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Purpose: Although it is important to recognize gender disparities in publishing to achieve gender diversity, women's authorship in Japan remains unclear. Therefore, this study aimed to investigate the percentage and analyze the trends of articles authored and published in anesthesiology journals by Japanese female authors. Methods: The genders of the first and last authors affiliated with Japanese institutions were surveyed in the Journal of Anesthesia (JA) (1990, 1995, and 2000–2022) and 11 international anesthesiology journals (2010–2022). Results: We included 845 and 819 original research articles from JA in the analyses of the first and last authors, respectively. The proportion of female first authors significantly increased from 41 (11.7%) out of 351 before 2009 to 119 (24.1%) out of 494 after 2010 (p < 0.001). The proportion of female last authors was 11 (3.3%) out of 335 before 2009 and 22 (4.5%) out of 484 after 2010, respectively, with no significant difference (p = 0.470). We included 624 and 572 original research articles from international anesthesiology journals in the analyses of first and last authors, respectively. Among these, there were 134 (21.5%) and 23 (4.0%) female first and last authors, respectively. These proportions in international anesthesiology journals did not significantly differ from those in JA (p = 0.334, p = 0.789, respectively). Conclusion: The percentage of female first authors has increased, commensurate with the percentage of female anesthesiologists. However, the percentage of female last authors has not increased and remains low in Japan.

The development of a predictive hepatotoxicity model is highly warranted, as the hepatotoxicity risk goes undetectable in nonclinical studies. Cholestatic drug induced liver injury (DILI) is a condition in which bile acids are not normally excreted into the capillary bile canaliculi and are accumulated in hepatocytes, caused by the inhibition of bile salt export pump (BSEP), a transporter that is mainly associated with excretion of bile acids. Although laboratory animals are used as predicting model, the use of human-derived cells is required due to species differences. Moreover, primary human hepatocytes (PHHs) show rapid loss of function, and difficulties in forming bile canaliculi in vitro. Therefore, we aimed to develop an in vitro culture method for efficient formation of bile canaliculi and the function of BSEP in PHHs. Here, PHHs were cultured from 1 h after thawing to day 2 with Z-VAD-FMK, a total caspase inhibitor, and RevitaCell™ supplement, an irreversible Rho -associated coiled-coil forming kinase (ROCK) inhibitor, in combination with RM-101. The PHHs were able to form bile canaliculi and show BSEP function on day 6 of culture. Therefore, these cultured PHHs may serve as an accurate predicting model for cholestatic DILI.

Erythropoiesis-stimulating agents (ESAs) are a standard treatment for patients with renal anemia to increase hemoglobin (Hb) levels and reduce their need for blood transfusions. However, treatments targeting high Hb levels require high doses of ESAs by the intravenous injection which are associated with an elevated risk of adverse cardiovascular events. In response to this key limitation other erythropoietin-promoting medications have been developed such as hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PH inhibitor). This post-hoc analysis of two clinical trials evaluates patients’ treatment satisfaction with a HIF-PH inhibitor, molidustat, compared to a standard ESA, darbepoetin alfa, as part of therapy for patients with non-dialysis chronic kidney disease (CKD) and renal anemia. Exploratory outcome data using the Treatment Satisfaction Questionnaire for Medicine version II (TSQM-II) showed that both arms in both trials had increased treatment satisfaction over the course of the study period as well as improvements in most TSQM-II domains at week 24. Molidustat was associated with convenience domain scores at multiple timepoints depending on the trial and more patients were highly satisfied with the convenience of molidustat compared to darbepoetin alfa. Patients treated with molidustat also had increases in global satisfaction domain scores compared to darbepoetin alfa, but the differences s in global satisfaction domain scores were not significant. These patient-reported satisfaction outcomes provide findings supporting the use of molidustat as a patient-centered treatment option for CKD-related anemia.

