Comprehensive Application of XFEL Microcrystallography for Challenging Targets in Various Organic Compounds.

There is a growing demand for structure determination from small crystals, and the three-dimensional electron diffraction (3D ED) technique can be employed for this purpose. However, 3D ED has certain limitations related to the crystal thickness and data quality. We here present the application of serial X-ray crystallography (SX) with X-ray free electron lasers (XFELs) to small (a few µm or less) and thin (a few hundred nm or less) crystals of novel compounds dispersed on a substrate. For XFEL exposures, two-dimensional (2D) scanning of the substrate coupled with rotation enables highly efficient data collection. The recorded patterns can be successfully indexed using lattice parameters obtained through 3D ED. This approach is especially effective for challenging targets, including pharmaceuticals and organic materials that form preferentially oriented flat crystals in low-symmetry space groups. Some of these crystals have been difficult to solve or have yielded incomplete solutions using 3D ED. Our extensive analyses confirmed the superior quality of the SX data regardless of crystal orientations. Additionally, 2D scanning with XFEL pulses gives an overall distribution of the samples on the substrate, which can be useful for evaluating the properties of crystal grains and the quality of layered crystals. Therefore, this study demonstrates that XFEL crystallography has become a powerful tool for conducting structure studies of small crystals of organic compounds.

Application and Efficacy of Vitamin E-Bonded Polysulfone Membrane in Acute Blood Purification Therapy.

INTRODUCTION: Acute blood purification therapy (BPT) has been evaluated in the context of intensive care for serious conditions related to systemic inflammation, but its mechanism and efficacy are not fully understood. OBJECTIVE: This study examined the feasibility of using vitamin E-bonded polysulfone membranes (VEPS) for BPT in a LPS-induced rat model of systemic inflammation. METHODS: To evaluate the efficacy of BPT with a VEPS membrane, polysulfone (PS) membranes conventionally used in intensive care were bonded with the antioxidant vitamin E and used in a rat model of lipopolysaccharide (LPS)-induced systemic inflammation. BPT using a PS membrane (PS group) or a VEPS membrane (VEPS group) was performed 6 h after administration of LPS. Extracorporeal circulation was established in normal rats as a control (sham group). Survival rates, histology of lung specimens, and levels of myeloperoxidase (MPO) and high mobility group box-1 (HMGB-1) were examined in each group. RESULTS: Survival rates at 24 h after LPS administration were 100% in the VEPS group and 50% in the PS group. Pulmonary architecture was largely maintained and the level of infiltration of inflammatory cells remained moderate in the VEPS group. Levels of active MPO before and after BPT were significantly higher in the PS and VEPS groups than in the sham group, with no significant differences between the PS and VEPS groups. HMGB-1 levels were significantly elevated after BPT in the PS group. CONCLUSIONS: This study demonstrated that use of the VEPS membrane for BPT increased survival rate and reduced lung injury in a rat model of systemic inflammatory response syndrome (SIRS), suggesting the possible use of VEPS membranes in the treatment of serious conditions related to systemic inflammation.

Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects.

BACKGROUND: A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler® device (IND/GLY/MF) is being developed for treatment of asthma. This study compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d. METHODS: This was a single-center, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 µg (inhaled corticosteroid [ICS] medium-dose) or 150/50/160 µg o.d. (ICS high-dose) for 14 days in each period. Pharmacokinetics were characterized up to 24 h post-dose on Days 1 and 14. RESULTS: In total, 16 Japanese (median age 31 years [range 20-40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range 21-43 years], mean weight 75.0 kg) were randomized. Geometric mean ratios (Japanese/Caucasian) [90% confidence interval (CI)] for Cmax for IND, GLY and MF at the high ICS dose on Day 14 were 1.31 [1.13, 1.51] 1.38 [1.13, 1.69] and 1.07 [0.969, 1.18], respectively. Geometric mean ratios (Japanese/Caucasian) [90% CI] for AUC0-24h on Day 14 for IND, GLY and MF at the high ICS dose were 1.17 [1.01, 1.35], 1.05 [0.920, 1.20] and 1.15 [1.05, 1.27] respectively. Similar trends were noted for all components for the medium ICS dose treatment. IND/GLY/MF was safe and well tolerated; no AEs suspected to be study drug-related were observed. CONCLUSION: Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as a fixed-dose combination were comparable between Japanese and Caucasian subjects. The IND/GLY/MF combination at the administrated doses was safe and well tolerated in both ethnic groups. TRIAL REGISTRATION: Japan Registry of Clinical Trial: jRCT2031200227, retrospectively registered on 04, December, 2020.

