Investigation of real-world heparin resistance and anticoagulation management prior to cardiopulmonary bypass: report from a nationwide survey by the Japanese Association for Thoracic Surgery heparin resistance working group.

OBJECTIVE: Heparin resistance is often encountered during cardiopulmonary bypass. Heparin dose and activated clotting time target values for the initiation of cardiopulmonary bypass are not yet universally standardized; further no consensus exists on the management of heparin resistance. This study aimed to investigate the current real-world practice on heparin management and anticoagulant treatment for heparin resistance in Japan. METHODS: A questionnaire survey was conducted at medical institutions nationwide with which The Japanese Society of Extra-Corporeal Technology in Medicine members are affiliated, targeting surgical cases with cardiopulmonary bypass performed from January 2019 through December 2019. RESULTS: Among 69% (230/332) of the participating institutions, the criterion for heparin resistance was defined as "the target activated clotting time value not reached even with an additional dose of heparin administration". Cases of heparin resistance were reported in 89.8% (202/225) of the responded institutions. Of note, 75% (106/141) of the responded institutions reported heparin resistance associated with antithrombin activity ≥ 80%. Antithrombin concentrate was used in 38.4% (238/619 responses) or third dose of heparin in 37.8% (234/619 responses) for advanced heparin resistance treatment. Antithrombin concentrate was found to be effective in resolving heparin resistance in patients having normal, as well as lower antithrombin activity. CONCLUSION: Heparin resistance has occurred in many cardiovascular centers, even among patients with normal antithrombin activities. Interestingly, the administration of antithrombin concentrate resolved heparin resistance, regardless of the baseline antithrombin activity value.

Comprehensive Structural and Electronic Properties of 2-Azaadamantane N-Oxyl Derivatives Correlated with Their Catalytic Ability.

Herein, a comprehensive kinetic study is performed to compare the catalytic efficiency of 2-azaadamantane N-oxyl (AZADO) derivatives with that of 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) used as radical catalysts in the aerobic oxidation of l-menthol. Furthermore, the correlation between the catalytic activity and structural/electronic parameters of AZADOs and TEMPO is elucidated. The reaction rate constants achieved with several AZADO derivatives exhibit moderate relationships with spectroscopic parameters, such as the hyperfine coupling constant of the N atom (AN) and NO stretching vibration frequency (νNO) observed in electron spin resonance and infrared spectra, respectively. The planarity C-(NO)-C angle (φ) at the N atom, determined by density functional theory (DFT) calculations, also strongly correlates with the AN and νNO. Moreover, the bond order of NO, which strongly depends on the structural and electronic properties of NO radicals, correlates with radical activity; thus, the radical activity can be predicted by DFT calculations, thereby accelerating the synthesis of new AZADO derivatives without requiring alcohol oxidation experiments.

Random laser oscillation from an organic fluorescent dye loaded inside a porous zirconia medium.

Porous zirconia medium (PZrM) has been fabricated successfully using polystyrene microparticles (MPs) as templates. The emission spectra of rhodamine B (RhB) [optical amplifying medium] loaded inside PZrM [porous scatterers] were obtained at numerous excitation light intensities. The lasing thresholds (I th) have been determined experimentally from the variations in the intensity of random laser oscillation peaks, which are suitably separated from the measured emission spectra. I th is closely related to the pore sizes of PZrM and the added amount of PZrM powder, and it clearly provided the minimum against the pore size. This fact is explained reasonably by the simulation of scattering efficiency on the basis of the Mie scattering theory. Consequently, PZrM as a porous scatterer is superior to Zr MPs from the viewpoint of random laser oscillation.

Near perfect head-to-head selectivity on the supramolecular photocyclodimerisation of 2-anthracenecarboxylate with self-organised gemini surfactant bilayers.

Silicificated self-organised crystalline bilayers of gemini surfactants were used as reaction templates for the supramolecular regioselective [4+4] photocyclodimerisation of 2-anthracenecarboxylate in water. A near perfect head-to-head cyclodimer selectivity, up to 97% at room temperature, was achieved with accelerated rate.

