Species-differences in the in vitro biotransformation of trifluoroethene (HFO-1123).

1,1,2-Trifluoroethene (HFO-1123) is anticipated for use as a refrigerant with low global warming potential. Inhalation studies on HFO-1123 in rats indicated a low potential for toxicity (NOAELs ≥ 20,000 ppm). In contrast, single inhalation exposure of Goettingen® minipigs (≥ 500 ppm) and New Zealand white rabbits (≥ 1250 ppm) resulted in severe toxicity. It has been suggested that these pronounced species-differences in toxicity may be attributable to species-differences in biotransformation of HFO-1123 via the mercapturic acid pathway. Therefore, the overall objective of this study was to evaluate species-differences in glutathione (GSH) dependent in vitro metabolism of HFO-1123 in susceptible versus less susceptible species and humans as a basis for human risk assessment. Biotransformation of HFO-1123 to S-(1,1,2-trifluoroethyl)-L-glutathione (1123-GSH) and subsequent cysteine S-conjugate ß-lyase-mediated cleavage of the corresponding cysteine conjugate (1123-CYS) was monitored in hepatic and renal subcellular fractions of mice, rats, minipigs, rabbits, and humans. While 1123-GSH formation occurred at higher rates in rat and rabbit liver S9 compared to minipig and human S9, increased ß-lyase cleavage of 1123-CYS was observed in minipig kidney cytosol as compared to cytosolic fractions of other species. Increased ß-lyase activity in minipig cytosol was accompanied by time-dependent formation of monofluoroacetic acid (MFA), a highly toxic compound that interferes with cellular energy production via inhibition of aconitase. Consistent with the significantly lower ß-lyase activity in human cytosols, the intensity of the MFA signal in human cytosols was only a fraction of the signal obtained in minipig subcellular fractions. Even though the inconsistencies between GSH and ß-lyase-dependent metabolism do not allow to draw a firm conclusion on the overall contribution of the mercapturic acid pathway to HFO-1123 biotransformation and toxicity in vivo, the ß-lyase data suggest that humans may be less susceptible to HFO-1123 toxicity compared to minipigs.

Giant spin polarization and a pair of antiparallel spins in a chiral superconductor.

Chiral molecules can exhibit spin-selective charge emission, which is known as chirality-induced spin selectivity1,2. Despite the constituent light elements of the molecules, their spin polarization can approach or even exceed that of typical ferromagnets. This powerful capability may lead to applications in the chiral spintronics2 field. Although the origin of spin selectivity is elusive, two microscopic phenomena have been suggested based on experimental results: effective enhancement of spin-orbit interactions3 and chirality represented by a pair of oppositely polarized spins4,5. However, the hypotheses remain to be verified. Here we report the simultaneous observation of these two phenomena in an organic chiral superconductor by magnetoresistance measurements in the vicinity of the superconducting transition temperature. A pair of oppositely polarized spins is demonstrated by spatially mapping the spin polarity in an electric alternating current excitation. The obtained spin polarization exceeds that of the Edelstein effect6-10 by several orders of magnitude, which indicates an effective enhancement of the spin-orbit interaction. Our results demonstrate a solid-state analogue of spin accumulations assumed for chiral molecules, and may provide clues to the origin of their molecular counterparts. In addition, the innovative capability of spin-current sourcing will invigorate superconducting spintronics research11.

Terahertz-field-induced polar charge order in electronic-type dielectrics.

Ultrafast electronic-phase change in solids by light, called photoinduced phase transition, is a central issue in the field of non-equilibrium quantum physics, which has been developed very recently. In most of those phenomena, charge or spin orders in an original phase are melted by photocarrier generations, while an ordered state is usually difficult to be created from a non-ordered state by a photoexcitation. Here, we demonstrate that a strong terahertz electric-field pulse changes a Mott insulator of an organic molecular compound in κ-(ET)2Cu[N(CN)2]Cl (ET = bis(ethylenedithio)tetrathiafulvalene), to a macroscopically polarized charge-order state; herein, electronic ferroelectricity is induced by the collective intermolecular charge transfers in each dimer. In contrast, in an isostructural compound, κ-(ET)2Cu2(CN)3, which shows the spin-liquid state at low temperatures, a similar polar charge order is not stabilized by the same terahertz pulse. From the comparative studies of terahertz-field-induced second-harmonic-generation and reflectivity changes in the two compounds, we suggest the possibility that a coupling of charge and spin degrees of freedom would play important roles in the stabilization of polar charge order.