In vitro blood compatibility evaluation method: incubating while rotating hemodialyzers filled with fresh human blood.

One of the often-used methods for in vitro evaluation of the blood compatibility of hemodialysis membranes is the circulation of human blood through a miniaturized hemodialyzer. The use of a rather small amount of human blood in its evaluation is one advantage of this method. However, because it is manufactured by a different process than actual ones, a miniaturized hemodialyzer membrane cannot always preserve the properties of actual hemodialyzers. To address this problem, we established a new experimental method that uses a relatively small amount of human blood and actual dialyzers. In this method, a test hemodialyzer and a control hemodialyzer filled with human blood obtained from the same donor is slowly rotated to prevent spontaneous blood cell sedimentation for 4 h at 37 °C. By use of this method, we were able to compare blood compatibility between a polysulfone (PS) membrane and a vitamin E (VE)-bonded PS membrane in terms of their relative antithrombotic, antioxidative, and anti-inflammatory properties. Consistent with many previous reports, the results clearly showed that compared with the PS membrane, VE-bonded PS membrane is more blood compatible. These findings suggest that our method is applicable, at least to in vitro blood compatibility evaluation of PS type dialysis membranes.

Modified enhanced recovery after surgery (ERAS) protocols for patients with obstructive colorectal cancer.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are now well-known to be useful for elective colorectal surgery, as they result in shorter hospital stays without adversely affecting morbidity. However, the efficacy and safety of ERAS protocols for patients with obstructive colorectal cancer have yet to be clarified. METHODS: We evaluated 122 consecutive resections for obstructive colorectal cancer performed between July 2008 and November 2012 at Tokyo Metropolitan Bokutoh Hospital. Patients with rupture or impending rupture and those who received simple colostomy were excluded. The first set of 42 patients was treated based on traditional protocols, and the latter 80 according to modified ERAS protocols. The main endpoints were length of postoperative hospital stay, postoperative short-term morbidity, rate of readmission within 30 days, and mortality. Differences in modified ERAS protocols relative to traditional care include intensive preoperative counseling (by both surgeons and anesthesiologists), perioperative fluid management (avoidance of sodium/fluid overload), shortening of postoperative fasting period and early provision of oral nutrition, intraoperative warm air body heating, enforced postoperative mobilization, stimulation of gut motility, early removal of urinary catheter, and a multidisciplinary team approach to care. RESULTS: Median (interquartile range) postoperative hospital stay was 10 (10-14.25) days in the traditional group, and seven (7-8.75) days in the ERAS group, showing a 3-day reduction in hospital stay (p < 0.01). According to the Clavien-Dindo classification, overall incidences of grade 2 or higher postoperative complications for the traditional and ERAS groups were 15 and 10% (p = 0.48), and 30-day readmission rates were 0 and 1.3% (p = 1.00), respectively. As for mortality, one patient in the traditional group died and none in the ERAS group (p = 0.34). CONCLUSION: Modified ERAS protocols for obstructive colorectal cancer reduced hospital stay without adversely affecting morbidity, indicating that ERAS protocols are feasible for patients with obstructive colorectal cancer.

Vitamin E-Coated Polysulfone Membrane-Based Hemodiafiltration Attenuates Inflammation in a Rat Model of Lipopolysaccharide-Induced Systemic Inflammation.

BACKGROUND: Acute blood purification (ABP) therapy is used regularly in the clinical setting and reportedly alleviates organ failure associated with severe systemic inflammatory responses, leading to reduced mortality. The present study aimed to determine whether there is a difference in efficacy between polysulfone (PS) membranes, which are currently used regularly in the clinical setting, and vitamin E-coated polysulfone (VEPS) membranes, which are anticipated to exhibit the antioxidant and anti-inflammatory properties of vitamin E. METHODS: Male Wistar rats (n=15/group) were intravenously administered 10 mg/kg of lipopolysaccharide (LPS) to establish a systemic inflammatory response model. Six hours after LPS administration, hemodiafiltration (HDF) was performed for 30 minutes using a PS or VEPS membrane under general anesthesia. Blood was collected at various time points, lung tissue was evaluated histologically, and 24-hour survival was assessed. RESULTS: The rats in the VEPS group tended to have a higher survival rate than those in the PS group when undergoing HDF, although the difference was not significant. With respect to lung tissue, the inflammatory response was suppressed to a greater extent in the VEPS group than the PS group. Serum interleukin (IL)-6 levels were reduced at an early stage, plasma antioxidant activity was increased, and oxidative stress was reduced in the VEPS group compared to the PS group. CONCLUSION: Relative to PS membrane-based HDF, the survival rate tended to improve and inflammation was subdued earlier due to the antioxidant activity and early attenuation of inflammation associated with VEPS membrane-based HDF.

