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The plasma spray technique was employed to produce an anode layer for solid oxide fuel cells (SOFCs) using calcined micro-sized nickel oxide-8 mol% yttria-stabilized zirconia (NiO-8YSZ) cermet particles as stock powder. The nanostructure of calcined micro-sized NiO-8YSZ cermet particles (CMCEP) generated through the sintering process is closely related to SOFC performance and varied with sintering conditions. Thus, the present study was conducted to analyze the effect of the sintering temperature on the diffusion and nanostructure of particles during the production of CMCEP for SOFC anode material. The distributions of Ni and Zr in grain boundary caused by molecular diffusion were quantified at different sintering temperatures in the range 1,100 °C-1,300 °C. The effects of sintering on nanosurface and structural properties of CMCEP were analyzed through scanning electron and back-scattered electron microscopies and specific surface area. The crystallinity of CMCEP was found to increase with increasing sintering temperature. Smoothing, neck formation, shrinkage, and densification of nano-sized NiO-8YSZ composite granules occurred due to the acceleration of molecular diffusion at sintering temperatures above 1,200 °C, resulting in distinct grain boundary formation. The width of interfacial transition gap between Ni and Zr measured with respect to the grain boundary increased by 69.1% as molecular diffusion accelerated with increasing sintering temperature from 1,100 to 1,300 °C. The results of the nanostructural analysis of the CMCEP surface showed a decrease in the specific surface area (measured by the Brunauer Emmett Teller (BET) method) with increasing calcination temperature. The results of this study are expected to contribute to performance optimization in the future via the control of the porosity, electrical conductivity, and triple phase boundary generation during SOFC anode layer production using plasma sprays. [ABSTRACT FROM AUTHOR]

Background: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC). Methods: Patients with Child-Pugh (CP) score ≤7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for ≤6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes. Conclusion: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP ≥7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation. [ABSTRACT FROM AUTHOR]