A case of pubic abscess after prostate cancer surgery and radiotherapy treated with rectus femoris muscle flap.

We report the case of a 95-year-old man with soft tissue deficiency associated with a pubic abscess that occurred 30 years after prostate cancer surgery and radiation therapy. A fistula with purulent discharge without any obvious cause appeared in the midline of the lower abdomen and progressed to a soft tissue defect in which several calcium phosphate stones of 5-8 mm in diameter were found. Computed tomography showed calcium deposits on the surface of the pubis and irregular zonal calcifications extending from the pubis to the medial region of both thighs. Conservative treatment did not improve the patient's condition; thus, surgical treatment was performed. The pedicled rectus femoris muscle flap was elevated from the left thigh and transferred to fill the tissue defect, then a split thickness skin graft was applied on it. The tissue defect was successfully repaired, and the patient was able to regain ambulation ability. In the present case, it was presumed that urine exudation around the bladder due to radiation cystitis was involved in the formation of ectopic calculi and subsequent infection. In reconstructing a complex defect associated with infection, using muscle flaps to fill the dead space with well vascularized tissue is considered to be appropriate. In our case, we chose a rectus femoris muscle flap, which has advantages in volume and versatility of transposition owing to long vascular pedicle and requires no microsurgical vascular anastomosis. As a result, the preoperative activity was maintained, the infection was treated, and a good course was obtained.

Successful treatment with hydroxychloroquine for systemic lupus erythematosus with cutaneous involvement accompanied by a xanthomatous reaction.

Antimalarials are usually recommended for the first-line systemic treatment of cutaneous lupus erythematosus. Alopecia in patients with discoid lupus erythematosus (DLE) is sometimes a refractory condition in spite of topical therapies. We herein described a case of DLE on the scalp with a pathological change of a xanthomatous reaction, which was successfully treated with hydroxychloroquine (HCQ). A 34-year-old woman presented with hair loss to the parietal region. She had been diagnosed with systemic lupus erythematosus (SLE) four years previously. Treatment with 30 mg/day of prednisolone (PSL) had been initiated, and the dose was gradually reduced. At 10 mg/day of PSL, she had noticed her hair loss. Physical examination revealed some small erythematous lesions to the parietal region with accompanying hair loss. Pathological findings of the erythematous lesion on her head revealed thickening of the basement membrane zone, the interface dermatitis with vacuolar degeneration, and both superficial perivascular and perifollicular infiltration of inflammatory cells in the dermis. In addition, there was an infiltrate of xanthomatous cells detected in the papillary dermis, which were positive for CD68 and CD163. The patient started treatment with HCQ at a dose of 200 mg/day. The skin lesions completely resolved within five months after initiation of HCQ without increase in the dose of PSL. Xanthomatous reactions are rarely recognized in lupus erythematosus. The chronic epithelial injury in DLE could be implicated in triggering the secondary reactive process of a xanthomatous reaction. We believe that the reaction seen in our patient was a secondary change to pathological alteration due to SLE. However, as yet unrecognized factors may play a role in the development of a xanthomatous reaction in DLE.

Topological charge transport by mobile dielectric-ferroelectric domain walls.

The concept of topology has been widely applied in condensed matter physics, leading to the identification of peculiar electronic states on three-dimensional (3D) surfaces or 2D lines separating topologically distinctive regions. In the systems explored so far, the topological boundaries are built-in walls; thus, their motional degrees of freedom, which potentially bring about new paradigms, have been experimentally inaccessible. Here, working with a quasi-1D organic material with a charge-transfer instability, we show that mobile neutral-ionic (dielectric-ferroelectric) domain boundaries with topological charges carry strongly 1D-confined and anomalously large electrical conduction with an energy gap much smaller than the one-particle excitation gap. This consequence is further supported by nuclear magnetic resonance detection of spin solitons, which are required for steady current of topological charges. The present observation of topological charge transport may open a new channel for broad charge transport-related phenomena such as thermoelectric effects.

Doublon-holon pairing mechanism via exchange interaction in two-dimensional cuprate Mott insulators.

