Picosecond-Scale Ultrafast Many-Body Dynamics in an Ultracold Rydberg-Excited Atomic Mott Insulator.

We report the observation and control of ultrafast many-body dynamics of electrons in ultracold Rydberg-excited atoms, spatially ordered in a three-dimensional Mott insulator (MI) with unity filling in an optical lattice. By mapping out the time-domain Ramsey interferometry in the picosecond timescale, we can deduce entanglement growth indicating the emergence of many-body correlations via dipolar forces. We analyze our observations with different theoretical approaches and find that the semiclassical model breaks down, thus indicating that quantum fluctuations play a decisive role in the observed dynamics. Combining picosecond Rydberg excitation with MI lattice thus provides a platform for simulating nonequilibrium dynamics of strongly correlated systems in synthetic ultracold atomic crystals, such as in a metal-like quantum gas regime.

Ultrafast Creation of Overlapping Rydberg Electrons in an Atomic BEC and Mott-Insulator Lattice.

We study an array of ultracold atoms in an optical lattice (Mott insulator) excited with a coherent ultrashort laser pulse to a state where single-electron wave functions spatially overlap. Beyond a threshold principal quantum number where Rydberg orbitals of neighboring lattice sites overlap with each other, the atoms efficiently undergo spontaneous Penning ionization resulting in a drastic change of ion-counting statistics, sharp increase of avalanche ionization, and the formation of an ultracold plasma. These observations signal the actual creation of electronic states with overlapping wave functions, which is further confirmed by a significant difference in ionization dynamics between a Bose-Einstein condensate and a Mott insulator. This system is a promising platform for simulating electronic many-body phenomena dominated by Coulomb interactions in the condensed phase.

MR Imaging-Based Analysis of Glioblastoma Multiforme: Estimation of IDH1 Mutation Status.

BACKGROUND AND PURPOSE: Glioblastoma multiforme is highly aggressive and the most common type of primary malignant brain tumor in adults. Imaging biomarkers may provide prognostic information for patients with this condition. Patients with glioma with isocitrate dehydrogenase 1 (IDH1) mutations have a better clinical outcome than those without such mutations. Our purpose was to investigate whether the IDH1 mutation status in glioblastoma multiforme can be predicted by using MR imaging. MATERIALS AND METHODS: We retrospectively studied 55 patients with glioblastoma multiforme with wild type IDH1 and 11 patients with mutant IDH1. Absolute tumor blood flow and relative tumor blood flow within the enhancing portion of each tumor were measured by using arterial spin-labeling data. In addition, the maximum necrosis area, the percentage of cross-sectional necrosis area inside the enhancing lesions, and the minimum and mean apparent diffusion coefficients were obtained from contrast-enhanced T1-weighted images and diffusion-weighted imaging data. Each of the 6 parameters was compared between patients with wild type IDH1 and mutant IDH1 by using the Mann-Whitney U test. The performance in discriminating between the 2 entities was evaluated by using receiver operating characteristic analysis. RESULTS: Absolute tumor blood flow, relative tumor blood flow, necrosis area, and percentage of cross-sectional necrosis area inside the enhancing lesion were significantly higher in patients with wild type IDH1 than in those with mutant IDH1 (P < .05 each). In contrast, no significant difference was found in the ADC(minimum) and ADC(mean). The area under the curve for absolute tumor blood flow, relative tumor blood flow, percentage of cross-sectional necrosis area inside the enhancing lesion, and necrosis area were 0.850, 0.873, 0.739, and 0.772, respectively. CONCLUSIONS: Tumor blood flow and necrosis area calculated from MR imaging are useful for predicting the IDH1 mutation status.

Preliminary study on the clinical application of augmented reality neuronavigation.