Background Remimazolam confers a lower risk of hypotension than propofol. However, no studies have compared the efficacy of remimazolam and propofol administered using target-controlled infusion (TCI). This study aimed to investigate hemodynamic effects of remimazolam and target-controlled propofol in middle-aged and elderly patients during the induction of anesthesia. Methods Forty adults aged 45–80 years with the American Society of Anesthesiologists Physical Status 1–2 were randomly assigned to remimazolam or propofol group (n = 20 each). Patients received either remimazolam (12 mg/kg/h) or propofol (3 μg/mL, TCI), along with remifentanil for inducing anesthesia. We recorded the blood pressure, heart rate (HR), and estimated continuous cardiac output (esCCO) using the pulse wave transit time. The primary outcome was the maximum change in mean arterial pressure (MAP) after induction. Secondary outcomes included changes in HR, cardiac output (CO), and stroke volume (SV). Results MAP decreased after induction of anesthesia in both groups, without significant differences between the groups (− 41.1 [16.4] mmHg and − 42.8 [10.8] mmHg in remimazolam and propofol groups, respectively; mean difference: 1.7 [95% confidence interval: − 8.2 to 4.9]; p = 0.613). Furthermore, HR, CO, and SV decreased after induction in both groups, without significant differences between the groups. Remimazolam group had significantly shorter time until loss of consciousness than propofol group (1.7 [0.7] min and 3.5 [1.7] min, respectively; p p = 0.341). Conclusions Hemodynamics were not significantly different between remimazolam and target-controlled propofol groups during induction of anesthesia. Thus, not only the choice but also the dose and usage of anesthetics are important for hemodynamic stability while inducing anesthesia. Clinicians should monitor hypotension while inducing anesthesia with remimazolam as well as propofol. Trial registration UMIN-CTR (UMIN000045612).

Background Elderly populations are particularly vulnerable to influenza and often require extensive clinical support. In Japan, nationwide passive surveillance monitors seasonal influenza but does not capture the full disease burden. We synthesized existing evidence on the epidemiology, vaccine effectiveness (VE), and economic burden of seasonal influenza in the elderly population. Methods PubMed, EMBASE, and ICHUSHI were searched for articles on seasonal influenza in Japan, published between 1997 and 2018, in English or Japanese. Grey literature was also assessed. A random‐effects meta‐analysis characterized VE of influenza vaccines among studies reporting this information. Results Of 1,147 identified articles, 143 met inclusion criteria. Reported incidence rates varied considerably depending on study design, season, study setting and, most importantly, case definition. In nursing homes, the maximum reported attack rate was 55.2% and in the 16 articles reporting mortality rates, case fatality rates varied from 0.009% to 14.3%. Most hospitalizations were in people aged >60; healthcare costs were partially mitigated by vaccine administration. Meta‐analysis estimated overall VE of 19.1% (95% CI: 2.3% ‐ 33.0%) with a high proportion of heterogeneity (I2: 89.1%). There was a trend of lower VE in older people (40.1% [−57.3‐77.2] in the

Single cell arrays provide an accurate classification of analyte cells through an image-based analysis of cellular phenotypes. Light-guided cell retrieval from a single cell array is a promising approach for the rapid and simple sorting of difficult to distinguish cells. In this study, we developed a single cell array enclosed with a photodegradable hydrogel in microwells to enable both comprehensive image-based single cell analysis and light-guided cell retrieval. In this system, individual cells became trapped in the microwells together with the photodegradable hydrogel at a high cell density on a chip regardless of cell type, adhesiveness, and motility. Fluorescence-stained model cells and vaccinated dendritic cells were identified by microscopic imaging and then selectively released through the light-induced degradation of the cell-embedding hydrogels. The target cells were selectively retrieved with a purity of95% from the cell mixture through rapid photorelease, and the retrieved cells were confirmed to grow normally. Our results provide proof-of-principle that the photoresponsive microwell array serves as a versatile tool for image-based cell sorting in cellular researches and the manufacturing processes of high-performance cells.