Coupling of charge and spin degrees of freedom is a critical feature of correlated electron oxides, as represented by the spin-related mechanism of a Cooper pair under high-T c superconductivity. A doublon-holon pair generated on an antiferromagnetic spin background is also predicted to attract each other via the spin-spin interaction J, similar to a Cooper pair, while its evidence is difficult to obtain experimentally. Here, we investigate such an excitonic effect by electroreflectance spectroscopy using terahertz electric field pulses in undoped cuprates: Nd2CuO4, Sr2CuO2Cl2, and La2CuO4. Analyses of the spectral changes of reflectivity under electric fields reveal that the splitting of odd-parity and even-parity excitons, a measure of doublon-holon binding energy, increases with J. This trend is reproduced by t-J-type model calculations, providing strong evidence of the spin-related doublon-holon pairing. Agreement with the calculations supports the s-wave symmetry of the doublon-holon pair in contrast to the d-wave Cooper pair in doped cuprates.

Autoantibody to transcriptional intermediary factor-1ß as a myositis-specific antibody: clinical correlation with clinically amyopathic dermatomyositis or dermatomyositis with mild myopathy.

BACKGROUND: Myositis-specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)-1γ and TIF-1α are known to be MSAs. Previously, we reported that TIF-1ß is also targeted in patients with DM with or without concomitant anti-TIF-1α/γ antibodies. OBJECTIVES: To evaluate the clinical features of seven cases with anti-TIF-1ß antibodies alone. METHODS: Serum autoantibody profiles were determined, and protein and RNA immunoprecipitation studies were conducted. Western blotting was performed to confirm autoantibody reactivity against TIF-1ß. RESULTS: Anti-TIF-1ß antibody was identified by immunoprecipitation assay in 24 cases. Among them, seven patients were positive for anti-TIF-1ß antibody alone. Six of the seven patients were classified as having DM. Among the six cases of DM, two patients had no muscle weakness and normal creatine kinase (CK) levels, and were classified as having clinically amyopathic DM. Four patients had muscle weakness, but three of them had normal serum CK levels that responded well to systemic steroids. Characteristic features of DM included skin rashes, such as Gottron sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of our cases, respectively. One of the seven patients had appendiceal cancer. None of the patients had interstitial lung disease. CONCLUSIONS: Seven patients were confirmed to have anti-TIF-1ß antibody without any other MSAs, including TIF-1α/γ antibodies, and six of them were diagnosed with DM. We suggest that anti-TIF-1ß antibody is an MSA, and that it is associated with clinically amyopathic DM or DM with mild myopathy.

Smallest Optical Gap for Pt(II)-Pt(IV) Mixed-Valence Pt-Cl and Pt-Br Chain Complexes Achieved by Using a Multiple-Hydrogen-Bond Approach.

A multiple-hydrogen-bond approach was applied to shorten Pt-X-Pt distances in Cl- and Br-bridged Pt chain complexes. [Pt(dabdOH)2Cl]Cl2 (5) and [Pt(dabdOH)2Br]Br2 (6) (dabdOH = (2 S,3 S)-2,3-diaminobutane-1,4-diol) contain hydroxy groups, which form additional hydrogen bonds with counteranions. 5 has the shortest Pt-Cl-Pt distance (5.0747(8) Å) of all Cl-bridged Pt chain complexes reported to date. Furthermore, the smallest optical gap (1.45 eV for 5 and 1.19 eV for 6) in any Cl- or Br-bridged Pt chain complex was achieved. 6 has the highest electrical conductivity (1.9 × 10-5 S cm-1 at room temperature) of all Br-bridged Pt chain complexes. This study shows that the introduction of additional hydrogen bonds between the ligands and halides is effective to enhance the electronic properties of halogen-bridged metal complexes.

Evidence for solitonic spin excitations from a charge-lattice-coupled ferroelectric order.

Topological defects have been explored in different fields ranging from condensed matter physics and particle physics to cosmology. In condensed matter, strong coupling between charge, spin, and lattice degrees of freedom brings about emergent excitations with topological characteristics at low energies. One-dimensional (1D) systems with degenerate dimerization patterns are typical stages for the generation of topological defects, dubbed "solitons"; for instance, charged solitons are responsible for high electrical conductivity in doped trans-polyacetylene. Here, we provide evidence based on a nuclear magnetic resonance (NMR) study for mobile spin solitons deconfined from a strongly charge-lattice-coupled spin-singlet ferroelectric order in a quasi-1D organic charge-transfer complex. The NMR spectral shift and relaxation rate associated with static and dynamic spin susceptibilities indicate that the ferroelectric order is violated by dilute solitonic spin excitations, which were further demonstrated to move diffusively by the frequency dependence of the relaxation rate. The traveling solitons revealed here may promise the emergence of anomalous electrical and thermal transport.

Palisaded neutrophilic and granulomatous dermatitis associated with systemic lupus erythematosus: possible involvement of CD163+ M2 macrophages in two cases, and a review of published works.

BACKGROUND: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a commonly occurring condition related to systemic autoimmune disease. It is characterized histopathologically by a distinct pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. The properties of granulomatous cells in PNGD are still uncertain. OBJECTIVE: We sought further investigation on the phenotype of the infiltrated cells in PNGD from two patients with systemic lupus erythematosus (SLE) and reviewed the previous published reports in order to provide a comprehensive summary on the clinical features of PNGD in SLE. METHODS: The immunohistochemical features of granulomatous cells in PNGD associated with SLE were analyzed. Immunohistochemical studies were performed on sections from our two cases using antibodies against CD68, CD163, CD15, Factor XIIIa, myeloperoxidase and neutrophil elastase. The clinical characteristics of the SLE patients who developed PNGD were also evaluated. We included all cases retrieved through a PubMed search with the key words PNGD and SLE. RESULTS: Cutaneous lesions consisted of erythematous plaques distributed on the face and upper limbs in both cases. The infiltrated cells were mainly positive for CD68 and CD163, a phenotype suggestive of M2 macrophages. Some mature neutrophils and lymphocytes were also present. A review of the literature of PNGD associated with SLE revealed a predominance in females, high prevalence of lupus nephritis and a good response to systemic steroids, with frequent skin lesions relapses during tapering of the treatment. LIMITATIONS: This study examined only two cases; the pathogenesis of the disease remains to be clarified. CONCLUSION: PNGD lesions were abundantly infiltrated by M2 macrophages, suggesting that they may have a role in this condition. SLE accompanied by PNGD might be associated with lupus nephritis and frequent relapses of skin lesions.

Ultrafast polarization control by terahertz fields via π-electron wavefunction changes in hydrogen-bonded molecular ferroelectrics.

Rapid polarization control by an electric field in ferroelectrics is important to realize high-frequency modulation of light, which has potential applications in optical communications. To achieve this, a key strategy is to use an electronic part of ferroelectric polarization. A hydrogen-bonded molecular ferroelectric, croconic acid, is a good candidate, since π-electron polarization within each molecule is theoretically predicted to play a significant role in the ferroelectric-state formation, as well as the proton displacements. Here, we show that a sub-picosecond polarization modulation is possible in croconic acid using a terahertz pulse. The terahertz-pulse-pump second-harmonic-generation-probe and optical-reflectivity-probe spectroscopy reveal that the amplitude of polarization modulation reaches 10% via the electric-field-induced modifications of π-electron wavefunctions. Moreover, the measurement of electric-field-induced changes in the infrared molecular vibrational spectrum elucidates that the contribution of proton displacements to the polarization modulation is negligibly small. These results demonstrate the electronic nature of polarization in hydrogen-bonded molecular ferroelectrics. The ultrafast polarization control via π-electron systems observed in croconic acid is expected to be possible in many other hydrogen-bonded molecular ferroelectrics and utilized for future high-speed optical-modulation devices.

Probing ultrafast spin-relaxation and precession dynamics in a cuprate Mott insulator with seven-femtosecond optical pulses.

A charge excitation in a two-dimensional Mott insulator is strongly coupled with the surrounding spins, which is observed as magnetic-polaron formations of doped carriers and a magnon sideband in the Mott-gap transition spectrum. However, the dynamics related to the spin sector are difficult to measure. Here, we show that pump-probe reflection spectroscopy with seven-femtosecond laser pulses can detect the optically induced spin dynamics in Nd2CuO4, a typical cuprate Mott insulator. The bleaching signal at the Mott-gap transition is enhanced at ~18 fs. This time constant is attributable to the spin-relaxation time during magnetic-polaron formation, which is characterized by the exchange interaction. More importantly, ultrafast coherent oscillations appear in the time evolution of the reflectivity changes, and their frequencies (1400-2700 cm-1) are equal to the probe energy measured from the Mott-gap transition peak. These oscillations can be interpreted as the interference between charge excitations with two magnons originating from charge-spin coupling.

Juvenile migration of the exclusively pelagic cyprinid, Gnathopogon caerulescens (Honmoroko) in Lake Biwa, Central Japan.

