Search

We are in the midst of the historic coronavirus infectious disease 2019 (COVID-19) pandemic caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Although countless efforts to control the pandemic have been attempted—most successfully, vaccination1–3—imbalances in accessibility to vaccines, medicines, and diagnostics among countries, regions, and populations have been problematic. Camelid variable regions of heavy chain-only antibodies (VHHs or nanobodies)4 have unique modalities: they are smaller, more stable, easier to customize, and, importantly, less expensive to produce than conventional antibodies5, 6. We present the sequences of nine alpaca nanobodies that detect the spike proteins of four SARS-CoV-2 variants of concern (VOCs)—namely, the alpha, beta, gamma, and delta variants. We show that they can quantify or detect spike variants via ELISA and lateral flow, kinetic, flow cytometric, microscopy, and Western blotting assays7. The panel of nanobodies broadly neutralized viral infection by pseudotyped SARS-CoV-2 VOCs. Structural analyses showed that a P86 clone targeted epitopes that were conserved yet unclassified on the receptor-binding domain (RBD) and located inside the N-terminal domain (NTD). Human antibodies have hardly accessed both regions; consequently, the clone buries hidden crevasses of SARS-CoV-2 spike proteins undetected by conventional antibodies and maintains activity against spike proteins carrying escape mutations.

BackgroundAnastomotic leakage after intestinal resection is one of the most serious complications of surgical intervention for hollow viscus injury. Adequate vascular perfusion of the anastomotic site is essential to prevent anastomotic leakage. Near-infrared imaging using indocyanine green (NIR-ICG) is useful for the objective assessment of vascular perfusion. The aim of this study was to evaluate the association of NIR-ICG with intestinal and mesenteric injuries.MethodsThis was a retrospective, single-center study of patients undergoing surgery for intestinal and mesenteric injuries due to abdominal trauma from December 2006 to March 2021. NIR-ICG was used to evaluate vascular perfusion. Postoperative complications were assessed between NIR-ICG and non-NIR-ICG groups. ResultsThe use of NIR-ICG was associated with a lower incidence of Clavien-Dindo grade ≥ III complications with a statistical tendency (p = 0.076). No Clavien-Dindo grade ≥ II intestinal complications were observed in the NIR-ICG group. When limited to patients that underwent intestinal resection, the use of NIR-ICG was significantly associated with a lower risk of perioperative complications (p = 0.009).ConclusionsThe use of NIR-ICG tended to associate with the lower incidence of postoperative complications after intestinal and mesenteric trauma surgery. NIR-ICG was associated with a significantly lower risk of complications in patients undergoing intestinal resection. The NIR-ICG procedure is simple and quick and is expected to be useful for intestinal and mesenteric trauma.

Silicon carbide (SiC) is a next-generation semiconductor material. However, SiC is difficult to machine because it has high mechanical hardness and chemical inertness. Therefore, high-quality processing technology with high efficiency is now required. In our previous study, the authors developed UV-assisted grinding method and clarified that the critical depth of cut is expanded by UV irradiation and that the surface roughness is reduced by applying this method with a composite-abrasive wheel containing diamond abrasive grains with a mean abrasive diameter of 6 μm. On the other hand, it is important to reduce the damaged layer left by lapping or polishing process after grinding. In this study, we developed UV-assisted constant-pressure grinding method as a new alterative processing method to lapping and polishing. In this method, UV-assisted grinding is applied to the constant-pressure grinding method. To obtain a higher-quality mirror surface, we used a superabrasive wheel containing diamond abrasive grains with a mean abrasive diameter of 0.5 μm. By investigating the influence of UV irradiation on processing characteristics, we clarified that the surface roughness and removal height were reduced by UV irradiation. Finally, a high quality surface with few grinding marks was obtained by UV-assisted constant-pressure grinding.

