DIFFUSION OF INJECTED COLLAGENASE CLOSTRIDIUM HISTOLYTICUM FOR DUPUYTREN´S DISEASE: AN IN-VIVO STUDY.

INTRODUCTION: While injecting Clostridium Histolyticum as a non-surgical tratment for Dupuytrens disease on the palmar side of the hand the recommended depth of the needle should be “around 2 to 3 mm in depth”. The diffusion of CCH inside the soft tissues around the cord might explain the occurrence of common adverse events reported in the literature such as oedema, injection site swelling, blood blisters, skin laceration, and pain in extremity. We hypothesized that the injected Collagenase Clostridium Histolyticum does not only concentrate inside the cord but also dissipates both along the cord and into the adjacent tissues. This study investigated our hypothesis by visual intraoperative findings after injecting Povidone iodine into the cord. MATERIAL AND METHODS: Povidone iodine  (PI)was injected into the cord on six patients with Dupuytrens contracture before an open surgical operation (partial fasciectomy). We marked three hypothetical Collagenase Clostridium Histolyticum injection points at 2 mm intervals on the skin above the cord around the metacarpo-phalangeal joint and the depth of the injection (distance from the skin surface to the middle of the cord) was measured by ultrasonography. After dispensing 0.25 ml of Povidone iodine into the three points at the measured depths, we performed careful dissection and investigated the extent of diffusion of Povidone iodine visually. RESULTS: The injection depth averaged 2.6 mm. In all cases, the cord was homogenously stained about 10 mm along its extent centrally to the injected sites and infiltration of Povidone iodine into the subcutaneous structure and fat tissue occurred. Three cases showed diffusion into the neurovascular bundles and two cases showed infiltration underneath the cord structure. CONCLUSIONS: This study simulated the likely diffusion outcomes of injected Collagenase Clostridium Histolyticum around the cord. This implies that even if Collagenase Clostridium Histolyticum is injected into the centre of the cord, it does not concentrate inside the cord only but also dissipates along the cord and infiltrates into the adjacent tissues with potential secondary damages.

OPTIMAL INJECTION DEPTH FOR COLLAGENASE CLOSTRIDIUM HISTOLYTICUM DETERMINED BY ULTRASONOGRAPHY IN THE TREATMENT OF DUPUYTREN´S DISEASE.

INTRODUCTION: A non-surgical procedure for the treatment of Dupuytrens disease is a palmar injection of Collagenase Clostridium Histolyticum to the recommended depth of “around 2-3 mm”. However, there is little supporting evidence from the literature to substantiate this. The aim of this study was to evaluate the “optimal depth” for injection of Collagenase Clostridium Histolyticum by ultrasonography for the treatment of Dupuytrens disease. MATERIAL AND METHODS: A total of 43 patients were enrolled in this study. We marked the collagenase injection point on the skin above the cord before injection. We then measured the distance from the surface of the skin to the middle of the cord by ultrasonography long axis imaging and defined this as the “optimal depth”. RESULTS: The average depth from the skin to the centre of the cord was 2.4 mm. The average distance from the surface of the skin to the proximal surface of the cord was 1.0 mm and the average thickness of the cord was 2.7 mm. CONCLUSION: By precise measurement of individual cases utilising ultrasonography we were able to confirm that the recommendations for injection depth as provided by the supplier of Collagenase Clostridium Histolyticum (2-3 mm) were in agreement with our findings. However no objective guide was supplied as with regards to interindividual variability between patients and we suggest that the use of preliminary ultrasonography will likely provide improved outcomes.

Tensile-Strain-Dependent Spin States in Epitaxial LaCoO_{3} Thin Films.

The spin states of Co^{3+} ions in perovskite-type LaCoO_{3}, governed by the complex interplay between the electron-lattice interactions and the strong electron correlations, still remain controversial due to the lack of experimental techniques which can directly detect them. In this Letter, we revealed the tensile-strain dependence of spin states, i.e., the ratio of the high- and low-spin states, in epitaxial thin films and a bulk crystal of LaCoO_{3} via resonant inelastic soft x-ray scattering. A tensile strain as small as 1.0% was found to realize different spin states from that in the bulk.

A Tenuous Lunar Ionosphere in the Geomagnetic Tail.