Background Previous studies showed that remifentanil-induced anesthesia can inhibit surgical stress response in non-diabetic adult patients and that low-dose glucose loading during anesthesia may attenuate fat catabolism. However, little is known about the influence of glucose loading on metabolism in elderly patients, whose condition may be influenced by decreased basal metabolism and increased insulin resistance. We hypothesized that, in elderly patients, intraoperative low glucose infusion may attenuate the catabolism of fat without causing harmful hyperglycemia during remifentanil-induced anesthesia. Methods Elderly, non-diabetic patients scheduled to undergo elective surgery were enrolled and randomized to receive no glucose (0G group) or low-dose glucose infusion (0.1 g/kg/hr. for 1 h followed by 0.05 g/kg/hr. for 1 h; LG group) during surgery. Glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, free fatty acid (FFA), creatinine (Cr), and ketone body levels were measured pre-anesthesia, 1 h post-glucose infusion, at the end of surgery, and on the following morning. Results A total of 31 patients (aged 75–85) were included (0G, n = 16; LG, n = 15). ACTH levels during anesthesia decreased significantly in both groups. In the LG group, glucose levels increased significantly after glucose loading but hyperglycemia was not observed. During surgery, ketone bodies and FFA were significantly lower in the LG group than the 0G group. There were no significant differences in insulin, Cr, 3-MH, and 3-MH/Cr between the two groups. Conclusion Remifentanil-induced anesthesia inhibited surgical stress response in elderly patients. Intraoperative low-dose glucose infusion attenuated catabolism of fat without inducing hyperglycemia. Trial registration This study has been registered with the University hospital Medical Information Network Center (http://www.umin.ac.jp/english/). Trial registration number: UMIN000016189. The initial registration date: January 12th 2015.

Herein, we evaluated CYPs and their nuclear receptor mRNA induction by exposure to typical inducers, omeprazole, rifampicin, and phenobarbital in cynomolgus monkey hepatocytes. Six freshly-isolated hepatocytes and 6 cryopreserved hepatocytes from cynomolgus monkey liver were prepared for a 14-day monolayer culture, 28-day co-culture with feeder cells, and 28-day 3D spheroid culture with feeder cells. Omeprazole and rifampicin respectively induced CYP1A1 and CYP3A8 mRNAs, while phenobarbital induced CYP2C43, CYP2C75, and CYP3A8, and slightly induced CYP2B6. The nuclear receptors AHR, PXR, and CAR mRNA levels, which were activated by omeprazole, rifampicin, and phenobarbital, respectively, tended to decrease via exposure to inducers despite the increase in CYP mRNA levels. These trends were similar for all three culture methods. No evident difference was observed in CYP mRNA induction between fresh and cryopreserved hepatocytes. Based on mRNA levels, the co-culture and 3D spheroid culture methods are more reasonable than monolayer culture for CYP evaluation, because the use of feeder cells can reduce the number of hepatocytes, improve the cell adhesion, and maintain the mRNA expression levels. In addition, co-culture method is more cost-effective, as common culture plates can be used.

International labor mobility is a key factor for a well-functioning labor market. Although educational attainment is known to affect regional labor mobility within a country, evidence of a relationship between schooling and international labor mobility is limited, particularly in developing countries. This study uses the across-cohort variation in the exposure to the 1988 free secondary education reform in the Philippines to examine the impact of years of education on the propensity of working abroad. The results suggest that free secondary education increased the years of education for men. Moreover, the additional years of education reduced the likelihood of working abroad by 3.2% points on average. However, an extra year of female education was not associated with the probability of working abroad. These results indicate that a program for improving access to secondary education may affect international labor mobility for men even after a few decades. It underscores the importance of considering the possible labor market consequences when designing the education reform in developing countries.

The liver microphysiological system (MPS) model is an in-vitro culture method that mimics physiological blood flow, which enhances basal cellular functions. However, the liver MPS model has not been tested in the preclinical stage because of its obscure utility. It can overcome the major problem of conventional systems-rapid loss of mitochondrial activity in cultured hepatocytes due to limited oxygen supply-by supplying oxygen to cultured hepatocytes using a perfusion device. In this study, we developed a new perfusion culture system that can detect mitochondrial toxicity. Primary mouse hepatocytes were cultured under perfusion condition for 48 hr. The hepatocytes showed increased oxygen consumption and reduced lactate release. These results indicated that the ATP-production pathway was switched from glycolysis to mitochondrial oxidative phosphorylation in the perfusion culture system. Furthermore, ATP levels were considerably reduced in the perfusion culture system after exposure to phenformin, a mitochondrial complex I inhibitor. To summarize, the perfusion culture system could improve the mitochondrial activity in primary mouse hepatocytes, and thus, has potential implications in the detection of mitochondrial toxicity.