Enhanced recovery after surgery (ERAS) protocols for colorectal cancer in Japan.

BACKGROUND: Japan has one of the highest five-year relative survival rates for colorectal cancer in the world, with its own traditions of perioperative care and a unique insurance system. The benefits of enhanced recovery after surgery (ERAS) protocols in the Japanese population have yet to be clarified. METHODS: We evaluated 352 consecutive cases of colorectal cancer resection at Tokyo Metropolitan Bokutoh Hospital between July 2009 and November 2012. Of these, 95 cases were performed according to traditional protocols (traditional group), and 257 according to ERAS protocols (ERAS group), which were introduced to the hospital in July 2010. Primary endpoints included length of postoperative hospital stay, postoperative short-term morbidity, and rate of readmission within 30 days. Intensive pre-admission counselling, no pre- and postoperative fasting (provision of oral nutrition), avoidance of sodium/fluid overload, intraoperative warm-air body heating, enforced postoperative mobilization, and multimodal team care were among the main changes brought about by the introduction of ERAS protocols. RESULTS: The median (interquartile range) length of postoperative hospital stay was 10 (10-12.75) days in the traditional group and seven (6-8) days in the ERAS group, i.e., a three-day reduction (p < 0.05) in the ERAS group. Moreover, the proportion of patients discharged within one week dramatically increased from 1 % to 77 % in the ERAS group. The overall incidence of grade 2 and 3 postoperative complications according to the Clavien-Dindo classification was 9.5 % in the traditional group and 9.3 % in the ERAS group, and 30-day readmission rates were 8.3 % and 6.6 % in the traditional and ERAS groups, respectively. There were no significant differences between the two groups. Although operative time and blood loss did not differ significantly between the two groups, the volume of intraoperative infusion was significantly decreased in the ERAS group (p < 0.05), possibly due to ERAS recommendations to avoid dehydration (i.e., avoidance of sodium/fluid overload, no preoperative fasting). CONCLUSION: ERAS protocols for colorectal surgery helped reduce the length of postoperative hospital stay without adversely affecting morbidity, indicating that ERAS protocols are feasible and effective in Japanese settings as well.

Fabrication of alumina films with laminated structures by ac anodization.

Anodization techniques by alternating current (ac) are introduced in this review. By using ac anodization, laminated alumina films are fabricated. Different types of alumina films consisting of 50-200 nm layers were obtained by varying both the ac power supply and the electrolyte. The total film thickness increased with an increase in the total charge transferred. The thickness of the individual layers increased with the ac voltage; however, the anodization time had little effect on the film thickness. The laminated alumina films resembled the nacre structure of shells, and the different morphologies exhibited by bivalves and spiral shells could be replicated by controlling the rate of increase of the applied potentials.

Flip-flop dynamics in smectic liquid-crystal organic semiconductors revealed by molecular dynamics simulations.

Asymmetric liquid-crystal (LC) organic semiconductors, such as 2-decyl-7-(p-tolyl)-[1]benzothieno[3,2-b][1]benzothiophene (pTol-BTBT-C10), exhibit high mobilities exceeding 10 cm2 V-1 s-1. The LC phases play important roles in thermal stability and self-assembly ordering during film deposition and annealing. In this study, we show molecular dynamics simulations of pTol-BTBT-C10 and reveal a unique mechanism of the molecular flip-flop motion at the smectic E/smectic B phase transition.

Control of Polar/Antipolar Layered Organic Semiconductors by the Odd-Even Effect of Alkyl Chain.

Some rodlike organic molecules exhibit exceptionally high layered crystallinity when composed of a link between π-conjugated backbone (head) and alkyl chain (tail). These molecules are aligned side-by-side unidirectionally to form self-organized polar monomolecular layers, providing promising 2D materials and devices. However, their interlayer stacking arrangements have never been tunable, preventing the unidirectional arrangements of molecules in whole crystals. Here, it is demonstrated that polar/antipolar interlayer stacking can be systematically controlled by the alkyl carbon number n, when the molecules are designed to involve effectively weakened head-to-head affinity. They exhibit remarkable odd-even effect in the interlayer stacking: alternating head-to-head and tail-to-tail (antipolar) arrangement in odd-n crystals, and uniform head-to-tail (polar) arrangement in even-n crystals. The films show excellent field-effect transistor characteristics presenting unique polar/antipolar dependence and considerably improved subthreshold swing in the polar films. Additionally, the polar films present enhanced second-order nonlinear optical response along normal to the film plane. These findings are key for creating polarity-controlled optoelectronic materials and devices.

