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Background Among assisted reproductive technologies, frozen thawed embryo transfer (FET) is associated with increased blood loss at delivery. Anesthesiologists need to be aware of new factors that affect postpartum blood loss. This study investigated whether FET cycles with or without hormonal support affect the amount of postpartum bleeding. Methods We conducted a retrospective cohort study of patients admitted for delivery at a single university hospital between January 2015 and December 2018. Patients were divided into no-assisted reproductive technology (No-ART), hormonal cycle FET (HC-FET) and natural cycle FET (NC-FET) group. The primary outcome was the amount of blood loss after delivery (median [interquartile range]), which was compared among the three groups. Multiple regression analysis was performed to investigate the factors affecting blood loss. Results Between 2015 and 2018, 3187 women delivered neonates. In vaginal delivery, postpartum blood loss in the HC-FET group (1060 [830] g) was significantly greater than in the NC-FET group (650 [485] g, P = 0.001) and in the No-ART group (590 [420] g P < 0.001). Multiple linear regression analysis showed that HC-FET (P < 0.001) was one of the independent factors for the amount of bleeding. In cesarean delivery, the HC-FET group had more blood loss than the No-ART group (910 [676] g vs. 784 [524] g, P = 0.039). However, HC-FET was not an independent factor for postpartum blood loss. Conclusions The HC-FET group had more blood loss than the No-ART group for both vaginal and cesarean deliveries. Furthermore, HC-FET was an independent factor that increased postpartum blood loss in vaginal deliveries.

Smooth and elaborate gut motility is based on cellular cooperation, including smooth muscle, enteric neurons and special interstitial cells acting as pacemaker cells. Therefore, spatial characterization of electric activity in tissues containing these electric excitable cells is required for a precise understanding of gut motility. Furthermore, tools to evaluate spatial electric activity in a small area would be useful for the investigation of model animals. We thus employed a microelectrode array (MEA) system to simultaneously measure a set of 8×8 field potentials in a square area of ∼1 mm(2). The size of each recording electrode was 50×50 µm(2), however the surface area was increased by fixing platinum black particles. The impedance of microelectrode was sufficiently low to apply a high-pass filter of 0.1 Hz. Mapping of spectral power, and auto-correlation and cross-correlation parameters characterized the spatial properties of spontaneous electric activity in the ileum of wild-type (WT) and W/W(v) mice, the latter serving as a model of impaired network of pacemaking interstitial cells. Namely, electric activities measured varied in both size and cooperativity in W/W(v) mice, despite the small area. In the ileum of WT mice, procedures suppressing the excitability of smooth muscle and neurons altered the propagation of spontaneous electric activity, but had little change in the period of oscillations. In conclusion, MEA with low impedance electrodes enables to measure slowly oscillating electric activity, and is useful to evaluate both histological and functional changes in the spatio-temporal property of gut electric activity.

Background: Down and feather materials have been commonly used and promoted as natural stuffing for warm clothing and bedding. These materials tend to become more allergenic as they become contaminated with microorganisms, in addition to being subjected to several kinds of chemical treatments. The biological or chemical contaminants in these materials pose a major risk to human health, to consumers and manufacturers alike. Here, we report the development of an integrative evaluation method for down and feather materials to assess bacterial contamination and in vivo toxicity. Methods: To assess bacterial contamination, we quantified 16S ribosomal RNA, performed culture tests, and established a conversion formula. To determine in vivo toxicity, we performed a zebrafish embryo toxicity testing (ZFET). Results: Washing the material appropriately decreases the actual number of bacteria in the down and feather samples; in addition, after washing, 16S rRNA sequencing revealed that the bacterial compositions were similar to those in rinse water. The ZFET results showed that even materials with low bacterial contamination showed high toxicity or high teratogenicity, probably because of the presence of unknown chemical additives. Conclusions: We established an integrative evaluation method for down and feather safety, based on bacterial contamination with in vivo toxicity testing.

