Quantitative and calculated estimated blood loss in cesarean deliveries for twin and singleton pregnancies: a retrospective analysis.

PURPOSE: This study retrospectively assessed blood loss during cesarean deliveries for twin and singleton pregnancies using two distinct methods, quantitative estimation measured during cesarean sections and hematocrit-based calculated estimation. METHODS: We included scheduled cesarean deliveries for twin or singleton pregnancies at ≥ 34 weeks of gestation. Quantitative blood loss was recorded based on the blood volume in the graduated collector bottle and by weighing the blood-soaked textiles during cesarean sections. The blood loss was calculated using the change in hematocrit levels before and after the cesarean delivery. RESULTS: We evaluated 403 cases including 44 twins and 359 singletons. Quantitative blood loss during cesarean section was significantly higher in twin pregnancies than that in singleton pregnancies (1117 [440] vs 698 [378] mL; p < 0.001). However, no significant differences were observed in the calculated blood loss between the two groups on the day after delivery (487 mL [692 mL] vs 507 mL [522 mL]; p = 0.861). On post-delivery days 4-5, twin pregnancies were associated with a significantly higher calculated blood loss than singleton pregnancies (725 [868] mL vs 444 [565] mL, p = 0.041). Although a significant moderate correlation between quantitative and calculated blood loss was observed in singleton pregnancies (r = 0.473, p < 0.001), no significant correlation was observed between twin pregnancies (r = 0.053, p = 0.735). CONCLUSION: Quantitative blood loss measurements during cesarean section may be clinically insufficient in twin pregnancies. Incorporating blood tests and continuous assessments are warranted for enhanced blood loss evaluation, especially in twin pregnancies, owing to the risk of persistent bleeding.

Hemodynamic impact of ephedrine on hypotension during general anesthesia: a prospective cohort study on middle-aged and older patients.

BACKGROUND: Ephedrine is a mixed α- and ß-agonist vasopressor that is frequently used for the correction of hypotension during general anesthesia. ß-responsiveness has been shown to decrease with age; therefore, this study aimed to determine whether aging would reduce the pressor effect of ephedrine on hypotension during general anesthesia. METHODS: Seventy-five patients aged ≥ 45 years were included in this study, with 25 patients allocated to each of the three age groups: 45-64 years, 65-74 years, and ≥ 75 years. All patients received propofol, remifentanil, and rocuronium for the induction of general anesthesia, followed by desflurane and remifentanil. Cardiac output (CO) was estimated using esCCO technology. Ephedrine (0.1 mg/kg) was administered for the correction of hypotension. The primary and secondary outcome measures were changes in the mean arterial pressure (MAP) and CO, respectively, at 5 min after the administration of ephedrine.  RESULTS: The administration of ephedrine significantly increased MAP (p < 0.001, mean difference: 8.34 [95% confidence interval (CI), 5.95-10.75] mmHg) and CO (p < 0.001, mean difference: 7.43 [95% CI, 5.20-9.65] %) across all groups. However, analysis of variance revealed that the degree of elevation of MAP (F [2, 72] = 0.546, p = 0.581, η2 = 0.015 [95% CI, 0.000-0.089]) and CO (F [2, 72] = 2.023, p = 0.140, η2 = 0.053 [95% CI, 0.000-0.162]) did not differ significantly among the groups. Similarly, Spearman's rank correlation and multiple regression analysis revealed no significant relation between age and the changes in MAP or CO after the administration of ephedrine. CONCLUSION: The administration of ephedrine significantly increased MAP and CO; however, no significant correlation with age was observed in patients aged > 45 years. These findings suggest that ephedrine is effective for the correction of hypotension during general anesthesia, even in elderly patients. TRIAL REGISTRATION: UMIN-CTR (UMIN000045038; 02/08/2021).

Comparison of hemodynamics during induction of general anesthesia with remimazolam and target-controlled propofol in middle-aged and elderly patients: a single-center, randomized, controlled trial.