OBJECTIVE: To develop an augmented reality (AR) neuronavigation system with Web cameras and examine its clinical utility. METHODS: The utility of the system was evaluated in three patients with brain tumors. One patient had a glioblastoma and two patients had convexity meningiomas. Our navigation system comprised the open-source software 3D Slicer (Brigham and Women's Hospital, Boston, Massachusetts, USA), the infrared optical tracking sensor Polaris (Northern Digital Inc., Waterloo, Canada), and Web cameras. We prepared two different types of Web cameras: a handheld type and a headband type. Optical markers were attached to each Web camera. We used this system for skin incision planning before the operation, during craniotomy, and after dural incision. RESULTS: We were able to overlay these images in all cases. In Case 1, accuracy could not be evaluated because the tumor was not on the surface, though it was generally suitable for the outline of the external ear and the skin. In Cases 2 and 3, the augmented reality error was ∼2 to 3 mm. CONCLUSION: AR technology was examined with Web cameras in neurosurgical operations. Our results suggest that this technology is clinically useful in neurosurgical procedures, particularly for brain tumors close to the brain surface.

Involvement of brown adipose tissue in subcutaneous fat necrosis of the newborn.

BACKGROUND: Subcutaneous fat necrosis (SCFN) of the newborn is a rare condition that manifests within days after birth. The interscapular region, axillae and shoulders are the most commonly affected sites, corresponding to anatomic sites of brown adipose tissue (BAT) in newborns. OBJECTIVE: We postulated a specific involvement of BAT in SCFN and searched for brown adipocytes at affected sites. METHODS: Biopsy specimens were immunostained with antibodies against uncoupling protein 1 (UCP-1) and examined by electron microscopy. We also examined BAT by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and computed tomography (PET-CT) scanning. RESULTS: A few cells in biopsy specimens from two patients bound antibodies against UCP-1, and brown adipocytes were detected at several stages of degeneration. PET-CT scans revealed lower uptake of (18)F-FDG at major sites of SCFN. CONCLUSION: SCFN and BAT can be found at the same sites, suggesting a pathophysiological connection.

Clinical course of abducens nerve palsy associated with skull base tumours.

BACKGROUND: The clinical course of abducens nerve palsy associated with skull base tumour is rarely reported. In this study, we examined the post-operative course of abducens nerve palsies associated with various skull base tumours. METHOD: Between January 2003 and December 2006, 240 patients with various skull base tumours underwent surgery at Kyushu University Hospital. Among them, nine patients presented with abducens nerve palsies (ten nerves) following surgery. The conditions included two pituitary adenomas, two trigeminal schwannomas and five meningiomas. We evaluated the function of the abducens nerves in these patients on admission, at discharge, and periodically in the outpatient clinic. FINDINGS: Four of the abducens nerve palsies already existed prior to surgery, and six of them developed post-operatively. In the four patients with pituitary adenomas and trigeminal schwannomas, all nerves were anatomically preserved and showed complete recovery of function within 6 months after surgery. In contrast, only two of the six palsies in patients with skull base meningiomas showed complete recovery. In three patients with petro-clival meningiomas, the abducens nerves were completely transected during surgery, and one was reconstructed using fibrin glue. This patient remarkably recovered from the abducens nerve palsy within 2 years. CONCLUSIONS: The abducens nerve palsies in pituitary adenomas and trigeminal schwannomas showed a better clinical course compared to those in skull base meningiomas. The abducens nerve palsies that occur with skull base meningiomas are less likely to recover. Nevertheless, it is important to preserve the nerves and to perform surgical repair if the nerve is transected.

Histopathological evidence of small-vessel vasculitis within the skin and lungs associated with interstitial pneumonia in an adult patient with dermatomyositis.

