occur at all times when tHb is measured via conductivity- and absorbance-based measurement methods. The absorbance method should be used when measuring tHb in patients with expected blood conductivity changes. However, when using this method, the added contribution of hemoglobin from hemolytic erythrocytes lacking oxygen carrying capacity must be considered. We recognize that discrepancy can occur between conductivity- and absorbance-based measurement methods when tHb is measured.

Tetraspanins play critical roles in various physiological processes, ranging from cell adhesion to virus infection. Here authors report the crystal structure of CD9 and the cryo-electron microscopic structure of CD9 in complex with its single membrane-spanning partner protein, EWI-2.

Abstract Background Cardiopulmonary resuscitation (CPR) requires immediate start of manual chest compression (MCC) and defibrillation as soon as possible. During dental surgery, CPR could be started in the dental chair considering difficulty to move the patient from the dental chair to the floor. However, all types of dental chairs are not stable for MCC. We previously developed a procedure to stabilize a dental chair by using a stool. EUROPEAN RESUSCITATION COUNCIL (ERC) guideline 2015 adopted our procedure when cardiac arrest during dental surgery. The objective of this study was to verify the efficacy of a stool as a stabilizer in different types of dental chairs. Methods Three health care providers participated in this study, and 8 kinds of dental chairs were examined. MCC were performed on a manikin that was laid on the backrest of a dental chair. A stool was placed under the backrest to stabilize the dental chair. The vertical displacement of the backrest by MCC was recorded by a camcorder and measured by millimeter. Next, the vertical displacement of the backrest by MCC were compared between with and without a stool. Results In all 8 dental chairs, the method by using a stool significantly reduced the vertical displacements of the backrest by during MCC. The reduction ratio (mean [interquartile range]) varied between nearly 27 [20] and 87 [5] %. In the largest stabilization case, the displacement was 3.5 [0.5] mm with a stool versus 26 [5.5] mm without a stool (p

The condition of arteriovenous fistula (AVF) blood flow is typically checked by using auscultation; however, auscultation should require a qualitative judgment dependent on the skills of doctors, and further attention to contact infection is required. For these reasons, this study developed a non-contact and non-invasive medical device to measure the pulse wave of AVFs by applying optical imaging technology. As a first step toward realization of the quantification judgment based on non-contact AVF measurement, we experimentally validated the developed system, whereby the hemodynamics of 168 subjects were visually and quantitatively evaluated based on clinical tests. Based on the evaluation results, the fundamental statistical characteristics of the non-contact measurement, including the average and median values, and distribution of measured signal-to-noise power ratio, were demonstrated. The clinical test results contributed to the future construction of quantified criteria for the AVF condition with the non-contact measurement.

Background. Heart failure is the leading cause of death in dialysis patients. Cardiac arrest due to hypotension may also occur during dialysis therapy. If cardiac arrest is elicited, manual chest compressions (MCCs) should be started as soon as possible. However, all types of dialysis chairs are not stable for MCC, because there is no steady support between the backboard of the dialysis chair and the floor. These conditions may alter the effectiveness of MCC. Methods. We investigated whether a round chair is effective in supporting the dialysis chair for MCC. Four adult males performed MCC on a mannequin placed on three dialysis chairs. MCC was performed in sets of 2 (each set was 100 times per minute) per person, with and without a round chair. A total of 4,800 compressions were performed by four executors. Results. When the chair was not used as a stabilizer, the mean values of the fluctuation range were 20.8 ± 8.1 mm, 18.7 ± 5.5 mm, and 12.8 ± 1.8 mm, respectively. When the chair was used, the mean values of the fluctuation range were 6.1 ± 1.1 mm, 7.5 ± 2.1 mm, and 1.0 ± 0 mm, decreasing by 70%, 59%, and 92%. Conclusion. MCC performed with the stool under the backrest as a stabilizer was effective in supporting the dialysis chair.

We report a case of a 59-year-old man with coronavirus disease 2019 (COVID-19). He had visited a hospital for fever and cough and been treated with antibiotics for pneumonia in the right upper lobe. However, he gradually progressed to dyspnea and consulted our hospital. His chest radiographs showed bilateral pneumonia shadows and his CT showed ground glass opacities and consolidation. Although we treated him with broad-spectrum antibiotics, the pneumonia shadow rapidly progressed and mechanical ventilation was administered. We collected sputum from the bronchus using bronchoscopy to detect microorganisms, and RT-PCR tests confirmed COVID-19 pneumonia. He was transferred to a designated hospital.In order to prevent the occurrence of nosocomial infections, close contacts within the hospital and medical staff were suspended from their work for two weeks. No secondary infection with COVID-19 appeared. This was the first case of COVID-19 occurring as community-acquired pneumonia in Hokkaido, Japan.

