Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling.
Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are genetically and phenotypically heterogeneous. Cardiac function is improved after treatment in some cardiomyopathy patients, but little is known about genetic predictors of long-term outcomes and myocardial recovery following medical treatment. To elucidate the genetic basis of cardiomyopathy in Japan and the genotypes involved in prognosis and left ventricular reverse remodeling (LVRR), we performed targeted sequencing on 120 DCM (70 sporadic and 50 familial) and 52 HCM (15 sporadic and 37 familial) patients and integrated their genotypes with clinical phenotypes. Among the 120 DCM patients, 20 (16.7%) had TTN truncating variants and 13 (10.8%) had LMNA variants. TTN truncating variants were the major cause of sporadic DCM (21.4% of sporadic cases) as with Caucasians, whereas LMNA variants, which include a novel recurrent LMNA E115M variant, were the most frequent in familial DCM (24.0% of familial cases) unlike Caucasians. Of the 52 HCM patients, MYH7 and MYBPC3 variants were the most common (12 (23.1%) had MYH7 variants and 11 (21.2%) had MYBPC3 variants) as with Caucasians. DCM patients harboring TTN truncating variants had better prognosis than those with LMNA variants. Most patients with TTN truncating variants achieved LVRR, unlike most patients with LMNA variants.


Implication of FKBP6 for male fertility in horses.
In stallions, impaired acrosome reaction (IAR) may often cause subfertility. Single nucleotide polymorphisms (SNPs) within FK506-binding protein (FKBP6) seem to be associated with IAR in stallions. However, their effect on stallion fertility has not yet been quantified. Using whole-genome sequence data of seven stallions, we searched FKBP6 for mutations to perform an association study in Hanoverian stallions with estimated breeding values for the paternal component of the pregnancy rate per oestrus cycle (EBV-PAT) as target trait. Genotyping five exonic mutations within FKBP6 revealed a significant association of the SNP g.11040379C>A (p.167H>N) with EBV-PAT in 216 Hanoverian stallions. The difference among the two homozygous genotypes was 7.62% in EBV-PAT, corresponding to one standard deviation of EBV-PAT. In conclusion, in Hanoverian stallions, the FKBP6-associated SNP g.11040379C>A confers higher conception rates in A/A homozygous and lower conception rates in C/C homozygous Hanoverian stallions. Thus, an FKBP6-associated missense mutation is significantly associated with stallion fertility.


Comparative study of monoclonal antibody B72.3 and gross cystic disease fluid protein-15 as markers of apocrine carcinoma of the breast.
Gross cystic disease fluid protein-15 (GCDFP-15) is a commonly used apocrine marker; however, its expression was recently found to decrease in infiltrating, larger, or metastasizing apocrine carcinomas of the breast. In the breast, monoclonal antibody (MAb) B72.3 has been reported to be useful as an apocrine marker although it is used for that purpose much less frequently than GCDFP-15. In the search for a more consistent apocrine marker, immunoreactivity for MAb B72.3 was examined in apocrine carcinomas at different stages and compared with GCDFP-15. 47 of 51 apocrine carcinomas (92%) and 9 of 62 ordinary carcinomas (15%) were MAb B72.3 positive, while 39 of 51 apocrine carcinomas (76%) and 13 of 62 ordinary carcinomas (21%) were GCDFP-15 positive. Thus, both sensitivity and specificity were higher for MAb B72.3. Furthermore, unlike GCDFP-15, MAb B72.3 exhibited positivity irrespective of infiltrating status, tumor size, or metastatic status. There was no correlation between MAb B72.3-immunoreactivity and GCDFP-15-expression. The combined usage of MAb B72.3 with GCDFP-15 was useful to confirm the diagnosis of apocrine carcinoma, especially for advanced tumors, with only two cases being negative for both MAb B72.3 and GCDFP-15. Whether these two cases should be differentiated from ordinary apocrine carcinomas remains to be investigated.


Construction of an RAPD linkage map and localization of QTLs for oleic acid level using recombinant inbreds in mustard (Brassica juncea).
RAPD markers were employed for construction of a linkage map and localization of QTLs for oleic acid level using a set of 94 recombinant inbred lines (RILs) of mustard (Brassica juncea L.) as a mapping population. Only 30% of the 235 random primers used were useful in terms of polymorphism detected and the reproducibility of those patterns. Normal Mendelian segregation was observed for the majority of the 130 markers obtained with 71 informative primers; only 13.1% deviated (P < 0.01) from the expected 1:1 ratio. One-hundred and fourteen markers were assigned to 21 linkage groups (LGs) covering a total length of 790.4 cM with an average distance of 6.93 cM between markers. Two quantitative trait loci (QTL) for oleic acid level were mapped to 14- and 10.6-cM marker intervals on two different LGs. Both loci together explained 32.2% of phenotypic variance. One major QTL explained 28.5% of the trait variance observed in this species.


Large-Scale G Protein-Coupled Olfactory Receptor-Ligand Pairing.
G protein-coupled receptors (GPCRs) conserve common structural folds and activation mechanisms, yet their ligand spectra and functions are highly diverse. This work investigated how the amino-acid sequences of olfactory receptors (ORs)-the largest GPCR family-encode diversified responses to various ligands. We established a proteochemometric (PCM) model based on OR sequence similarities and ligand physicochemical features to predict OR responses to odorants using supervised machine learning. The PCM model was constructed with the aid of site-directed mutagenesis, in vitro functional assays, and molecular simulations. We found that the ligand selectivity of the ORs is mostly encoded in the residues up to 8 Å around the orthosteric pocket. Subsequent predictions using Random Forest (RF) showed a hit rate of up to 58%, as assessed by in vitro functional assays of 111 ORs and 7 odorants of distinct scaffolds. Sixty-four new OR-odorant pairs were discovered, and 25 ORs were deorphanized here. The best model demonstrated a 56% deorphanization rate. The PCM-RF approach will accelerate OR-odorant mapping and OR deorphanization.


Pregnancy management for a patient with graft occlusion after right iliac artery bypass surgery.
We describe an extremely rare case of a pregnant woman who had a successful delivery despite developing bypass graft occlusion after right external iliac bypass surgery. External and common iliac artery bypass surgery is often performed when arteriosclerosis obliterans or thromboangiitis obliterans result in iliac artery occlusion or when revascularization is required because of iliac artery injury. Because arteriosclerosis obliterans and thromboangiitis obliterans rarely develop in young women or girls, most physicians have little experience with graft occlusion after iliac artery bypass surgery. Here we describe and discuss the published work pertaining to this extremely rare case.


[Non-obstetric indications for cesarean section from five years of material].
During the period 1990-94, in the Institute of Obstetrics and Gynecology. The Medical Academy of Gdańsk 13,079 deliveries took place including 1635 cesarean section, which makes 12.5%. In 282 women (17 percent of these) surgical procedures were performed due to a non-obstetrical indications, 122 pregnancies were complicated by maternal diabetes mellitus-these women were excluded from the present study. A constant percentage increase of cesarean sections was observed-by 1.45% every year, from 10.23% to 15.97%, but the percentage of non-obstetrical indications for operative delivery was stabilized to approximately 9.79%. The most frequent non-obstetrical indications for the cesarean section were pregnancies complicated by: hypertension-33.75%, ophtalmological-20.57%, uterine myomas-16%, women heart diseases-10%, pelvic pathology-8.75%, neurological disorders-8.12%. The indications for cesarean section did not have influence on gestational age.