Dermatomyositis (DM) often has a poor prognosis, due to complications associated with malignancy or interstitial pneumonia (IP). It is uncommon to find histopathological small-vessel vasculitis within cutaneous lesions and pulmonary capillaritis in patients with DM. A 64-year-old woman was diagnosed with DM based on the presence of quadriparesis, typical heliotropic rash, Gottron's papules, increased serum levels of muscle enzymes and typical muscle biopsy findings. She also had associated IP, which subsequently developed into a rapidly progressive condition. We found a high titre of Krebs von den Lunge (KL)-6 in her serum. Measurement of serum KL-6 level is widely accepted as a diagnostic test to monitor the activity of interstitial lung diseases. Histopathological examinations of the cutaneous and lung-associated features showed small-vessel vasculitis. We suggest that investigation of KL-6 levels in patients with DM and associated conditions should be carried out to determine if raised KL-6 levels are useful at predicting outcome or severity of various features.

Perfusion imaging of brain tumors using arterial spin-labeling: correlation with histopathologic vascular density.

BACKGROUND AND PURPOSE: We investigated the relationship between tumor blood-flow measurement based on perfusion imaging by arterial spin-labeling (ASL-PI) and histopathologic findings in brain tumors. MATERIALS AND METHODS: We used ASL-PI to examine 35 patients with brain tumors, including 11 gliomas, 9 meningiomas, 9 schwannomas, 1 diffuse large B-cell lymphoma, 4 hemangioblastomas, and 1 metastatic brain tumor. As an index of tumor perfusion, the relative signal intensity (SI) of each tumor (%Signal intensity) was determined as a percentage of the maximal SI within the tumor per averaged SI within normal cerebral gray matter on ASL-PI. Relative vascular attenuation (%Vessel) was determined as the total microvessel area per the entire tissue area on CD-34-immunostained histopathologic specimens. MIB1 indices of gliomas were also calculated. The differences in %Signal intensity among different histopathologic types and between high- and low-grade gliomas were compared. In addition, the correlations between %Signal intensity and %Vessel or MIB1 index were evaluated in gliomas. RESULTS: Statistically significant differences in %Signal intensity were observed between hemangioblastomas versus gliomas (P < .005), meningiomas (P < .05), and schwannomas (P < .005). Among gliomas, %Signal intensity was significantly higher for high-grade than for low-grade tumors (P < .05). Correlation analyses revealed significant positive correlations between %Signal intensity and %Vessel in 35 patients, including all 6 histopathologic types (rs = 0.782, P < .00005) and in gliomas (rs = 0.773, P < .05). In addition, in gliomas, %Signal intensity and MIB1 index were significantly positively correlated (rs = 0.700, P < .05). CONCLUSION: ASL-PI may predict histopathologic vascular densities of brain tumors and may be useful in distinguishing between high- and low-grade gliomas and in differentiating hemangioblastomas from other brain tumors.

A case of intracranial hypoglossal neurinoma without hypoglossal nerve palsy: operative view of the preserved rostral trunk.

Hypoglossal neurinomas usually manifest with hemiatrophy and weakness of the tongue. A rare case of intracranial hypoglossal neurinoma without preoperative hypoglossal nerve dysfunction and its operative view are presented. A 36-year-old female who presented with headaches and vertigo was admitted to our hospital. The neurological examination revealed bilateral papilledema and mild truncal ataxia, although weakness and atrophy of the tongue were not observed. Magnetic resonance and computed tomography images demonstrated a large foramen magnum tumor without enlargement of the hypoglossal canal. Total removal of the tumor was performed via a lateral suboccipital craniotomy and C1 partial laminectomy. During the operation, two trunks were observed for the hypoglossal nerve at the entrance of the hypoglossal canal. The tumor arose from the caudal trunk, while the intact rostral trunk entered the hypoglossal canal normally. The tumor only developed intracranially, and since the rostral trunk of the hypoglossal nerve was intact, the patient did not present with hypoglossal nerve palsy preoperatively.

Episodic release of methane bubbles from peatland during spring thaw.

