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Purpose Several studies indicate that assisted reproductive technology (ART) including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies carries increased risk of complications including postpartum hemorrhage (PPH). However, the association between IVF/ICSI and the bleeding risk particularly in cesarean delivery has not been systematically assessed. The aim of this study was to evaluate bleeding risk during and after cesarean delivery in parturients who conceived using IVF or ICSI. Methods This is a retrospective observational study analyzing data from 310 parturients who underwent cesarean delivery: 155 who had conceived using IVF or ICSI (IVF/ICSI group) and 155 age and year of delivery matched controls who had conceived spontaneously (control group). The primary outcome measure was the amount of blood lost during and within 24 h after cesarean delivery. Secondary outcome measure was the incidence of severe PPH. With 132 parturients in each group, we had 90% power to detect a 200 mL difference in the bleeding amount, at a 0.05 two-sided significance level. Results The amount of bleeding in the IVF/ICSI group was 1234 ± 669 mL, which was 124 mL (11.2%) greater than that in the control group (95% CI - 34 to 282; p = 0.12). The incidence of severe PPH in the IVF/ICSI group and in the control group was 23.9% and 16.8%, respectively (p = 0.16), and the unadjusted odds ratio was 1.6 (95% CI, 0.9-2.7; p = 0.12). No significant independent effect of IVF/ICSI on the bleeding amount and the incidence of severe PPH was observed in multivariable regression analyses (p = 0.22, p = 0.16). Conclusion In this study, IVF and ICSI were not associated with increasing risk of bleeding in cesarean delivery., Author(s): Mariko Aizawa [sup.1], Satoshi Ishihara [sup.1], Takeshi Yokoyama [sup.1] Author Affiliations: (1) https://ror.org/03wqxws86, grid.416933.a, 0000 0004 0569 2202, Department of Anesthesia, Teine Keijinkai Hospital, , 1-12-1-40 Maeda, Teine, 006-8555, [...]

Purpose Inflammation after stent graft surgery is known as postimplantation syndrome (PIS) and it causes leukocytosis. However, we have experienced leukopenia in the very early postoperative phase of endovascular surgery at our institution. We investigated leukopenia, an under-recognized phenomenon that occurred after transcatheter aortic valve implantation (TAVI), endovascular aortic repair (EVAR), and thoracic endovascular aortic repair (TEVAR). Methods Records of patients who underwent TAVI, EVAR, and TEVAR between March 2018 and February 2019 were retrospectively reviewed. Primary outcomes were the decline rate of white blood cell count (DR-WBC) in the immediate postoperative period and its differences among surgical procedures. The secondary endpoint was the relationship between DR-WBC and infectious complications. Furthermore, the incidence of PIS and its differences among the procedures and associations with DR-WBC were evaluated. Results A total of 108 patients (TAVI 41, EVAR 37, TEVAR 30) were included. DR-WBC immediately after surgery was higher in the TAVI group when compared with other groups (TAVI, 43.1 ± 22.6%; EVAR, 27.6 ± 17.3%; TEVAR, 25.4 ± 27.4%; P < 0.01). DR-WBC was not significantly different regardless of postoperative infection (P = 0.45) or PIS (P = 0.62). The incidence rate of PIS was higher in the EVAR group compared with the TAVI group, and was not associated with DR-WBC. Conclusions Leukopenia was a common phenomenon immediately after endovascular surgery, especially TAVI. It resolved a day after surgery and was not associated with PIS or infectious complications. Therefore, it seems to be a transient abnormal hematological finding and a self-limiting condition., Author(s): Takashi Soejima [sup.1], Kazuyuki Mizunoya [sup.1], Yuki Izumi [sup.2], Takeshi Yokoyama [sup.2], Ryo Takagi [sup.3], Yuji Morimoto [sup.1] Author Affiliations: (1) grid.412167.7, 0000 0004 0378 6088, Department of Anesthesiology, [...]

SIRT5, one of the mammalian sirtuins, specifically recognizes succinyl‐lysine residues on proteins and catalyzes the desuccinylation reaction. In this study, we characterized SIRT5 mutants with hydrophobic amino acid substitutions at Q140 and N141, in addition to the catalytic residue H158, known as an active site residue, by the Michaelis–Menten analysis and X‐ray crystallography. Kinetic analysis showed that the catalytic efficiency (kcat/Km) of the Q140L and N141V mutants decreased to 0.02 times and 0.0038 times that of the wild‐type SIRT5, respectively, with the activity of the N141V mutant becoming comparable to that of the H158M mutant. Our findings indicate that N141 contributes significantly to the desuccinylation reaction. [ABSTRACT FROM AUTHOR]

Inducible dimerization systems, such as rapamycin‐induced dimerization of FK506 binding protein (FKBP) and FKBP–rapamycin binding (FRB) domain, are widely employed chemical biology tools to manipulate cellular functions. We previously advanced an inducible dimerization system into an inducible oligomerization system by developing a bivalent fusion protein, FRB–FKBP, which forms large oligomers upon rapamycin addition and can be used to manipulate cells. However, the oligomeric structure of FRB–FKBP remains unclear. Here, we report that FRB–FKBP forms a rotationally symmetric trimer in crystals, but a larger oligomer in solution, primarily tetramers and pentamers, which maintain similar inter‐subunit contacts as in the crystal trimer. These findings expand the applications of the FRB–FKBP oligomerization system in diverse biological events. [ABSTRACT FROM AUTHOR]