Insulinoma cells contain an isoform of Ca2+/calmodulin-dependent protein kinase II delta associated with insulin secretion vesicles.
The Ca2+/calmodulin dependent protein kinase II (CaM kinase II) is thought to play an important part in glucose-stimulated insulin secretion. To determine which of the known subtypes (alpha, beta, gamma, delta) occur in insulin-secreting cells, we amplified all types of CaM kinase II by RT-PCR and found the beta3-, gamma-, delta2- and delta6-subtypes in RINm5F insulinoma cells. None of the other 8 delta-subtypes was present. Antibodies generated against the bacterially expressed association domain of the delta2-subtype recognized the recombinant gamma and delta-subtypes. In INS-1 and RINm5F cells, as well as freshly isolated rat islets, only a 55-kDa protein corresponding in size to the delta2-subtype expressed in NIH3T3 fibroblasts was detected. The delta2-subtype therefore appears to represent the predominant subtype of CaM kinase II present in insulin secreting cells. The enzyme was primarily associated with cytoskeletal structures, and very little was present in the soluble compartment or detergent soluble fraction in INS-1- or RINm5F-cells. An analysis of its subcellular distribution was performed by sucrose and Nycodenz density gradient fractionation of INS-1 cells and detection of CaM kinase II delta by immune blots. The enzyme codistributed with insulin used as a marker for secretory granules but not with the lighter synaptic-like microvesicles detected with an antibody against synaptophysin, plasma membranes (syntaxin 1), lysosomes (arylsulfatase), or mitochondria (cytochrome c oxidase). CaM kinase II delta2 thus is identified as the subtype associated with insulin secretory granules and is likely to be involved in insulin secretion.


Addition of MT, D16S10, D16S4, and D16S91 to the linkage map within 16q12.1-q22.1.
A 10-point genetic linkage map of the region 16q12.1 to 16q22.1 has been constructed using the CEPH reference families. Four loci, MT, D16S10, D16S91, and D16S4, not previously localized on a multipoint linkage map, were incorporated on the map presented here. The order of loci was cen-D16S39-MT, D16S65-D16S10-FRA16B-D16S38, D16S4, D16S91, D16S46-D16S47-HP-qter. The interval between D16S10 and 4D16S38 is 3.1 cM in males and 2.3 cM in females, and contains FRA16B. The cloning strategy for FRA16B will now be based on YAC walking from D16S10 and D16S38. The location of FRA16B between D16S10 and D16S38 provides a physical reference point for the multipoint linkage map on the short arm of chromosome 16.


[Endoscopic injection of dextranomer/hyaluronic acid for vesico-ureteral reflux--preliminary results].
Endoscopic injection is a minimal invasive treatment for vesico-ureteral reflux, an alternative for prophylactic antibiotics or open surgery. Concerns of safety were raised regarding traditional injectable materials used in the past. The recently introduced dextranomer/hyaluronic acid is a new biocompatable substance. Its safety and efficacy has been investigated and demonstrated. To report our preliminary results with the endoscopic injection of dextranomer/hyaluronic acid. Twenty nine pediatric patients of mean age 58 months (range 6-144) underwent endoscopic treatment. A total of 42 refluxing ureteral units were treated. Reflux grade was 2, 3, and 4 in 10, 24, and 8, respectively. The procedure was performed under general anesthesia, using a 9.5FR pediatric cystoscope and a semi-rigid needle. The substance was injected submucosally at the 6-o'clock position of the ureteral orifice. A mean of 0.87 ml of the substance was injected (range: 0.6-1.2). In the latter part of the series we injected a minimum of 1 ml for each ureter. During follow-up, ultrasonography and a voiding cystography were performed after 1 and 3 months respectively. Vesico-ureteral reflux resolved in 32/42 (76%) of the ureters. The rate of success was 10/10 (100%), 19/24 (79%) and 4/8 (50%) in reflux grades 2, 3, and 4, respectively. De-novo contralateral reflux was noted in 5 patients. A single complication occurred: acute venous bleeding originating in the injection site, which was managed endoscopically. Endoscopic injection of dextranomer/ hyaluronic acid is a safe and effective treatment. We recommend the injection of 1 ml, the entire volume available for each ureter.


Wear performance evaluation of a contemporary dual mobility hip bearing using multiple hip simulator testing conditions.
The dual mobility hip bearing concept combines a small bearing with a large diameter bearing through a dual articulation system, potentially increasing the stability of the hip. Bearings with two articulations introduce concerns of whether or not wear might be increased compared to a conventional bearing. We therefore evaluated the wear performance of a dual mobility hip bearing using sequentially cross-linked and annealed polyethylene under the conditions of impingement, abrasion, and when the mobile liner becomes immobilized at either the inner or outer diameter. We found the wear performance of this dual mobility hip is dictated by the conditions experienced by the smaller inner articulation and by the polyethylene material. The highest wearing group wore 75% less than a single articulating conventional gamma/inert polyethylene bearing.


Carboxypeptidase B2 and N play different roles in regulation of activated complements C3a and C5a in mice.
Essentials Two basic carboxypeptidases are present in plasma, B2 (CPB2) and N (CPN). Cpb2-/- and Cpn-/- mice were challenged in a hemolytic uremic syndrome (HUS) model vs. wild type. Cpb2-/- exacerbates HUS while Cpn-/- exacerbates cobra venom factor challenge vs. wild type mice. CPB2 and CPN have overlapping but non-redundant roles. Background There are two basic carboxypeptidases in plasma. Carboxypeptidase B2 (CPB2) is activated from a circulating zymogen, proCPB2, and carboxypeptidase N (CPN) is constitutively active with both inactivating complement C3a and C5a. Aims To test the roles of CPB2 and CPN in complement-driven mouse models of cobra venom factor (CVF) challenge and hemolytic-uremic syndrome (HUS). Methods Cpb2-/- , Cpn-/- and wild-type (WT) mice were compared in an HUS model induced by Shiga toxin and lipopolysaccharide administration and following CVF administration. Results HUS was exacerbated in Cpb2-/- mice more than in Cpn-/- mice, compared with WT mice. Cpb2-/- mice developed the HUS clinical triad of microangiopathic hemolytic anemia, uremia and thrombocytopenia. Treatment with anti-C5 antibody improved survival of both Cpb2-/- and Cpn-/- mice. In contrast, when challenged acutely with CVF, the reverse phenotype was observed. Cpn-/- mice had markedly worse disease than Cpb2-/- mice, whereas the WT mice were resistant. Conclusions CPN and CPB2 play overlapping but non-redundant roles in regulating complement activation in vivo. The constitutively active CPN is key for inactivation of systemic C5a, whereas CPB2 functions as an on-demand supplementary anaphylatoxin inhibitor in inactivating excessive C5a formed locally.


Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus.
Staphylococcus aureus causes pathologies ranging from minor skin infections to life-threatening diseases. Pathogenic effects are largely due to production of bacterial toxin, which is regulated by an RNA molecule, RNAIII. The S. aureus protein called RAP (RNAIII activating protein) activates RNAIII, and a peptide called RIP (RNAIII inhibiting peptide), produced by a nonpathogenic bacteria, inhibits RNAIII. Mice vaccinated with RAP or treated with purified or synthetic RIP were protected from S. aureus pathology. Thus, these two molecules may provide useful approaches for the prevention and treatment of diseases caused by S. aureus.