The trochanteric soft tissue attenuates impact force or absorbs impact energy during a fall on the hip (thereby helps to reduce a risk of hip fracture). While the benefits should be affected by contractions of muscles spanning the hip joint, no information is available to date. We examined how the stiffness (force attenuation capacity) and energy absorption of the trochanteric soft tissue were affected by hip muscle activation during a fall. Thirteen healthy young individuals (5 males, 8 females) participated in the pelvis release experiment. Falling trials were acquired with three muscle contraction conditions: 0-20% ("relaxed"), 20-50% ("moderate"), and 60-100% ("maximal") of the maximal voluntary isometric contraction of the gluteus medius muscle. During trials, we measured real-time force and deformation behaviour of the trochanteric soft tissue. Outcome variables included the stiffness and energy absorption of the soft tissue. The stiffness and energy absorption ranged from 56.1 to 446.9 kN/m, and from 0.15 to 2.26 J, respectively. The stiffness value increased with muscle contraction, and 59% greater in "maximal" than "relaxed" condition (232.2 (SD = 121.4) versus 146.1 (SD = 49.9)). However, energy absorption decreased with muscle contraction, and 58.9% greater in "relaxed" than "maximal" condition (0.89 (SD = 0.63) versus 0.56 (SD = 0.41)). Our results provide insights on biomechanics of the trochanteric soft tissue ("natural" padding device) during impact stage of a fall, suggesting that soft tissues' protective benefits are largely affected by the level of muscle contraction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Risk of hip fracture depends on the bone strength as well as the impact force delivered to the proximal femur during falls, and femoral soft tissue may help to reduce the hip fracture risk by attenuating the impact force. Femoral soft tissue stiffness was measured from a large sample, and compared how this was affected by age, gender and site. One hundred fifty healthy individuals (fifty-two young (aged between 19 and 29), forty-eight middle-aged (30-64), and fifty old (over 65)) participated. Each age group included an equal number of males and females. Using an automated hand-held indentation device, soft tissue stiffness was measured over twelve sites with respect to the greater trochanter (GT). For both left and right hips, the stiffness was associated with age (p < 0.0005), gender (p < 0.0005), and site (p < 0.0005). On average, the stiffness was 26% greater in older than young adults (321.5 versus 254.3 N/m). On average across twelve sites, the regression analysis indicated that the stiffness increases 1.33 N/m every year ("soft tissue stiffness over the hip = 1.33*age + 221.8"; R = 0.518, p < 0.0005). Furthermore, the stiffness was 18% greater in male than female (308.8 versus 262.6 N/m), and differed across twelve sites over the hip, being greatest (424.2 N/m) at the GT, and least (206.3 N/m) at the superior gluteal region. The results provide insights into the shock absorbing property of soft tissue over the hip, and inform the improvement of fall-related injury prevention interventions (i.e., hip protector, safe landing strategies) in older adults., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The objective of this study was to determine the expression and transferability of tetracycline and erythromycin resistance among 188 MRSA strains from a Malaysian tertiary hospital. The minimum inhibitory concentrations (MICs) for oxacillin, erythromycin, tetracycline and ciprofloxacin ranged from 4 to 512 μg/ml, 0.25 to 256 μg/ml, 0.5 to 256 μg/ml and 0.5 to 512 μg/ml, respectively. Tetracycline-resistant strains showed co-resistance towards ciprofloxacin and erythromycin. There was a significant increase (P<0.05) of high-level tetracycline (≥MIC 256 μg/ml) and erythromycin (≥MIC 128 μg/ml) resistant strains in between the years 2003 and 2008. All erythromycin-resistant strains harboured ermA or ermC gene and all tetracycline-resistant strains harboured tetM or tetK gene. The blaZ was detected in all MRSA strains, whereas ermA, tetM, ermC, tetK and msrA genes were detected in 157 (84%), 92 (49%), 40 (21%), 39 (21%) and 4 (2%) MRSA strains, respectively. The blaZ, tetM, ermC and tetK genes were plasmid-encoded, with ermC gene being easily transmissible. Tn5801-like transposon was present in 78 tetM-positive strains. ermA and tetM genes were the most prevalent erythromycin and tetracycline resistance determinants, respectively, in MRSA strains. The association of resistance genes with mobile genetic elements possibly enhances the spread of resistant traits in MRSA.

Background: Gun-related crime offences have increased in the Republic of Ireland steadily over the past number of years. Regional trauma units are witnessing unprecedented numbers of injuries in the Republic of Ireland with limited prior experience., Aims: Eight-year retrospective study analysing demographic data, management and outcome of firearm-related injuries., Results: Patients who experience gunshot injuries in this region are statistically likely to be young, male and unemployed with a single shotgun injury to an extremity. Post-operative survival rates of 100% for those who undergo an exploratory laparotomy., Conclusion: Ireland has comparable survival outcomes to other international centres with similar patient demographics due to timely and appropriate operative intervention. These results serve to provide a template for further patient management.