We conducted a systematic review to investigate the effectiveness of clinical treatments for wet age-related macular degeneration (wAMD) in Japanese patients in the decade since anti-vascular endothelial growth factor (VEGF) therapies were introduced.PubMed was searched for articles published in English between 1 January 2008 and 30 September 2018 using a multistring search strategy. Reviews were scanned for additional relevant studies and select gray literature was evaluated. Mean and/or median for the logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), central retinal thickness (CRT), and the number of injections after 12 months of treatment were calculated using extracted data. Data were stratified by disease type and treatment modality.Of 335 studies identified, 94 were selected for data extraction (147 treatment arms; typical AMD, n = 25; polypoidal choroidal vasculopathy [PCV], n = 85). Mean (median) logMAR VA was 0.44 (0.32) for typical AMD and 0.34 (0.31) for PCV; the respective mean number of anti-VEGF injections was 5.6 and 4.6. The mean CRT was approximately 220 μm for both groups. For typical AMD, anti-VEGF monotherapy resulted in better VA outcomes than photodynamic therapy (PDT) alone. For PCV, anti-VEGF monotherapy or anti-VEGF plus PDT combination therapy resulted in better VA and CRT outcomes than PDT monotherapy. Combination therapy required fewer injections than anti-VEGF monotherapy (PCV, 3.2 versus 5.3).wAMD treatment has advanced dramatically in the years since anti-VEGF drugs were introduced in Japan. Discrete patient populations may benefit from differing management regimens, including the fewer injections required with combination therapy.

The black crystalline (aza)triangulene-based covalent organic framework TANG-COF was synthesized from its trinitro-TANG precursor via a one-pot, two-step reaction involving Pd-catalyzed hydrogenati...

Two types of amniotic fluid embolism (AFE) have been described : cardiopulmonary collapse type and disseminated intravascular coagulation (DIC) type, with the latter proposed as uterine type. This report describes a healthy 28-year-old woman who developed AFE during a cesarean section. Because of a previous cesarean section, the patient underwent an elective cesarean section, under combined spinal-epidural anesthesia, at 38 weeks of pregnancy. She began coughing 5 minutes after delivery of the fetus, subsequently becoming unconscious and developing glossoptosis and bradycardia. Her blood pressure decreased to 76/43 mmHg, and AFE was suspected. Her uterus was atonic, and she experienced persistent noncoagulant bleeding, with a final blood loss of 6300 ml. Considerable blood transfusion was required. The patient survived, and she and her baby were discharged without any sequelae on the eighth postoperative day. This patient met the Japanese criteria for clinical AFE, with an obstetrical DIC score of 21 meeting the criteria for obstetrical DIC. Early diagnosis and treatment likely resulted in patient survival. J. Med. Invest. 67 : 207-210, February, 2020.

Cholestatic drug-induced liver injury (DILI) is a type of hepatotoxicity. Its underlying mechanisms are dysfunction of bile salt export pump (BSEP) and multidrug resistance-associated protein 2/3/4 (MRP2/3/4), which play major roles in bile acid (BA) excretion into the bile canaliculi and blood, resulting in accumulation of BAs in hepatocytes. The sandwich-cultured hepatocyte (SCH) model can simultaneously analyze hepatic uptake and biliary excretion. Therefore, we investigated whether sandwich-cultured human induced pluripotent stem cell (iPS cell)-derived hepatocytes (SCHiHs) are suitable for evaluating cholestatic DILI. Fluorescent N-(24-[7-(4-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole)]amino-3α,7α,12α-trihydroxy-27-nor-5β-cholestan-26-oyl)-2'-aminoethanesulfonate (tauro-nor-THCA-24-DBD, a BSEP substrate) was accumulated in bile canaliculi, which supports the presence of a functional bile canaliculi lumen. MRP2 was highly expressed in the Western blot analysis, whereas the mRNA expression of BSEP was hardly detectable. MRP3/4 mRNA levels were maintained. Of the 22 compounds known to cause DILI with BAs, 7 showed significant cytotoxicity. Most high-risk drugs were detected using the developed SCHiH system. However, a shortcoming was the considerably low expression level of BSEP, which prevented the detection of some relevant drugs whose risks should be detected in primary human hepatocytes.