Methane (CH(4)) flux into the atmosphere during spring thaw was investigated in a small ombrotrophic peatland (141 degrees 48'E, 43 degrees 19'N, Japan) using the conventional chamber method. More than 50 chamber deployments on top of the snow cover were carried out and continued for more than 165h until the surface snow and underlying ice cover on top of the peat layer had thawed completely. Methane emissions were almost absent in the presence of snow cover. At the very moment the surface ice cover thawed, a large CH(4) flush (>10mgCH(4)m(-2)h(-1)) was recorded, which was on the same order of magnitude as episodic ebullition previously observed in the high-summer. Gas bubbles trapped in the ice layer on top of the waterlogged peat were preliminarily analyzed for the volumetric percentage in the total ice volume and their gas species compositions. Results showed that the bubbles occupied about 3.2% volume and that the mixing ratio of CH(4) in the bubbles was about 20%. The abundance of the bubble-form CH(4) was sufficient to explain the observed episodic CH(4) release during the thaw. Results of this study show that CH(4) emissions during the thaw season have great temporal variability; emission occurs as an episodic release of bubble-form CH(4) stored in the frozen layer. The results also imply the possibility that gas-phase CH(4) plays an important role, not only during the growing season but also in cold-season CH(4) dynamics in northern peatlands.

Expression of matrilysin (matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma.

BACKGROUND: Matrilysin (MMP-7), a member of the matrix metalloproteinase (MMP) family of proteins, is expressed in various types of malignant tumours. There have been no previous studies of the correlation between matrilysin expression and melanoma. OBJECTIVES: Protein expression of matrilysin was evaluated in human cutaneous melanomas, metastatic melanomas, acquired common melanocytic naevi and Spitz naevi, and the data were corrected with the clinicopathological factors. METHODS: We retrospectively investigated 18 primary melanomas, 15 metastatic melanomas, 10 common melanocytic naevi and five Spitz naevi samples at our clinic using immunohistochemistry (IHC). Both promatrilysin and active matrilysin were found in the melanoma tissue extracts by Western immunoblotting. In situ hybridization demonstrated that melanoma cells selectively express matrilysin mRNA. RESULTS: Of the melanoma samples, 29 of 33 (87 x 9%) were positive for matrilysin, including 14 of 18 (77 x 8%) primary cutaneous melanomas and 15 of 15 (100%) metastatic melanomas. In contrast, matrilysin was not expressed in common naevi or Spitz naevi. The matrilysin IHC staining score in primary melanomas was associated with the presence of metastases, tumour thickness and TNM staging (P=0 x 001, 0 x 025 and 0 x 021, respectively). The 5-year overall survival was 26.3% for matrilysin-positive cases and 100% for matrilysin-negative cases among melanoma specimen. CONCLUSIONS: We found matrilysin expression in primary melanomas and in metastatic melanomas. We further demonstrated that the matrilysin IHC staining score was associated with invasive depth of primary melanoma lesions and metastases. Our observations indicate that matrilysin may be associated with melanoma progression, and may enhance melanoma tumour cell invasion. Therefore, matrilysin may be potentially valuable as a prognostic indicator to predict the clinical behaviour of melanoma.