First birth following assisted sperm fusion insemination using sperm bound to zona pellucida.

PURPOSE: To report a live birth after transfer of a vitrified-warmed blastocyst produced by assisted sperm fusion insemination (ASFI). METHODS: Oocyte retrieval and in vitro fertilization (IVF) were performed on a 37-year-old woman. Six hours after IVF, an oocyte exhibited a single polar body and so was defined as an unfertilized oocyte. A motile sperm was collected from the zona pellucida of the unfertilized oocyte by an injection needle. The motile sperm was pressed onto the membrane of the unfertilized oocyte. RESULTS: Two oocytes were matured and subjected to IVF. One of the 2 oocytes exhibited only one polar body and was defined as an unfertilized oocyte at 6 h after IVF; this oocyte then was subjected to ASFI. Two pronuclei were observed on the next day and cultured to the blastocyst stage. This embryo achieved blastocyst status and was vitrified on day 5. The resulting vitrified-warmed blastocyst was transferred, resulting in pregnancy and subsequent delivery of a healthy boy. CONCLUSION: This report describes the first case of a successful birth following transfer of a vitrified-warmed blastocyst produced by ASFI.

Solvent Effects and Aggregation Phenomena Studied by Vibrational Optical Activity and Molecular Dynamics: The Case of Pantolactone.

Raman and Raman optical activity (ROA), IR, and vibrational circular dichroism (VCD) spectra of (R)- and (S)-pantolactone have been recorded in three solvents. ROA has been employed on water and DMSO solutions, VCD on DMSO and CCl4 solutions. In the last solvent, monomer-dimer equilibrium is present. Due to the low conformational flexibility of the isolated molecule and to the possibility of aggregation, this compound has been used here to test different protocols for computation of the spectroscopic responses taking into account solvent effects. Molecular dynamics (MD) simulations have been carried out together with statistical clustering methods based on collective variables to extract the structures needed to calculate the spectra. Quantum mechanical DFT calculations based on PCM are compared with approaches based on different representations of the solvent shell (MM or QM level). Appropriate treatment of the solvent permits obtaining of good band-shapes, with the added advantage that the MD analysis allows one to take into account flexibility of dimeric structures justifying the broadness of observed bands and the absence of intense VCD couplets in the carbonyl and OH stretching regions.

Efficient Light-Harvesting Antennae Resulting from the Dense Organization of Dyes into DNA Junctions through d-Threoninol.

Herein we report the construction of efficient light-harvesting antennae by hybridization of DNA oligonucleotides containing high densities of fluorophores into DNA junctions through d-threoninol. Six pyrene donors could be incorporated into each arm without self-quenching. A perylene acceptor was located at the center of the junction. Antenna effects of a duplex and three- to eight-way junctions were systematically compared. Six- and eight-way junctions had the highest antenna effects, and their effective absorption coefficients were 8.5 times higher than that of perylene. Interestingly, even-numbered junctions had higher efficiencies than odd-numbered junctions. Nondenaturing gel analyses and fluorescence lifetime measurements demonstrated that the strong odd-even effects were derived from differences in the stability of junctions. The results presented will guide the design of efficient artificial photosynthetic systems.

Fertilization with human sperm bound to zona pellucida by pressing onto the oocyte membrane.