We utilize measurements of electron plasma frequency oscillations made by the two-probe Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun mission to investigate the charged particle density in the lunar environment as the Moon passes through the Earth's geomagnetic tail. We find that the Moon possesses a tenuous ionosphere with an average density of ~0.1-0.3 cm-3, present at least 50% of the time in the geomagnetic tail, primarily confined to within a few thousand kilometers of the dayside of the Moon. The day-night asymmetry and dawn-dusk symmetry of the observed plasma suggests that photoionization of a neutral exosphere with dawn-dusk symmetry produces the majority of the lunar-derived plasma. The lunar plasma density commonly exceeds the ambient plasma density in the tail, allowing the presence of the lunar ionosphere to appreciably perturb the local plasma environment.

Effect of amino group protonation on the carboxyl group in aqueous glycine observed by O 1s X-ray emission spectroscopy.

The valence electronic structures of the amino acid glycine in aqueous solution were investigated in detail through X-ray emission spectroscopy at O 1s excitation under selective excitation conditions of the C[double bond, length as m-dash]O site in the carboxyl group. The X-ray emission spectra of glycine were similar to that of acetic acid (CH3COOH), suggesting a resemblance between the molecular orbitals associated with the carboxyl groups in the two molecules. The changes of O 1s X-ray emission spectra as a function of pH were investigated in detail. In addition to spectral changes due to protonation/deprotonation of the carboxyl group for lower pH-values around the pKa value (∼2.3), the spectra of glycine exhibited further changes in the higher-pH region near the pKb value of glycine (dissociation constant of amino group ∼9.5). These results show the effects of amino group protonation on the electronic state around the carboxyl group. X-ray emission spectroscopy might be a tool to investigate intramolecular interactions between functional groups in a molecule.

Photoemission and electrostatic potentials on the dayside lunar surface in the terrestrial magnetotail lobes.

Despite the need to accurately predict and assess the lunar electrostatic environment in all ambient conditions that the Moon encounters, photoemission and electrostatic potentials on the dayside lunar surface in the terrestrial magnetotail lobes remain poorly characterized. We study characteristics and variabilities of lunar photoelectron energy spectra by utilizing Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun (ARTEMIS) and Apollo measurements in combination with the Flare Irradiance Spectral Model (FISM). We confirm that the photoelectron spectral shapes are consistent between ARTEMIS and Apollo and that the photoelectron flux is linearly correlated with the FISM solar photon flux. We develop an observation-based model of lunar photoelectron energy distributions, thereby deriving the current balance surface potential. The model predicts that dayside lunar surface potentials in the tail lobes (typically tens of volts) could increase by a factor of 2 - 3 during strong solar flares.

Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH) is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD). The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB, SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene) has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

Electron-Phonon Coupling in the Bulk of Anatase TiO2 Measured by Resonant Inelastic X-Ray Spectroscopy.

We investigate the polaronic ground state of anatase TiO2 by bulk-sensitive resonant inelastic x-ray spectroscopy (RIXS) at the Ti L3 edge. We find that the formation of the polaron cloud involves a single 95 meV phonon along the c axis, in addition to the 108 meV ab-plane mode previously identified by photoemission. The coupling strength to both modes is the same within error bars, and it is unaffected by the carrier density. These data establish RIXS as a directional bulk-sensitive probe of electron-phonon coupling in solids.

Monocyte CD64 expression as a novel biomarker for the disease activity of systemic lupus erythematosus.

OBJECTIVE: Interferon alpha (IFN-α) is a key cytokine associated with systemic lupus erythematosus (SLE). IFN-α induces the expression of CD64 on monocytes (mCD64). Although enhanced mCD64 expression has been reported in patients with SLE, it has never been assessed quantitatively. The aim of this study was to investigate whether or not mCD64 expression correlates with SLE disease activity. METHODS: The mCD64 expression levels were assessed quantitatively in 40 patients with active or inactive SLE by using flow cytometry. The mCD64 expression levels were subsequently compared with the SLE disease activity index (SLEDAI) and levels of existing SLE activity biomarkers, such as anti-DNA antibody, complements, and so on. RESULTS: The mCD64 expression was significantly higher in active disease than in inactive disease SLE (median molecules/cell, interquartile range: 34,648, 8174-24,932 and 20,865, 6357-21,503, respectively; p < 0.001). The levels of mCD64 expression strongly correlated with SLEDAI (r = 0.68, p < 0.001). CONCLUSION: The mCD64 expression is a simple and useful biomarker for evaluating disease activity in patients with SLE.

