Utility of cranial MRI in non-traumatic headache patients with prior negative head CT within 1 month.

AIM: To investigate the importance of additional cranial magnetic resonance imaging (cMRI) in non-traumatic headache patients with a prior negative head computed tomography (CT) examination within 1 month. MATERIALS AND METHODS: This retrospective study analysed 162 adult patients with non-traumatic headache who underwent cMRI within 1 month of a negative initial head CT at the emergency department (ED). The diagnostic yield and false-referral rate were analysed according to the revisit duration (early [≤1 week] versus late [>1-4 weeks] revisits), patient care settings (ED versus outpatient clinics [OPC]), and clinical variables. Subsequent patient management change (PMC), such as admission and treatment (AT) or outpatient clinic treatment (OT), were also investigated. RESULTS: The overall diagnostic yield of cMRI was 17.3% (28/162) and the false-referral rate was 1.2% (2/162). The diagnostic yield of cMRI was significantly different according to the patient care settings (ED, 24.7% [21/85] versus OPC, 9.1% [7/77]; p=0.02). The diagnostic yield was highest in the ED-early-revisit group (25.4% [18/71]), 45% (9/20) in those with systemic signs, and 46.7% (14/30) in those with symptom change. Among patients with positive cMRI findings, 90% (27/30) received AT and 3.3% (1/30) received OT. Among OPC-revisit-negative cMRI patients, PMC occurred in 0% (0/50). CONCLUSION: The diagnostic yield of cMRI was relatively high for headache patients who revisited the ED earlier, especially in those with systemic signs or symptom change. Most positive cMRI cases experienced PMC. Negative cMRI in OPC-revisit patients might help clarify the benign nature of a condition.

The efficiency of potential food waste-degrading bacteria under harsh conditions.

AIMS: Investigate the impact of highly adapted bacterial strains and their ability in waste degradation under a wide range of temperatures. METHODS AND RESULTS: Bacteria isolated from soil and food waste were grown in various media under fluctuated temperatures. After screening for organic compound degradation, the seven strongest bacterial strains have been selected for further experiments. Their enzyme activities were expressed in terms of the size of the hydrolysis zone in a wide temperature range of 2·5-70°C. The enzyme production assay was carried out for each protease, cellulase and amylase. The waste degradation was determined with a maximum 80% decrease in the volume of food waste in 21 days compared to the control in lab scale with enriched bacterial cultures and soil bacteria as additives at room temperature around 18-20°C. CONCLUSION: These seven bacteria are promising candidates for food waste biodegradation in composting especially in the winter without heating expense for maintaining ambient temperature. SIGNIFICANCE AND IMPACT OF THE STUDY: It is necessary to coax the uncultured bacteria from the various environments into the laboratory for investigating their valuable functions. Herein, using enrichment culture of consortium and additive of soil has illustrated the significant mean in food waste degradation.

Characteristics of extracellular cyclic AMP-dependent protein kinase as a biomarker of cancer in dogs.

OBJECTIVE: Early and proper diagnosis of cancer is the most critical factor for the survival and treatment of veterinary cancer patients. In this study, we evaluated extracellular cyclic AMP-dependent protein kinase A (ECPKA) level in serum as a useful cancer biomarker in dogs. METHODS: ECPKA levels were detected in sera from dogs with cancers (n = 48), benign tumours (n = 18), and non-tumour diseases (n = 102) as well as healthy control dogs (n = 54) utilizing enzyme-linked immunosorbent assay (ELISA). RESULTS: Sera from dogs bearing various types of cancer exhibited markedly increased levels of ECPKA by up to 7.1-, 8.8-, and 10.9-fold compared with those from dogs harbouring benign tumours, dogs with non-tumour diseases, and healthy control dogs, respectively (P < .0001). In addition, serum ECPKA level did not show statistically significant correlation with gender, breed, or age of dogs or their non-cancerous disease conditions. CONCLUSION: Our data strongly propose that detection of serum ECPKA level is a potential and specific diagnostic tool for cancer in dogs.

MRI to differentiate benign from malignant soft-tissue tumours of the extremities: a simplified systematic imaging approach using depth, size and heterogeneity of signal intensity.