This study aimed to determine whether fertilization can be obtained by assisted fusion of oocyte and sperm without breaking the oocyte membrane. A total of 79 infertile couples, each with at least one unfertilized oocyte after in vitro fertilization (IVF), were recruited. Sperm collected from the zona pellucida (ZP) were pressed onto the membrane of unfertilized oocytes at either 6 h or 24 h after IVF, a procedure that we designated as assisted sperm fusion insemination (ASFI). The results of ASFI were compared with those obtained in a previous trial on oocytes in which rescue intracytoplasmic sperm injection (ICSI) was performed at 6 h after IVF. Acrosome reaction (AR) rate of sperm bound to ZP, fertilization rate, degeneration rate, and blastocyst formation rate were evaluated. The AR rate of sperm collected from the ZP was significantly higher than that of the motile sperm recovered from around the oocytes but not bound to the ZP after IVF (98.0% vs. 28.6%). ASFI which was performed at 6 h after IVF yielded a mean fertilization rate of 73.4% (58/79), a degeneration rate of 0% (0/79) and a blastocyst formation rate of 60.8% (31/51). Rescue ICSI which was performed at 6 h after IVF yielded a mean fertilization rate of 70.0% (70/100), a degeneration rate of 4% (4/100) and a blastocyst formation rate of 42.4% (25/59). Binding of sperm to the ZP typically results in AR. ASFI with acrosome-reacted sperm collected from the ZP yielded the fertilization rates similar to those obtained with rescue ICSI.

Complications after Radiofrequency Ablation for Hepatocellular Carcinoma: A Multicenter Study Involving 9,411 Japanese Patients.

INTRODUCTION: Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered a safe and minimally invasive procedure. We previously reported that the mortality and complication rates for RFA were 0.038% (5/13,283 patients) and 3.54% (579 complications/16,346 procedures), respectively, from 1999 to 2010 (previous period). In this study, we investigated the clinical criteria for RFA and the mortality and complication rates from 2011 to 2015 (recent period). METHODS: Data were collected from 25 centers by using a questionnaire developed by the Chugoku-Shikoku Society for Local Ablation Therapy of HCC. The criteria for RFA, RFA modification, use of image-guidance modalities, mortality, and complications during the previous and recent periods were compared. RESULTS: We evaluated 11,298 procedures for 9,411 patients, including those that involved new devices (bipolar RFA and internally adjustable electrode system). The criterion of hepatic function for RFA increased from a Child-Pugh score ≤8 during the previous period to ≤9 during the recent period. The criteria regarding the tumor location and other risk factors have been expanded recently because of the increased use of several modifications of the RFA procedure and image-guidance modalities. The mortality rate was 0.064% (6/9,411 patients), and the complication rate was 2.92% (330 complications/11,298 procedures). There was no difference in mortality rates between the 2 periods (p = 0.38), but the complication rates was significantly lower during the recent period (p = 0.038). DISCUSSION AND CONCLUSIONS: Our findings confirmed that RFA, including the use of new devices, is a low-risk procedure for HCC, despite the expansion of the criteria for RFA during the recent period.

Effect of artificial saliva on permeability of dentin treated with phosphate containing desensitizer measured by digital flow meter.

The aim of this study was to investigate the effects of artificial saliva on permeability measured using a highly sensitive digital flow meter of dentin discs treated with a phosphate containing desensitizer compound (Teethmate desensitizer; TD). Four random groups (n=10) were treated either with TD or distilled water (DW), then stored in artificial saliva (AS) or DW for 1 day, 1 week and 1 month. Flow rates under 2 kPa pressure were calculated as percentage reduction (PR%) from the baseline. The PR% of TD/AS group was significantly lower after 1 day and 1 week, but the PR%s of 1 month groups among TD/AS, TD/DW and DW/AS were not significantly different. The SEM photograph of TD/AS group displayed that the dentin surface was densely covered with mineral deposits. Ca and phosphate ions from the artificial saliva could penetrate into the tubules and precipitate as hydroxyapatite, resulting in the reduction in permeability.

Observation of Granulocyte Adsorption in Adacolumn Cellulose Acetate Beads after Granulocytapheresis.