Krokinobacter eikastus rhodopsin 2 (KR2) is the first light-driven Na + pump discovered, and is viewed as a potential next-generation optogenetics tool. Since the positively charged Schiff base proton, located within the ion-conducting pathway of all light-driven ion pumps, was thought to prohibit the transport of a non-proton cation, the discovery of KR2 raised the question of how it achieves Na + transport. Here we present crystal structures of KR2 under neutral and acidic conditions, which represent the resting and M-like intermediate states, respectively. Structural and spectroscopic analyses revealed the gating mechanism, whereby the flipping of Asp116 sequesters the Schiff base proton from the conducting pathway to facilitate Na + transport. Together with the structure-based engineering of the first light-driven K + pumps, electrophysiological assays in mammalian neurons and behavioural assays in a nematode, our studies reveal the molecular basis for light-driven non-proton cation pumps and thus provide a framework that may advance the development of next-generation optogenetics. KR2 light-driven Na + pump structure Known microbial rhodopsins were classified into two groups, either outward proton pumps or inward chloride pumps, until the recent discovery of a light-driven Na + -pumping rhodopsin from the marine bacterium Krokinobacter eikastus . This novel protein, termed KR2, is attracting attention as a potential tool for use in optogenetics: its activation would change the sodium concentration of a targeted cell, not just the pH or chloride concentration. Now Osamu Nureki and colleagues have solved two X-ray crystal structures of KR2 and they use them to propose a working model for Na + transport. Based on these structures the authors have designed several mutants of KR2 and successfully engineered a K + -transporting pump.

Background No study has directly compared the outcomes of surgery and concurrent chemoradiotherapy (cCRT) in patients with stage III non-small cell lung cancer (NSCLC) to date. This study aimed to compare the treatment efficacy of complete resection and definitive cCRT. Methods Patients were recruited in this retrospective study from Yokohama Municipal Citizens’ Hospital between January 2013 and December 2022. We analyzed patients with pathological stage III NSCLC who underwent complete surgical resection and those with clinical stage III NSCLC who underwent definitive cCRT. Propensity score matching was performed to balance baseline clinicopathological factors, and the prognoses of patients in each treatment group were examined using Cox proportional hazards regression. Results Of the 923 patients with NSCLC who underwent surgery, 97 with pathologic stage III NSCLC underwent complete resection (surgery group) and 125 with clinical stage III NSCLC underwent cCRT (cCRT group), of whom 54 (43.2%) received consolidation therapy with durvalumab. Overall survival (OS) was significantly higher in the surgery group than in the cCRT group (5-year OS: 60.5% versus 43.0%), hazard ratio [HR] = 0.585, 95% confidence interval [CI]: 0.390–0.877, p  = 0.010). However, no significant difference in OS was found between the two groups after propensity score matching (5-year OS: 59.8% versus 48.1%, HR = 0.728, 95% CI: 0.416–1.277, p  = 0.268). Conclusions The outcomes of the surgery and cCRT groups did not significantly differ in the treatment of stage III NSCLC. Appropriate evaluation of the treatment required should be reviewed on a case-by-case basis.

2-Methylcyclopropane pyrethroid insecticides bearing chiral cyanohydrin esters or chiral ethers and two asymmetric centers on the cyclopropane ring, were synthesized. These compounds were designed using a “reverse connection approach” between the isopropyl group in Fenvalerate, and between two dimethyl groups in an Etofenprox analogue (the methyl, ethyl form), respectively. These syntheses were achieved by accessible ring opening reactions of commercially available (±)-, (R)-, and (S)-propylene oxides using 4-chlorobenzyl cyanide anion as the crucial step, giving good overall yield of the product with >98% ee. The insecticidal activity against the common mosquito (Culex pipiens pallens) was assessed for pairs of achiral diastereomeric (1R*,2S*)-, (1R*,2R*)-cyanohydrin esters, and (1R*,2S*)-, (1R*,2R*)-ethers; only the (1R*,2R*)-ether was significantly effective. For the enantiomeric (1S,2S)-ether and (1R,2R)-ether, the activity was clearly centered on the (1R,2R)-ether. The present stereostructure‒activity relationship revealed that (i) cyanohydrin esters derived from fenvalerate were unexpectedly inactive, whereas ethers derived from etofenprox were active, and (ii) apparent chiral discrimination between the (1S,2S)-ether and the (1R,2R)-ether was observed. During the present synthetic study, we performed alternative convergent syntheses of Etofenprox and novel 4-EtO-type (1S,2S)- and (1R,2R)-pyrethroids from the corresponding parent 4-Cl-type pyrethroids, by utilizing a recently-developed hydroxylation cross-coupling reaction.