Introduction The use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in trauma patients has been controversial, but VV-ECMO plays a crucial role when the lungs are extensively damaged and when conventional management has failed. VV-ECMO provides adequate tissue oxygenation and an opportunity for lung recovery. However, VV-ECMO remains contraindicated in patients with a risk of bleeding because of systemic anticoagulation during the treatment. The most important point is controlling the bleeding from severe trauma. Case A 32-year-old male experienced blunt trauma due to a traffic accident. He presented with bilateral hemopneumothorax and bilateral flail chest. We performed emergency thoracotomy for active bleeding and established circulatory stability. After surgery, the oxygenation deteriorated under mechanical ventilation, so we decided to establish VV-ECMO. However, bleeding from the bilateral lung contusions increased after VV-ECMO was established, and the patient was switched to heparin-free ECMO. After conversion, we could control the bronchial bleeding, especially the lung hematomas, and the oxygenation recovered. The patient was discharged without significant complications. VV-ECMO and mechanical ventilation were stopped on days 10 and 11, respectively. He was discharged from the ICU on day 15. Conclusion When we consider the use of ECMO for patients with uncontrollable, severe bleeding caused by blunt trauma, it may be necessary to use a higher flow setting for heparin-free ECMO than typically used for patients without trauma to prevent thrombosis.

Background Although some predictors of COVID-19 pneumonia severity and mortality have been identified, much of the pathophysiology of this emerging infectious disease remains unclear. We hypothesized that a patient’s cholinesterase level on admission could predict COVID-19 pneumonia severity and mortality. Methods We retrospectively collected data of 26 COVID-19 pneumonia patients from February–May 2020. Outcomes were aggravation of symptoms and in-hospital mortality. We compared receiver operating curves of cholinesterase, C-reactive protein, lymphocytes, albumin, D-dimer, and PaO2/FiO2 ratio and examined prediction accuracy. Regarding the interaction between cholinesterase and other variables, each independent variable was divided into two groups using cutoff values, and interaction terms were created. Results Cholinesterase levels on admission were significantly lower in the severe group than in the mild-to-moderate group (326 vs. 218 IU/L, p = 0.006; area under the curve: 0.81; 95% confidence interval 0.61–0.94). When comparing the area under the curve, cholinesterase was comparable to C-reactive protein, albumin, lymphocytes, and PaO2/FiO2 ratio other than D-dimer in the prediction accuracy of severe cases and mortality. Cholinesterase levels on admission were significantly lower in the death group than in the survival group (274 vs. 187.5 IU/L, p = 0.028; area under the curve: 0.79; 95% interval 0.58–0.93). Regarding the interaction between cholinesterase and established predictors, the prediction accuracy of both severity and death was higher when cholinesterase was combined with each predictor than when cholinesterase was used alone. Conclusions Cholinesterase may reflect the disease state of COVID-19 pneumonia, suggesting that a patient’s cholinesterase level on admission may be useful as a predictor of severity and prognosis.

Background Veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) is one of the ultimate treatments for acute respiratory failure. However, the effectiveness of ECMO in patients with novel coronavirus disease (COVID‐19) is unknown. Case Presentation A 72‐year‐old woman who was a passenger of a cruise ship tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) while in quarantine on board using throat swab. Three days after admission, her condition deteriorated, and she was subsequently intubated. On day 6, VV‐ECMO was introduced. Lopinavir/ritonavir was given; continuous renal replacement therapy was also introduced. On day 10, her chest radiography and lung compliance improved. She was weaned off ECMO on day 12. Conclusion Treatment of severe pneumonia in COVID‐19 by ECMO should recognize lung plasticity considering time to ECMO introduction and interstitial biomarkers. In Japan, centralization of ECMO patients has not been sufficient. Thus, we suggest nationwide centralization and further research to respond to the crisis caused by COVID‐19., ECMO is one of the treatment options in severe ARDS by SARS‐CoV‐2. It is important to recognize lung plasticity. Centralization of COVID‐19 ECMO patients may be effective in Japan.

Retinoic acid-related orphan receptor gamma (RORγ) plays pivotal roles in autoimmune diseases by controlling the lineage of interleukin 17 (IL-17)-producing CD4+ T cells (Th17 cells). Structure-based drug design has proven fruitful in the development of inhibitors targeting the ligand binding domain (LBD) of RORγ. Here, we present the crystal structure of a novel RORγ inhibitor co-complex, in the presence of a corepressor (CoR) peptide. This ternary complex with compound T reveals the structural basis for an inhibitory mechanism different from the previously reported inverse agonist. Compared to the inverse agonist, compound T induces about 2 Å shift of helix 5 (H5) backbone and side-chain conformational changes of Met365 on H5. These conformational changes correlate to reduced CoR peptide binding to RORγ-LBD in the presence of compound T, which suggests that the shift of H5 is responsible. This crystal structure analysis will provide useful information for the development of novel and efficacious drugs for autoimmune disorders.

Initial fluid resuscitation is presumed to be important for treating shock in the resuscitation phase. However, little is known how quickly and easily a physician could perform a rapid infusion with a syringe.We hypothesised that using a high-flow three-way stopcock (HTS) makes initial fluid resuscitation faster and easier than using a normal-flow three-way stopcock (NTS).This was a simulation study with a prospective, nonblinded randomised crossover design. Twenty physicians were randomly assigned into two groups. Each participant used six peripheral intravenous infusion circuits, three with the HTS and the others with the NTS, and three cannulae, 22, 20, and 18 gauge (G). The first group started with the HTS first, while the other started with the NTS first. They were asked to inject the fluid as quick as possible. We compared the time until the participants finished rapid infusions of 500 ml of 0.9% saline and the practitioner's effort.In infusion circuits attached with the 22G cannula, the mean difference using the HTS and the NTS (95% confidence interval [CI]) was 16.30 ml/min (7.65-24.94) (p 0.01). In those attached with the 20G cannula, the mean difference (95% CI) was 23.47 (12.43-34.51) (p 0.01). In those attached with the 18G cannula, the mean difference (95% CI) was 42.53 (28.68-56.38) (p 0.01).This study revealed that the push-and-pull technique using the HTS was faster, easier, and less tiresome than using the NTS, with a statistically significant difference. In the resuscitation phase, initial and faster infusion is important. If only a single physician or other staff member such as a nurse is attending or does not have accessibility to any other devices in such an environment where medical resources are scarce, performing the push-and-pull technique using the HTS could help a physician to perform fluid resuscitation faster. By setting up the HTS instead of the NTS from the beginning, we would be able to begin fluid resuscitation immediately while preparing other devices.

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) for patients with traumatic torso hemorrhagic shock is available to keep a minimum level of circulatory status as a bridge to definitive therapy. However, the trajectory for placement of REBOA in the aorta has not yet been clearly defined. Methods We conducted a retrospective observational cohort study in the two tertiary critical care and emergency center from December 2014 to October 2018. A total of 28 patients who underwent focused assessment with sonography for trauma (FAST) were studied via contrast computed tomography (CT), and 27 were analyzed. Results We divided patients into two groups based on our CT findings. The REBOA deflate group included 16 patients, and the inflate group included 11 patients. The median trace value (interquartile range) of the blood vessel center line from the common femoral artery to the tip of REBOA (blood vessel length) and the length of REBOA itself from the common femoral artery to the tip of REBOA (REBOA insertion length) were 56.2 cm (54.5–57.2) and 55.2 cm (54.2–55.6), respectively (p

Whirling Electrical Discharge Texturing (WEDT) was developed as a method of creating microstructures by a single-pulse discharge on the inner surface of a cylinder. In a previous study, a textured surface was successfully created on the inner surface of a cylinder, and it was clarified that the surface characteristics of the textured surface such as the texture-area ratio can be controlled by adjusting the texturing conditions. In this study, a new WEDT device was developed to create microstructures on the surface of a disc workpiece for the ball-on-disc or the pin-on-disc friction test. This paper describes texturing characteristics such as the texture-area ratio, crater depth and crater diameter on a disc workpiece surface and friction characteristics measured by the pin-on-disc friction test. From the results of texturing experiments, it was confirmed that the texture-area ratio can be controlled by adjusting the feed speed of the workpiece, and the diameter and depth of a crater do not depend on the feed speed. In the pin-on-disc friction test, the tip of a pin has a spherical shape with large spherical radius to prevent partial contact. As a result, the friction coefficients under the boundary lubrication condition and the mixed lubrication condition near the boundary lubrication condition were decreased by WEDT. It was confirmed that the textured surface created by WEDT is effective for reducing friction coefficient and an optimal texture-area ratio exists depending on the lubrication conditions.

