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It is difficult to predict the development of carotid stenosis by means of the known risk factors. Using a computational fluid dynamics analysis, we examined the hemodynamic risks for carotid stenosis, focusing on wall shear stress (WSS) disturbances.In 59 patients with unilateral carotid stenosis, the plaque was removed from the original three-dimensional computed tomography angiographic images, and the vessel shape before stenosis was artificially reproduced. A multivariate regression analysis was performed to determine the associations between the degree of area stenosis and hemodynamic and morphologic factors after adjustment for 6 known risk factors.Metrics for WSS disturbances were higher at and distal to a bifurcation in the carotid arteries after plaque removal compared with the normal carotid arteries, and metrics for WSS magnitudes were lower. In the plaque-removed arteries, the degree of stenosis was significantly negatively correlated with the ratio of stenotic to distal values of metrics for WSS disturbances and the diameter ratio of the external to common carotid artery, and positively correlated with the ratio of proximal to stenotic values of metrics for WSS magnitudes.Rapid increases in WSS from the common carotid artery toward the bifurcation, rapid decreases in WSS disturbance from the bifurcation toward the internal carotid artery, and lower diameter ratio of the external to common carotid artery are more likely than other risk factors to cause future severe stenosis. In patients with these hemodynamic risks, underlying diseases should be controlled more strictly, with imaging examinations at shorter intervals.

Vanadium oxides (V3O7) have been used as electrode materials for supercapacitor applications because of its multiple oxidation states. V3O7 nanoparticles were coated on reduced graphene oxide (rGO) from a peroxovanadate-rGO composite by thermal microexplosive decomposition method. These V3O7 decorated rGO were made composite with the flexible multi redox conducting polymer (Polyaniline). The performance of the composite materials as electrode for supercapacitors was analyzed in a 3-electrode cell, obtaining a specific capacitance of about 579 F g−1 at 0.2 A g−1 specific current. Cycling stability is one of the main barriers noticed in V3O7, which limits the practical performance of supercapacitors. This is overcome by modifying V3O7 with rGO and polyaniline composites which produces good electrical contact resulting in higher capacitances and enhanced cycling stability when compared to pristine V3O7. A superior electrochemical performance and ultra-long cyclic stability of 94% over 2500 cycles was obtained through these developed electrodes.

A polyaniline (PANi)-carbon quantum dots (CQDs) nanocomposite material with CQDs made from a PEG (polyethylene glycol and NaOH) source was synthesized. This unique synthesis technique was developed to overcome the setbacks of the PEG method by using UG (urea and glycine). PANi was synthesized by chemical oxidation in the presence of CQDs, which were prepared according to the two above-mentioned methods. The sample was further characterized by morphological, optical, and electrochemical experiments. FE-SEM showed ridge-like morphology and UV-Vis studies revealed the presence of PANi and CQDs. HRTEM images gave details on the uniformly distributed polyaniline, which showed lengthy rod-like rough surfaces with interconnected tiny CQDs. The electrochemical results from CV and GCD studies indicated an enhancement of the specific capacitance for sample PCQ-2 (CQDs synthesized via the UG method as a source) compared to only PANi and PCQ-1 (CQDs prepared by the PEG method). The cyclic stability established was 84.5% retention from initial capacitance values over 3000 cycles. A two-electrode prototype device was also developed with the PCQ-2 sample and it achieved a reasonable capacitance of 161.3 mF/cm2 and demonstrated good retention stability over 5000 cycles. These results may be due to a variety of factors related to compositing CQDs (with urea and glycine as a source) with PANi.

Objective C-type natriuretic peptide (CNP), a potent stimulator of endochondral ossification, acts through guanylyl cyclase B (GC-B), a subtype of membranous guanylyl cyclase. In previous studies, we revealed that CNP stimulates the longitudinal growth of vertebrae and long bones formed through endochondral ossification in mice. Furthermore, we showed that CNP stimulates endochondral ossification in the craniofacial region and is crucial for midfacial skeletogenesis using cartilage-specific CNP transgenic mice and systemic CNP knockout mice. In the present report, we investigated the effect of increased circulating CNP on craniofacial skeletogenesis in a murine model. Methods We analyzed the craniofacial morphology of transgenic mice in which CNP is expressed under the control of the human serum amyloid P component promoter (SAP-Nppc-Tg mice), resulting in elevated levels of circulating CNP. Next we crossed these SAP-Nppc-Tg mice with CNP knockout mice to clarify whether midfacial hypoplasia in CNP knockout mice will be rescued or not. Results SAP-Nppc-Tg mice exhibited longitudinal overgrowth along the cranial length through endochondral ossification. The midfacial hypoplasia in CNP knockout mice was significantly rescued by increasing circulating CNP level. In addition, the foramen magnum stenosis of CNP knockout mice was significantly ameliorated in the rescued mice. Conclusions Circulating CNP affects cartilage and promotes endochondral ossification in craniofacial region. Systemic administration of CNP might have therapeutic potential not only against midfacial hypoplasia, but also against other aspects of impaired craniofacial skeletal growth, including foramen magnum stenosis, in patients suffering from skeletal dysplasias.