Two pharmacological phases in antigen-induced immediate airway response in rats.
The pharmacological profiles of antigen-induced immediate airway response (IAR) in rats are not fully understood. In this study, we established an ovalbumin (OVA)-induced IAR model using noninvasive measurement in rats, and evaluated the effects of commonly used and effective antiasthmatic drugs, i.e. ketotifen (antihistamine), pranlukast (anti-leukotriene C(4)/D(4)/E(4) (LT)), seratrodast (anti-thromboxane A(2) (TXA(2))), salbutamol (beta2-agonist), and prednisolone (steroid). The rat IAR model exhibited an optimal rapid airway response, and salbutamol inhalation completely suppressed the IAR. Ketotifen inhibited only the quick phase (QP; the reaction from 3 to 6 min after challenge), while pranlukast and seratrodast suppressed only the early phase (EP; the reaction from 6 to 30 min after challenge). Prednisolone inhibited both QP and EP. Further, continuous administration of compound 48/80, which depletes connective tissue mast cells (CTMC), partially inhibited QP but not EP. In conclusion, these findings suggest that the pharmacological profiles of noninvasive rat IAR are similar to those of asthmatic patients, and that rat IAR exhibits additional, immunological diverse characteristics, i.e. QP caused by the exocytosis of mediators in CTMCs and EP mediated by LT and TXA(2), which are produced by mucosal mast cells (MMCs) and possibly by other types of cells. This is the first report about the comprehensive pharmacological profiles of rodent IAR model, and these analyses of rat IAR model may help expand our understanding of the diverse mechanisms underlying human asthmatic diseases.


Activation of human embryonic gene expression in cytoplasmic hybrid embryos constructed between bovine oocytes and human fibroblasts.
Cross-species somatic all number transfer (SCNT) provides a potential solution to overcome the problem of oocyte shortage for therapeutic cloning. To further characterize the system, we constructed cytoplasm hybrid embryos between bovine oocytes and human fibroblasts and examined dynamics of human gene activation during preimplantation stages. Data from this study showed that human embryonic genes, OCT4, SOX2, NANOG, E-CADHERIN, as well as beta-ACTIN, were activated by enucleated bovine oocytes. Activation of human genes was correlated with developmental potential of the embryos. The extent of human gene activation varied drastically and was incomplete in a large proportion of the embryos. Activation of human genes in the human-bovine cytoplasm hybrid embryos occurs in a temporal pattern resembling that of the bovine species. Results from this study suggest that human gene products are required for hybrid embryos to develop to later preimplantation stages. Facilitating human genome activation may improve successful rates in cross-species SCNT.


[Early evaluation of treatment effectiveness using 131I iodine radiotherapy in patients with differentiated thyroid cancer].
This paper presents the preliminary results of a prospective randomized trial on early effectiveness of 30 mCi versus 60 mCi for ablation of thyroid remnants in patients with WDTC after total thyroidectomy. Since April 1998 to January 2000, 220 patients with papillary thyroid cancer in stage T1b-3, N0-x, M0 had entered the study. 106 patients received 60 mCi and 114 received 30 mCi as the first ablation dose. The subject for the analysis was the uptake over the neck, post-therapeutic whole body scintigraphy and Tg level 6 months after ablation. The early effectiveness of ablation was estimated using a 5-degree scale: 0--very good effect, 1--good effect, 2--dubious effect-required repetition of WBS and Tg assessment in 6-12 months, 3--insufficient ablation--required repetition of radioiodine treatment, 4--for evident dissemination or local recurrence. Grades 0 were obtained in 29 (53%) after 30 mCi (group I) and in 38 patients (86%) after 60 mCi (group II). Grades 1 were obtained in group I in 15 patients (28%) and in 4 patients (9%) of group II. Grades 2 were obtained in group I in 9 patients (17%) and in group II in 1 (2.3%). Grade 3 was obtained only in 1 (2%) patient after 30 mCi. Grade 4 was obtained in one patient after 60 mCi (2.3%). The difference in uptake over the neck in the two groups was statistically significant (p < 0.05), although the differences in early effectiveness between the both groups according to the 5-degree scale were on the borderline of significance (p = 0.075). There was a correlation between uptake before and after ablation in 30 mCi group, which was not seen present in 60 mCi group. For the ablation of thyroid remnants 60 mCi should be considered as a standard dose.


Bronchogenic adenocarcinoma metastatic tumor mimicking a dentoalveolar abscess in the maxilla.
Intraosseous metastatic tumors (IOM) in maxilla are less frequent than the soft tissue metastatic tumors. Lung and bronchogenic metastatic tumors are uncommon in the maxilla. We present a maxillary bronchogenic metastasis with a rare clinical appearance. IOM was misdiagnosed as a dentoalveolar abscess and treated with antibiotics for 3 weeks. After not responding to antibiotics, the patient's general dental practitioner forwarded the patient to the Department of Oral and Maxillofacial Surgery. The associated tooth was extracted and the patient was recalled 1 week later. No signs of improvement were observed, and cytology, biopsy, and radiology diagnostics were performed. Cytologic results and biopsy could not differentiate a metastatic tumor from a salivary duct carcinoma. Ultimately, negative androgen receptors immunohistochemistry supported the diagnosis of bronchogenic metastatic adenocarcinoma. This case report stresses the importance of taking a thorough medical history. To our knowledge, this is the third bronchogenic IOM to the maxilla reported, mimicking a dentoalveolar abscess. General dental practitioners are among the first in contact with oral metastatic tumors and it is therefore important to report unusual clinical cases, as they present a diagnostic challenge for both the clinician and the pathologist.


Precursor medications as a source of methamphetamine and/or amphetamine positive drug testing results.
Medical Review Officer interpretation of laboratory results is an important component of drug testing programs. The clinical evaluation of laboratory results to assess the possibility of appropriate medical use of a drug is a task with many different facets, depending on the drug class considered. This intercession prevents the reporting of positive results unless it is apparent that drugs were used illicitly. In addition to the commonly encountered prescribed drugs that yield positive drug testing results, other sources of positive results must be considered. This review describes a series of compounds referred to as "precursor" drugs that are metabolized by the body to amphetamine and/or methamphetamine. These compounds lead to positive results for amphetamines even though neither amphetamine nor methamphetamine were used, a possibility that must be considered in the review of laboratory results. Description of the drugs, their clinical indications, and results seen following administration are provided. This information allows for the informed evaluation of results with regard to the potential involvement of these drugs.


Comprehensive Analysis of the Great Lakes Top Predator Fish for Novel Halogenated Organic Contaminants by GC×GC-HR-ToF Mass Spectrometry.
The U.S. Environmental Protection Agency's Great Lakes Fish Monitoring and Surveillance Program (GLFMSP) has traced the fate and transport of anthropogenic chemicals in the Great Lakes region for decades. Isolating and identifying halogenated species in fish is a major challenge due to the complexity of the biological matrix. A nontargeted screening methodology was developed and applied to lake trout using a 2-dimensional gas chromatograph coupled to a high resolution time-of-flight mass spectrometer (GC×GC-HR-ToF MS). Halogenated chemicals were identified using a combination of authentic standards and library spectral matching, with molecular formula estimations provided by exact mass spectral interpretation. In addition to the halogenated chemicals currently being targeted by the GLFMSP, more than 60 nontargeted halogenated species were identified. Most appear to be metabolites or breakdown products of larger halogenated organics. The most abundant compound class was halomethoxyphenols accounting for more than 60% of the total concentration of halogenated compounds in top predator fish from all five Great Lakes illustrating the need and utility of nontargeted halogenated screening of aquatic systems using this platform.