International audience; A molecular packing model of poly(3-hexylthiophene)-block-peracetylated maltopheptaose (P3HT-b-AcMal7) was proposed based on the X-ray and electron diffraction measurements. The P3HT and AcMal7 segments are confined in the lamellae in which the AcMal7 segments are aligned side by-side. The extended P3HT chain segments are tilted with respect to the lamellar plane and strongly π-stacked. This molecular arrangement results from a subtle balance between segregation strength of the P3HT and AcMal7 blocks, strong π–π interactions of the P3HT backbones, geometrical mismatch between two blocks, space filling requirement, and entropic penalties. The small-angle X-ray scattering (SAXS) analysis above the melting temperature of P3HT block indicates strong segregation strength between P3HT and AcMal7 blocks. Differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, and SAXS measurements underline the improved thermal stability of P3HT crystalline domains in the phase-separated P3HT-b-AcMal7.

Robot-assisted laparoscopic radical prostatectomy (RALRP) is commonly performed in the surgical treatment of prostate cancer. However, the steep Trendelenburg position (25) and pneumoperitoneum required for this procedure can sometimes cause hemodynamic changes. Although blood pressure is traditionally monitored invasively during RALRP, the ClearSight system (BMEYE, Amsterdam, The Netherlands) enables a totally noninvasive and simple continuous blood pressure and cardiac output monitoring based on finger arterial pressure pulse contour analysis. We therefore investigated whether noninvasive continuous arterial blood pressure measurements using the ClearSight system were comparable to those obtained invasively in patients undergoing RALRP. Ten patients scheduled for RALRP with American Society of Anesthesiologists physical status I-II were included in this study. At each of the seven defined time points, noninvasive and invasive blood pressure measurements were documented and compared in each patient using Bland-Altman analysis. Although the blood pressure measured with the ClearSight system correlated with that measured invasively, a large difference between the values obtained by the two devices was noted. The ClearSight system was unable to detect blood pressure accurately during RALRP, suggesting that blood pressure monitoring using this device alone is not feasible in this small patient population. J. Med. Invest. 65:69-73, February, 2018.

Background. It is well known that the programmed intermittent epidural bolus (PIEB) technique effectively provides epidural anesthesia in labor. This randomized double-blind trial compared the postoperative analgesic efficacy of PIEB with that of continuous epidural infusion (CEI) in patients undergoing gynecological surgery under combined general-epidural anesthesia. Methods. Patients undergoing open gynecological surgery under combined general-epidural anesthesia were randomized at a 1 : 1 ratio to receive PIEB or CEI. In the PIEB group, the pump delivered 4 mL ropivacaine 0.2% plus fentanyl 2 μg/mL every hour. In the CEI group, the pump delivered the same solution at a rate of 4 mL/h. In both groups, additional 4 mL boluses of ropivacaine 0.2% plus fentanyl 2 μg/mL were provided, when necessary, by patient-controlled epidural analgesia after surgery. The primary outcome was the total ropivacaine dose 40 hours after surgery. The secondary outcomes were the number of PCEA boluses and postoperative pain (evaluated on an 11-point numerical rating scale) 3, 24, and 48 hours after surgery. Results. In total, 57 patients were randomized (n=28 and 29 in the PIEB and CEI groups, resp.). The two groups differ significantly in terms of the total ropivacaine dose 40 hours after surgery (mean (standard deviation): 155.38 (4.55) versus 159.73 (7.87) mL, P=0.016). Compared to the CEI group, the PIEB group had significantly lower numerical rating scale scores 3 hours (median [lower–upper quartiles]: 0 [0–0.5] versus 3 [0–5.5], P=0.002), 24 hours (1 [0–2] versus 3 [1–4], P=0.003), and 48 hours (1 [0–2] versus 2 [2–3.5], P=0.002) after surgery. Conclusion. PIEB was better than CEI in terms of providing postoperative analgesia after open gynecological surgery under combined general-epidural anesthesia.

This paper illustrates the sharp contrast in welfare impacts between the rich and the poor caused by typhoon Milenyo in a Philippine village. We find that fish prices dropped sharply due to the damage caused to fish pens near the village, leading to positive net welfare gains among the wealthy. In contrast , the poor do not consume much fish and thus did not gain from the sharp decline in prices. Finally, co nsumption reallocation played an important role as an ex post risk coping measure, albeit only among the wealthy, who are relatively well protected against typhoons., Embargo Period 24 months, http://www.grips.ac.jp/list/jp/facultyinfo/estudillo_jonna/