Elevated serum IgA anticardiolipin antibody levels in adult Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis characterized by palpable purpura on the lower extremities and IgA-dominant immune complex deposition within the wall and lumen of dermal vessels in the lesions. This disorder is associated, to varying degrees, with joint, gastrointestinal and renal involvement. Antiphospholipid antibodies, including anticardiolipin antibodies (aCL Abs), are a heterogeneous group of circulating autoantibodies found in patients with autoimmune and infectious diseases. OBJECTIVES: To investigate the possible role of aCL Abs in adult HSP, we measured levels of serum IgA, C-reactive protein (CRP), aCL Abs of the IgG, IgM and IgA isotypes and anti-beta(2)-glycoprotein I (beta(2)GPI)-dependent aCL Abs in adult patients with HSP. We evaluated the correlation between these biological parameters and the clinical manifestations. METHODS: Adult patients with HSP with an initial cutaneous manifestation of palpable purpura on their lower extremities seen between 2001 and 2005 in our department were retrospectively reviewed. Patients with known connective tissue diseases were not included in the study. Histological examination of all patient skin biopsy specimens revealed leucocytoclastic vasculitis in the upper and mid-dermis. Direct immunofluorescence analysis showed prominent deposits of IgA in the capillary walls of all patients. Blood samples were taken at the time that the patient presented. Serum levels of aCL Abs and anti-beta(2)GPI-dependent aCL Abs were measured by enzyme-linked immunosorbent assay. RESULTS: Twenty adult patients with HSP (12 men and eight women), mean age 62.2 years (range 23-81) were enrolled. IgA aCL Abs were found in 15 of the 20 patients (75%). All were negative for IgG aCL Abs, IgM aCL Abs and anti-beta(2)GPI-dependent aCL Abs. The elevation of serum IgA aCL Abs in the 15 patients showed a significant correlation with serum IgA and CRP levels (r(s) = 0.91, P = 0.0007; r(s) = 0.80, P = 0.0026, respectively). Levels of serum IgA aCL Abs were also significantly associated with arthralgia (P = 0.022) and proteinuria according to urinalysis (P = 0.013). CONCLUSIONS: Serum levels of IgA aCL Abs are elevated in the initial active stage of adult HSP, suggesting that serum IgA aCL Abs may play some role in the onset of adult HSP. We believe that serum IgA aCL Abs might be an indicator of adult HSP activity.

Enhanced skin regeneration by nanoegg formulation of all-trans retinoic acid.

All-trans retinoic acid (atRA) which could smooth wrinkles and produce less pigmented skin after a few months of treatment has been studied in research into topical treatments for a potent inhibitor of new melanin production. However, the clinical responses of commercial atRA cream predominantly comprise severe inflammation. We report a novel nanotechnology "nanoegg" system giving improved effects of atRA self-assembly which were coated by CaCO3. Dorsal areas of hairless mouse and porcine skin were employed for administration of nanoegg ointment and commercial products. The mRNA for heparin-binding epidermal growth factor-like growth factor (HB-EGF) from tissues was measured by a real-time PCR method. All tissues were stained for detection of hyaluronate and the thickness of the epidermis. A clinical trial in humans was carried out at St. Marianna University in Japan. As a result, the irritation and inflammation associated with atRA molecules were substantially reduced. The physicochemical instability of atRA was also dramatically improved. Furthermore, nanoegg enhanced marked expression of mRNA for HB-EGF from keratinocytes, which is known as one of the markers of keratinocyte turnover. Also, production of hyaluronate was surprisingly in the intercellular spaces of the basal and spinous cell layers 2 days after treatment. Even at the low concentration of atRA in the nanoegg system, the proliferation and differentiation of keratinocyte was somewhat enhanced. A nanoegg may thus not only prevent adverse effects, but also markedly enhance the main effect.

A successfully treated case of mycetoma due to Nocardia veterana.

We report a successfully treated case of mycetoma from which an unusual Nocardia species was isolated. The isolate was identified as N. veterana by biochemical characterization and 16S ribosomal RNA gene sequencing, and it has not been previously reported as a causative agent of human mycetomas. Treatment with various antibiotics over 6 years and surgical resection failed to cure the disease. However, the combination of intravenous imipenem/cilastatin and amikacin along with oral clarithromycin and minocycline proved very effective in this case. This is the first case report of mycetoma due to N. veterana in a clinical setting.

Acquired symmetrical dermal melanocytosis (naevus of Hori) developing after aggravated atopic dermatitis.