Background: T-705 (favipiravir) is a potent inhibitor of RNA-dependent RNA polymerases of influenza viruses and no favipiravir-resistant virus has been isolated. Poliovirus RNA polymerase has been well characterized and isolation of resistant virus was examined in poliovirus. Methods: Susceptibility variants of poliovirus I (Sabin strain) were isolated during passages in the presence of favipiravir and characterized for their susceptibility and the sequence of RNA polymerase. Results: Five variants with 0.47–1.88 times the 50% inhibitory concentration for plaque formation of the parent poliovirus had amino acid variations in the 3D gene of the RNA polymerase. The distribution of amino acid variations was not related to ribavirin resistance, and two amino acid variation sites were found near the finger domain. Conclusion: Favipiravir as a chain terminator would not be incorporated and replicate to cause lethal mutagenesis as a mutagen like ribavirin, and resistant mutants were not isolated. A high replication level would generate mutations leading to favipiravir resistance as ribavirin resistance was generated, but generated mutations would be lethal to the RNA polymerase function. Keywords: Poliovirus, T-705, Favipiravir, Mutants, Resistance, RNA dependent RNA polymerase

Abstract Background Goal-directed therapy (GDT) is beneficial for surgical patients, especially for those undergoing high-risk surgery. However, little has been reported on the hemodynamic effects of GDT in extensive surgery. We conducted a study to determine the impact of GDT on intraoperative management of extensive surgery. Findings We retrospectively collected data from 90 patients who underwent pancreaticoduodenectomy: 44 who received intraoperative GDT (GDT group) and 46 who received conventional hemodynamic management (control group). Intraoperative use of fluids and catecholamines and physiologic variables, including mean arterial pressure, heart rate, and urine output, were compared. We also examined the correlation between the amount of fluid administered and urine output. The amount of fluid administered was comparable, and urine output was significantly larger in the GDT group than in the control group. Fluid balance was significantly smaller in the GDT group (49.7 versus 61.7 mL/kg; 95% confidence interval, − 19.5 to − 4.6 mL/kg; P = 0.0019). There was a trend toward higher mean arterial pressure in the GDT group despite lower fluid balance. We found a rank correlation between the amount of fluid administered and urine output in the GDT group (rank correlation coefficient, 0.68; P

Abstract Background Symptomatic anterior mediastinal mass in pregnancy is rare, and cesarean section for such patients poses a risk of cardiopulmonary collapse. Case presentation A 30-year-old woman at 40 weeks’ gestation complained of breathlessness and cough, and she was not able to lie supine because of respiratory distress. Computed tomography scan revealed a large anterior-superior mediastinal mass severely compressing the trachea, bilateral main bronchus, and superior vena cava. Because clinical symptoms and computed tomographic findings suggested imminent respiratory catastrophe, urgent cesarean section was planned. The patient was able to lie in the semi-recumbent position with minimal symptoms; therefore, we considered it safe to perform cesarean section with combined spinal epidural anesthesia. In the event of cardiopulmonary collapse, emergent intubation and extracorporeal membrane oxygenation were also planned. The operation was performed successfully with combined spinal epidural anesthesia. The infant was healthy, and the postoperative hospital course was uneventful. Conclusions Combined spinal epidural anesthesia is preferable in the anesthetic management of cesarean section with symptomatic anterior mediastinal mass. A well-designed preoperative strategy can lead to favorable outcomes even in this complicated situation.

Special needs patients with mental retardation are recognized to have poorer oral health condition. Oral health related quality of life reflects daily activity and well-being. Dental treatment under general anesthesia is often an option for such patients. Trisomy 18 is characterized by congenital heart disease, craniofacial abnormality and mental retardation. Congenital heart disease can be greater risk during anesthesia. In the case of trisomy 18 with untreated tetralogy of Fallot, especially right-to-left shunting and/or pulmonary artery stenosis may reduce pulmonary blood flow, and may develop life-threatening hypoxemia. We anesthetized a patient with trisomy 18 accompanying untreated tetralogy of Fallot for dental treatment. The hemodynamics including cardiac output has been monitored non-invasively using electrical velocimetry method. Its systemic vascular resistance and pulmonary vascular resistance were maintained appropriately, and dental treatments were successfully completed.

Familial amyloid polyneuropathy (FAP) is a genetic, adult-onset, neurodegenerative disorder caused by amyloid formation of transthyretin (TTR), a thyroxine-binding protein. Mutation in TTR causes a propensity of TTR tetramer to dissociate to monomer, which is the first step to amyloidosis. Thus, a drug that can stabilize the tetramer structure will have therapeutic benefit. Here, by virtual screening and biochemical assays, we identified small molecule 6-benzoyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione (L6) that can prevent the dissociation of TTR to monomer. X-ray crystallography reveals that L6 binds to the T4 binding pocket of TTR. These findings show that L6 is a candidate TTR stabilizer.