Adacolumn is a therapeutic mode for ulcerative colitis that achieves therapeutic efficacy through the adhesion of leukocytes to cellulose acetate beads. We used scanning electron microscopy and observed leukocyte adsorption on Adacolumn beads after granulocytapheresis/granulocyte and monocyte adsorption apheresis. We then compared results between two patients with a low and high C-reactive protein (CRP) levels to determine whether adhesion is affected by a difference in leukocyte activity depending on the level of inflammation. We found that the surface layers of the beads from both patients were covered by a clay-like layer, and spherical granulocytes were adsorbed here and there on top of it. In cross-section the adsorbed granulocytes were visible in the clay-like layer and the surface layer alike. The clay-like layer had a maximum thickness of approximately 12 µm in the low CRP patient and approximately 50 µm in the high CRP patient, so in the high CRP patient the clay-like adsorption layer was thicker. Taken together, adsorption onto beads is considered to involve an immunological mechanism. Our findings suggest that granulocytes contact and adhere to each other at the surface layer after adsorption, and that granulocyte-granulocyte adhesion is enhanced by a higher inflammatory response.

Effects of cyclophosphamide administration on the in vitro fertilization of mice.

PURPOSE: To evaluate the oocyte fertilization ability and embryo growth after cyclophosphamide (CPA) treatment in mice. METHODS: Mice were treated with CPA at different doses (0-800 mg/kg body weight). The oocytes then were retrieved and evaluated for their in vitro fertilization efficiency. RESULTS: The average number of metaphase II (MII) oocytes significantly decreased by ≥400 mg/kg CPA administration. The fertilization rate also decreased in the group that was treated with ≥400 mg/kg CPA. However, after fertilization, the embryos demonstrated normal growth ability. Two weeks after CPA administration, the number of mice from which the oocytes could be retrieved markedly decreased, but the fertilization rate and development of morphological features in the embryos were similar to those of the controls. One month after CPA administration, the number of mice from which the oocytes could be retrieved, fertilization rate, and development of the morphological features in the embryos were similar to those of the controls. CONCLUSION: The number of oocytes decreased as the CPA administration level increased; however, the oocytes' potential for fertilization and development to the blastocyst stage was not significantly affected. One month after CPA administration, the number of oocytes and the potential for development into blastocysts were recovered.

Concentration-dependent photophysical switching in mixed self-assembled monolayers of pentacene and perylenediimide on gold nanoclusters.

Photophysical control and switching on organic-inorganic hybrid interfaces are of great interest in diverse fundamental and applicative research areas. 6,13-Bis(triisopropylsilylethynyl)pentacene (TP) is well-known to exhibit efficient singlet fission (SF) for generation of high-yield triplet excited states in aggregated forms, whereas perylenediimide (PDI) ensembles show the characteristic excimer formation. Additionally, a combination of pentacene (electron donor: D) and PDI (electron acceptor: A) is expected to undergo an efficient photoinduced electron transfer (PET), and absorption of two chromophores combined covers the entire visible region. Therefore, the concentration-dependent mixed self-assembled monolayers (SAMs) composed of two chromophores enable us to control and switch the photophysical processes on a surface. In this work, a series of mixed SAMs composed of TP and PDI units on gold nanoclusters (GNCs) were newly synthesized by changing the relative molecular concentration ratios. Structural control of mixed SAMs on a gold surface based on the concentration ratios was successfully achieved. Time-resolved femtosecond and nanosecond transient absorption measurements clearly demonstrate photophysical control and switching of the above competitive reactions such as SF, electron transfer (ET) and excimer formation. The maximum quantum yields of triplet states (ΦT = ∼170%) and electron transfer (ΦET = ∼95%) were quantitatively evaluated by changing the concentration ratios. The rate constants of SF and excimer processes are largely dependent on the concentration ratios, whereas the rate constants of ET processes approximately remain constant. These findings are also discussed based on the statistical framework of the assembly of chromophores on the gold surface.

Nomograms to Predict the Disease-free Survival and Overall Survival after Radiofrequency Ablation for Hepatocellular Carcinoma.