OBJECTIVE: Differentiating between malignant and benign lesions on the basis of MR images depends on the experience of the radiologist. For non-experts, we aimed to develop a simplified systematic MRI approach that uses depth, size and heterogeneity on T(2) weighted MR images (T(2)WI) to differentiate between malignant and benign lesions, and evaluated its diagnostic accuracy. METHODS: MR images of 266 patients with histologically proven soft-tissue tumours of the extremities (102 malignant, 164 benign) were analysed according to depth (superficial or deep), size (<50, ≥50 mm) and signal intensity (homogeneous or heterogeneous) on T(2)WI, to determine the ability of each to predict benign and malignant tumours. These three parameters were categorised into systematic combinations of different orders of application, and each combination was assessed for its ability to differentiate between benign and malignant lesions. RESULTS: Univariate analysis showed that depth, size and heterogeneity on T(2)WI differed significantly between benign and malignant masses (p<0.0001 each). Multiple logistic regression analysis, however, showed that depth was not helpful in distinguishing benign from malignant lesions. The systematic combination of signal intensity, size and depth, in that order, was superior to other combinations, resulting in higher diagnostic values for malignancy, with a sensitivity of 64%, a specificity of 85%, a positive predictive value of 32%, a negative predictive value of 59% and an accuracy of 77%. CONCLUSION: A simplified systematic imaging approach, in the order signal intensity, size and depth, would be a reference to distinguish between benign and malignant soft-tissue tumours for non-experts.

Factors predictive of perforation during endoscopic submucosal dissection for the treatment of colorectal tumors.

BACKGROUND AND AIM: Although perforation of the colon is known as one of the main complications of endoscopic submucosal dissection (ESD) for colorectal tumor management, factors predictive of perforation have not been fully evaluated. This study aimed to determine the factors associated with perforation during colorectal ESD. METHODS: Patients with colorectal tumors undergoing ESD were enrolled and their records were reviewed retrospectively. Age, sex, co-morbidity, medication history, procedure time, resection method, tumor size, location, gross morphology, the presence of fibrosis, and histologic findings were included as possible risk factors. In the cases where perforation had occurred, factors associated with the duration of hospitalization were analyzed. RESULTS: One hundred eight lesions in 108 patients were eligible for inclusion in the study (68 patients were male; mean patient age was 63.01 ± 10.71 years). Mean tumor size was 27.59 ± 10.10 mm (range: 8 - 53 mm). Laterally spreading tumor was the most common type (75 %), followed by the protruding type (25 %). Procedure time was 61.95 ± 41.90 minutes (range: 5 - 198 minutes). Complete en bloc resection was achieved for 85 lesions (78.7 %). Perforation occurred in 22 patients (20.4 %). Multivariate analysis confirmed that tumor size [odds ratio (OR): 1.084; 95 % confidence interval (CI): 1.015 - 1.158; P = 0.017] and the presence of fibrosis (OR: 4.551; 95 %CI: 1.092 - 18.960; P = 0.037) were independent risk factors for perforation. All cases of perforation were managed with nonsurgical treatment. Younger age and abdominal pain appeared to be related to prolonged hospitalization. CONCLUSION: Tumor size and fibrosis are important factors related to complications during colorectal ESD. Younger age and development of abdominal pain can predict the hospital course in patients with perforation after ESD.

Adverse childhood experiences and risk of physical violence in adolescent dating relationships.

BACKGROUND: This study evaluates associations of commonly co-occurring childhood adversities with physical violence in dating relationships to identify potential strategies for refining and targeting dating violence prevention programmes. METHODS: Data on 5130 adult respondents to a nationally representative survey with at least one dating relationship before the age of 21 years were analysed. Logistic regression models assessed associations between 12 childhood adversities and physical dating violence (PDV). RESULTS: Adjusting for the number of co-occurring adversities, 10 of the 12 childhood adversities were significantly associated with PDV perpetration or victimisation (OR 1.5-2.8). The population attributable risk proportion of PDV due to all 12 childhood adversities was 53.4%. Childhood adversities with the highest attributable risk proportions were sexual abuse (13.8%), interparental violence (11.6%) and parent mental illness (10.7%). Multivariate prediction equations ranked respondents by their childhood adversity risk profiles; 46.4% of PDV cases occurred in the top two risk deciles. CONCLUSIONS: Assessment of a broad range of childhood exposures to familial adversities may help to identify adolescents at particularly high risk of PDV and to guide prevention efforts.