BACKGROUND: Acquired symmetrical dermal melanocytosis (ASDM) is a pigmentary disorder characterized by blue-brown macules most frequently seen on the face of young and middle-aged Asian women. ASDM developing after other skin diseases has not been previously reported. OBJECTIVES: To characterize the clinical and histopathological features of ASDM associated with atopic dermatitis (AD) and to elucidate the differences between AD-associated ASDM and idiopathic ASDM. METHODS: Sixteen patients with ASDM associated with AD were examined clinically and histopathologically and were compared with 69 patients with idiopathic ASDM. RESULTS: The AD patients associated with ASDM consisted of four men and 12 women with a mean age of 32.8 +/- 13.1 years. Most patients remembered that the pigmented macules appeared in places where refractory eczema had existed for a long time. The marked preponderance in females and the appearance in the early reproductive period were common features of AD-associated ASDM and idiopathic ASDM. AD-associated ASDM was most commonly observed on the forehead (68.8%) and on the backs of the hands (50.0%), whereas 89.9% of idiopathic ASDM was seen on the cheeks. There was no significant difference in the number of dermal melanocytes between AD-associated ASDM and idiopathic ASDM. Electron microscopic studies demonstrated many mature melanocytes and smaller numbers of immature melanocytes in the dermis. Some melanocytes were seen adjacent to mast cells. CONCLUSIONS: AD-associated ASDM does not appear to be rare in Japan. ASDM may be triggered in AD patients by sunlight exposure, some alterations in sex hormones and/or persistent cutaneous inflammation. Histamine and stem cell factor produced by mast cells may play crucial roles in the pathogenesis of AD-associated ASDM.

Excessive expression of Txk, a member of the Tec family of tyrosine kinases, contributes to excessive Th1 cytokine production by T lymphocytes in patients with Behcet's disease.

Excessive Th1 cell function is importantly involved in the pathogenesis of Behcet's disease (BD). We previously found that Txk, a member of the Tec family of tyrosine kinases, acts as a Th1 cell specific transcription factor. To investigate immune aberration in the pathogenesis of BD, we studied the expression of Txk and Th1 cytokines in peripheral blood lymphocytes (PBL) and skin lesions in patients with BD. Cytokine production by the lymphocytes was assessed using ELISA. PBL produced excessive Th1 associated cytokines including IFN-gamma and IL-12 spontaneously and in response to exogenous HSP60-derived peptide stimulation, which was shown to induce proliferation of PBL, in patients with BD. Circulating CD4+ T cells expressed excessive Txk protein. A majority of cells infiltrating into skin lesions expressed IFN-gamma in the BD specimens. IL-12 and IL-18 were also expressed in the mononuclear cell aggregates. Lymphocytes accumulating in the skin lesion expressed higher levels of Txk as compared with atopic dermatitis lesions, a typical Th2 disease. IFN-gamma, IL-18 and Il-12 were detected in the BD skin lesions, which may induce preferential development of Th1 cells in patients with BD. The mononuclear cell aggregates contained Txk expressing cells in such skin lesions. Collectively, Txk expressing Th1 cells and the Th1 associated cytokines may play a critical role in the development of skin lesions in BD.

Combination therapy consisting of week pulses of oral terbinafine plus topical application of terbinafine cream in the treatment of onychomycosis.

BACKGROUND: Terbinafine, based on its pharmacokinetic properties, is a good candidate for pulse therapy. There are, as yet, no current guidelines for a terbinafine 1-week pulse regimine. OBJECTIVE: To determine the optimal 1-week pulse dosing regimen for combination therapy of oral terbinafine with complementary 1% terbinafine cream for the treatment of onychomycosis. DESIGN: A total of 69 onychomycosis patients received 250 mg terbinafine, given orally once daily for 7 days as 1-week pulses, separated by intervals of 2-3 weeks, until the desired improvement was observed. A daily application of 1% terbinafine cream was advised through to the evaluation date at 12 months follow-up. The treatment regimens were compared based on the number of pulses and the duration of treatment. RESULTS: The 45 patients (65.2%) who achieved complete cure received an average of 7.8+/-3.5 pulse treatments over 4.8+/-2.6 months. The optimal terbinafine dosing regimen consisted of alternate 1-week pulses, with most patients on this regimen (19/20 cases; 95%) achieving total cure. CONCLUSION: Favorable treatment outcome was gained from this terbinafine 1-week pulse regimen and also better compliance compared with a standard daily regimen.