Cell Differentiation Trajectory in Liver Cirrhosis Predicts Hepatocellular Carcinoma Prognosis and Reveals Potential Biomarkers for Progression of Liver Cirrhosis to Hepatocellular Carcinoma.
Most hepatocellular carcinoma (HCC) patients occur on a background of liver cirrhosis, the molecular mechanisms of liver cirrhosis and its progression to HCC remain to be fully elucidated. Single cell differentiation trajectory analysis has been used in cell classification and tumor molecular typing, which correlated with disease progression and patient prognosis. Here we use cell differentiation trajectory analysis to investigate the relevance of liver cirrhosis and HCC. Single-cell RNA sequencing (scRNA-seq) data of liver cirrhosis and bulk RNA-seq and clinical data of HCC were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) for analysis. HCC samples were divided into three subtypes, based on differentiation-related genes (DRGs) of liver cirrhosis, each with a different expression profile and overall survival (OS). A two- DRGs (CD34 and RAMP3) based prognostic risk scoring (RS) signature was established which could differentiate OS between high-risk and low-risk groups. And expression levels of CD34 and RAMP3 were predominantly high in endothelial cells. By integrating the RS and clinicopathological features, a nomogram was constructed and can accurately predicted the 1-year, 3-years, and 5-years OS. In conclusion, cell differentiation trajectory of liver cirrhosis can predict the prognosis of HCC, and provides new perspectives on the mechanisms of progression of liver cirrhosis to HCC.


Looking at young millennials' risk perception and purchase intention toward GM foods: Exploring the role of source credibility and risk attitude.
This study investigated young millennials' risk perception, benefit perception, and purchase intention toward GM foods by testing the effects of source credibility and risk attitude. By comparing two samples collected in the U.S. (N = 207) and China (N = 242), we found that source credibility positively influenced benefit perceptions of GM foods among Chinese millennial consumers. Results also revealed risk attitude significantly influenced both American and Chinese millennial consumers' intention to purchase GM foods. Furthermore, a significant interaction effect between source credibility and risk attitude was found on Chinese millennial consumers' risk perception of GM foods.


Synthesis of Nanometer Sized Bis- and Tris-trityl Model Compounds with Different Extent of Spin-Spin Coupling.
Tris(2,3,5,6-tetrathiaaryl)methyl radicals, so-called trityl radicals, are emerging as spin labels for distance measurements in biological systems based on Electron Paramagnetic Resonance (EPR). Here, the synthesis and characterization of rigid model systems carrying either two or three trityl moieties is reported. The monofunctionalized trityl radicals are connected to the molecular bridging scaffold via an esterification reaction employing the Mukaiyama reagent 2-chloro-methylpyridinium iodide. The bis- and tris-trityl compounds exhibit different inter-spin distances, strength of electron-electron exchange and dipolar coupling and can give rise to multi-spin effects. They are to serve as benchmark systems in comparing EPR distance measurement methods.


Current State of Imaging of Pediatric Pancreatitis: AJR Expert Panel Narrative Review.
Pancreatitis is as common in children as it is in adults, though causes and accepted imaging strategies differ in children. In this narrative review we discuss the epidemiology of childhood pancreatitis and key imaging features for pediatric acute, acute recurrent, and chronic pancreatitis. We rely heavily on our collective experience in discussing advantages and disadvantages of different imaging modalities; practical tips for optimization of ultrasound, CT, and MRI with MRCP in children; and image interpretation pearls. Challenges and considerations unique to imaging pediatric pancreatitis are discussed, including timing of imaging, role of secretin-enhanced MRCP, utility of urgent MRI, severity prediction, autoimmune pancreatitis, and best methods for serial imaging. We suggest a methodical approach to pancreatic MRI interpretation in children and have included a sample structured report, and we provide consensus statements according to our experience imaging children with pancreatitis.


Isosorbide dinitrate plasma concentrations and bioavailability in human subjects after administration of standard oral and sublingual formulations.
The bioavailability of isosorbide dinitrate from formulations containing 5, 10, and 20 mg in tablets and 10 mg in solution for oral use and 5 mg in tablets for sublingual use, has been compared. When adjusted for dose, the peak mean plasma drug concentrations after oral administration were similar (e.g., 9.2 ng/mL after a 10-mg tablet) and about one-half that obtained after sublingual administration. Drug concentrations declined monoexponentially with mean half-lives ranging from 25-36 min. The relative bioavailability of isosorbide dinitrate from the oral formulations was not significantly different (p greater than 0.05) over the dose range studied, whereas the relative bioavailability after sublingual administration was about twice as great (p less than 0.01) as that after oral administration. The plasma drug concentration-time profile after administering the 5-mg sublingual tablet was similar to that obtained after administering orally a solution containing 10 mg, indicating that the latter should be as clinically effective as the former.


Nucleotide sequence analysis of alpha-amylase and thiol protease genes that are hormonally regulated in barley aleurone cells.
We have determined the nucleotide sequences of Amy32b, a type A alpha-amylase gene, and of the gene for aleurain, a thiol protease closely related to mammalian cathepsin H. Both are expressed in barley aleurone cells under control of the plant hormones gibberellic acid and abscisic acid, but only aleurain is expressed at high levels in other barley tissues. Sequence analysis indicates that the 5' end of the aleurain gene, comprising 3 exons and 2 introns, may have become associated with the remainder of the gene, encoding the protease domain of the protein, by some sort of recombination event. This 5' domain of the gene is very G + C-rich and is flanked by inverted repetitive sequences. We found two different groups of homologous sequence elements. The first group consists of four blocks of sequences conserved in the same spatial arrangement in both genes; these are arranged at similar intervals upstream from the Amy32b TATA box and from a TATA box present in intron 3 of aleurain, outside of the 5' domain and upstream from the protease domain. A part of two of these conserved sequences is similar to the core sequence of certain enhancer elements characterized from mammalian cells. The second group of homologous elements is present in the upstream region of both genes. We speculate that these conserved sets of sequences may have some role in either the tissue specificity of expression of the genes or in some part of the hormonal regulation imposed on them.


Various types of diets, sources of energy, and positive energy balance in the induction of fatty liver hemorrhagic syndrome.
Adult female chickens were force-fed a corn-soy base diet at 150% of the daily amount consumed by those allowed the same diet ad libitum. Other hens were force-fed diets isocaloric to the 150% group just mentioned, but diet composition was adjusted so that 2/3 of the metabolizable energy (M.E.) came from the corn-soy diet and 1/3 from either corn oil or glucose; or force-fed a low energy diet accounting for 2/3 of the M.E. and corn oil 1/3 of M.E., or a purified diet accounting for all M.E. Fatty liver-hemorrhagic syndrome (FLHS) was induced in all force-fed groups with only the low energy diet plus corn oil having produced a significantly lower score for FLHS. However, the livers from the hens of the latter group had as much lipid, and the hens gained at least as much weight as those in other force-fed groups. During the third week of the experiment M.E. was determined along with a partition of energy among eggs, basal metabolism, body weight gain, and subsistance plus heat increment (H.I). The data showed that the hens force-fed corn oil had lower H.I. values indicative of associative dynamic action of fats at a plane of nutrition above normal. The data revealed that various types of diets and sources of energy in excess can induce FLHS, and this is discussed in terms of FLHS arising out of a positive energy balance.


Ab initio molecular dynamics investigations of low-energy recoil events in Ni and NiCo.
Low-energy recoil events in pure Ni and the equiatomic NiCo alloy are studied using ab initio molecular dynamics simulations. We found that the threshold displacement energies are strongly dependent on orientation and weakly dependent on composition. The minimum threshold displacement energies are along the [1 1 0] direction in both pure Ni and the NiCo alloy. Compared to pure Ni, the threshold displacement energies increase slightly in the NiCo alloy due to the stronger bonds in the alloy, irrespective of the element type of the PKA. A single Ni interstitial occupying the center of a tetrahedron formed by four Ni atoms and a <1 0 0> split interstitial is produced in pure Ni by the recoils, while only the <1 0 0> split interstitial is formed in the NiCo alloy. Compared to the replacement sequences in pure Ni, anti-site defect sequences are observed in the alloy, which have high efficiency for both producing defects and transporting energy outside of the cascade core. These results provide insights into energy transfer processes occurring in equiatomic alloys under irradiation.


Either/or. A contribution to the problem of symbolization and sublimation.
Symbol proper and symbolic equation (Segal) represent two extreme positions of many possible experiences which lie between them. A patient complained, that a game like cricket is the symbolic presentation of a fight, in which one person is to be shot. He considered this game reprehensible and a trick by which the participants act out their aggressive feelings without admitting them to themselves. This idea was traced back to an inability to establish a meaningful synthesis of the two aspects: the symbolic representation and the idea of a game. A meaningful synthesis was not possible as any contact was felt as a powerful collision demonstrated by clinical examples (dreams, fantasies, powerful projective ideas). The powerful projective ideas were derivatives of greedy taking possession of the desired object. In addition to the disturbance of symbol formation this led to an inhibition of activities and wishes. As a result the patient became the prisoner of the desired object (fixation). The powerful projective mechanisms were also related to anality. It was remarkable that in spite of these limitations, which concerned mainly his private life, the patient retained clear intellectual faculties and could successfully fill a very responsible professional position.


BF2 complex of fluorinated dipyrrolyldiketone: a new class of efficient receptor for acetate anions.
The beta-fluorinated derivative (2b) of the 1,3-dipyrrolyl-1,3-propanedione BF2 complex has been prepared from 3,4-difluoropyrrole and malonyl chloride, followed by treatment with BF3.OEt2. Despite the simple, acyclic, and neutral structure, 2b exhibits efficient 1:1 binding for anions in CH2Cl2 using the bridging CH and pyrrole NH as interaction sites. The binding constant (Ka) of 2b for acetate (CH3CO(2-)), associating more effectively than anions such as F-, Cl-, Br-, H2PO(4-), and HSO(4-), is estimated to be 9.6 x 10(5) M(-1), approximately 9 times larger than that of the beta-H derivative 2a (1.1 x 10(5) M(-1)). The UV-vis and fluorescence spectral changes of 2b elucidate the effective recognition of an amino acid, such as phenylalanine, in the anionic form; this is also supported by CD spectral changes with mirror images by L- and D-isomers. Furthermore, in the solid state, BF2 complex 2b provides Cl- -bridged supramolecular networks and, in sharp contrast, deprotonated "anionic" self-assembled structures by F- binding.


Microtubule polymerases and depolymerases.
The variety of shapes and sizes of the microtubule cytoskeleton is as great as the number of different cell types. This large variety is a consequence of the dynamic properties of microtubules, which allow them to adopt distributions of arbitrary size and form. How is the distribution of microtubule lengths controlled? Recent work suggests that the length distribution is controlled, at least in part, by the activity of microtubule polymerases and depolymerases, which accelerate microtubule growth and shrinkage. Specifically, biochemical and single-molecule studies have shown how MCAK (kinesin-13) and Kip3p (kinesin-8) accelerate depolymerization and how XMAP215 may accelerate growth. Studies on the yeast Dam1 complex have shown how proteins can couple a cellular structure, the kinetochore, to the ends of polymerizing and depolymerizing microtubules.


Spontaneous Activity of CB2 Receptors Attenuates Stress-Induced Behavioral and Neuroplastic Deficits in Male Mice.
The monoaminergic theory of depression/anxiety disorders cannot fully explain the behavioral and neuroplastic changes observed after ADs chronic treatment. Endocannabinoid system, which comprises CB2 receptors, has been associated with the chronic effects of these drugs, especially in stressed mice. CB2-KO mice display more vulnerability to stressful stimuli. In the present study, we hypothesized that the behavioral and neuroplastic effects observed after repeated treatment with the AD escitalopram (Esc) in chronically stressed mice depend on CB2 receptor signaling. Male mice submitted to chronic unpredictable stress (CUS) paradigm (21 days) were treated daily with AM630 (0.01; 0.03 or 0.3 mg/kg, i.p) a CB2 receptor antagonist/inverse agonist. At e 19th day of the CUS protocol, mice were submitted to Open field test and Tail-suspension test to evaluate antidepressant-like behavior. At the end of the stress protocol, mice were submitted to Novel Suppressed Feeding test (day 22nd) to evaluate anxiety-like behavior. In a second series of experiments, male mice treated with Esc (10 mg/kg, daily, 21 days) in the presence or not of AM630 (0.30 mg/kg) were submitted to the same round of behavioral tests in the same conditions as performed in the dose-response curve protocol. Animals were then euthanized under deep anesthesia, and their brains/hippocampi removed for immunohistochemistry (Doublecortin-DCX) or Western Blot assay. Our results demonstrated that chronic treatment with AM630, a CB2 antagonist/inverse agonist, induces anxiolytic-like effects in stressed mice. Moreover, chronic reduction of CB2 receptor endogenous activity by AM630 attenuated the neuroplastic (potentiating stress-induced decreased expression of pro-BDNF, but enhanced pmTOR and DAGL expression in the hippocampus reduced in stressed mice), the antidepressant- but not the anxiolytic-like effects of Esc. AM630 alone or in combination with Esc decreased the expression of DCX + cell in both the subgranular and granular layers of the dentate gyrus (DG), indicating a general reduction of DCX + neuroblasts and a decrease in their migration through the DG layers. We suggest that the antidepressant-like behavior and the pro-neurogenic effect, but not the anxiolytic like behavior, promoted by Esc in stressed mice are, at least in part, mediated by CB2 receptors.


Synthesis of highly strained bicyclic[3.n.1]alkenes by a metal-catalyzed Conia-ene reaction.
A high yielding metal-catalysed Conia-ene reaction of 2-acetylenic ketones for the synthesis of bicyclo[3.n.1]alkenes has been developed. This simple and efficient 6-endo-dig-cyclization protocol enables the synthesis of a wide variety of bicyclic systems, present in many natural products.


Cognitive Control Modulates Effects of Episodic Simulation on Delay Discounting in Aging.
Enhancing prospective thinking by tagging the future with specific episodic events has been shown to reduce delay discounting in young age ("tag-effect"). So far, it is unclear whether such beneficial effect extends to old adulthood. Since the general ability of future thinking and cognitive control are crucial modulators of temporal discounting in young age, potential age-related decline in these functions might impact on the effect. We focused on this issue by combining functional magnetic resonance imaging (fMRI) with an established intertemporal choice task including episodic "tags" in healthy older participants. Future thinking ability was assessed using autobiographical interviews for future event simulations and a visual search task was applied to assess participants' cognitive control ability. In contrast to previous data in young adults, the group of older participants did not benefit from tagging the future with episodic events. Older participants' cognitive control function was directly associated with discounting rates in the episodic conditions: the less the older adults were able to focus their attention the less they benefited from the inclusion of episodic events. Consistent with this, imaging results revealed that: (a) subjective value (SV) signals in the hippocampus and the anterior cingulate cortex (ACC) as well as; (b) hippocampal-striatal coupling during the episodic condition were positively related to participants' control capacity. Our findings highlight the critical role of executive functioning for the simultaneous integration of episodic information with future value computation in aging. Boosting delay gratification by including episodic tags might hence be limited in older individuals with pronounced decline in distraction control.


Virus Infection Induces Keap1 Binding to Cytokine Genes, Which Recruits NF-κB p50 and G9a-GLP and Represses Cytokine Transcription.
Proinflammatory cytokine gene transcription must be moderated to avoid the pathological consequences of excess cytokine production. The relationships between virus infection and the mechanisms that moderate cytokine transcription are incompletely understood. We investigated the influence of Keap1 on cytokine gene induction by Sendai virus infection in mouse embryo fibroblasts. Virus infection induced Keap1 binding to the Ifnb1, Tnf, and Il6 genes. Keap1 moderated viral induction of their transcription by mechanisms that did not require Nrf2. Keap1 was required for NF-κB p50 recruitment, but not for NF-κB p65 or IRF3 recruitment, to these genes. Keap1 formed complexes with NF-κB p50 and NF-κB p65, which were visualized using bimolecular fluorescence complementation analysis. These bimolecular fluorescence complementation complexes bound chromosomes in live cells, suggesting that Keap1 could bind chromatin in association with NF-κB proteins. Keap1 was required for viral induction of G9a-GLP lysine methyltransferase binding and H3K9me2 modification at cytokine genes. G9a-GLP inhibitors counteracted transcription repression by Keap1 and enhanced Keap1 and NF-κB recruitment to cytokine genes. The interrelationships among Keap1, NF-κB, and G9a-GLP recruitment, activities, and transcriptional effects suggest that they form a feedback circuit, which moderates viral induction of cytokine transcription. Nrf2 counteracted Keap1 binding to cytokine genes and the recruitment of NF-κB p50 and G9a-GLP by Keap1. Whereas Keap1 has been reported to influence cytokine expression indirectly through its functions in the cytoplasm, these findings provide evidence that Keap1 regulates cytokine transcription directly in the nucleus. Keap1 binds to cytokines genes upon virus infection and moderates their induction by recruiting NF-κB p50 and G9a-GLP.


Surgery of the rheumatoid foot and ankle.
Numerous reconstructive procedures have been used to address the manifestations of rheumatoid arthritis in the foot and ankle. Clinical studies have documented that these procedures relieve pain, however they often sacrifice motion essential to the normal function of the foot. In the forefoot, metatarsophalangeal joint resection arthroplasty shortens the lever arm of the foot, defunctions the toes, and disables the plantar plate and fat pad. Arthrodesis of the ankle and hindfoot alters gait and the effective transmission of weight-bearing stresses through the foot and ankle. These ablative procedures may provoke the deterioration of adjacent joints and may cripple the long-term function of the lower extremity. The introduction of reconstructive procedures designed to preserve motion in joints essential to function and the recognition and treatment of muscle imbalances associated with bone and joint deformities are recent advances in the surgical management of the rheumatoid foot and ankle.


Neurosurgical management of neurenteric cysts in children.
Neurenteric cysts (NCs) are endothelium-lined structures of presumed endodermal origin. There have been few pediatric series of intracranial NCs reported previously. The authors present their experience in the management of these lesions. A retrospective chart review of all cases of NCs identified between 1977 and 2007 was carried out. Demographics, details of clinical presentation, surgical therapy, and outcome data were extracted. Eleven cases were identified, involving 6 girls and 5 boys. The patients' average age was 4.6 years (range 1 day-14 years). Limb weakness was the most common presenting symptom. The location of the cysts was cervical in 2 cases, cervicothoracic in 4 cases, and thoracic in 3 cases. One cyst was anterior to the pons with extension to the left cerebellopontine angle and 1 cyst was at the craniocervical junction. Five patients had an apparently complete initial excision, with 1 recurrence. Four patients were initially treated with incomplete excision and/or cyst drainage, usually into an Ommaya reservoir. A neonate with a large cervicothoracic cyst died of multiple congenital anomalies without any intervention. All other patients were alive at last follow-up. One patient with a radiologically identified presumed cyst, which remained stable, was simply followed up. Several patients required multiple procedures and 1 patient developed hydrocephalus after aseptic meningitis and was treated with CSF shunting. Neurenteric cysts are rare in the pediatric population. Total resection, if possible, provides the best long-term outcome. Incomplete excision may lead to multiple procedures, including cyst drainage, but can lead to long-term stability.


Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model.
Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines. Newborn piglets were randomized to NT (n = 5) or HT (n = 6) lasting 2-26 h after HI. Serum samples were obtained 4-6 h before, during and at 6-12 h intervals after HI; CSF was obtained at 48 h. Concentrations of interleukin (IL)-1β, -4, -6, -8, -10 and TNF-α were measured and pro/anti-inflammatory status compared between groups. White matter and thalamic voxel lactate/N-acetyl aspartate (Lac/NAA) (a measure of both oxidative metabolism and neuronal loss) were acquired at baseline, after HI and at 24 and 36 h. Lac/NAA was reduced at 36 h with HT compared to NT (p = 0.013 basal ganglia and p = 0.033 white matter). HT showed lower serum TNF-α from baseline to 12 h (p < 0.05). Time-matched (acquired within 5 h of each other) serum cytokine and MRS showed correlations between Lac/NAA and serum IL-1β and IL-10 (all p < 0.01). The pro/anti-inflammatory ratios IL-1β/IL-10, IL-6/IL-10, IL-4/IL-10 and IL-8/IL-10 were similar in NT and HT groups until 36 h (24 h for IL-6/IL-10); after this, 36 h pro/anti-inflammatory cytokine ratios in the serum were higher in HT compared to NT (p < 0.05), indicating a pro-inflammatory cytokine surge after rewarming in the HT group. In the CSF at 48 h, IL-8 was lower in the HT group (p < 0.05). At 48 h, CSF TNF-α correlated with Lac/NAA (p = 0.02) and CSF IL-8 correlated with white matter TUNEL positive cell death (p = 0.04). Following cerebral HI, there was a systemic pro-inflammatory surge after rewarming in the HT group, which is counterintuitive to the putative neuroprotective effects of HT. While serum cytokines were variable, elevations in CSF inflammatory cytokines at 48 h were associated with MRS Lac/NAA and white matter cell death.