This communication describes the application of a modified sandwich enzyme-linked immunosorbent assay (ELISA), termed Multimer Detection System (MDS) for the detection of disease-associated multimeric forms of the prion protein (PrPd) in hamster blood. PrPd was detected in plasma of prion-affected hamsters while MDS revealed no PrPd in identically-treated plasma of healthy animals. This is the first report of a single ELISA- based immune detection of PrPd from blood samples., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Modulation of mast-cell activation may provide novel ways to control allergic diseases. Here, we show that protein tyrosine phosphatase epsilon (PTPepsilon; Ptpre) plays key regulatory roles during mast-cell activation mediated by the high-affinity IgE receptor (FcepsilonRI). Bone marrow-derived mast cells (BMMC) from Ptpre(-/-) mice exhibited enhanced FcepsilonRI-induced Ca(2+) mobilization and mitogen-activated protein kinase (MAPK) (JNK and p38) activation, and showed corresponding enhancement of evoked degranulation and cytokine production, but not leukotriene production. Examination of proteins linking tyrosine kinase activation and Ca(2+) mobilization revealed that the absence of PTPepsilon leads to increased phosphorylation of the linker for activation of T cells and SH2 domain-containing leucocyte phosphoproteins of 76 kDa, but not Grb2-associated binder-2 (Gab2). Because Gab2 is considered to be situated downstream of Fyn kinase, we reasoned that Fyn may not be a target of PTPepsilon. In the event, Syk but not Lyn was hyperphosphorylated in PTPepsilon-deficient BMMC. Thus, PTPepsilon most likely exerts its effects at the level of Syk, inhibiting downstream events including phosphorylation of SLP-76 and linker of activated T cells and mobilization of Ca(2+). Consistent with the in vitro data, antigen- and IgE-mediated passive systemic anaphylactic reactions were augmented in Ptpre(-/-) mice. Given that the number of mast cells is unchanged in these mice, this observation most likely reflects alterations of mast cell-autonomous signalling events. These data suggest that PTPepsilon negatively regulates FcepsilonRI-mediated signalling pathways and thus constitutes a novel target for ameliorating allergic conditions.

Objective: This study was carried out to investigate the anti-inflammatory potentials of 24 kDa glycoprotein isolated from Zanthoxylum piperitum DC fruit (ZPDC glycoprotein) in lipopolysaccharide (LPS)-stimulated murine macrophage cell line (RAW 264.7 cells)., Material and Methods: RAW 264.7 cells were treated with ZPDC glycoprotein (50-200 microg/ml) in presence of LPS (2 microg/ml). The changes of the levels of inflammation-related factors were determined by using Western blot, EMSA, and RT-PCR., Results: ZPDC glycoprotein has inhibitory effects on the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK), on the DNA binding activity of activator protein-1 (AP-1), and on the expression of c-Jun and c-Fos in LPS-stimulated RAW 264.7 cells. Interestingly, the DNA binding activity of AP-1 was attenuated by treatment with inhibitors of p38 MAP kinase and JNK. In addition, ZPDC glycoprotein (200 microg/ml) not only diminished the production of superoxide anion, hydrogen peroxide, and nitric oxide, but also suppressed the expression of pro-inflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha) and proteins (iNOS, COX-2, and MMP-9) in LPS- stimulated RAW 264.7 cells., Conclusions: The present study demonstrates that ZPDC glycoprotein is a natural anti-oxidant and one of the modulators of pro-inflammatory signal transduction pathways in RAW 264.7 cells.

Glycoprotein from Geranium sibiricum Linne (GSL) with 18 kDa was isolated and it consists of carbohydrate moiety (10.45%) and protein moiety (89.55%). The GSL glycoprotein was characterised by its radical scavenging activity under various experimental conditions. When GSL glycoprotein was treated with deactivation agents (pronase E or NaIO(4)), its scavenging activity decreased in both cases. It has optimal and maximal activity in acidic, neutral pH (up to pH 9), and up to 85 degrees C. Also, its activity reduced in the case of Ca(2+) and Mn(2+), with the exception of the Mg(2+) case. Its activity in the presence of Mn(2+) declined more than in the case of the Ca(2+). Also, GSL glycoprotein (500 microg mL(-1)) has antioxidative effects on hydroxyl and superoxide anion radicals in cell-free systems, and GSL glycoprotein (200 microg mL(-1)) significantly protected from cytotoxicity in the GO (100 mU mL(-1))-treated Chang liver cells for 4 h.