Revision of the Massarineae (Pleosporales, Dothideomycetes).

We here taxonomically revise the suborder Massarineae (Pleosporales, Dothideomycetes, Ascomycota). Sequences of SSU and LSU nrDNA and the translation elongation factor 1-alpha gene (tef1) are newly obtained from 106 Massarineae taxa that are phylogenetically analysed along with published sequences of 131 taxa in this suborder retrieved from GenBank. We recognise 12 families and five unknown lineages in the Massarineae. Among the nine families previously known, the monophyletic status of the Dictyosporiaceae, Didymosphaeriaceae, Latoruaceae, Macrodiplodiopsidaceae, Massarinaceae, Morosphaeriaceae, and Trematosphaeriaceae was strongly supported with bootstrap support values above 96 %, while the clades of the Bambusicolaceae and the Lentitheciaceae are moderately supported. Two new families, Parabambusicolaceae and Sulcatisporaceae, are proposed. The Parabambusicolaceae is erected to accommodate Aquastroma and Parabambusicola genera nova, as well as two unnamed Monodictys species. The Parabambusicolaceae is characterised by depressed globose to hemispherical ascomata with or without surrounding stromatic tissue, and multi-septate, clavate to fusiform, hyaline ascospores. The Sulcatisporaceae is established for Magnicamarosporium and Sulcatispora genera nova and Neobambusicola. The Sulcatisporaceae is characterised by subglobose ascomata with a short ostiolar neck, trabeculate pseudoparaphyses, clavate asci, broadly fusiform ascospores, and ellipsoid to subglobose conidia with or without striate ornamentation. The genus Periconia and its relatives are segregated from the Massarinaceae and placed in a resurrected family, the Periconiaceae. We have summarised the morphological and ecological features, and clarified the accepted members of each family. Ten new genera, 22 new species, and seven new combinations are described and illustrated. The complete ITS sequences of nrDNA are also provided for all new taxa for use as barcode markers.

Electronic excitations of a magnetic impurity state in the diluted magnetic semiconductor (Ga,Mn)As.

The electronic structure of doped Mn in (Ga,Mn)As is studied by resonant inelastic x-ray scattering. From configuration-interaction cluster-model calculations, the line shapes of the Mn L3 resonant inelastic x-ray scattering spectra can be explained by d-d excitations from the Mn ground state dominated by charge-transferred states, in which hole carriers are bound to the Mn impurities, rather than a pure acceptor Mn2+ ground state. Unlike archetypical d-d excitation, the peak widths are broader than the experimental energy resolution. We attribute the broadening to a finite lifetime of the d-d excitations, which decay rapidly to electron-hole pairs in the host valence and conduction bands through the hybridization of the Mn 3d orbital with the ligand band.

Physical impairment and walking function required for community ambulation in patients with cervical incomplete spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To identify the physical impairments and walking function required for community ambulation in patients with cervical incomplete spinal cord injury (ISCI). SETTING: Chubu Rosai Hospital, Nagoya, Japan. METHODS: Forty patients with cervical ISCI (mean age: 49.9 years, American Spinal Injury Association Impairment Scale D) were included. The primary outcome measure was community ambulation based on Spinal Cord Independence Measure outdoor scores for a distance of >480 m. We measured the upper- and lower-extremity motor scores (UEMS and LEMS), sensory and spasticity. The walking tests included 10 m of walking at a comfortable- and maximum-walking speed (CWS and MWS; m s(-1)), 6 min walking test (6 MWT; m) and the walking index for spinal cord injury II (WISCI II). Multivariate logistic regression models were used to assess the physical impairments associated with community ambulation. Receiver operating characteristic curves were analyzed to determine the cutoff points for physical impairment and walking function. RESULT: The LEMS (beta coefficient (ß)=0.71) and UEMS (ß=0.41) were independently associated with community ambulation in patients with cervical ISCI. The cutoff points of the LEMS, UEMS, CWS, MWS, 6MWT and WISCI II were 41.5, 36.5, 1.00 m s(-1), 1.32 m s(-1), 472.5 m and 17.5, respectively, which suggests moderate to high accuracy. CONCLUSION: The LEMS and UEMS were the most important factors affecting community ambulation in patients with cervical ISCI. The cutoff points of the walking function tests were highly accurate; therefore, these points can serve as targets for walking training in the future.