Introduction and importance Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors originating in the wall of the gastrointestinal tract. Jejunal GIST is the rarest subtype. Large GIST can present with an abdominopelvic mass which can be preoperatively misdiagnosed as a gynecological tumor. Case history A 44-year regularly menstruating woman presented with lower abdominal pain which was diagnosed as a malignant ovarian tumor preoperatively with an MRI. However, intraoperatively, a lobulated mass was present in the abdominal cavity arising from a jejunal portion of the small intestine. With an intraoperative diagnosis of jejunal GIST, the mass was excised and jejunum anastomosed. Histopathology examination report showed GIST which was further confirmed by immunohistochemistry. Discussion GIST presenting as a large abdominopelvic mass can mimic a gynecological tumor. Contrast-enhanced CT scan is the preferred imaging modality for the evaluation of patients with suspected GIST to determine the extent of the tumor, the presence or absence of metastatic disease alongside evaluation of the possibility of complete resection. Adjuvant imatinib therapy following complete excision can decrease the disease recurrence. Conclusion Gynecologists should keep in mind that primary gastrointestinal tumors can present as a pelvic mass. A proper histopathological examination helps to confirm the diagnosis. Complete surgical removal of the tumor should be obtained as it determines the prognosis of the disease., Highlights • If a pelvic mass is detected, a non-gynecological tumor like a gastrointestinal stromal tumor (GIST) has to be considered. • Every effort should be made to identify the origin of the tumor and related anatomic structures, especially the ovaries. • Misdiagnoses may have significant therapeutic implications because of the availability of targeted imatinib-based therapy.

We demonstrate a high surface area of manganese sulfide (MnS) nanoparticles via a simple solution method and investigated its morphology, physicochemical, and electrochemical studies. For the first time, we attempted to exploit the polymerization of aniline without adding HCl, as it is corrosive to the metal sulfide. Instead, the acidic group present on the graphene oxide surface plays a significant role to some extent as an acidic dopant in the polymerization process. This in-situ polymerization results in the uniform coverage of granular PANI on the entire MnS/GO nanocomposite, which enhances the interfacial interactions between PANI and MnS/GO nanoparticles. The introduction of graphene oxide (GO) to pristine MnS improved the specific capacitance, surface area, and average pore size. And incorporating PANI to MnS/GO leads to an increase in the interfacial interaction between the different pore sized nanoparticles giving enhanced specific capacitance. The specific capacitance for MnS/GO/PANI nanocomposite as measured by galvanostatic charge-discharge measurements was found to be 773 F/g at 1 A/g current density, and even at higher current density, it showed a specific capacitance of 484 F/g at 3.8 A/g. The specific capacitance obtained for MnS/GO/PANI nanocomposite from CV shows 822 F/g at 10 mV/s and 315 F/g at 200 mV/s. The combinatorial effects without destroying the metal sulfide nanostructure can provide an alternate route to design, promising electroactive nanocomposites is an ideal choice as a cost-effective, next-generation high-performance supercapacitor application.