Childhood and adolescent onset psychiatric disorders, substance use, and failure to graduate high school on time.

We examined the joint predictive effects of childhood and adolescent onset psychiatric and substance use disorders on failure to graduate high school (HS) on time. Structured diagnostic interviews were conducted with a US national sample of adults (18 and over). The analysis sample included respondents with at least 8 years of education who were born in the US or arrived in the US prior to age 13 (N = 29,662). Psychiatric disorders, substance use and substance use disorders were examined as predictors of termination or interruption of educational progress prior to HS graduation, with statistical adjustment for demographic characteristics and childhood adversities. Failure to graduate HS on time was more common among respondents with any of the psychiatric and substance use disorders examined, ranging from 18.1% (specific phobia) to 33.2% (ADHD-combined type), compared with respondents with no disorder (15.2%). After adjustment for co-occurring disorders, significant associations with failure to graduate on time remained only for conduct disorder (OR = 1.89, 95% CI 1.57-2.26) and the three ADHD subtypes (Inattentive OR = 1.78, 95% CI 1.44-2.20, Hyperactive-Impulsive OR = 1.38, 95% CI 1.14-1.67, and Combined OR = 2.06, 95% CI 1.66-2.56). Adjusting for prior disorders, tobacco use was associated with failure to graduate on time (OR = 1.97, 95% CI 1.80-2.16). Among substance users, substance use disorders were not associated with on-time graduation. The findings suggest that the adverse impact of childhood and adolescent onset psychiatric disorders on HS graduation is largely accounted for by problems of conduct and inattention. Adjusting for these disorders, smoking remains strongly associated with failure to graduate HS on time.

Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy.

Cervical cancer is the second most common type of malignant tumor among women worldwide. When the disease is confined locally, it can be controlled with surgical resection and radiotherapy. However, patients with recurrent or metastatic disease often have a poor prognosis. Measurement of serum levels of squamous cell carcinoma (SCC) antigens has been widely used as serological markers for SCC of uterine cervix. Recently, it has been demonstrated that cervical cancer patients with elevated squamous cell carcinoma antigen-2 (SCCA2) expression in tumor cells carry a poor prognosis. Here, by using a luciferase reporter assay, we show that SCCA2 promoter was active in SCCA2-producing human cervical cancer cell lines, including Cx, Cxwj, SiHa and HeLa cells, but relatively quiescent in normal cervical epithelial cells. We then developed a conditionally replicating adenovirus, designated Ad-KFH, under the transcriptional control of the SCCA2 promoter. This E1B-55 kDa-deleted oncolytic adenovirus replicated specifically in and lysed SCCA2-producing cervical cancer cells. Furthermore, in a peritoneal metastatic tumor model, Ad-KFH retarded Cxwj tumor growth in NOD/severe combined immunodeficient mice and prolonged survival of tumor-bearing mice, especially when combined with cisplatin. These results suggest that Ad-KFH may provide a new strategy of gene therapy for advanced or recurrent uterine cervical cancer.

Gain-clamped Raman fiber oscillator.

Gain band expansion of a Raman amplifier based on a Raman fiber oscillator (RFO) was tested with two Raman lasers, which yielded a broad gain spectrum of about 40 nm. However, they also introduced gain-clamping behavior in the short-wavelength range and abnormal excessive gain in long-wavelength channels, which were undesirable for practical application. The proper mechanism of the behavior was analyzed and experimentally demonstrated to apply to a gain-clamped (GC) amplifier based on a RFO. Appropriate configuration of the GC-RFO for wide gain bandwidth was proposed and characterized.

Participation of protein kinase C beta in osteoclast differentiation and function.

Protein kinase C (PKC) proteins have been shown to be involved in diverse cellular responses of various cell types. In experiments to identify genes regulated during osteoclast differentiation by a cDNA microarray approach, we found that the gene expression of PKC-betaII was upregulated in differentiated cells. Reverse transcription-polymerase chain reaction and Western blotting analyses also showed an increase in PKC-betaI as well as PKC-betaII during osteoclast formation in mouse bone marrow cell cultures in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB ligand (RANKL). Use of an antisense oligonucleotide to PKC-betaII resulted in a reduction in the RANKL-driven osteoclastogenesis. Pharmacological intervention with PKC-beta activity by the specific inhibitor CG53353 suppressed cellular differentiation and fusion processes during osteoclastogenesis and inhibited bone-resorbing function of mature osteoclasts. PKC-beta inhibition abolished the ERK and MEK activation by macrophage-colony stimulating factor and RANKL in osteoclast precursor cells whereas the cytokine-induced NF-kappaB activation was not hampered by the PKC-beta inhibition. Our findings indicate that PKC-beta has a role in regulation of osteoclast formation and function potentially by participating in the ERK signaling pathway of M-CSF and RANKL.

Waste load allocation for water quality management of a heavily polluted river using linear programming.

A waste load allocation model using linear programming has been developed for economic water quality management. A modified Qual2e model was used for water quality calculations and transfer coefficients were derived from the calculated water quality. This allocation model was applied to the heavily polluted Gyungan River, located in South Korea. For water quality management of the river, two scenarios were proposed. Scenario 1 proposed to minimise the total waste load reduction in the river basin. Scenario 2 proposed to minimise waste load reduction considering regional equity. Waste loads, which have to be reduced at each sub-basin and WWTP, were determined to meet the water quality goal of the river. Application results of the allocation model indicate that advanced treatment is required for most of the existing WWTPs in the river basin and construction of new WWTPs and capacity expansion of existing plants are necessary. Distribution characteristics of pollution sources and pollutant loads in the river basin was analysed using Arc/View GIS.

Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK.

Differentiated osteoclasts have a short life span. We tested various cytokines and growth factors for the effects on the survival of purified mature osteoclasts. In the absence of any added factors, osteoclasts exhibited the survival rate of less than 25% after a 24-h incubation. Among the tested factors, tumor necrosis factor-alpha (TNF-alpha) was found to increase the survival rate to approximately 80%. The TNF-alpha-enhanced survival of osteoclasts appeared to be associated with reduction in apoptosis and suppression of caspase activation. The antiapoptotic signaling pathways involved in the TNF-alpha-induced osteoclast survival were investigated. TNF-alpha treatment increased the phosphorylation of Akt in osteoclasts, which was suppressed by a phosphatidylinositol 3-kinase inhibitor LY294002 and an Src family kinase-selective inhibitor PP1. These inhibitors also attenuated the TNF-alpha stimulation of osteoclast survival. In addition an increase in the phosphorylation of ERK was observed upon TNF-alpha stimulation. PD98059, a specific inhibitor of the ERK-activating kinase MEK-1, abolished the TNF-alpha-induced ERK phosphorylation and osteoclast survival, and in these responses the involvement of Grb2 and ceramide was observed. These results suggest that TNF-alpha promotes the survival of osteoclasts by engaging the phosphatidylinositol 3-kinase Akt and MEK/ERK signaling pathways.

Selective involvement of reactive oxygen intermediates in platelet-activating factor-mediated activation of NF-kappaB.

Although it has been suggested that some biological activities of platelet-activating factor (PAF) are mediated by, at least in part, reactive oxygen intermediates (ROI), the precise mechanisms underlying the interaction between the two remains to be elucidated. Antioxidants, such as alpha-tocopherol acid succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF-induced immediate systemic reactions such as lethality, symptoms of disseminated intravascular coagulation, and histological changes such as pulmonary edema and hemorrhage in renal medullae 10 min following PAF injection. In contrast. antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF-kappaB activation and NF-kappaB-dependent TNF-alpha expression. The effects of the antioxidants were due to their inhibition of PAF-induced degradation of IkappaBalpha, a protein responsible for keeping NF-kappaB in an inactive form. A protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive serine protease were involved in both PAF- and H2O2-induced NF-kappaB activation. Collectively, these data indicate that the PAF-induced NF-kappaB activation is selectively mediated through the generation of ROI.