Study Objective : the incidence of postoperative nausea and vomiting (PONV) following single-injection intraarticular anesthesia was compared to that following continuous epidural anesthesia. Design : Prospective, double-blind, randomized study. Setting : University-affiliated teaching hospital. Patients : Forty-eight patients finally participated in this study, and each group contained twenty-four patients. Interventions : Patients scheduled to undergo lower limb surgery under general anesthesia were randomly allocated into two groups, to receive either single-injection intraarticular or continuous epidural anesthesia for postoperative analgesia. Measurements : The incidence and severity of PONV, complete response rates (i.e., no vomiting or rescue antiemetic use), and pain scores were recorded 2, 24, and 48 h postoperatively. Main results : No significant differences between groups were observed in the incidence and severity of PONV, rescue antiemetic use, or complete response rate at any of the time points, but only the use of rescue analgesics was significantly less in continuous epidural anesthesia group during the 2-24h postoperative period (P=0.04). Conclusion : While the use of single-injection intraarticular anesthesia following lower limb surgery did not prevent PONV more than continuous epidural anesthesia in this study, the intraarticular technique still provides greater simplicity, safety, and cost-effectiveness. J. Med. Invest. 66 : 303-307, August, 2019.

Bilirubin oxidase has a post-translationally formed covalent-bond between the imidazole ring of His398 coordinated to type I copper and the indole ring of Trp396 located in the outer-coordination sphere. We performed point mutations at Trp396 with Ala, Thr, Phe, and Tyr with the aim of elucidating the role of the imidazole-indole moiety found only in bilirubin oxidase. The result showed shifts in the redox potential of type I copper towards negative direction by > 100 mV and decreases in cathodic current in electrochemistry, whereas optical and magnetic properties of type I copper were not affected or sparingly affected. Along with the conspicuous changes in redox properties enzymatic activities of the Trp396 mutants were prominently decreased. Further, chemical modification of the Trp residues with N-bromosuccinimide and photo-induced formylations of bilirubin oxidase exerted more pronounced effects on both redox properties and enzymatic activities compared to the Trp396 mutants. All these results unequivocally indicate that the covalent-bond formed between Trp396 and His398 plays a crucial role to enhance enzymatic activities of bilirubin oxidase by shifting the redox potential of type I Cu towards positive direction and also by functioning as the effective pathway of electron transport.

In this study, freshly isolated and cryopreserved cynomolgus monkey hepatocytes were seeded on Cell-able® plates with feeder cells to form spheroids and were cultured for 28 days. As a control, hepatocytes were also cultured with or without feeder cells on collagen-coated plates. We verified the mRNA expression levels of drug-metabolizing enzyme-related genes and the leakage of enzymes (AST, ALT, LDH, and γ-GTP) as indicators of cell survival. As a result, the patterns of target mRNA expression in fresh and cryopreserved hepatocytes were very similar during the culture period between culture methods. mRNA expression levels were highly maintained at day 28 using the 3D spheroid and co-culture methods, demonstrating that these methods are useful for maintenance of liver function. Leakage of AST and ALT was higher at day 3 but decreased at day 14. LDH was not detected, suggesting that the cell viability was also maintained during the culture period. Furthermore, the functional differences between fresh and cryopreserved hepatocytes were not clearly detected. The co-culture method was useful for long-term culture not requiring 3D structure, and the 3D spheroid culture method was effective as well. With these techniques, cynomolgus monkey hepatocytes are expected to exhibit smaller individual differences and high reproducibility.

We investigated the effectiveness of the ClearSight system for hemodynamic management during kidney transplantation for a recipient. The recipient was to receive a kidney transplant from his mother under general anesthesia. We used continuous noninvasive finger-cuff-based monitoring of blood pressure, provided by the ClearSight system, and stroke volume variation to predict fluid responsiveness. We used of a balanced anesthetic technique and stringent monitoring standards to ensure a successful outcome for the patient. This case demonstrated that ClearSight has the potential to improve patient monitoring in hemodynamically stable patients who received kidney transplantation under general anesthesia. J. Med. Invest. 65:139-141, February, 2018.