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 < 0.001). However, MAP, HR, CO, and SV were not significantly different between the groups despite adjusting time until loss of consciousness as a covariate. Seven (35%) and 11 (55%) patients in the remimazolam and propofol groups, respectively, experienced hypotension (MAP < 65 mmHg over 2.5 min), without significant differences between the groups (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).

Development of a Communication Tool between Patients and Physicians for Recognizing COPD Exacerbations in Japan.

In Japan, exacerbations are underreported compared with other countries, possibly due in part to a failure to recognize them. This study aimed to create a simple chronic obstructive pulmonary disease (COPD) Exacerbation Recognition Tool (CERT-J) specifically for Japanese patients. Patients ≥40 years with confirmed COPD or asthma-COPD overlap were included. Focus groups were held to identify words and phrases used by patients to describe symptoms associated with an exacerbation, resulting in candidate items being identified. Following cognitive debriefing, the items were refined based on item frequency, level of endorsement and effect of demographic factors. Exploratory factor analysis (EFA) was then performed to inform an expert panel's choice of items to form the new tool. A total of 41 patients were included in the focus groups and nine patients performed the cognitive debrief. Following this, the expert panel identified 26 items for testing in a further 100 patients (mean age 72 years, forced expiratory volume in 1 s 54.8% predicted and 1.8 exacerbations in the preceding 12 months). Eleven items were associated with breathlessness or activity limitation and seven of these were the most frequently endorsed. EFA identified four factors, with one (breathlessness) being dominant. The expert panel recommended that the CERT-J should include six items: breathlessness and activity limitation (3 items), cough (1 item) and phlegm (2 items). The final CERT-J should benefit patients with COPD by providing them with an increased understanding and recognition of exacerbations.Clinical Trial Registration: GSK K.K (jRCT1080224526).

Authorship by gender in anesthesiology journals: a retrospective cross-sectional study for Japan.

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.

Desflurane improves lung collapse more than propofol during one-lung ventilation and reduces operation time in lobectomy by video-assisted thoracic surgery: a randomized controlled trial.

BACKGROUND: This study evaluated whether desflurane improved lung collapse during one-lung ventilation (OLV) more than propofol, and whether it could reduce the operation time of video-assisted thoracic surgery. METHODS: Sixty patients undergoing lobectomy by video-assisted thoracic surgery (VATS) were randomly assigned to general anesthesia with desflurane or propofol. Lungs were inspected by thoracoscope at 10, 30, and 60 min after initiation of OLV. After surgery, the Lung Collapse Score, a composite of lung color and volume assessments, was assigned by two clinicians blinded to the anesthetic regimen. The primary outcome was operation time. The secondary outcome included the complication rate. RESULTS: Of the 60 participants, 50 completed the study, 26 in Desflurane group and 24 in Propofol group. The Lung Collapse Scores at 30 and 60 min after OLV initiation were significantly better in Desflurane group than in Propofol group, and operation time was significantly shorter in Desflurane group (214 (57) min vs. 262 (72) min [mean (SD)], difference in means, -48; 95% CI, -85 to -11; P = 0.01). The incidence of multiple complications was 1/26 (3%) and 6/24 (25%) in Desflurane and Propofol group, respectively (relative risk, 0.1; 95% CI, 0.02 to 1.18; P = 0.04). CONCLUSIONS: Desflurane improved lung collapse during OLV and significantly shortened VATS lobectomy operation time compared to propofol in our studied patients. Desflurane resulted in fewer postoperative complications. Thus, desflurane may be an appropriate anesthetic during lobectomy by VATS requiring OLV. TRIAL REGISTRATION: The study was registered with the University Hospital Medical Information Network ( UMIN000009412 ). The date of disclosure of this study information is 27/11/2012. On this date, we registered the study into UMIN; patients were included from 2013 to 2014. However, on 11/27/2015, the UMIN system administrator suggested a detailed description. Thereafter, we added it to the Randomization Unit. Despite being prospective, it was retrospectively registered on UMIN for the above reasons.