Objective The purpose of this study was to construct nomograms for the disease-free survival (DFS) and overall survival (OS) of post-radiofrequency ablation (RFA) patients with hepatocellular carcinoma (HCC). Furthermore, we compared the prognostic predictive ability of these nomograms for estimating per-patient outcomes with that of traditional staging systems. Methods We retrospectively enrolled 298 patients in the training set and 272 patients in the validation set who underwent RFA for HCC. The nomograms for the DFS and OS were constructed from the training set using the multivariate Cox proportional hazards model. The discriminatory accuracy of the models was compared with traditional staging systems by analyzing the Harrell's C-index. Results The DFS nomogram was developed based on the tumor size, tumor number, aspartate aminotransferase (AST), albumin, age, and α-fetoprotein. The OS nomogram was developed based on the tumor size, the model for end-stage liver disease, AST, and albumin. Our DFS and OS nomograms had good calibration and discriminatory abilities in the training set, with C-indexes of 0.640 and 0.692, respectively, that were greater than those of traditional staging systems. The C-indexes of our DFS and OS nomograms were also greater than those of traditional staging systems in the validation set, with C-indexes of 0.614 and 0.657, respectively. RFA patients were stratified into low- and high-risk groups based on the median nomogram scores. High-risk patients receiving surgical resection (SR) were associated with a better DFS and OS than those undergoing RFA. However, the DFS and OS were similar between the low-risk RFA and SR groups. Conclusion We constructed reliable and useful nomograms that accurately predict the DFS and OS after RFA for early-stage HCC patients. These graphical tools are easy to use and will assist physicians during the therapeutic decision-making process.

Bilateral tubal pregnancies after a single-embryo transfer.

Case: To present an extremely rare case of bilateral tubal pregnancies following a single-embryo transfer in a woman with a 4 year history of infertility prior to seeking assisted reproductive technology. Outcome: A pregnancy resulted from the transfer of an embryo that had been thawed from a frozen blastocyst during a hormone replacement cycle. An ultrasound that was performed at 5 weeks and 5 days of gestation revealed a gestational sac, embryo, and heartbeat in the right fallopian tube and similar signs of a gestational sac in the left fallopian tube. A laparoscopy revealed clear signs of an ectopic pregnancy in the ampulla of the right fallopian tube. Signs of swelling also were seen in the ampulla of the left fallopian tube. As the possibility of bilateral tubal pregnancies could not be ruled out, both fallopian tubes were removed. Pathological tests revealed chorionic villi and trophoblasts in both the left and right fallopian tubes. Conclusion: All previously reported cases of bilateral tubal pregnancies have been a result of multiple ovulations or multiple-embryo transfer and no case of bilateral tubal pregnancies after a single-embryo transfer has ever been reported. No genetic testing was performed; thus, it cannot be definitively stated that the divided chorionic villi and trophoblasts came from only one embryo.

Agarose capsules as new tools for protecting denuded mouse oocytes/embryos during handling and freezing-thawing and supporting embryonic development in vivo.

Oocytes without a zona pellucida (ZP) often occur as a result of congenital or operational effects, but they are difficult to handle, and embryonic survival is low. Such zona-free (ZF) oocytes are therefore not used in clinics or laboratories. Furthermore, in the laboratory, removal of the ZP is often necessary for genetic manipulation by viral infection or twin production by blastomere separation, but adverse effects on development have been reported. It would therefore be extremely valuable if the embryo could be covered with a structure similar to that of the ZP. In this study, we sought to determine whether an agarose capsule could serve as a substitute for the ZP. Our results indicate that embryos derived from these agarose capsules were able to develop normally, and could be transplanted to obtain viable offspring, without having to remove the agarose capsule. Furthermore, before compaction, the agarose capsule embryos exhibited good freezing tolerance, and survival rate was extremely high compared to ZF embryos. Thus, agarose capsules represent a valuable tool for utilizing oocytes and embryos that lack a ZP, both in a clinical and livestock setting.

Cryopreservation of very low numbers of spermatozoa from male patients undergoing infertility treatment using agarose capsules.