Accuracy of Rhenium-188 SPECT/CT activity quantification for applications in radionuclide therapy using clinical reconstruction methods.
The main applications of 188Re in radionuclide therapies include trans-arterial liver radioembolization and palliation of painful bone-metastases. In order to optimize 188Re therapies, the accurate determination of radiation dose delivered to tumors and organs at risk is required. Single photon emission computed tomography (SPECT) can be used to perform such dosimetry calculations. However, the accuracy of dosimetry estimates strongly depends on the accuracy of activity quantification in 188Re images. In this study, we performed a series of phantom experiments aiming to investigate the accuracy of activity quantification for 188Re SPECT using high-energy and medium-energy collimators. Objects of different shapes and sizes were scanned in Air, non-radioactive water (Cold-water) and water with activity (Hot-water). The ordered subset expectation maximization algorithm with clinically available corrections (CT-based attenuation, triple-energy window (TEW) scatter and resolution recovery was used). For high activities, the dead-time corrections were applied. The accuracy of activity quantification was evaluated using the ratio of the reconstructed activity in each object to this object's true activity. Each object's activity was determined with three segmentation methods: a 1% fixed threshold (for cold background), a 40% fixed threshold and a CT-based segmentation. Additionally, the activity recovered in the entire phantom, as well as the average activity concentration of the phantom background were compared to their true values. Finally, Monte-Carlo simulations of a commercial [Formula: see text]-camera were performed to investigate the accuracy of the TEW method. Good quantification accuracy (errors <10%) was achieved for the entire phantom, the hot-background activity concentration and for objects in cold background segmented with a 1% threshold. However, the accuracy of activity quantification for objects segmented with 40% threshold or CT-based methods decreased (errors >15%), mostly due to partial-volume effects. The Monte-Carlo simulations confirmed that TEW-scatter correction applied to 188Re, although practical, yields only approximate estimates of the true scatter.


Brain and Cardiorespiratory Responses to Exercise in Hot and Thermoneutral Conditions.
The aim of this study was to test whether or not concurrent evaluations of brain (electroencephalography [EEG]) and cardiorespiratory responses to exercise are influenced by environmental conditions. 10 adult male participants performed a standardized incremental exercise test to exhaustion on a cycle ergometer in an environment controlled laboratory on 2 separate occasions, in a randomized order; one in a hot condition (34.5°C) and one in a thermoneutral condition (20°C). EEG, heart rate and expired air were collected throughout. EEG data were decontaminated for artefacts, log-transformed and expressed as aggregated alpha and beta power responses across electrodes reflecting the frontal cortex of the brain. Performance outcomes showed there was no difference in V˙O2 peak across hot (42.5 ml/kg/min) and neutral (42.8 ml/kg/min) conditions, although ventilatory threshold (VT) occurred at a lower threshold (68%) in hot compared to neutral condition (74%) (p<0.05). EEG alpha and beta wave responses both demonstrated significant increases from baseline to VT (p<0.01). EEG beta-band activity was significantly elevated in the heat compared to the neutral condition. In conclusion, elevated EEG beta-band activity in response to incremental exercise in the heat suggests that beta-band activation and cortical awareness increases as exercise becomes increasingly intense.


Liver lipophagy ameliorates nonalcoholic steatohepatitis through extracellular lipid secretion.
Nonalcoholic steatohepatitis (NASH) is a progressive disorder with aberrant lipid accumulation and subsequent inflammatory and profibrotic response. Therapeutic efforts at lipid reduction via increasing cytoplasmic lipolysis unfortunately worsens hepatitis due to toxicity of liberated fatty acid. An alternative approach could be lipid reduction through autophagic disposal, i.e., lipophagy. We engineered a synthetic adaptor protein to induce lipophagy, combining a lipid droplet-targeting signal with optimized LC3-interacting domain. Activating hepatocyte lipophagy in vivo strongly mitigated both steatosis and hepatitis in a diet-induced mouse NASH model. Mechanistically, activated lipophagy promoted the excretion of lipid from hepatocytes, thereby suppressing harmful intracellular accumulation of nonesterified fatty acid. A high-content compound screen identified alpelisib and digoxin, clinically-approved compounds, as effective activators of lipophagy. Administration of alpelisib or digoxin in vivo strongly inhibited the transition to steatohepatitis. These data thus identify lipophagy as a promising therapeutic approach to prevent NASH progression.


Populus cathayana males are less affected than females by excess manganese: comparative proteomic and physiological analyses.
The comprehension of sexually different responses in dioecious plants to excess manganese (Mn) stress requires molecular explanation. Physiological and proteomic changes in leaves of Populus cathayana males and females were analyzed after 4 wk of exposure to Mn stress. Under excess Mn conditions, shoot height and photosynthesis decreased more in females than in males. Females also showed severe browning and subcellular damage, higher Mn2+ absorption, and different antioxidant enzyme activities compared with males. There were ten differently regulated protein spots induced by excess Mn stress. They were mainly related to photosynthesis, ROS cleaning, and cell signaling associated to ROS, plant cell death, heat shock, cell defense and rescue, and gene expression and regulation. Variation in protein expression between the sexes clearly showed that males have evolved more efficient photosynthesis capacity, more stable gene expression and regulation, and better cell defense and rescue to prevent further injury under excess Mn stress.


Expression of human inducible nitric oxide synthase is regulated by both promoter and 3'-regions.
One of the mechanisms underlying the induction of human inducible nitric oxide synthase (hiNOS) by cytokines is transcriptional regulation. However, previous reports suggest that in human cells, the cytokine activation of the hiNOS expression is accompanied by a drastic increase in cellular mRNA and protein content, but by little increment in transcriptional activity. We designed luciferase reporter constructs containing the hiNOS 5'-flanking region and 3'-untranslated region (UTR). The construct containing both 5'-flanking region and 3'-UTR plus its downstream canceled the constitutive activity of the reporter gene, and was more responsive to the cytokines. This is an initial attempt to highlight the important role played by the 3'-region of the hiNOS gene. Our studies provide the evidence that the cooperative interaction between the 5'-promoter and the 3'-region conveys marked induction of the gene in the presence of cytokines.


Economic impact of delays in listing decisions by provincial drug plans after a positive Common Drug Review recommendation: the case of a smoking-cessation treatment.
Although varenicline (Champix), a smoking-cessation treatment, was recommended for listing by the Common Drug Review (CDR) in 2007, only one CDR-participating drug insurance plan listed it in March 2011 (Saskatchewan). This study estimated the economic impact of delays in the public listing of varenicline in Canada. Using statistical data and peer-reviewed research, social costs and benefits of reimbursing varenicline were estimated. Flows of attempted and successful quitters were projected over a five-year period for three scenarios: immediate listing (2007), one- to four-year listing delays, and no reimbursement. Benefits of public reimbursement of varenicline would have been greatest in the first year ($271 million) and then decreased due to the erosion in smoking prevalence. The current three-year listing delay prevented a projected 17,729 current smokers from quitting, translating into a projected additional lifetime social burden of $700 million. The sizeable opportunity cost of delaying varenicline reimbursement implies broader economic issues for policy makers.


Zosteriform lichen planus after herpes zoster: report of a new case of Wolf's isotopic phenomenon and literature review.
The Wolf's isotopic phenomenon corresponds to the occurrence of a skin disease at a body site affected previously by a different, already healed dermatosis. We report a 74-year-old man who presented with a zosteriform eruption consisting of erythematous-scaly, slightly pruritic papules on the right flank some weeks after herpes zoster (HZ) had healed on the same area. Histologic examination showed typical changes of lichen planus, confirming the diagnosis of post-HZ zosteriform lichen planus (ZLP). The lesions regressed with topical steroid treatment. Zosteriform lichen planus (ZLP) is one example of Wolf's isotopic phenomenon appearing after HZ. So far, only 17 cases have been reported in the literature. The precise pathogenesis of ZLP is not well known, although persisting viral proteins could be responsible for the hypersensitivity reaction. We review and discuss the salient clinicopathologic features of this rare entity based on a thorough literature review.