Unlabelled: BACKGROUND All neonates have free open access to the Baby Clinic at the maternity hospitals in Dublin for assessment of neonatal health issues. Through observation, however there is an increase in number of neonates attending the hospital outside the Baby Clinic hours., Aims: To determine the number of neonates attending the acute neonatal service out of hours and to identify the percentage of neonates treated as true emergency., Methods: Retrospective chart review over a twelve-month period., Results: Seven hundred and thirty-two neonates attended the hospital out of hours. The majority were diagnosed with gastrointestinal problems (228/31%), jaundice (101/13.7%), respiratory problems (82/11.1%) and skin disorders (79/10.7%). Only 106 (14.4%) attendances warranted admissions., Conclusions: A large number of neonatal attendances did not require acute assessment out of hours and were managed by reassurance and maternal education. A centralized phone-in-triage system was suggested to relieve the strain on the acute neonatal service.

Solanum nigrum L. (SNL) has been used in traditional folk medicine to treat numerous cancers. We isolated a glycoprotein (150 kDa) from SNL and tested its effect on the modulation of transcriptional factors (NF-kappa B and AP-1) and iNO production in TPA induced-MCF-7 cells, which are part of the human breast cancer cell line, without estrogen receptors. However, the mechanism of SNL glycoprotein in pharmacological and biochemical actions in cancer cells has not been studied. To test the effect of SNL glycoprotein on the DNA-binding activities of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), and nitric oxide (NO) production, these experiments were carried out using electrophoretic mobility shift assays (EMSA), western blot analysis, and the Griess method. Results in this experiment showed that SNL glycoprotein inhibits 12-O-Tetra decanoylphorbol-13-acetate (TPA; 100 nM)-induced DNA-binding activities of NF-kappaB and AP-1, and enhances NO production in MCF-7 cells. That is, our results indicated that SNL glycoprotein has the capacity to modulate the TPA-induced DNA-binding activities of transcription factors and NO production, which play a critical role with respect to cytotoxicity in MCF-7 cells. Therefore, SNL glycoprotein might be one of the agents that blocks TPA-mediated signal responses in tumor cells.

Background: The treatment of cryptorchidism has changed, with surgery now advocated before the age of two years. Delayed treatment affects fertility, malignant potential and psychological stress., Aims: To assess the pattern of referral of cryptorchid patients to a surgical clinic, management and follow-up., Methods: A four-year review of 114 cryptorchid patients examined age at presentation, waiting time, timing of surgery and length of follow-up., Results: The mean age at presentation to the surgical clinic was 6.7 years (neonatal to 71). The mean age at orchidopexy was 5.6 years. Seventy per cent had a surgical procedure within eight weeks of presentation to a surgeon. Seven per cent were kept under surveillance until a maximum age of three years before orchidopexy was considered. Only 29% proceeded to surgery before the age of two. Seventeen were referred to a paediatric urology unit for further management., Conclusions: Orchidopexy seems prudent between one and two years of age. Only one-quarter of patients underwent early orchidopexy. It is vital that it is detected early, by paediatricians at birth or the general practitioners (GPs) at the six-week check up. Prompt referral to a surgeon with a paediatric interest is essential in order to permit surveillance or surgery.

In this study, the antioxidant, cytotoxic, and antitumorigenic activities of a fractionated, ethanol extract derived from Rhus verniciflua Stokes (RVS), a plant indigenous to Korea, China, and Japan, were determined. Physicochemical analysis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results indicated that the active component of a Sephadex G-150-fractionated RVS extract (PII fraction) was a copper-containing glycoprotein, possibly a plant laccase. Antioxidant activity of the fractionated RVS extract, observed in both aqueous and lipid in vitro oxidation reactions using 1,1-diphenyl 2-picrylhydrazyl (DPPH) radical, site-specific Fenton-reaction deoxyribose, and a model lipid emulsion test system, indicated an affinity for protection against hydroxyl and peroxyl radicals. Cultured mouse brain neurons were protected against glucose oxidase-induced hydroxyl radical in the presence of the fractionated RVS extract (e.g., 58% protection at 4.9 microM and 95% protection with 22.7 microM RVS). RVS was further shown to protect against in vitro Fenton-reaction-induced single- and double-strand scission in supercoiled plasmid DNA. Further testing for bioactivity of the fractionated RVS extract was based on the affinity to inhibit cell proliferation in cultured HeLa and CT-26 tumor cells. The presence of RVS resulted in 70% cell death after 24 h of incubation in both cell lines at a minimum concentration of 2.48 microM RVS. Data demonstrate multiple bioactive chemopreventative properties of a Sephadex G-150-fractionated extract derived from RVS.