Transition in eye gaze as a predictor of emergence from general anesthesia in children and adults: a prospective observational study.

BACKGROUND: It is useful to monitor eye movements during general anesthesia, but few studies have examined neurological finding of the eyes during emergence from general anesthesia maintained with short-acting opioids and volatile anesthetics. METHODS: Thirty children aged 1-6 years and 30 adults aged 20-79 years were enrolled. Patients received general anesthesia maintained with sevoflurane and remifentanil. The timing of three physical-behavioral responses-eye-gaze transition (the cycle from conjugate to disconjugate and back to conjugate), resumption of somatic movement (limbs or body), and resumption of respiration-were recorded until spontaneous awakening. The primary outcome measure was the timing of the physical-behavioral responses. Secondary outcome measures were the incidence of eye-gaze transition, and the bispectral index, concentration of end-tidal sevoflurane, and heart rate at the timing of eye-gaze transition. RESULTS: Eye-gaze transition was evident in 29 children (96.7%; 95% confidence interval, 82.8-99.9). After the end of surgery, eye-gaze transition was observed significantly earlier than resumption of somatic movement or respiration (472 [standard deviation 219] s, 723 [235] s, and 754 [232] s, respectively; p < 0.001). In adults, 3 cases (10%; 95% CI, 0.2-26.5) showed eye-gaze transition during emergence from anesthesia. The incidence of eye-gaze transition was significantly lower in adults than in children (p < 0.001). CONCLUSION: In children, eye-gaze transition was observed significantly earlier than other physical-behavioral responses during emergence from general anesthesia and seemed to reflect emergence from anesthesia. In contrast, observation of eye gaze was not a useful indicator of emergence from anesthesia in adults.

Roles of the indole ring of Trp396 covalently bound with the imidazole ring of His398 coordinated to type I copper in bilirubin oxidase.

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.

The effect of 1% glucose loading on metabolism in the elderly patients during remifentanil-induced anesthesia: a randomized controlled trial.

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.

Effect of oral carbohydrate with amino acid solution on serum oxidative/anti-oxidative status in healthy volunteers.

The aim of this work was to investigate the effect of oral carbohydrate with amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in healthy persons. Fourteen healthy volunteers were segregated into control and ONS groups. Volunteers in the ONS group ingested 250 ml of Arginaid Water (Nestle Japan, Tokyo, Japan) in the evening before the experiment and at 7:00 am on the day of the experiment. Volunteers in the control group fasted after dinner and drank only water until 7:00 am on the day of the experiment. In both groups, blood was collected at 9:00 am. The serum total oxidant levels and antioxidant capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites) test and BAP (biological antioxidant potential) test, respectively. In the ONS group, the serum d-ROMs level was significantly lower than in the control group (297 ± 43 and 327 ± 41 U.CARR, respectively, p = 0.018), while the serum BAP level was significantly higher than the control group (2410 ± 432 and 1979 ± 397 µmol/l, respectively, p = 0.005). The OXY level of Arginaid Water was much higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that an ONS with arginine loading could decrease oxidative stress and increase antioxidant capacity in healthy volunteers.

Exendin-4 ameliorates cardiac ischemia/reperfusion injury via caveolae and caveolins-3.