Hemodialysis therapy is an extracorporeal circulation treatment that serves as a substitute for renal function. In Japan, patients receive this efficient four-hour treatment, three times per week, allowing them to maintain a social life nearly equivalent to that of healthy individuals. Before the treatment, two punctures are performed to establish extracorporeal circulation, and a high blood flow rate is essential to ensure efficient therapy. Specialized blood vessels created through arteriovenous fistula (AVF) surgery are utilized to achieve high blood flow rates. Although the AVF allows safe and efficient dialysis treatment, AVF stenosis leads to a serious problem in dialysis. To early detect this abnormal blood flow, auscultation and palpation methods are widely used in hospitals. However, these methods can only provide qualitative judgment of the AVF condition, so the results cannot be shared among other doctors and staff. Additionally, since the conventional methods require contact with the skin, some issues require consideration regarding infection and low reproducibility. In our previous study, we proposed an alternative method for auscultation using non-contact optical imaging technology. This study aims to construct a reliable AVF stenosis detection method using Thrill waveform analysis based on the developed non-contact device to solve the problem with the contact palpation method. This paper demonstrates the performance validation of the non-contact imaging in the normal AVF group (206 total data, 75 patients, mean age: 69.1 years) and in the treatable stenosis group (107 total data, 17 patients, mean age: 70.1 years). The experimental results of the Mann–Whitney U test showed a significant difference ( p = 0.0002 ) between the normal and abnormal groups, which indicated the effectiveness of the proposed method as a new possible alternative to palpation. [ABSTRACT FROM AUTHOR]

The rapid emergence of multi-drug-resistant bacteria has raised a serious public health concern. Therefore, new antibiotic developments have been highly desired. Here, we propose a new method to visualize antibiotic actions on translating ribosomes in the cell-free system under macromolecular crowding conditions by cryo-electron microscopy, designated as the DARC method: the Direct visualization of Antibiotic binding on Ribosomes in the Cell-free translation system. This new method allows for acquiring a more comprehensive understanding of the mode of action of antibiotics on the translation inhibition without ribosome purification. Furthermore, with the direct link to biochemical analysis at the same condition as cryo-EM observation, we revealed the evolution of 2-DOS aminoglycosides from dibekacin (DBK) to arbekacin (ABK) by acquiring the synthetic tailored anchoring motif to lead to stronger binding affinity to ribosomes. Our cryo-EM structures of DBK and ABK bound ribosomes in the cell-free environment clearly depicted a synthetic tailored γ-amino-α-hydroxybutyryl (HABA) motif formed additional interactions with the ribosome enhancing antibiotic bindings. This new approach would be valuable for understanding the function of antibiotics for more efficient drug development. [ABSTRACT FROM AUTHOR]

Biparatopic antibodies (bpAbs) are engineered antibodies that bind to multiple different epitopes within the same antigens. bpAbs comprise diverse formats, including fragment‐based formats, and choosing the appropriate molecular format for a desired function against a target molecule is a challenging task. Moreover, optimizing the design of constructs requires selecting appropriate antibody modalities and adjusting linker length for individual bpAbs. Therefore, it is crucial to understand the characteristics of bpAbs at the molecular level. In this study, we first obtained single‐chain variable fragments and camelid heavy‐chain variable domains targeting distinct epitopes of the metal binding protein MtsA and then developed a novel format single‐chain bpAb connecting these fragment antibodies with various linkers. The physicochemical properties, binding activities, complex formation states with antigen, and functions of the bpAb were analyzed using multiple approaches. Notably, we found that the assembly state of the complexes was controlled by a linker and that longer linkers tended to form more compact complexes. These observations provide detailed molecular information that should be considered in the design of bpAbs. [ABSTRACT FROM AUTHOR]

Purpose There are no sufficient evidences for the sedative effect of gabapentin during anesthesia, especially intravenous sedation (IVS). The purpose of this study was to evaluate the sedative effect of gabapentin as preanesthetic medication during the IVS with propofol. Methods 10 volunteer subjects joined this study. They underwent propofol IVS three times on separate days. On the first day, the IVS without gabapentin was performed as a control. On the second and the third day, gabapentin 200 mg and 400 mg were administered before the IVS, respectively. The target blood concentration (C.sub.T) of propofol was gradually increased, and the bispectral index (BIS) value and Ramsay sedation score (RSS) were evaluated at each propofol C.sub.T. Postanesthetic complications and influences on vital signs were also evaluated. Results Compared to the control group, the propofol C.sub.Ts in the gabapentin 400 mg group significantly reduced at the BIS values of 60 and 70 (p = 0.031 and p = 0.043, respectively), and at RSS 3, 4, 5 and 6 (p = 0.040, p = 0.004, p = 0.001 and p = 0.004, respectively). There was no significant difference in propofol C.sub.Ts between the control group and the gabapentin 200 mg group. There were no abnormality and no deterioration in circulation and respiration in all groups. There were no significant increases in complications with the administration of gabapentin. Conclusion The oral administration of 400 mg dose of gabapentin reduced the propofol C.sub.Ts for achieving an adequate sedation level on IVS., Author(s): Rumiko Hosokawa [sup.1] , Shinichi Ito [sup.1] , Jun Hirokawa [sup.1] , Yu Oshima [sup.1] , Takeshi Yokoyama [sup.1] Author Affiliations: (Aff1) 0000 0001 2242 4849, grid.177174.3, Department of [...]