Glucocorticoids are widely used for treating autoimmune conditions or inflammatory disorders. Long-term use of glucocorticoids causes impaired skeletal growth, a serious side effect when they are used in children. We have previously demonstrated that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth. In this study, we investigated the effect of CNP on impaired bone growth caused by glucocorticoids by using a transgenic mouse model with an increased circulating CNP level. Daily administration of a high dose of dexamethasone (DEX) to 4-week-old male wild-type mice for 4weeks significantly shortened their naso-anal length, which was restored completely in DEX-treated CNP transgenic mice. Impaired growth of the long bones and vertebrae by DEX was restored to a large extent in the CNP transgenic background, with recovery in the narrowed growth plate by increased cell volume, whereas the decreased proliferation and increased apoptosis of the growth plate chondrocytes were unaffected. Trabecular bone volume was not changed by DEX treatment, but decreased significantly in a CNP transgenic background. In young male rats, the administration of high doses of DEX greatly decreased N-terminal proCNP concentrations, a marker of CNP production. In organ culture experiments using fetal wild-type murine tibias, longitudinal growth of tibial explants was inhibited by DEX but reversed by CNP. These findings now warrant further study of the therapeutic potency of CNP in glucocorticoid-induced bone growth impairment.

Herein, we have developed a simple and facile technique at 210 °C to obtain nano-structured organic compounds, instead of making carbon dots at a relatively higher temperature. Taking the advantage of stable dispersion of organic nanostructures in an aqueous medium, composite of polyaniline has been developed and subsequently utilized as an active electrode material for supercapacitor application. This composite material confirms noteworthy enhancement in specific capacitance (779 F/g) and also divulges the attractive capacitance retention using three-electrode systems. The suitability of the materials for the solid-state device was tested with a prototype two-electrode device. The symmetric device exhibits 130 F/g gravimetric capacitance and 650 mF/cm2 areal capacitance. The improved performance in the specific capacitance is observed due to the generation of more active charge storage sites in the interfacial interaction of organic nanostructures and polyaniline in the composite. The cyclic stability of the symmetric device reveals excellent retention of 96% in specific capacitance over 5000 cycles.

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus and is caused by insulin insufficiency. Hypothermia is defined as a core temperature of less than 35°C and is sometimes accompanied by DKA. We report two patients with diabetes who were admitted for DKA accompanied by hypothermia.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since samedi 30 juillet 2016

Long bone abnormality (lbab/lbab) is a spontaneous mutant mouse characterized by dwarfism with shorter long bones. A missense mutation was reported in the Nppc gene, which encodes C-type natriuretic peptide (CNP), but it has not been confirmed whether this mutation is responsible for the dwarf phenotype. To verify that the mutation causes the dwarfism of lbab/lbab mice, we first investigated the effect of CNP in lbab/lbab mice. By transgenic rescue with chondrocyte-specific expression of CNP, the dwarf phenotype in lbab/lbab mice was completely compensated. Next, we revealed that CNP derived from the lbab allele retained only slight activity to induce cGMP production through its receptor. Histological analysis showed that both proliferative and hypertrophic zones of chondrocytes in the growth plate of lbab/lbab mice were markedly reduced. Our results demonstrate that lbab/lbab mice have a hypomorphic mutation in the Nppc gene that is responsible for dwarfism caused by impaired endochondral ossification.

Electron paramagnetic resonance (EPR) and optical absorption studies have been carried out for VO2+ ions in calcium aluminoborate glasses. The EPR spectra of all the glass samples exhibit resonance signals, characteristic of VO2+ ions. The values of spin-Hamiltonian parameters indicate that the VO2+ ions in calcium aluminoborate glasses were present in octahedral co-ordination with a tetragonal compression and belong to C4v symmetry. The number of spins (N) participating in resonance was calculated as a function of concentration as well as temperature. It is observed that variation of N with temperature obeys the Boltzmann law. From the EPR data, the paramagnetic susceptibility (χ) is calculated at various temperatures and the Curie constant (C) was evaluated from the 1/χ–T graph. The Fermi contact interaction parameter (k), dipolar hyperfine coupling parameter (P) have been calculated and these values are found to be independent of V2O5 content and temperature. The optical absorption spectrum exhibits two bands corresponding to the d–d transition 2B2g → 2Eg and 2B2g → 2A1g in the order of increasing energy. The theoretical values of optical basicity (Λth) of the glasses have also been evaluated.