Retinoid-related orphan receptor gamma (RORγ) directly controls the differentiation of Th17 cell and the production of interleukin-17, which plays an integral role in autoimmune diseases. To obtain insight into RORγ, we have determined the first crystal structure of a ternary complex containing RORγ ligand-binding domain (LBD) bound with a novel synthetic inhibitor and a repressor peptide, 22-mer peptide from silencing mediator of retinoic acid and thyroid hormone receptor (SMRT). Comparison of a binary complex of nonliganded (apo) RORγ-LBD with a nuclear receptor co-activator (NCoA-1) peptide has shown that our inhibitor displays a unique mechanism different from those caused by natural inhibitor, ursolic acid (UA). The compound unprecedentedly induces indirect disruption of a hydrogen bond between His479 on helix 11 (H11) and Tyr502 on H12, which is crucial for active conformation. This crystallographic study will allow us to develop novel synthetic compounds for autoimmune disease therapy.

Discharge duration and pulse frequency are studied to determine the optimum conditions for creating a single crater. In addition, the relationships between pulse frequency and surface characteristics using Whirling Electrical Discharge Texturing (WEDT) are determined. It is confirmed that the texture-area ratio and the total removal volume of craters, but not crater diameter or crater depth, can be controlled by adjusting pulse frequency. Moreover, after honing, surface characteristics decrease owing to the removal of protrusions. With honing, the surface roughness of the textured surface leads to a reduced friction coefficient as expected.

This paper describes a highly efficient deburring technology that employs Whirling Electrical Discharge Machining (Whirling EDM). Whirling EDM was developed because burrs on the backside of smalldiameter holes, such as cross-drilled holes are not easy to remove. Many short circuits occur, due to the design of the compliant tool and the tool’s uncontrollable deflection. Therefore, a feedback circuit was developed in order to increase the probability of normal discharge. In conclusion, normal discharge increased due to the feedback circuit, and Whirling EDM can successfully deburr the backside of small-diameter holes in a highly efficient manner.

The authors developed Whirling Electrical Discharge Texturing (WEDT) in order to reduce friction coefficient of cylinder-shaped parts. In previous research, the authors verified fundamental characteristics of WEDT by observation of textured surface. It was found that a crater shape and texture-area ratio can be controlled by WEDT. The texture-area ratio depends on feed speed of tool electrode. In this research, crater depth, crater diameter, texture area ratio and total removal volume of craters were investigated to confirm characteristics of WEDT in detail. In addition, tungsten wire was used as a whirling shaft in order to improve stability of whirling phenomenon. Moreover, a textured surface was finished by lapping-film in order to remove protrusions around craters and reduce friction coefficient. As a result, it was verified that the texture-area ratio slightly increased with decreasing feed speed and it was confirmed that crater depth, crater diameter, and total removal volume of craters were also related to feed speed.

The structures of old yellow enzyme from Trypanosoma cruzi which produces prostaglandin F2α from PGH2 have been determined in the presence or absence of menadione., Old yellow enzyme (OYE) is an NADPH oxidoreductase which contains flavin mononucleotide as prosthetic group. The X-ray structures of OYE from Trypanosoma cruzi (TcOYE) which produces prostaglandin (PG) F2α from PGH2 have been determined in the presence or absence of menadione. The binding motif of menadione, known as one of the inhibitors for TcOYE, should accelerate the structure-based development of novel anti-chagasic drugs that inhibit PGF2α production specifically.

Now, it is possible to discuss qualitatively the effects of skis, skier’s ski control and slope on a ski turn by simulation. The reliability of a simulation depends on the accuracy of the models used in the simulation. In the present study, we attempt to develop a new ski control model for a “parallel turn” using a computer graphics technique. The “ski control” necessary for the simulation is the relative motion of the skier’s center of gravity to the ski and the force acting on the ski from the skier. The developed procedure is as follows. First, the skier is modeled using a multibody system consisting of body parts. Second, various postures of the skier during the “parallel turn” are drawn using a 3D-CAD (three dimensional computer aided design) system referring to the pictures videotaped on a slope. The position of the skier’s center of gravity is estimated from the produced posture. Third, the skier’s ski control is obtained by arranging these postures in a time schedule. One can watch the ski control on a TV. Last, the three types of forces acting on the ski from the skier are estimated from the gravity force and the three relative types of inertia forces acting on the skier. Consequently, one can obtain accurate ski control for the simulation of the “parallel turn”, that is, the relative motion of the skier’s center of gravity to the ski and the force acting on the ski from the skier. Furthermore, it follows that one can numerically estimate the edging angle from the ski control model.