A prospective, randomized, double-blind, controlled trial on the efficacy of carbon dioxide insufflation in gastric endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Carbon dioxide (CO2) insufflation is expected to be safe and effective in endoscopic submucosal dissection (ESD) as well as in other endoscopic procedures. The present study aimed to clarify the usefulness and safety of CO2 insufflation in gastric ESD. PATIENTS AND METHODS: A total of 102 consecutive patients were randomly assigned to CO2 insufflation (CO2 group, n = 54) or air insufflation (Air group, n = 48). Abdominal pain and distension were chronologically recorded on a 100-mm visual analog scale (VAS). The volume of residual gas in the digestive tract was measured by computed tomography performed immediately after ESD. RESULTS: Abdominal pain on a 100-mm VAS in the CO2 vs. Air group was 4 vs. 3 immediately after ESD, 4 vs. 4 one hour after the procedure, 3 vs. 3 three hours after the procedure, and 1 vs. 4 the next morning, showing no difference between the groups. In addition, there was no difference in abdominal distension on the 100-mm VAS over the time course of the study. The volume of residual gas in the digestive tract in the CO2 group was significantly smaller than that in the Air group (643 mL vs. 1037 mL, P < 0.001). The dose of sedative drugs did not differ between the groups. Neither the incidences of complications nor clinical courses differed between the groups. CONCLUSIONS: Compared with air insufflation, CO2 insufflation during gastric ESD significantly reduced the volume of residual gas in the digestive tract but not the VAS score of abdominal pain and distension.

Marked depletion of the water-channel protein, AQP5, in the canine nictitating membrane glands might contribute to the development of KCS.

The objectives of this study were to investigate the normal histological localization of aquaporin (AQP) 5 protein in the lacrimal and nictitating membrane glands and to compare this localization in healthy and keratoconjunctivitis sicca (KCS) dogs. Lacrimal and nictitating membrane glands of 5 healthy Beagles and nictitating membrane glands of 5 KCS dogs (3 Beagles and 2 mongrel dogs: 0-13 years) were used for the present study. The owners of the KCS dogs did not consent to perform biopsies of the lacrimal glands. The localization and distribution of AQP5 protein were investigated by an immunohistochemical technique. In immunohistochemical staining, AQP5 was localized in the apical site of acinar epithelial and ductal epithelial cells from both the lacrimal and nictitating membrane glands in healthy dogs. However, AQP5 was not detected in the 5 KCS dogs. These results for immunohistochemical AQP5 localization might correlate with the deficiency in tear secretion found in KCS dogs.

A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers.

From chromosomal region 17q21.3, where a tumour suppressor gene(s) for breast and ovarian cancers is thought to be present, we have isolated a novel gene from a cosmid clone that revealed somatic rearrangements in two breast cancers. The gene (MDC) encodes a 524-amino acid metalloprotease-like, disintegrin-like and cysteine-rich protein with sequence similarity to members of the snake-venom metalloprotease/disintegrin family and guinea-pig sperm-surface protein PH-30. These proteins have been implicated in cell-cell or cell-extracellular matrix interactions. Rearrangements in both tumours involve multiple exons and disrupt the coding region of the new MDC.

A pilot study to assess mediastinal emphysema after esophageal endoscopic submucosal dissection with carbon dioxide insufflation.

BACKGROUND AND AIMS: Mediastinal emphysema sometimes develops following esophageal endoscopic submucosal dissection (ESD) without perforation because the esophagus has no serosa. Carbon dioxide (CO2) insufflation during esophageal ESD may reduce the incidence of mediastinal emphysema. The aim of the present study was to compare the incidence and severity of post-ESD mediastinal emphysema in patients receiving CO2 insufflation vs. standard air insufflation during esophageal ESD. PATIENTS AND METHODS: A total of 27 patients who had undergone esophageal ESD with insufflation of CO2 between July 2009 and March 2010 were enrolled in this study (CO2 group). Another 105 patients who had undergone esophageal ESD with air insufflation between March 2004 and May 2009 were included as historical controls (air group). Multi-detector row computed tomography (MDCT) was carried out immediately after ESD. A conventional chest radiograph was taken the next day. Mediastinal emphysema findings on MDCT and radiography were compared between the groups. RESULTS: Mediastinal emphysema detected by chest radiography was 0 % in the CO2 group vs. 6.6 % in the air group (n.s.). Mediastinal emphysema on MDCT was significantly less frequent in the CO2 group compared with the air group (30 % vs. 63 %; P = 0.002). The severity of mediastinal emphysema also tended to be lower in the CO2 group. CONCLUSIONS: Whereas mediastinal emphysema detected by radiography is not so common, MDCT immediately after ESD revealed a certain prevalence of post-ESD mediastinal emphysema. Insufflation of CO2 rather than air during esophageal ESD significantly reduced postprocedural mediastinal emphysema. CO2 can be considered as insufflating gas for esophageal ESD.