Continuous ultrasound navigation for safe and precise anatomic resection of the liver.

BACKGROUND/AIM: Anatomic resection of the liver is one of the essential techniques in liver surgery. However, parenchymal transection precisely along intersegmental planes is still a technically demanding procedure, and an optimal navigation method is required. METHODOLOGY: Real-time ultrasound monitoring with a probe applied from behind the liver was tried as a means of locating the site where resection was proceeding in the liver and confirming the direction of hepatic parenchymal transection to facilitate anatomic resection of the liver. RESULTS: The ultrasound navigation technique was performed during 11 hepatectomies in 10 patients in whom adequate retrohepatic space could be obtained to position the ultrasound probe. Continuous monitoring of the site in the liver where the resection was being performed was feasible, and the optimal direction of parenchymal transection was easily determined on the basis of the ultrasound images without interrupting the surgical maneuvers. The mean speed of parenchymal transection was faster (2.4cm2/min vs. 1.2cm2/min, p=0.009) and the amount of blood loss per transected area was smaller (4.4mL/cm2 vs. 7.2mL/cm2, p=0.05) in patients treated with the current technique. CONCLUSIONS: Continuous ultrasound monitoring of the liver facilitates the safe and precise parenchymal transection during anatomic resections of the liver.

Cognitive process modelling of controllers in en route air traffic control.

In recent years, various efforts have been made in air traffic control (ATC) to maintain traffic safety and efficiency in the face of increasing air traffic demands. ATC is a complex process that depends to a large degree on human capabilities, and so understanding how controllers carry out their tasks is an important issue in the design and development of ATC systems. In particular, the human factor is considered to be a serious problem in ATC safety and has been identified as a causal factor in both major and minor incidents. There is, therefore, a need to analyse the mechanisms by which errors occur due to complex factors and to develop systems that can deal with these errors. From the cognitive process perspective, it is essential that system developers have an understanding of the more complex working processes that involve the cooperative work of multiple controllers. Distributed cognition is a methodological framework for analysing cognitive processes that span multiple actors mediated by technology. In this research, we attempt to analyse and model interactions that take place in en route ATC systems based on distributed cognition. We examine the functional problems in an ATC system from a human factors perspective, and conclude by identifying certain measures by which to address these problems. This research focuses on the analysis of air traffic controllers' tasks for en route ATC and modelling controllers' cognitive processes. PRACTITIONER SUMMARY: This research focuses on an experimental study to gain a better understanding of controllers' cognitive processes in air traffic control. We conducted ethnographic observations and then analysed the data to develop a model of controllers' cognitive process. This analysis revealed that strategic routines are applicable to decision making.

[A case of small intestinal cancer with peritoneal metastases treated with FOLFOX regimen].

A38 -year-old man complaining of abdominal pain was diagnosed with small intestinal cancer. Small intestinal endoscopy and PET-CT showed a primary jejunal cancer and five peritoneal metastases. Partial resection of the jejunum with three metastases was performed, but the others were unresectable. After surgery, FOLFOX chemotherapy was adapted. Follow-up pelvic CT showed a remarkable reduction of tumor size during FOLFOX chemotherapy after 4 courses, and follow-up PET-CT showed no tumor intake FDG after 10 courses. We judged him to be a complete response and stopped chemotherapy. After 7 months, the patient's level of tumor markers elevated, and there was recurrence. We resumed FOLFOX, and the chemotherapy for this patient is still being continued.

Insulating Polymer Blend Organic Thin-Film Transistors Based on Bilayer-Type Alkylated Benzothieno[3,2-b]naphtho[2,3-b]thiophene.

Herein, we developed a practical method to produce high-performance organic thin-film transistors (OTFTs) based on highly layered crystalline organic semiconductors (OSCs) that form bilayer-type layered herringbone (b-LHB) packing and exhibit high intrinsic mobility. We applied the insulating polymer blend technique using a typical b-LHB OSC of 2-octyl-benzothieno[3,2-b]naphtho[2,3-b]thiophene (2-C8-BTNT) and fabricated polycrystalline thin-film transistors (TFTs) via short-duration spin coating and subsequent annealing. The use of blends and the choice of polymer additive strongly affected the performance of the polycrystalline TFTs, and poly(methyl methacrylate) (PMMA) blend TFTs exhibited a high mobility exceeding 4 cm2/(V s) and small device-to-device variations. Using extended techniques in atomic force microscopy (AFM), we investigated the thin-film morphologies by bimodal AFM and the carrier transport properties by Kelvin probe force microscopy (KPFM). We demonstrated that the PMMA blend system enables the formation of a well-ordered polycrystalline thin film induced by vertical phase separation between the OSC and PMMA over a large area, resulting in uniform TFT performance. These findings pave the way for obtaining high-performance TFTs using simple processes, representing a substantial advancement toward the realization of printed electronics.