BACKGROUND: Exendin-4, an exogenous glucagon-like peptide-1 receptor (GLP-1R) agonist, protects the heart from ischemia/reperfusion injury. However, the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for exendin-4 induced cardiac protection using in vitro and in vivo studies in control and caveolin-3 (Cav-3) knockout mice (Cav-3 KO). METHODS: Myocytes were treated with exendin-4 and then incubated with methyl-ß-cyclodextrin (MßCD) to disrupt caveolae formation. This was then followed by simulated ischemia/reperfusion (SI/R). In addition, cardiac protection in vivo was assessed by measuring infarct size and cardiac troponin levels. RESULTS: Exendin-4 protected cardiac myocytes (CM) from SI/R [35.6 ± 12.6% vs. 64.4 ± 18.0% cell death, P = 0.034] and apoptosis but this protection was abolished by MßCD (71.8 ± 10.8% cell death, P = 0.004). Furthermore, Cav-3/GLP-1R co-localization was observed and membrane fractionation by sucrose density gradient centrifugation of CM treated with MßCD + exendin-4 revealed that buoyant (caveolae enriched) fractions decreased Cav-3 compared to CM treated with exendin-4 exclusively. Furthermore, exendin-4 induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 25.1 ± 8.2% vs. 41.4 ± 4.1%, P < 0.001; troponin: 36.9 ± 14.2 vs. 101.1 ± 22.3 ng/ml, P < 0.001). However, exendin-4 induced cardiac protection was abolished in Cav-3 KO mice (infarct size: 43.0 ± 6.4%, P < 0.001; troponin: 96.8 ± 26.6 ng/ml, P = 0.001). CONCLUSIONS: We conclude that caveolae and caveolin-3 are critical for exendin-4 induced protection of the heart from ischemia/reperfusion injury.

Quantitative measurement of femoral condyle cartilage in the knee by MRI: validation study by multireaders.

PURPOSE: To determine reproducibility of the femoral condyle cartilage volume (CV) in cross-sectional and longitudinal studies using various 3D imaging techniques at 1.5 T and 3 T. MATERIALS AND METHODS: In 21 subjects with osteoarthritis, magnetic resonance imaging (MRI) including four different sequences (sagittal 3D fat suppressed spoiled gradient-echo [SPGR] at 1.5 T, fat suppressed fast low angle shot [FLASH] at 3 T, water-excitation dual echo steady state [DESS] at 3 T, and water-excitation multiecho data image combination [MEDIC] at 3 T) were acquired at baseline and ∼1 year later. The CV measured using semiautomated segmentation software by three readers was analyzed. RESULTS: The mean of the interclass correlation coefficient between each reader from SPGR, FLASH, DESS, and MEDIC was 0.899, 0.948, 0.943, and 0.954, respectively. The mean CV (×10(4) mm(3) ) measured by each reader from SPGR/FLASH/DESS/MEDIC sequences was the following in this order: 1.34/1.52/1.50/1.35, 1.21/1.43/1.40/1.27, 1.22/1.37/1.36/1.22, and 1.17/1.36/1.35/1.21 by readers 1, 2, 3 (first analysis), and 3 (second analysis), respectively. There was no statistically significant difference in CV between any readers in any sequences. The CV measured on FLASH and DESS tended to be greater than that on SPGR or MEDIC. CONCLUSION: Inter- and intraobserver reproducibility of cartilage segmentation using semiautomated software was validated. Although there was no statistical significance, there was a tendency of under- or overestimating CV by each sequence.

Simplification of the genetic code: restricted diversity of genetically encoded amino acids.

At earlier stages in the evolution of the universal genetic code, fewer than 20 amino acids were considered to be used. Although this notion is supported by a wide range of data, the actual existence and function of the genetic codes with a limited set of canonical amino acids have not been addressed experimentally, in contrast to the successful development of the expanded codes. Here, we constructed artificial genetic codes involving a reduced alphabet. In one of the codes, a tRNAAla variant with the Trp anticodon reassigns alanine to an unassigned UGG codon in the Escherichia coli S30 cell-free translation system lacking tryptophan. We confirmed that the efficiency and accuracy of protein synthesis by this Trp-lacking code were comparable to those by the universal genetic code, by an amino acid composition analysis, green fluorescent protein fluorescence measurements and the crystal structure determination. We also showed that another code, in which UGU/UGC codons are assigned to Ser, synthesizes an active enzyme. This method will provide not only new insights into primordial genetic codes, but also an essential protein engineering tool for the assessment of the early stages of protein evolution and for the improvement of pharmaceuticals.