Endotherms increase the rate of metabolism in metabolic organs as one strategy to cope with a decline in the temperature of the external environment. However, an additional major contributor to maintenance of body temperature in a cold environment is contraction-based thermogenesis in skeletal muscle. Here, we show that impairment of hind limb muscle contraction by cast immobilization induced a loss of function of skeletal muscle and activated brown adipose tissue (BAT) thermogenesis as a compensatory mechanism. BAT utilizes free branched-chain amino acids (BCAAs) derived from skeletal muscle as an energy substrate for thermogenesis, and interleukin-6 released by skeletal muscle stimulates BCAAs production in muscle for support of BAT thermogenesis. Additionally, this thermoregulatory system between BAT and skeletal muscle may also play an important role in response to cold temperatures or acute stress. Our findings suggest that BAT and skeletal muscle cooperate to maintain body temperature in endotherms.

Background Intraductal papillary neoplasm of the bile duct (IPNB) is a subtype of biliary tumor. The 5-year survival rate of patients with IPNB who underwent curative resection is 81%. However, IPNB is known to often recur in other parts of the bile duct. Nevertheless, its mechanism remains poorly understood. Herein, we report the case of a patient with recurrent IPNB, which was considered to be attributed to intraductal dissemination in the common bile duct at 12 months after curative resection. We also made a review of the existing literature. Case presentation A 69-year-old man was referred to our hospital for the evaluation and dilation of an intrahepatic bile duct (IHBD) mass. Computed tomography (CT) findings confirmed a mass in the left hepatic duct. Left trisectionectomy, extrahepatic bile duct resection with biliary reconstruction, and regional lymph node dissection were performed. Intraoperative examination of the resection margin at the common bile duct and posterior segmental branch of the hepatic duct was negative for the presence of malignant cells. Histologically, the tumor showed intraductal papillary growth of the mucinous epithelium and was diagnosed as non-invasive IPNB. It had a papillary structure with atypical epithelial cells lined up along the neoplastic fibrovascular stalks. Immunohistochemically, this was as a gastric-type lesion. At 12 postoperative months, CT revealed a 1.5-cm mass in the lower remnant common bile duct. We performed subtotal stomach-preserving pancreaticoduodenectomy. The tumor exhibited papillary growth and was microscopically and immunohistochemically similar to the first tumor. At approximately 16 months after the patient’s second discharge, CT showed an abdominal mass at the superior mesenteric plexus, which was diagnosed as recurrent IPNB. Chemotherapy is ongoing, and the patient is still alive. In this case, as described in many previous reports, IPNB recurred below the primary lesion in the bile duct. Conclusion Based on our review of previous reports on IPNB recurrence, intraductal dissemination was considered one of the mechanisms underlying recurrence after multicentric development. Considering the high frequency and oncological conversion of recurrence in IPNB, regular follow-up examination is essential to achieve better prognosis in patients with recurrent IPNB.

Background Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury. Methods To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined. Results Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH 2 O, 95% CI 0.047–0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH 2 O, 95% CI 0.031–0.053, p  = 0.02) and lower static elastance (BH 18.8 cmH 2 O/mL, [95% CI 15.4–22.2] vs. BA 26.7 cmH 2 O/mL [95% CI 19.6–33.8], p  = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6–4.5%] vs. 1.1% [95% CI 0.3–1.8%], p  = 0.008). Conclusions The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury.