Passive near-field imaging via grating-based spectroscopy.

Passive scattering-type scanning near-field optical microscopy (s-SNOM) has recently been developed for studying long-wavelength infrared (LWIR) waves. It detects surface-localized waves without any external illumination or heating and enables the imaging of hot-electron energy dissipation and nanoscale Joule heating. However, the lack of a wavelength selection mechanism in the passive LWIR s-SNOM makes it difficult to perform a thorough analysis of the surface-localized waves. Here, we develop a novel passive scanning near-field optical spectroscopy with a diffraction grating. The spectroscopic optics are designed to exhibit a high signal efficiency and mechanical performance at the temperature of liquid helium (4.2 K). Using the developed passive LWIR near-field spectroscopy, the spectral information of thermally excited evanescent waves can be directly obtained without any influence from the external environment factors, including environmental heat. We have detected the thermally excited evanescent waves on a SiC/Au micropatterned sample at room temperature with a spatial resolution of 200 nm and a wavelength resolution of 500 nm at several wavelengths in the range of 14-15 µm. The obtained spectra are consistent with the electromagnetic local density of states calculated based on the fluctuation-dissipation theorem. The developed passive LWIR near-field spectroscopy enables the spectral analysis of ultrasmall surface-localized waves, making it a high-performance surface analysis tool.

Correction: Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis.

Owing to the insufficient specificity of the anti-myeloproliferative leukemia protein (MPL) antibody in the original version of this Article, Figure 6 and parts of Figures 2a, 4e, and 5a do not represent the correct information. The corrected version of Figure 6 is in this correction and those of Figures 2a, 4e, and 5a are shown in the supplemental information.

Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis.

Myelofibrosis (MF) may be caused by various pathogenic mechanisms such as elevation in circulating cytokine levels, cellular interactions and genetic mutations. However, the underlying mechanism of MF still remains unknown. Recent studies have revealed that fibrocytes, the spindle-shaped fibroblast-like hematopoietic cells, and the thrombopoietin (TPO)/myeloproliferative leukemia protein (MPL; TPO receptor) signaling pathway play a certain role in the development of MF. In the present study, we aimed to investigate the relationship between fibrocytes and MPL activation. We showed that TPO or a TPO receptor agonist directly induces fibrocyte differentiation using murine fibrocyte cell lines and a murine MF model. Conversely, elimination of macrophages expressing MPL by clodronate liposomes reversed the MF phenotype of the murine model, suggesting that fibrocyte differentiation induced by MPL activation contributes to the progression of MF. Furthermore, we revealed that SLAMF7high MPLhigh monocytes in human peripheral blood mononuclear cells were possible fibrocyte precursors and that these cells increased in number in MF patients not treated with ruxolitinib. Our findings confirmed a link between fibrocytes and the TPO/MPL signaling pathway, which could result in a greater understanding of the pathogenesis of MF and lead to the development of novel therapeutic interventions.

Successful management of complete placenta previa after intrauterine fetal death in a second-trimester pregnancy by uterine artery embolization: case report and literature review.

A 27-year-old woman with complete placenta previa was referred at 22 weeks of gestation because of vaginal bleeding and fetal growth restriction. At 24 weeks, sudden fetal death occurred, but bleeding continued and transvaginal sonography revealed abundant periplacental blood flow in the uterine wall. To avoid cesarean section, the authors performed uterine artery embolization (UAE) be- fore vaginal delivery of the fetus. Subsequently, there was little bleeding when laminaria was inserted for cervical ripening and the fetus was delivered vaginally by using vaginal gemeprost. Total blood loss was only 149 ml. The present case suggests that UAE may be an option for patients with placenta previa who desire vaginal delivery after intrauterine fetal death (IUFD) in a second-trimester pregnancy.

Pericardiectomy and pericardium window creation to treat recurrent pericardial tamponade involving a borderline ovarian tumor.

PURPOSE OF INVESTIGATION: Pericardial effusion with cardiac tamponade is an uncommon metastatic manifestation of ovarian tumors, with only one previously reported case involving a borderline ovarian tumor (BOT). CASE: A 50-year-old woman was diagnosed and treated for a primary Stage IIc BOT. The disease recurred as an emergency pericardiocentesis eight years later, which was resected following pericardial effusion with a cardiac tamponade. This occurred two more times, and on the last occasion, drainage failed to relieve her symptoms. However, her symptoms resolved after the creation of a pericardium pleural window together with a pericardiectomy. CONCLUSION: For patients with a metastatic BOT, the creation of a pericardium pleural window and pericardiectomy is effective for recurrent pericardial tamponade, if the pericardial space is posteriorly located and/or segmented.

Predictors of inhalation burn injury using fire site information.

Inhalation burn injury (IBI) is a risk factor for mortality in burn patients. However, it is difficult to diagnose IBI using traditional physical examination alone, especially in prehospital settings. Therefore, facial burn patients are usually treated for suspected IBI. In the present study, we investigated whether fire site information could predict IBI as an alternative to traditional physical examination. This retrospective single-centre analysis involved 27 facial burn patients with suspected IBI who were admitted between 2014 and 2016. The patients were divided into two groups (IBI and non-IBI) according to bronchoscopy findings. Fire site information was compared between the two groups. The IBI (n = 13) and non-IBI (n = 14) groups were compared. Domestic fire was more frequent in the IBI group (69% vs. 29%, P = 0.035). The IBI group included one patient with carboxyhemoglobin ≥10% on admission. Prehospitalization fire site information, particularly domestic fires, might predict IBI in facial burn patients..

L'inhalation de fumées (IF) est un facteur de mortalité chez les brûlés. Son diagnostic clinique est difficile, en particulier en préhospitalier, ce qui fait que les brûlés du visage sont souvent traités comme ayant subi une IF. Cette étude s'est penchée sur les données recueillies sur le site de l'incendie pouvant permettre, mieux que l'examen clinique, de poser le diagnostic d'IF. Cette étude monocentrique rétrospective a revu les dossiers de 27 patients avec brûlures faciales admis entre 2014 et 2016, divisés en 2 groupes (IF, 13 patients et non IF, 14 patients) selon les données endoscopiques. Les données de l'incendie ont ensuite été comparées entre ces 2 groupes. L'incendie était plus fréquemment survenu au domicile dans le groupe IF (65% VS 29%, p = 0,035). Un patient IF avait une HbCO > 10% à l'entrée. La survenue de la brûlure pendant un incendie au domicile pourrait être prédictive d'une IF.

Individual differences in the distribution of sperm acrosome-associated 1 proteins among male patients of infertile couples; their possible impact on outcomes of conventional in vitro fertilization.

The aims of this study were to show the existence of individual differences in the distribution of sperm acrosome-associated 1 (SPACA1) among male patients of infertile couples and to examine their possible impact on the outcomes of conventional in vitro fertilization (IVF). The spermatozoa were collected from male patients of infertile couples, washed by centrifugation, collected by the swim-up method, and then used for clinical treatments of conventional IVF. The surplus sperm samples were fixed and stained with an anti-SPACA1 polyclonal antibody for the immunocytochemistry. In the clinical IVF treatments, fertilization rates and blastocyst development rates were evaluated. The immunocytochemical observations revealed that SPACA1 were localized definitely in the acrosomal equatorial segment and variedly in the acrosomal principal segment. Specifically, the detection patterns of SPACA1 in the acrosomal principal segment could be classified into three categories: (A) strong, (B) intermediate or faint, and (C) almost no immunofluorescence. The SPACA1 indexes were largely different among male patients with the wide range from 13 to 199 points. The SPACA1 indexes were significantly correlated with developmental rates of embryos to blastocysts (r = 0.829, P = 0.00162), although they were barely associated with fertilization rates at 19 h after insemination (r = 0.289, P = 0.389). These results suggest that the distribution of SPACA1 in sperm affects the outcomes of conventional IVF. In conclusion, this study provides initial data to promote large-scale clinical investigation to demonstrate that the SPACA1 indexes are valid as molecular biomarkers that can predict the effectiveness of conventional IVF of infertile couples.

Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients.

To clarify the cooperative roles of recurrently identified mutations and to establish a more precise risk classification system in acute myeloid leukemia (AML), we comprehensively analyzed mutations in 51 genes, as well as cytogenetics and 11 chimeric transcripts, in 197 adult patients with de novo AML who were registered in the Japan Adult Leukemia Study Group AML201 study. We identified a total of 505 mutations in 44 genes, while only five genes, FLT3, NPM1, CEBPA, DNMT3A and KIT, were mutated in more than 10% of the patients. Although several cooperative and exclusive mutation patterns were observed, the accumulated mutation number was higher in cytogenetically normal AML and lower in AML with RUNX1-RUNX1T1 and CBFB-MYH11, indicating a strong potential of these translocations for the initiation of AML. Furthermore, we evaluated the prognostic impacts of each sole mutation and the combinations of mutations and/or cytogenetics, and demonstrated that AML patients could be clearly stratified into five risk groups for overall survival by including the mutation status of DNMT3A, MLL-PTD and TP53 genes in the risk classification system of the European LeukemiaNet. These results indicate that the prognosis of AML could be stratified by the major mutation status in combination with cytogenetics.

Effect of related donor availability on outcome of AML in the context of related and unrelated hematopoietic cell transplantation.

Although allogeneic hematopoietic cell transplantation (HCT) from a related donor is effective therapy for younger patients with AML, it remains unknown how the availability of a related donor affects the outcome when unrelated HCT is a treatment option for patients without a related donor. To address this issue, we retrospectively analyzed 605 cytogenetically non-favorable AML patients younger than 50 years for whom a related donor search was performed during first CR (CR1). The 4-year OS was 62% in 253 patients with a related donor and 59% in 352 patients without a related donor (P=0.534). Allogeneic HCT was performed during CR1 in 62% and 41% of patients with and without a related donor, respectively. Among patients transplanted in CR1, the cumulative incidence of non-relapse mortality was significantly higher in patients without a related donor (P=0.022), but there was no difference in post-transplant OS between the groups (P=0.262). These findings show the usefulness of unrelated HCT in younger patients with cytogenetically non-favorable AML who do not have a related donor. The extensive use of unrelated HCT for such patients may minimize the potential disadvantage of lacking a related donor.

Chemical shift tensor determination using magnetically oriented microcrystal array (MOMA): 13C solid-state CP NMR without MAS.

Chemical shift tensors for the carboxyl and methyl carbons of L-alanine crystals were determined using a magnetically oriented microcrystal array (MOMA) prepared from a microcrystalline powder sample of L-alanine. A MOMA is a single-crystal-like composite in which microcrystals are aligned three-dimensionally in a matrix resin. The single-crystal rotation method was applied to the MOMA to determine the principal values and axes of the chemical shift tensors. The result showed good agreement with the literature data for the single crystal of L-alanine. This demonstrates that the present technique is a powerful tool for determining the chemical shift tensor of a crystal from a microcrystal powder sample.

M-CSF attenuates severity of chronic GVHD after unrelated BMT.

To study the effects of M-CSF administration on long-term outcomes of unrelated BMT, we retrospectively analyzed data from patients transplanted through the Japan Marrow Donor Program. We obtained data from 54 patients who received M-CSF just after BMT and 500 patients who did not receive M-CSF or G-CSF acted as controls. There were no significant differences between the two cohorts with respect to OS, acute GVHD or relapse. Although the incidence of chronic GVHD was comparable between the two groups, extensive chronic GVHD was observed significantly less often in the M-CSF cohort than in the control group. Multivariate analysis identified M-CSF as a significant factor for attenuating extensive chronic GVHD (relative risk: 0.73; 95% confidence interval: 0.55-0.94; P=0.012). We also found the same results in matched-pair analysis. Our observation suggests the potential for clinical use of M-CSF to dampen severe chronic GVHD.

Virus activation and immune function during intense training in rugby football players.

Epidemiological studies suggest that highly trained athletes are more susceptible to upper respiratory tract infections (URTI) compared with the general population. Upper respiratory symptoms (URS) often appear as either primary invasion of pathogenic organisms and/or reactivation of latent viruses such as Epstein-Barr virus (EBV). The purpose of this study was to examine the relationship between EBV reactivation and the appearance of URS during intensive training in collegiate rugby football players. We evaluated EBV-DNA expression in saliva and examined the relationship between onset of URS and daily changes in EBV-DNA as well as secretory immunoglobulin A (SIgA) levels among 32 male collegiate rugby football players during a 1-month training camp. The EBV-DNA expression tended to be higher in subjects who exhibited sore throat (p=0.07) and cough (p=0.18) than that of those who had no symptoms, although their differences were not significant. The SIgA level was significantly lower 1 day before the EBV-DNA expression (p<0.05). The number of URS increased along with the EBV-DNA expression and decrease of SIgA levels. These results suggest that the appearance of URS is associated with reactivation of EBV and reduction of SIgA during training.

Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer.

BACKGROUND: Intracellular phosphoprotein activation significantly regulates cancer progression. However, the significance of circulating phosphoproteins in the blood remains unknown. We investigated the serum phosphoprotein profile involved in pancreatic cancer (PaCa) by a novel approach that comprehensively measured serum phosphoproteins levels, and clinically applied this method to the detection of PaCa. METHODS: We analysed the serum phosphoproteins that comprised cancer cellular signal pathways by comparing sera from PaCa patients and benign controls including healthy volunteers (HVs) and pancreatitis patients. RESULTS: Hierarchical clustering analysis between PaCa patients and HVs revealed differential pathway-specific profiles. In particular, the components of the extracellular signal-regulated kinase (ERK) signalling pathway were significantly increased in the sera of PaCa patients compared with HVs. The positive rate of p-ERK1/2 (82%) was found to be superior to that of CA19-9 (53%) for early stage PaCa. For the combination of these serum levels, the area under the receiver-operator characteristics curves was showing significant ability to distinguish between the two populations in independent validation set, and between cancer and non-cancer populations in another validation set. CONCLUSION: The comprehensive measurement of serum cell signal phosphoproteins is useful for the detection of PaCa. Further investigations will lead to the implementation of tailor-made molecular-targeted therapeutics.

IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation.

Macrophage colony-stimulating factor (M-CSF) regulates the production, survival and function of macrophages through Fms, the receptor tyrosine kinase. Recently, interleukin-34 (IL-34), which shares no sequence homology with M-CSF, was identified as an alternative Fms ligand. Here, we provide the first evidence that these ligands indeed resemble but are not necessarily identical in biological activity and signal activation. In culture systems tested, IL-34 and M-CSF showed an equivalent ability to support cell growth or survival. However, they were different in the ability to induce the production of chemokines such as MCP-1 and eotaxin-2 in primary macrophages, the morphological change in TF-1-fms cells and the migration of J774A.1 cells. Importantly, IL-34 induced a stronger but transient tyrosine phosphorylation of Fms and downstream molecules, and rapidly downregulated Fms. Even in the comparison of active domains, these ligands showed no sequence homology including the position of cysteines. Interestingly, an anti-Fms monoclonal antibody (Mab) blocked both IL-34-Fms and M-CSF-Fms binding, but another MAb blocked only M-CSF-Fms binding. These results suggested that IL-34 and M-CSF differed in their structure and Fms domains that they bound, which caused different bioactivities and signal activation kinetics/strength. Our findings indicate that macrophage phenotype and function are differentially regulated even at the level of the single receptor, Fms.

Electric and mass transport of a carbon nanotube encapsulating a copper nano-rod studied by in-situ transmission electron microscopy.

Electric properties and current-induced structural changes of carbon nanotubes (CNTs) encapsulating copper nano-rods were studied by in-situ transmission electron microscopy (TEM). The diameter and the length of a copper filled CNT were 18 nm and 256 nm, respectively. The thickness of the graphite layer was about 1 nm. The bias voltage was applied between the two ends of the CNT inside the TEM, and the current as well as TEM images were recorded simultaneously. At a bias voltage of 1.4 V, the current increased to 10 microA, corresponding to a current density of 4.0 x 10(6) A/cm2, and at the same time the nano-rods inside the CNT started to move to an end of the CNT. After the movement of the nano-rods, an empty CNT was left. Resistivities of the CNT and the copper nano-rod were measured to be 3.0 x 10(-5) ohm m and 1.2 x 10(-4) ohm m, respectively.

Amiodarone-induced liver cirrhosis and parkinsonism: a case report.

BACKGROUND: Amiodarone-induced hepatotoxicity consists of mild liver test abnormalities and rare cases of acute hepatitis and chronic hepatic lesions, and histologically resembles the whole spectrum of alcoholic liver disease, i.e., non-alcoholic steatohepatitis. Amiodarone-induced neurotoxicity, including tremor, ataxia and peripheral neuropathy, is known, and some cases of parkinsonism following amiodarone use have also been reported. OBJECTIVE: To study the pathology of amiodarone-associated parkinsonism. DESIGN: Light and electromicroscopic examinations of a patient with liver cirrhosis and amiodarone-induced parkinsonism. RESULTS: On postmortem examination, the liver showed micronodular cirrhosis. Striking steatosis and frequent Mallory bodies were present on light microscopy. There were lysosomal inclusion bodies on electron microscopy. From these findings, amiodarone-induced liver cirrhosis was diagnosed. Brain atrophy and infarcts were not observed, and pigmentation in the substantia nigra was preserved. Histologically, there was a slightly lesser degree of neuronal loss with astrocytosis in the substantia nigra, locus ceruleus, and dorsal vagal nucleus. Lewy bodies were not found. In the cerebral white matter and basal ganglia, Alzheimer Type II astrocytes, which are abundant in hepatic encephalopathy, had deposition of electron-dense materials within the lysosomes and mitochondrial matrices. The materials were compatible with the accelerated amiodarone. CONCLUSIONS: This is the first case in which the accumulation of amiodarone in the brain was morphologically observed. Amiodarone accumulation in the brain may play a role in neurotoxicity inducing parkinsonism.