The tsunami's impact on mortality in a town severely damaged by the 2011 Great East Japan Earthquake.

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.

Geranylgeranylacetone and volatile anesthetic-induced cardiac protection synergism is dependent on caveolae and caveolin-3.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Self-assembly of maltoheptaose-block-polystyrene into micellar nanoparticles and encapsulation of gold nanoparticles.

The present paper discusses the controlled self-assembly of sugar-containing block copolymer, maltoheptaose-block-polystyrene (MH(1.2k)-b-PS(4.5k)), into micellar nanoparticles of ca. 30 nm radius in aqueous media and their possibility of gold encapsulation. Micellar association of MH(1.2k)-b-PS(4.5k) into nanoparticles was demonstrated by mixing a large amount of water (MH-selective solvent) with a solution of MH(1.2k)-b-PS(4.5k) in a mixture of tetrahydrofuran (THF) (PS-selective solvent) and water with a certain weight fraction [4:1 (w/w) THF/water], where MH(1.2k)-b-PS(4.5k) exists as well-swollen single chains, followed by evaporation of THF. The mean hydrodynamic radii (Rh) of the nanoparticles were determined by dynamic light scattering (DLS) to be ca. 30 and 80 nm depending upon the method of preparation. The resulting nanoparticles were clearly visualized by transmission electron microscopy (TEM), atomic force microscopy (AFM), and field emission gun-scanning electron microscopy (FEG-SEM) imaging and complemented by nanoparticle tracking analysis (NTA) using a NanoSight instrument. The preliminary study of the self-assembly of MH(1.2k)-b-PS(4.5k) in the presence of gold nanoparticles functionalized with PS chains grafted on their surface indicated potential possibilities of encapsulation of gold nanoparticles into the block copolymer nanoparticles in aqueous media.

Culture methods focusing on bile canalicular formation using primary human hepatocytes in a short time.

The development of models for predicting hepatotoxicity is warranted, as the hepatotoxicity risk of 38-51% of compounds is undetectable in nonclinical studies. Cholestatic drug-induced liver injury (DILI) is a condition in which bile acids are abnormally 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 models, the use of human-derived cells is required owing to species differences. Unfortunately, primary human hepatocytes (PHHs) show rapid loss of function in culture and difficulties in forming bile canaliculi. Therefore, we aimed to develop an in vitro culture method for the efficient formation of bile canaliculi and for assessing 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 formed bile canaliculi and showed BSEP function on day 6 of culture. Our findings suggest that cultured PHHs may improve the prediction accuracy of the risks of cholestatic DILI-contained toxicity on bile canaliculi.

A discrete choice experiment on oral and injection treatment preferences among moderate-to-severe psoriasis patients in Japan.

Long-term psoriasis (PsO) management remains challenging. With growing variation in treatment efficacy, cost, and modes of administration, patient preferences for different treatment characteristics are not well understood. A discrete choice experiment (DCE), informed by qualitative patient interviews, was conducted to assess patient preferences for different attributes of PsO treatments; 222 adult patients with moderate-to-severe PsO receiving systemic therapy participated in the DCE web survey. Better long-term efficacy and lower cost were preferred (preference weights p < 0.05). Long-term efficacy had the highest relative importance (RI) and mode of administration was as important as the outcome attributes (efficacy and safety). Patients also preferred oral to injectable administration. In subgroup analyses by disease severity, residence, psoriatic arthritis as a comorbidity, and gender, the trends for each subgroup were the same as the overall population although the extent of RI for administration mode varied. Mode of administration was more important for patients with moderate versus severe disease, or rural versus urban residence. This DCE utilized attributes related to both oral and injectable treatment as well as a broad study population of systemic treatment users. Preferences were further stratified by patient characteristics to explore trends in different subgroups. Understanding the RI of treatment attributes and the attribute trade-offs acceptable to patients helps inform moderate-to-severe PsO systemic treatments decisions.