Temporal appearance of the presynaptic cytomatrix protein bassoon during synaptogenesis.

Bassoon is a 420-kDa presynaptic cytomatrix protein potentially involved in the structural organization of neurotransmitter release sites. In this study, we have investigated a possible role for Bassoon in synaptogenesis and in defining synaptic vesicle recycling sites. We find that it is expressed at early stages of neuronal differentiation in which it is selectively sorted into axons. As synaptogenesis begins, Bassoon clusters appear along dendritic profiles simultaneously with synaptotagmin I, sites of synaptic vesicle recycling, and the acquisition of functional excitatory and inhibitory synapses. A role for Bassoon in the assembly of excitatory and inhibitory synapses is supported by the colocalization of Bassoon clusters with clusters of GKAP and AMPA receptors as well as GABA(A) receptors. These data indicate that the recruitment of Bassoon is an early step in the formation of synaptic junctions.

Piccolo, a presynaptic zinc finger protein structurally related to bassoon.

Piccolo is a novel component of the presynaptic cytoskeletal matrix (PCM) assembled at the active zone of neurotransmitter release. Analysis of its primary structure reveals that Piccolo is a multidomain zinc finger protein structurally related to Bassoon, another PCM protein. Both proteins were found to be shared components of glutamatergic and GABAergic CNS synapses but not of the cholinergic neuromuscular junction. The Piccolo zinc fingers were found to interact with the dual prenylated rab3A and VAMP2/Synaptobrevin II receptor PRA1. We show that PRA1 is a synaptic vesicle-associated protein that is colocalized with Piccolo in nerve terminals of hippocampal primary neurons. These data suggest that Piccolo plays a role in the trafficking of synaptic vesicles (SVs) at the active zone.

Noninvasive evaluation of coronary artery bypass graft patency using three-dimensional angiography obtained with contrast-enhanced electron beam CT.

OBJECTIVE: The purpose of this study was to determine the accuracy of three-dimensional coronary angiography obtained with electron beam CT in the assessment of the patency of coronary artery bypass grafts. SUBJECTS AND METHODS: Twenty-five patients who had undergone coronary artery bypass graft surgery were included. All patients underwent electron beam CT and conventional coronary angiography for the evaluation of the status of their bypass grafts. Three-dimensional reconstructions of the heart and bypass grafts were compared with selective angiographic images of the bypass grafts. RESULTS: Fifty-seven saphenous vein grafts and 22 left internal mammary artery grafts were evaluated for occlusion or patency. Sensitivity and specificity of electron beam CT in revealing left internal mammary artery patency were 80% and 82.4%, respectively. Sensitivity and specificity of electron beam CT in revealing saphenous vein graft patency were 91.7% and 91.1%, respectively. Sensitivity and specificity of electron beam CT for evaluating saphenous vein grafts according to coronary area were as follows: saphenous vein grafts to left anterior descending artery, 100% and 100%, respectively; to diagonal branch, 100% and 100%; to left circumflex artery, 100% and 88.9%; and to right coronary artery, 75% and 85.7%. CONCLUSION: Three-dimensional coronary angiography obtained with electron beam CT is a promising, useful, and relatively accurate diagnostic imaging technique for the evaluation of graft patency in patients who have undergone coronary artery bypass graft surgery.

Transcriptional activation of cyclooxygenase-2 in Wnt-1-transformed mouse mammary epithelial cells.

Wnt-1 acts as a mammary oncogene when ectopically expressed in the mouse mammary gland. APC is a tumor suppressor gene, mutations in which cause intestinal tumorigenesis in humans and rodents. Both Wnt-1 expression and APC mutation activate a common signaling pathway involving transcriptional activation mediated by beta-catenin/Tcf complexes, but few targets relevant to carcinogenesis have yet been identified. Expression of the inducible prostaglandin synthase cyclooxygenase-2 appears critical for intestinal tumorigenesis resulting from APC mutation, suggesting that cyclooxygenase-2 might be a transcriptional target for beta-catenin/Tcf complexes. Here, we have investigated the effect of Wnt-1 on cyclooxygenase-2 expression. Wnt-1 expression in the mouse mammary epithelial cell lines RAC311 and C57MG induces stabilization of cytosolic beta-catenin and morphological transformation. Expression of Wnt-1 in these cells caused transcriptional up-regulation of the cyclooxygenase-2 gene, resulting in increased levels of cyclooxygenase-2 mRNA and protein. Prostaglandin E2 production was increased as a consequence of the elevated cyclooxygenase-2 activity and could be decreased by treatment with a selective cyclooxygenase-2 inhibitor. Cyclooxygenase-2 thus appears to be a common downstream target for APC mutation and Wnt-1 expression. In view of the critical role of cyclooxygenase-2 in intestinal tumorigenesis, cyclooxygenase-2 up-regulation in response to Wnt signaling may contribute to Wnt-induced mammary carcinogenesis.