Background : Recent studies have shown that strict perioperative blood glucose management may reduce mortality and morbidity in critically ill adult patients. The purpose of this study was to assess the accuracy and efficacy of the intraoperative application of a newly developed, next-generation artificial endocrine pancreas (STG-55, Nikkiso Co., Ltd., Tokyo, Japan). Methods : Twenty patients scheduled to undergo surgery were enrolled in this study. The STG-55 is designed to be more user-friendly than its conventional counterpart (STG-22) while maintaining the latter’s fundamental functions, such as a closed-loop system using algorithms for insulin and glucose infusion. After anesthetic induction, a 20G intravenous catheter was inserted into a peripheral forearm vein and connected to a continuous blood glucose monitor. The resultant 105 scores for paired blood glucose values were compared by Bland-Altman analysis. Results : Stable blood glucose values were maintained automatically, and there were no complications related to use of the STG-55. A close correlation (r=0.96) was observed between continuous glucose measurements using the STG-55 and conventional intermittent glucose measurements. The difficulty of manipulation using this system was decreased by improved preparation procedures. Conclusion : The glycemic control system using the STG-55 could provide an alternative way to achieve effective and safe perioperative glycemic control.

We here report the synthesis of a new class of carbohydrate-based block copolymers, poly(3-hexylthiophene)-block-peracetylated maltoheptaose (P3HT-b-AcMal7) and poly(3-hexylthiophene)-block-maltoheptaose (P3HT-b-Mal7), and their bulk and self-assembled thin films morphological characterizations by atomic force microscopy, transmission electron microscopy, and small-angle X-ray scattering. The block copolymers were synthesized via copper(I)-catalyzed 1,3-dipolar azide–alkyne cycloaddition of azido-functionalized AcMal7 and end-functionalized P3HT with alkyne group prepared by modified Grignard metathesis polymerization, followed by deacetylation of the AcMal7 block. The half-pitch of sub-10 nm scale lamellar structures, one of the smallest domain sizes of microphase separated block copolymers reported to date, was self-organized in the bulk and thin films of P3HT-b-AcMal7 by thermal annealing above the melting temperature of the P3HT segment. Meanwhile, thermodynamic microphase separation of P3HT-b-Mal7 wa...

This study identifies the relationship between tsunami damage and mortality through a demographic pyramid of a town severely damaged by the tsunami following the Great East Japan Earthquake of 11 March 2011. It uses cross-sectional data collection. Volunteers visited all households, including shelters, and asked residents about the whereabouts of family members and neighbours. The information was collated with lists of evacuees and the dead to confirm the whereabouts of all residents about 50 days after the disaster. Demographic pyramids for the whole population based on pre- and post-disaster data were drawn. In all, 1,412 (8.8 per cent) were dead or missing, 60.2 per cent of whom were aged 65 and over and 37.5 per cent aged 75 and over, suggesting that the very old should be located beyond the reach of tsunamis. The mortality rate of children was lower than that in other studies, which may indicate the efficacy of disaster evacuation drills.

Aims Geranylgeranylacetone (GGA) is commonly utilized to protect the gastric mucosa in peptic ulcer disease. Recently GGA has been shown to protect the myocardium from ischemia/reperfusion by activating heat shock proteins. However, the exact mechanism as to how GGA activates these protective proteins is unknown. Caveolae and caveolin-3 (Cav-3) have been implicated in ischemia, anesthetic, and opioid induced cardiac protection. Given the lipophilic nature of GGA it is our hypothesis that GGA induced cardiac protection requires caveolae and Cav-3. Main methods We used an in vivo mouse model of ischemia–reperfusion injury and performed biochemical assays in excised hearts. Key findings GGA treated control mice revealed increased caveolae formation and caveolin-3 in buoyant fractions, mediating heat shock protein 70 activation. Furthermore, control mice treated with GGA were protected against ischemia/reperfusion injury whereas Cav-3 knockout (Cav-3 KO) mice were not. Troponin levels confirmed myocardial damage. Finally, Cav-3 KO mice treated with GGA were not protected against mitochondrial swelling whereas control mice had significant protection. Significance This study showed that caveolae and caveolin-3 are essential in facilitating GGA induced cardiac protection by optimizing spatial and temporal signaling to the mitochondria.