The aim of the present work was to examine the efficacy of using FISH for the rapid prenatal diagnosis of common chromosome aneuploidies. A total of 100 analyses over a six month period were included in the study. Diagnosis was possible in all cases. A mosaic for trisomy 21 proved, by comparison with an extensive analysis of long term cultures, to be an apparent false positive. Otherwise the technique was reliable, accurate and relatively straightforward to perform. Results could be available within 24 hrs. In most cases an additional long term full analysis was also done, so as to exclude rarer aneuploidies and structural rearrangements. This methodology is seen as a useful addition to the prenatal diagnostic repertoire.

The neurotoxic effects of methylmercury on cerebral neuron cultures derived from neonatal mouse were studied. Exposure of cerebral neurons to methylmercury chloride resulted in significant cell damage and death in a time-dependent manner in cerebral neuron cultures. The methylmercury neurotoxicity was blocked by oxygen radical scavengers such as glutathione, catalase, selenium, and cysteine. Antagonists of the N-methyl-D-aspartate (NMDA) receptor, including MK-801 (a non-competitive NMDA antagonist), D-2-amino-5-phosphonovaleric acid (APV) (a competitive NMDA antagonist), and 7-chlorokynurenic acid (an antagonist at the glycine site associated with the NMDA receptor), similarly blocked methylmercury-induced neurotoxicity in cerebral neuron cultures. These results indicate that both oxygen radicals and excitotixic amino acids are involved in the methylmercury-induced neurotoxicity of cerebral neuron cultures.

Griseofulvin(GF) has become the drug of choice as an antifungal agent for patients who suffer from many kinds of fungal infection. In order to clarify hepatic injury by griseofulvin(GF) overload and the effect of UDCA on GF-induced hepatic injury, the authors carried out biochemical, histologic, and ultrastructural studies of liver following treatment with griseofulvin and ursodeoxycholic acid(UDCA) in mice. Urine porphobilinogen excretion in the group treated with GF alone was significantly increased and reached the highest level in the 4th week and declined thereafter. Biochemical studies of the liver function showed no remarkable changes of serum bilirubin levels throughout the experimental period in all groups, except for SGPT and alkaline phosphatase activities which were significantly elevated and reached the highest level in the second week. Then they slightly decreased in GF treated groups(GF alone and GF plus UDCA) in comparison with the control group. Pathologic findings in the group treated with GF alone include focal liver cell necrosis(esp, zone 3), Mallory bodies in hepatocytes(esp, zone 1), Kupffer cell activation, and brown protoporphyrin pigments in the hepatocytes, bile canaliculi and interlobular bile ducts with a marked inflammatory cell infiltration in the portal tracts. Under the polarizing light microscope, bile ductular and canalicular thrombi showed a "Maltese cross" birefringence in mice treated with GF alone. There is no definite finding of fatty change in hepatocyte. Under the microscope, the liver appeared normal with an intact lobular architecture in the GF plus UDCA treated group. Electron microscopically, GF-induced changes include swelling of mitochondria, globular protoporphyrin crystals in the hepatocyte cytoplasm, markedly dilated bile cannaliculi and bile ducts and the formation of a Mallory hyaline bodies in the hepatocytes. There were no noticeable structural changes in the GF plus UDCA-treated group. Therefore the results suggest that GF causes hepatic injury, namely porphyria and cholestasis, and the treatment of UDCA may have cytoprotective and choleretic effects on GF-induced hepatic injuries.