A model Post-Termination Complex (PoTC) used for the discovery of Ribosome Recycling Factor (RRF) was purified and characterized by cryo-electron microscopic analysis and biochemical methods. We established that the model PoTC has mostly one tRNA, at the P/E or P/P position, together with one mRNA. The structural studies were supported by the biochemical measurement of bound tRNA and mRNA. Using this substrate, we establish that the release of tRNA, release of mRNA and splitting of ribosomal subunits occur during the recycling reaction. Order of these events is tRNA release first followed by mRNA release and splitting almost simultaneously. Moreover, we demonstrate that IF3 is not involved in any of the recycling reactions but simply prevents the re-association of split ribosomal subunits. Our finding demonstrates that the important function of RRF includes the release of mRNA, which is often missed by the use of a short ORF with the Shine-Dalgarno sequence near the termination site.

Transthyretin-related amyloidosis is a slowly progressive disorder caused by deposition of insoluble amyloid plaques formed by fibrillization of mutant or defective transthyretin (TTR) monomers that leads to neurodegeneration and organ failure. Thus, any compound exhibiting TTR amyloid formation inhibitory activity or TTR amyloid fibril disrupting activity might be a potential candidate for the development of therapies for these disorders. Our aim in this study was the evaluation of the TTR amyloid fibril disrupting potential of extracts of leaves and immature fruits of two Juglans plants, i.e., Juglans mandshurica var. sachalinensis and Juglans mandshurica var. cordiformis. The TTR amyloid fibril disrupting activity was measured by Thioflavin-T (ThT) assay and PROTEOSTAT® Protein aggregation assay methods. A fifty percent acetone extract of the fruits of Juglans mandshurica var. cordiformis showed strong amyloid fibril disrupting activity, and was further fractionated using different solvents. Ethyl acetate and n-butanol fractions showed significant activity in both assays. Syringic acid was isolated and identified as main compound in both of these fractions; however, it did not show any activity. Furthermore, some of the previously reported compounds from Juglans plants including naphthoquinone derivatives and phenolic compounds were evaluated to identify the potential bioactive compounds. Among them, juglone, a naphthoquinone derivative showed promising activity. However, juglone also showed strong cytotoxicity in HEK293 cells. Thus, future studies should focus on the isolation and identification of naphthoquinone derivatives or other compounds from Juglans plan ts with potent bioactivity and low cytotoxicity.

Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca2+-activated K+ (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (INMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated INMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on INMDA-OUT. A direct perfusion of 3,5′-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated INMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of INMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons.

One way that aerobic biological systems counteract the generation of reactive oxygen species (ROS) is with superoxide dismutase proteins SOD1 and SOD2 that metabolize superoxide radicals to molecular oxygen and hydrogen peroxide or scavenge oxygen radicals produced by the extensive oxidation-reduction and electron-transport reactions that occur in mitochondria. We characterized SOD1 and SOD2 of Bombyx mori isolated from the fat body of larvae. Immunological analysis demonstrated the presence of BmSOD1 and BmSOD2 in the silk gland, midgut, fat body, Malpighian tubules, testis and ovary from larvae to adults. We found that BmSOD2 had a unique expression pattern in the fat body through the fifth instar larval developmental stage. The anti-oxidative functions of BmSOD1 and BmSOD2 were assessed by exposing larvae to insecticide rotenone or vasodilator isosorbide dinitrate, which is an ROS generator in BmN4 cells; however, exposure to these compounds had no effect on the expression levels of either BmSOD protein. Next, we investigated the physiological role of BmSOD1 and BmSOD2 under environmental oxidative stress, applied through whole-body UV irradiation and assayed using quantitative RT-PCR, immunoblotting and microarray analysis. The mRNA expression level of both BmSOD1 and BmSOD2 was markedly increased but protein expression level was increased only slightly. To examine the differences in mRNA and protein level due to UV irradiation intensity, we performed microarray analysis. Gene set enrichment analysis revealed that genes in the insulin signaling pathway and PPAR signaling pathway were significantly up-regulated after 6 and 12 hours of UV irradiation. Taken together, the activities of BmSOD1 and BmSOD2 may be related to the response to UV irradiation stress in B. mori. These results suggest that BmSOD1 and BmSOD2 modulate environmental oxidative stress in the cell and have a specific role in fat body of B. mori during pupation.