EPR and optical absorption spectra of 0.5 mol% MnO 2 doped x Li 2 O–(30 − x )Na 2 O–69.5B 2 O 3 (5 ⩽ x ⩽ 25) glasses have been studied. The EPR spectra exhibit resonance signals characteristic of Mn 2+ ions. The resonance signal at g ≅ 2.0 is due to Mn 2+ ions in an environment close to octahedral symmetry, whereas the resonances at g ≅ 4.3 and g ≅ 3.3 are attributed to the rhombic surroundings of the Mn 2+ ions. The ionic character ( A ), the number of spins participating in resonance ( N ), optical band gap energies ( E opt ) and Urbach energies (Δ E ) show the mixed alkali effect (MAE) with composition. The present study gives an indication that the size of alkalis we choose, is also an important contributing factor in showing the MAE. The variation of N with temperature obeys the Boltzmann law. The optical absorption spectra show a single broad band at ∼21 000 cm −1 corresponding to the transition 6 A 1g (S) → 4 T 1g (G) which exhibits a blue shift with x . The theoretical values of optical basicity ( Λ th ) have also been evaluated.

Electron Paramagnetic Resonance (EPR) and optical absorption spectra of 0.5 mol% CuO doped $xLi_{2}O-(30-x)Na_{2}O-{69.5}B_{2}O_{3}$ (5 \leq x \leq 25) mixed alkali glasses have been investigated. The EPR spectra of all the investigated samples exhibit resonance signals characteristic of $Cu^{2+}$ ions in octahedral sites with tetragonal distortion. It is found that the spin-Hamiltonian parameters do not vary much with x. It is interesting to observe that the number of $Cu^{2+}$ ions participating in resonance (N) and its paramagnetic susceptibility (χ) exhibits the mixed alkali effect with composition. It is observed that the temperature dependence of paramagnetic susceptibility (χ) obeys Curie–Weiss law. The paramagnetic Curie temperature $(\theta_p)$ is negative for the investigated sample, which suggests that the copper ions are antiferromagnetically coupled by negative super exchange interactions at very low temperatures. A broad band corresponding to the transition $(^{2}B_{1g}\longrightarrow^{2}B_{2g})$ in the optical absorption spectrum shows a blue shift with x. By correlating the EPR and optical absorption data, the molecular orbital coefficients $\alpha^{2}$ and $\beta^{2}_{2}$ have been evaluated. It is interesting to observe that the optical band gap $(E_{opt})$ and Urbach energies $(\Delta{E})$ exhibit the mixed alkali effect. The theoretical values of optical basicity $({\Delta}_{th})$ have also been evaluated.

This paper reports the interesting results on mixed alkali effect (MAE) in $xLi_2O–(30-x)Na_2O-{69.5}B_2O_3$ (5\leq x\leq 28) glasses containing Fe2O3 studied by electron paramagnetic resonance (EPR) and optical absorption techniques. The EPR spectra in these glasses exhibit three resonance signals at g = 7.60, 4.20 and 2.02. The resonance signal at g = 7.60 has been attributed to $Fe^{3+}$ ions in axial symmetry sites whereas the resonance signal at g = 4.20 is due to isolated $Fe^{3+}$ ions in rhombic symmetry site. The resonance signal at g = 2.02 is due to $Fe^{3+}$ ions coupled by exchange interaction. It is interesting to observe that the number of spins participating in resonance (N) and its paramagnetic susceptibility (χ) exhibits the mixed alkali effect with composition. The present study also gives an indication that the size of alkali ions we choose in mixed alkali glasses is also an important contributing factor in showing the mixed alkali effect. It is observed that the variation of N with temperature obeys Boltzmann law. A linear relationship is observed between 1/χ and T in accordance with Curie–Weiss law. The paramagnetic Curie temperature $(\theta_p)$ is negative for the investigated sample, which suggests that the iron ions are antiferromagnetically coupled by negative super exchange interactions at very low temperatures. The optical absorption spectra exhibit only one weak band corresponding to the transition $(^{6}A_{1g}(S)\longrightarrow^{4}A_{1g}(G))$; $^4{E}_g{(G)}$ at 446 nm which is a characteristic of $Fe_{3+}$ ions in octahedral symmetry.

HL1 gene encoding haemolysin from Vibrio harveyi SF-1 was expressed in yeast cells and the expressed haemolysin was displayed on the cell surface. After induction for 36 h in galactose-containing medium, one-third of the cells contained the displayed protein and the displayed cells had haemolytic activity on erythrocytes from flounder. The double diffusion agar analysis showed that the sera from the flounder immunized with the displayed yeast cells having the haemolytic activity could form precipitate with the purified haemolysin. ELISA analysis indicated that immunization times had great influence on increased production of the specific antibody against haemolysin in turbot immunized with the displayed yeast cells having the haemolytic activity. After the challenge with V. harveyi SF-1, it was found that earlier protection in flounder and significant protection in turbot, both of which were immunized with the displayed yeast cells having the haemolytic activity, were achieved. These results suggested that the displayed yeast cells with the haemolytic activity could be used as potential live vaccine in marine fish.