Inhibition of cyclooxygenase-2 gene expression by p53.

Oncogenes enhance the expression of cyclooxygenase (Cox)-2, but interactions between tumor suppressor genes and Cox-2 have not been studied. In the present work, we have compared the levels of Cox-2 and the production of prostaglandin E2 in mouse embryo fibroblasts that do not express any p53 ((10)1) versus the same cell line ((10. 1)Val5) engineered to overexpress wild-type (wt) p53 at 32 degrees C or mutant p53 at 39 degrees C. Cells expressing wt p53 showed about a 10-fold decrease in synthesis of prostaglandin E2 compared with those expressing mutant p53. Levels of Cox-2 protein and mRNA were markedly suppressed by wt p53 but not by mutant p53. Nuclear run-offs revealed decreased rates of Cox-2 transcription in cells expressing wt p53. The activity of the Cox-2 promoter was reduced by 85% in cells expressing wt p53 but was reduced only by 30% in cells expressing mutant p53 compared with cells null for p53. The effect of p53 on the suppression of Cox-2 promoter activity was localized to the first 40 base pairs 5' from the transcription start site. Electrophoretic mobility shift assay revealed that p53 competed with TATA-binding protein for binding to mouse Cox-2 or human Cox-2 promoter extending from -50 to +52 base pairs. The results of this study suggest that interactions between p53 and Cox-2 could be important for understanding why levels of Cox-2 are undetectable in normal cells and increased in many tumors.

Growth and development of Gymnophalloides seoi in immunocompetent and immunosuppressed C3H/HeN mice.

The growth and development of Gymnophalloides seoi were studied in C3H/HeN mice and effects of immunosuppression of the host on the worm development were observed. Two hundred metacercariae of G. seoi were orally administered to each mouse, and worms were recovered on days 1, 3, 5, 7, 14 and 21 post-infection (PI). The worm recovery rate was significantly higher in immunosuppressed (ImSP) mice than in immunocompetent (ImCT) mice except on days 1 and 3 PI. The worms attained sexual maturity by day 3 PI with eggs in the uterus, and worm dimensions and the number of uterine eggs continuously increased until day 14 PI in ImSP mice. Worms recovered from ImSP mice were significantly larger in size than those from ImCT mice on days 1 and 3 PI, and the number of uterine eggs was significantly larger in ImSP mice on days 5 and 7 PI. Genital organs such as the ovary, testes, and vitellaria, that were already developed in the metacercarial stage, grew a little in size until day 14 PI. The results show that the C3H/HeN mouse is, though not excellent, a suitable laboratory host for G. seoi.

Resveratrol inhibits cyclooxygenase-2 transcription in human mammary epithelial cells.

A large body of evidence suggests that inhibiting cyclooxygenase-2 (COX-2), the inducible form of COX, will be an important strategy for preventing cancer. In this study, we investigated whether resveratrol, a chemopreventive agent found in grapes, could suppress phorbol ester (PMA)-mediated induction of COX-2 in human mammary and oral epithelial cells. Treatment of cells with PMA induced COX-2 mRNA, COX-2 protein, and prostaglandin synthesis. These effects were inhibited by resveratrol. Nuclear runoffs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by resveratrol. Resveratrol inhibited PMA-mediated activation of protein kinase C and the induction of COX-2 promoter activity by c-Jun. Phorbol ester-mediated induction of AP-1 activity was blocked by resveratrol. These data are likely to be important for understanding the anticancer and anti-inflammatory properties of resveratrol.