Fabrication of silica glass containing yellow oxynitride phosphor by the sol-gel process.

We have prepared silica glass by the sol-gel method and studied its ability to disperse the Ca-α-SiAlON:Eu2+ phosphor for application in white light emitting diodes (LEDs). The emission color generated by irradiating doped glass with a blue LED at 450 nm depended on the concentration of SiAlON and the glass thickness, resulting in nearly white light. The luminescence efficiency of 1-mm-thick glass depended on the SiAlON concentration, and was highest at 4 wt% SiAlON.

[Change of surgeons' opinion against anesthesiologists after introduction of enhanced recovery after surgery (ERAS) protocols: questionnaire survey among surgeons who participated ERAS care].

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols aim to improve patient care, reducing complication rates, and shortening hospital stay following colorectal surgery in Europe. In cooperation of colorectal surgeons and anesthesiologists, ERAS protocols were initially introduced in our hospital to the patients who underwent open colorectal resection in July 2010. METHODS: Using a questionnaire, we surveyed the change of surgeons' opinion against anesthesiologists after introduction of ERAS among 15 surgeons at Metropolitan Bokutoh hospital. RESULTS: Surgeons realized that introduction of ERAS made strong communication between surgeons and anesthesiologists. And they also thought it is not surgeons themselves nor anesthesiologists themselves but 'team care' which could produce positive outcome of ERAS. CONCLUSIONS: Introduction of ERAS as collaboration of surgeons and anesthesiologists resulted in facilitating communication of surgeons and anesthesiologists.

Corrigendum: Protein and Organic-Molecular Crystallography with 300kV Electrons on a Direct Electron Detector.

[This corrects the article DOI: 10.3389/fmolb.2020.612226.].

Electrochemical design of two-dimensional Au nanocone arrays using porous anodic alumina membranes with conical holes.

We report step-by-step electrochemical design of two-dimensional (2D) Au nanocone arrays by using novel porous anodic alumina membranes with conical holes. The cones with desirable aspect ratios can be fabricated by using the PAA templates with different aspect ratios. The Au nanocone arrays show high potentials as SERS (Surface Enhanced Raman Scattering)-active substrates and Au electrodes with high surface area.

Aerosol-assisted synthesis of thiol-functionalized mesoporous silica spheres with Fe3O4 nanoparticles.

Thiol-functionalized mesoporous silica spheres having Fe3O4 nanoparticles are fabricated in one-pot by aerosol-assisted synthesis. A TEM image shows that Fe3O4 nanoparticles are successfully embedded within the mesoporous silica spheres. SEM images and SAXS profiles reveals that the encapsulating Fe3O4 nanoparticles do not affect the ordering of a mesoporous structure. The spherical morphologies are also well retained. The presence of cage-type mesopores with uniform size is confirmed by N2 adsorption-desorption isotherms and TEM observations. The spray-dried thiol-functionalized particles with Fe3O4 nanoparticles effectively adsorb mercury (II) ions due to their strong interaction to thiol groups embedded in the framework. The particles with the amount of Fe3O4 nanoparticles (3.5 wt%) show a saturated magnetization (over 1.0 emu/g). This magnetic property is useful for practical collection with magnet.

Protein and Organic-Molecular Crystallography With 300kV Electrons on a Direct Electron Detector.

Electron 3D crystallography can reveal the atomic structure from undersized crystals of various samples owing to the strong scattering power of electrons. Here, a direct electron detector DE64 was tested for small and thin crystals of protein and an organic molecule using a JEOL CRYO ARM 300 electron microscope. The microscope is equipped with a cold-field emission gun operated at an accelerating voltage of 300 kV, quad condenser lenses for parallel illumination, an in-column energy filter, and a stable rotational goniometer stage. Rotational diffraction data were collected in an unsupervised manner from crystals of a heme-binding enzyme catalase and a representative organic semiconductor material Ph-BTBT-C10. The structures were determined by molecular replacement for catalase and by the direct method for Ph-BTBT-C10. The analyses demonstrate that the system works well for electron 3D crystallography of these molecules with less damaging, a smaller point spread, and less noise than using the conventional scintillator-coupled camera.