We previously reported that C-type natriuretic peptide (CNP) stimulates endochondral ossification and corrects the reduction in body length of achondroplasia model mouse with constitutive active fibroblast growth factor receptor 3 (FGFR-3). In order to examine the interaction between CNP and FGFR-3, we studied intracellular signaling by using ATDC5 cells, a mouse chondrogenic cell line, and found that FGF2 and FGF18 markedly reduced CNP-dependent intracellular cGMP production, and that these effects were attenuated by MAPK inhibitors. Western blot analysis demonstrated that the level of GC-B, a particulate guanylyl cyclase specific for CNP, was not changed by treatment with FGFs. Conversely, CNP and 8-bromo-cGMP strongly and dose-dependently inhibited the induction of ERK phosphorylation by FGF2 and FGF18 without changing the level of FGFR-3, although they did not affect the phosphorylation of STAT-1. In the organ-cultured fetal mouse tibias, CNP and FGF18 counteracted on the longitudinal bone growth, and both the size and number of hypertrophic chondrocytes. The FGF/FGFR-3 pathway is known as the negative regulator of endochondral ossification. We found that FGFs inhibited CNP-stimulated cGMP production by disrupting the signaling pathway through GC-B while CNP antagonized the activation of the MAPK cascade by FGFs. These results suggest that the CNP/GC-B pathway plays an important role in growth plate chondrocytes and constitutes the negative cross talk between FGFs and the activity of MAPK. Our results may explain one of the molecular mechanisms of the growth stimulating action of CNP and suggest that activation of the CNP/GC-B pathway may be effective as a novel therapeutic strategy for achondroplasia.

Thyroid hormones enhance osteoclast formation and their excess is an important cause of secondary osteoporosis. 3,5,3' -Triiodo-L-thyronine (T3) induced the mRNA expression of receptor activator of nuclear factor-kappa B ligand (RANKL), which is a key molecule in osteoclast formation, in primary osteoblastic cells (POB). This effect was amplified in the copresence of 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Although T3 alone did not induce octeoclasts in coculture of bone marrow cells with POB, T3 enhanced 1,25(OH)(2)D(3)-induced osteoclast formation. Thyroxine (T4) also enhanced 1,25(OH)(2)D(3)-induced osteoclast formation. These data suggested that T4 was locally metabolized to T3 for its action, since T4 is a prohormone with little hormonal activity. The mRNA expression of type-2 iodothyronine deiodinase (D2), which is responsible for maintaining local T3 concentration, was induced by 1,25(OH)(2)D(3) dose- and time-dependently. Our data would facilitate our understanding of the mechanism of osteoclast formation by thyroid hormones and suggest a novel interaction between thyroid hormones and 1,25(OH)(2)D(3).

The natriuretic peptide family consists of three structurally related endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which act as cardiac hormones, are produced mainly by the atrium and ventricle, respectively, and are involved in body fluid homeostasis and blood pressure control. The ANP and BNP gene expressions are markedly augmented in ventricles of patients with a wide variety of cardiovascular diseases. It has been demonstrated that the ANP and BNP genes are tightly linked on mouse chromosome 4 and on the distal short arm of human chromosome 1. However, the precise physical map of the ANP and BNP genes has never been elucidated. In the present study, we characterized the genomic DNA fragment containing the ANP and BNP genes in mice and humans. Three genomic DNA clones harboring the entire mouse BNP gene were isolated from a 129/Sv mouse genomic DNA library. Nucleotide sequence analysis revealed that a phage clone (λmBNP#3) contains at its 3′-end the 5′-flanking region and the first 209-bp sequence of the first exon of the mouse ANP gene. In mice, the BNP gene was located about 12 kb upstream of the ANP gene. By polymerase chain reaction, we isolated an approximately 11-kb human genomic DNA fragment containing the third exon of the BNP gene and the first and second exons of the ANP gene. In humans, the BNP gene was located upstream of the ANP gene, approximately 8 kb apart. The present study provides the direct evidence that the ANP and BNP genes are organized in tandem in the mouse and human genomes.

C-type natriuretic peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial natriuretic peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [ 3 H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of “bone natriuretic peptide system.”