Recovery of the blood flow around the femoral head during early corticosteroid therapy: dynamic magnetic resonance imaging in systemic lupus erythematosus patients.

Disturbance of blood supply to the femoral head is a risk factor for corticosteroid-associated osteonecrosis. The aim was to measure blood supply of the proximal femur during corticosteroid therapy in systemic lupus erythematosus (SLE) patients. We repeatedly performed 78 dynamic MRIs of 19 hip joints in 19 SLE patients after initiation of corticosteroid administration for one year. Blood supply of the femoral head (epiphysis, growth plate, and metaphysis), the femoral neck, and the medial circumflex femoral artery were measured in terms of peak percent enhancement. At the first month, blood supply of the growth plate was significantly higher in the pediatric group (<15 years old) than in the adolescent and adult group (>15 years old). At the fourth month, blood supply in every part of the femoral head (epiphysis, growth plate, and metaphysis) was significantly higher in the pediatric group than in the adolescent and adult group. Multiple regression analysis revealed that blood supply to the femoral head depended on the number of days after initiation of corticosteroid administration and the age at the time of dynamic MRI. Blood supply to the femoral head is abundant in pediatric patients and is a function of the number of days after initiation of corticosteroid administration.

Thrombopoietin receptor agonists in refractory immune thrombocytopenia: differential responses to eltrombopag and romiplostim: a case report and possible explanations.

WHAT IS KNOWN AND OBJECTIVE: Although new thrombopoietin (TPO) receptor agonist drugs, such as romiplostim and eltrombopag, are highly effective and well tolerated for patients with immune thrombocytopenia (ITP) refractory to first-line treatments such as prednisolone, the cross-resistance of these two TPO receptor agonists is still unknown. CASE SUMMARY: An 84-year-old Japanese female patient with steroid-refractory ITP received eltrombopag with a gradually increasing dose schedule from 12.5 to 25 mg/day, 37.5 mg/day and finally 50 mg/day. As no increase in platelet count was observed even at the maximum dose of 50 mg/day, and eltrombopag-related grade 3 elevation of aspartate aminotransferase was observed, another TPO receptor agonist, romiplostim, was administered at 1 µg/kg/week subcutaneously. A rapid increase in platelet count was observed 1 week after the first injection. The dose of romiplostim was escalated to 4 µg/kg according to the platelet count and a complete response was achieved 7 weeks after the first injection without any adverse events. WHAT IS NEW AND CONCLUSION: The successful treatment of ITP refractory to eltrombopag with romiplostim strongly suggests that the absence of cross-resistance between these two approved TPO receptor agonists and possible differences in mechanism of action. Further study of the mechanisms of action of TPO receptor agonists is called for along with further exploration of the potential of romiplostim in refractory ITP.

The inhomogeneous structure of water at ambient conditions.

Small-angle X-ray scattering (SAXS) is used to demonstrate the presence of density fluctuations in ambient water on a physical length-scale of approximately 1 nm; this is retained with decreasing temperature while the magnitude is enhanced. In contrast, the magnitude of fluctuations in a normal liquid, such as CCl(4), exhibits no enhancement with decreasing temperature, as is also the case for water from molecular dynamics simulations under ambient conditions. Based on X-ray emission spectroscopy and X-ray Raman scattering data we propose that the density difference contrast in SAXS is due to fluctuations between tetrahedral-like and hydrogen-bond distorted structures related to, respectively, low and high density water. We combine our experimental observations to propose a model of water as a temperature-dependent, fluctuating equilibrium between the two types of local structures driven by incommensurate requirements for minimizing enthalpy (strong near-tetrahedral hydrogen-bonds) and maximizing entropy (nondirectional H-bonds and disorder). The present results provide experimental evidence that the extreme differences anticipated in the hydrogen-bonding environment in the deeply supercooled regime surprisingly remain in bulk water even at conditions ranging from ambient up to close to the boiling point.