Cells must coordinate adjustments in genome expression to accommodate changes in their environment. We hypothesized that the amount of transcriptome change is proportional to the amount of environmental change. To capture the effects of environmental changes on the transcriptome, we compared transcriptome diversities (defined as the Shannon entropy of frequency distribution) of silkworm fat-body tissues cultured with several concentrations of phenobarbital. Although there was no proportional relationship, we did identify a drug concentration "tipping point" between 0.25 and 1.0 mM. Cells cultured in media containing lower drug concentrations than the tipping point showed uniformly high transcriptome diversities, while those cultured at higher drug concentrations than the tipping point showed uniformly low transcriptome diversities. The plasticity of transcriptome diversity was corroborated by cultivations of fat bodies in MGM-450 insect medium without phenobarbital and in 0.25 mM phenobarbital-supplemented MGM-450 insect medium after previous cultivation (cultivation for 80 hours in MGM-450 insect medium without phenobarbital, followed by cultivation for 10 hours in 1.0 mM phenobarbital-supplemented MGM-450 insect medium). Interestingly, the transcriptome diversities of cells cultured in media containing 0.25 mM phenobarbital after previous cultivation (cultivation for 80 hours in MGM-450 insect medium without phenobarbital, followed by cultivation for 10 hours in 1.0 mM phenobarbital-supplemented MGM-450 insect medium) were different from cells cultured in media containing 0.25 mM phenobarbital after previous cultivation (cultivation for 80 hours in MGM-450 insect medium without phenobarbital). This hysteretic phenomenon of transcriptome diversities indicates multi-stability of the genome expression system. Cellular memories were recorded in genome expression networks as in DNA/histone modifications.

Tissue culture is performed to maintain isolated portions of multicellular organisms in an artificial milieu that is outside the individual organism and for considerable periods of time; cells derived from cultured explants are, in general, different from cells of the corresponding tissue in a living organism. The changes in cultured tissues that precede and often explain the subsequent cell proliferation of explant-derived cells have been partially studied, but little is known about the molecular and genomic basis of these changes. Comparative transcriptomics of intact and cultured (90 hours in MGM-450 insect medium) Bombyx mori tissues revealed that fewer genes represented a larger portion of the transcriptome of intact fat body tissues than of cultured fat body tissues. This analysis also indicated that expression of genes encoding sugar transporters and immune response proteins increased during culture and that expression of genes encoding lipoproteins and cuticle proteins decreased during culture. These results provide support for hypotheses that cultured tissues respond immunologically to surgery, adapt to the medium by accelerating sugar uptake, and terminate their identity as part of an intact organism by becoming independent of that organism.

Supragingival plaque is permanently in contact with saliva. However, the extent to which the microbiota contributes to the salivary bacterial population remains unclear. We compared the compositional shift in the salivary bacterial population with that in supragingival plaque following periodontal therapy. Samples were collected from 19 patients with periodontitis before and after periodontal therapy (mean sample collection interval, 25.8 ± 2.6 months), and their bacterial composition was investigated using barcoded pyrosequencing analysis of the 16S rRNA gene. Phylogenetic community analysis using the UniFrac distance metric revealed that the overall bacterial community composition of saliva is distinct from that of supragingival plaque, both pre- and post-therapy. Temporal variation following therapy in the salivary bacterial population was significantly smaller than in the plaque microbiota, and the post-therapy saliva sample was significantly more similar to that pre-therapy from the same individual than to those from other subjects. Following periodontal therapy, microbial richness and biodiversity were significantly decreased in the plaque microbiota, but not in the salivary bacterial population. The operational taxonomic units whose relative abundances changed significantly after therapy were not common to the two microbiotae. These results reveal the compositional stability of salivary bacterial populations against shifts in the supragingival microbiota, suggesting that the effect of the supragingival plaque microbiota on salivary bacterial population composition is limited.

We synthesized a "cyborg protein," wherein a synthetic molecule partially substitutes the main peptide chain by linking 2 protein domains with a synthetic oligomer. Green fluorescent protein (GFP) served as the model for constructing the cyborg proteins. We prepared circularly permuted GFP (cpGFP) with new termini between β10 and β11, where the original N- and C-termini were linked by a cleavable peptide loop. The cyborg GFP was constructed from cpGFP by linking the β10 and β11 with oligo(ethylene glycol) (OEG) using maleimide-cysteine couplings, followed by the enzymatic cleavage of the N- and C-termini linking loop by thrombin. With the help of machine learning, we were able to obtain the cpGFP mutants that significantly alter the fluorescence intensity (53% increase) by thrombin treatment, which splits cpGFP into 2 fragments (fragmented GFP), and by heat shock. When the cyborg GFP was constructed using this mutant, the fluorescence intensity increased by 13% after heat treatment, similar to cpGFP (33% increase), and the behavior was significantly different from that of the fragmented GFP. This result suggests the possibility that the OEG chain in the cyborg protein plays a similar role to the peptide in the main chain of the protein. [ABSTRACT FROM AUTHOR]