This study tried to cryopreserve low numbers of spermatozoa from men undergoing infertility treatments by inserting into agarose capsules. The capsules were transferred into a drop of cryoprotectant solution and injected 3-4 motile spermatozoa that were selected by the swim-up method by conventional intracytoplasmic sperm injection. These capsules were put on a Cryotop® and frozen in liquid nitrogen vapor, and then submerged into liquid nitrogen and subsequently thawed and recovered. The motile spermatozoa in the capsules were counted. Eventually, we cryopreserved 2142 motile spermatozoa in 702 agarose capsules from 26 male patients and 1356 (63%) spermatozoa maintained their motility after thawing. The spermatozoa motility rates after thawing (MRAT) ranged from 20.0% (5/25) to 95.1% (58/61) among patients. The median MRAT was 68.3% (interquartile range 46.1-75.7). The total number of motile spermatozoa collected by swim-up method strongly correlated with MRAT (r = 0.746). It was possible to cryopreserve spermatozoa from male patients undergoing infertility treatment using agarose capsules. However, there were wide differences in MRAT among patients. It seems the spermatozoa from semen where there were many motile spermatozoa may have higher freezing resistance. Further studies using this method in cryptozoospermic semen, testicular and epididymal spermatozoa are required.

Surgical Resection for Hepatocellular Carcinoma with Cardiac Cirrhosis after the Fontan Procedure.

A 29-year-old woman who underwent the Fontan procedure at 10 years of age had an incidental finding of liver masses on abdominal ultrasonography. Subsequent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid magnetic resonance imaging showed a 15 mm hypervascular mass with washout in the hepatobiliary phase in liver segment 4 (S4), and an 18 mm hypervascular mass without washout in the hepatobiliary phase in liver segment 2 (S2). The S2 liver mass was pathologically diagnosed to be a regenerative nodule by an ultrasound-guided needle biopsy, and the S4 liver mass was pathologically diagnosed as a poorly differentiated hepatocellular carcinoma after partial hepatectomy.

Effect of the presence of trophectoderm vesicles on blastocyst in relation to in vitro hatching, clinical pregnancy, and miscarriage rates.

Trophectoderm vesicles (TVs) are observed in some blastocysts that penetrate cells from the zona pellucida to the outer margin. Therefore, we compared this incidence in relation to hatching, pregnancy, and miscarriage rates between conventional in vitro fertilization (c-IVF) and intracytoplasmic sperm injection (ICSI). Vitrified/warmed blastocysts (n = 112) were derived from surplus embryos. The blastocysts were then observed using time-lapse cinematography to resolve the relationship between hatching and implantation. Another study was conducted that comprised 681 embryo transfer cycles in 533 patients who received a single vitrified/warmed blastocyst from our clinic. The incidence of TV was significantly higher in embryos inseminated by ICSI compared with c-IVF [ICSI: 51/56 (91 %); c-IVF: 25/56 (45 %); P < 0.01]. The successful hatching rate was significantly lower in ICSI than in c-IVF [ICSI: 11/56 (20 %); c-IVF: 29/56 (52 %); P < 0.01]. In addition, the hatching rate was significantly lower when TVs were present (14/76; 18 %) than in non-TV embryos (26/36; 72 %) (P < 0.01). In regard to the clinical study results, no significant differences were found between the groups in the pregnancy rate (TV present group: 107/183, 58.5 %; TV absent group: 273/498, 54.8 %) and miscarriage rate (TV present group: 21/107, 19.6 %; TV absent group: 53/273, 19.4 %). In vivo, we hypothesized that hatching and hatched would occur naturally by assisting protease action in the uterus; therefore, these results suggest that the presence of TV has no effect on pregnancy rates in the clinical setting.

Protonation-induced red-coloured circularly polarized luminescence of [5]carbohelicene fused by benzimidazole.

Benzimidazole-fused [5]carbohelicene ([5]HeliBI) was newly synthesized to examine the spectroscopic and chiroptical properties. The reversible protonation and deprotonation processes of [5]HeliBI were successfully investigated using (1)H NMR, absorption and fluorescence spectral measurements. We also confirmed the circularly polarized luminescence of protonated [5]HeliBI (H(+)-[5]HeliBI). This is the first observation of red-coloured CPL of a helicene derivative.