Pharmacological preconditioning, including that with geranylgeranylacetone (GGA) and volatile anesthetics, has been shown to confer cardiac protection from ischemia/reperfusion injury although the mechanisms for this protection are poorly understood. Caveolins, integral membrane proteins that act as scaffolding proteins in caveolar membranes, localize molecules involved in cardiac protection. We have tested the hypothesis that caveolin-3 (Cav-3), the predominant isoform in cardiac myocytes, is essential for the synergistic effect observed between GGA and volatile anesthetics.Mice were randomly assigned to receive GGA, isoflurane [0.5 and 1.0 minimum alveolar concentration (MAC)], or GGA + isoflurane (0.5 MAC). An in vivo mouse model of ischemia/reperfusion injury was tested in wild-type and Cav-3 knockout mice, and the infarct size was determined. Biochemical assays were also performed in excised hearts.Geranylgeranylacetone and therapeutic isoflurane (1.0 MAC) independently reduced infarct size (31.6 ± 6.1 and 28.0 ± 5.0% of the area at risk, respectively; n = 10) as compared to the controls (45.8 ± 9.4%; n = 10). The combination GGA + sub-therapeutic isoflurane (0.5 MAC) further decreased the infarct size to 19.3 ± 5.1% (n = 10). Preconditioning [GGA, isoflurane (1.0 MAC), and GGA + isoflurane] increased the amount of Cav-3 protein in the discontinuous sucrose-gradient buoyant fractions. Additionally, cardiac protection was not observed in Cav-3 knockout mice following the administration of GGA, isoflurane, and GGA + isoflurane.Combined administration of GGA + isoflurane had a synergistic effect, enhancing the protection against myocardial infarction to a greater extent than either drug alone. This beneficial effect is mediated by Cav-3 expression.

Toxicological approaches in screening drugs that cause drug-induced liver injury (DILI) are urgently needed to reduce the risk of developing DILI and avoid immense costs resulting from late-stage drug withdrawal from clinical trials. Cholestatic DILI is characterized by bile acid (BA) accumulation in hepatocytes, typically caused by drug-induced inhibition of important bile transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2/3/4 (MRP2/3/4). Therefore, NTCP expression is essential for construction of an in vitro hepatocellular toxicity evaluation system. Here, we investigated whether sandwich-cultured HepG2-hNTCP-C4 (SCHepG2-hNTCP-C4) cells were applicable for evaluation of cholestatic DILI. In SCHepG2-hNTCP-C4 cells, NTCP and MRP2/4 expression levels were comparable to those in human primary hepatocytes; however, BSEP expression was low. In addition, the substrates tauro-nor-THCA-24 DBD and CDF confirmed the functionality of NTCP and MRP2, respectively. When 22 known hepatotoxins were exposed to BAs to evaluate cholestatic DILI, cytotoxicity in SCHepG2-hNTCP-C4 cells was more frequent than that in SCHepG2 cells. Thus, SCHepG2-hNTCP-C4 cells may be useful preclinical screening tools to predict the risk of cholestatic DILI induced by drug candidates. However, further studies are needed to determine why the cholestatic cytotoxicity of some compounds would be still insufficient in SCHepG2-hNTCP-C4 cells.

Background : Propofol causes vasodilation via endothelium-dependent and -independent mechanisms. Because endothelial function is impaired with aging, the effects of propofol on endothelium-dependent vasodilation might be altered by aging. The aim of this study was thus to determine the effects of aging on vascular responses to propofol. Methods : Young (4-6 weeks old) or adult (16-25 weeks old) rats were anesthetized with sevoflurane. The thoracic aorta was dissected and cut into pieces 3-4mm in length. In some rings, the endothelium was deliberately removed. The ring segment of the aorta was mounted for isometric force recording at a resting tension of 0.5-1.0 g in a 2 ml organ bath, containing Krebs-Ringer bicarbonate buffer. Arteries were precontracted with phenylephrine, and the function of endothelium was confirmed with acetylcholine. Then, we studied the concentration-dependent effects of propofol in endothelium-intact (control group) and -denuded aortic rings (denuded group), as well as those treated with N[ω]-nitro-L-arginine methylester (L-NAME group). Results : Relaxation due to propofol was observed in the control groups of both young and adult rats in a concentration-dependent manner, but the magnitude of relaxation was significantly greater in young rats. In addition, in young rats, relaxation due to propofol was significantly and equally reduced in both L-NAME and denuded groups at all propofol concentrations that we studied (10[-6]-10[-3] M). In adult rats, relaxation due to propofol was quite similar between control and L-NAME groups at all propofol concentrations, whereas it was significantly reduced in the denuded group. Conclusion : These results suggest that endothelium-derived nitric oxide plays an important role in propofol-induced vasodilation in young rats, but not in adult rats.