Migration of wild and cultivated juvenile honmoroko Gnathopogon caerulescens of from the spawning and nursery areas in Lake Biwa were investigated, both in the Ibanaiko Lagoon and its outlet to Daido River, using beam-trawl surveys in 2013 and 2014. The study demonstrated migration of G. caerulescens from a nursery lagoon toward Lake Biwa after the juvenile stage. These findings appear to be the first direct evidence for migration of an exclusively pelagic cyprinid species from a littoral nursery to a pelagic adult habitat in a large deep lake.

Residual carcinoma cells after chemoradiotherapy for esophageal squamous cell carcinoma patients: striving toward appropriate judgment of biopsy.

In esophageal squamous cell carcinoma (ESCC) patients who are treated with chemoradiotherapy (CRT), identification of the presence or absence of residual or recurrent carcinoma is usually pivotal in their clinical management. In addition, the extent of carcinoma invasion into the esophageal wall could determine the clinical outcome of these patients following CRT. Therefore, in this study, we evaluated the response to CRT both macroscopically and histologically in a consecutive series of 42 ESCC patients receiving neoadjuvant chemoradiotherapy following curative esophageal resection at Tohoku University Hospital between August 2011 and December 2012. The histological grading of tumor regression was as follows: grade 3, markedly effective (no viable residual tumor cells); grade 2, moderately effective (residual tumor cells in less than one-third of the tumor); grade 1, slightly effective (1b, residual tumor cells in one-third to two-thirds of the tumor; 1a, residual tumor cells in more than two-thirds of the tumor); and grade 0, ineffective. In this study, we selected grade 2 and 1b cases because they might show a complete response with definitive CRT. We evaluated the presence of any residual in situ lesions and tumor depth in detail. The grading of tumor regression in primary sites was as follows: grade 3 (7 cases), grade 2 (16 cases), grade 1b (13 cases), and grade 1a (6 cases). The concordance rate between macroscopic and histopathological evaluation on the depth of the tumor was 40% (17/42). Among 29 cases (grade 2 and grade 1b), intraepithelial lesions were not detected in 17 cases, and tumor nests were not detected in the lamina propria mucosae in 9 cases. The results of this study highlight the difficulties of detecting residual carcinoma cells using conventional endoscopic biopsy in patients who have received CRT. Therefore, when residual cancer is clinically suspected in patients who have received CRT, the biopsy specimen should be obtained from the deep layer of the esophagus whenever possible. Additionally, close follow-up is required using positron emission tomography/computed tomography, endoscopy, and other radiological evaluations.

ICTV Virus Taxonomy Profile: Hepeviridae.

The family Hepeviridae includes enterically transmitted small non-enveloped positive-sense RNA viruses. It includes the genera Piscihepevirus, whose members infect fish, and Orthohepevirus, whose members infect mammals and birds. Members of the genus Orthohepevirus include hepatitis E virus, which is responsible for self-limiting acute hepatitis in humans and several mammalian species; the infection may become chronic in immunocompromised individuals. Extrahepatic manifestations of Guillain-Barré syndrome, neuralgic amyotrophy, glomerulonephritis and pancreatitis have been described in humans. Avian hepatitis E virus causes hepatitis-splenomegaly syndrome in chickens. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Hepeviridae, which is available at www.ictv.global/report/hepeviridae.

Current assessment of choledochoduodenostomy: 130 consecutive series.

Introduction Cholelithiasis usually can be managed successfully by endoscopic sphincterotomy. Choledochoduodenostomy (CDD) is one of the surgical treatment options but its acceptance remains debated because of the risk of reflux cholangitis and sump syndrome. The aim of this study was to assess the current features and outcomes of patient undergoing CDD. Patients and methods We retrospectively analysed the surgical results of consecutive 130 patients treated by CDD between 1991 and 2013 and excluded five cases with a malignant disorder. Indications for surgery included endoscopic management where stones were difficult or failed to pass and primary common bile duct stones with choledochal dilatation. Incidences of reflux cholangitis, stone recurrence, pancreatitis or sump syndrome were investigated and the data between end-to-side and side-to-side CDD were compared. Results Reflux cholangitis and stone recurrence was 1.6% (2/125) and 0% (0/125) of cases by CDD. There is no therapeutic-related pancreatitis in CDD. Sump syndrome was not also observed in side-to-side CDD. Conclusions This study is a first comparative study between end-to-side and side-to-side CDD. The surgical outcomes for CDD treatment of choledocholithiasis were acceptable. The incidence of reflux cholangitis, stone recurrence, pancreatitis and sump syndrome was very low.