Global, regional, and cryptic population structure in a high gene-flow transatlantic fish.
Lumpfish (Cyclopterus lumpus) is a transatlantic marine fish displaying large population sizes and a high potential for dispersal and gene-flow. These features are expected to result in weak population structure. Here, we investigated population genetic structure of lumpfish throughout its natural distribution in the North Atlantic using two approaches: I) 4,393 genome wide SNPs and 95 individuals from 10 locations, and II) 139 discriminatory SNPs and 1,669 individuals from 40 locations. Both approaches identified extensive population genetic structuring with a major split between the East and West Atlantic and a distinct Baltic Sea population, as well as further differentiation of lumpfish from the English Channel, Iceland, and Greenland. The discriminatory loci displayed ~2-5 times higher divergence than the genome wide approach, revealing further evidence of local population substructures. Lumpfish from Isfjorden in Svalbard were highly distinct but resembled most fish from Greenland. The Kattegat area in the Baltic transition zone, formed a previously undescribed distinct genetic group. Also, further subdivision was detected within North America, Iceland, West Greenland, Barents Sea, and Norway. Although lumpfish have considerable potential for dispersal and gene-flow, the observed high levels of population structuring throughout the Atlantic suggests that this species may have a natal homing behavior and local populations with adaptive differences. This fine-scale population structure calls for consideration when defining management units for exploitation of lumpfish stocks and in decisions related to sourcing and moving lumpfish for cleaner fish use in salmonid aquaculture.


Confinement-modulated junctionless nanowire transistors for logic circuits.
We report the controlled formation of nanoscale constrictions in junctionless nanowire field-effect transistors that efficiently modulate the flow of the current in the nanowire. The constrictions act as potential barriers and the height of the barriers can be selectively tuned by gates, making the device concept compatible with the crossbar geometry in order to create logic circuits. The functionality of the architecture and the reliability of the fabrication process are demonstrated by designing decoder devices.


Nickel-Catalyzed Domino Heck Cyclization/Suzuki Coupling for the Synthesis of 3,3-Disubstituted Oxindoles.
The first nickel-catalyzed domino Heck cyclization/Suzuki coupling reaction for the synthesis of 3,3-disubstituted oxindoles bearing quaternary all-carbon centers is reported. A wide range of electrophiles, such as aryl iodides, bromides, triflates, and chlorides, are all compatible with the reaction conditions. Moreover, cheap aryl esters, which undergo catalytic C-O bond cleavage, could also be employed as electrophiles. The approach shows good yields and broad scope, complementing a more practical and sustainable alternative to the conventional palladium-based analogues.


Diattenuation and polarization preservation of retinal nerve fiber layer reflectance.
The diattenuation spectrum of the retinal nerve fiber layer (RNFL) reflectance has been predicted to depend strongly on the relative refractive index (m) of light-scattering cylinders. To constrain the values of m, diattenuation of the RNFL reflectance of isolated rat retina was measured with a multispectral imaging micropolarimeter. The RNFL reflection has very weak intrinsic diattenuation at all wavelengths (400-830 nm), which rejects all values of m > or = 1.03. Degree of polarization (DOP) for reflection from the RNFL was also measured. DOP was close to unity at all wavelengths, which indicates that the RNFL is a polarization-preserving reflector.


Direct PCR amplification and sequencing of specimens' DNA from preservative ethanol.
DNA extraction is the first step in many molecular biology protocols. However, we hypothesized that DNA from a preserved specimen can leak into its preservative medium, allowing the medium itself to be directly PCR-amplified. We successfully tested this idea on mescal-the alcoholic beverage famous for the "worm" (a caterpillar) that is placed in the bottle of many brands-and indeed obtained amplifiable quantities of caterpillar DNA. We then successfully amplified and sequenced DNA from the 95% ethanol preservative of 70 freshly collected specimens and 7 archival specimens 7-10 years old. These results suggest that DNA extraction is a superfluous step in many protocols and that preservative ethanol can be used as a source of genetic material for non-invasive sampling or when no tissue specimen is left for further DNA analyses.


Examining the Effects of Religious Attendance on Resilience for Older Adults.
Growing older often brings hardship, adversity, and even trauma. Resilience is a broad term used to describe flourishing despite adversity. To date, resilience and the connections to religion have not been well studied, despite compelling evidence that religious practice can promote psychological health. This research examines the role that religion plays in promoting resilience among older adults. Research questions include: (a) What is the relationship between religion and trait resilience? and (b) Does religion promote resilient reintegration following traumatic life events? Results indicate that religious service attendance is tied to higher levels of trait resilience and that both service attendance and trait resilience directly predict lower levels of depression and higher rates of resilient reintegration following traumatic life events. Findings suggest that religious service attendance has protective properties that are worthy of consideration when investigating resilience.


Optic nerve head morphology and visual field function in patients with AIDS and without infectious retinitis.
To evaluate morphology of the optic nerve head and visual field in AIDS patients without retinitis. One randomly selected eye from 246 patients with AIDS without retinitis was evaluated from prospective multicenter Longitudinal Studies of Ocular Complications of AIDS. Stereo fundus photographs of OHN and serial VF data over 5-years were analyzed. Main outcomes included vertical cup-to-disc ratio (CDR), mean deviation, and pattern standard deviation scores on VF testing. The median CDR was 0.39 at enrollment and 0.40 at 5-year follow-up. An unadjusted linear regression model revealed a mean change in CDR of 0.004 after 5-years (P = 0.04). After adjustment for practice effect, there were no statistically significant changes in VF performance observed during the 5 years of follow-up. We detected clinically minimal, but statistically significant changes in ONH morphology and no change in VF performance among eyes of patients with AIDS and without retinitis.


[The contribution of nephro-urotomography in the diagnosis of unilateral non-functioning kidney in the adult (author's transl)].
The aetiological diagnosis of a unilateral nonfunctioning kidney is achieved by angiographic or retrograde techniques. Pyelography indicates only that organ is non-functioning. 71 patients were explored by nephro-urotomography carried out using high doses of contrast medium (2 cm3/kg) with rapid injection (10cm3/sec.) and repeated tomographic sections taken during the first minute after injection. These tomographic sections, three in number, made it possible to study the three phases of the nephrogram: cortical nephrography, cortico-medullary nephrography and tubular nephrography. The aim of this study was to assess the contribution of this technique in the aetiological diagnosis of a unilateral non-functioning kidney. In the majority of cases it is possible to suspect the vascular or neoplasic origin of the non-functioning kidney. Obstructive non-functioning kidneys have two distinct nephrographic appearances. Pelvic and retroperitoneal obstructions are visualised chiefly during the phase of cortical nephrography, which shows marked parenchymatous atrophy with the presence of rounded intrarenal lacunae. By contrast, obstruction secondary to pyelo-ureteral junction syndrome results in total destruction of the parenchyma. The phenomenon of total corporeal opacification plays a major role in the visualisation of the fibrous speta which form the limits of the pseudocystic pockets. In these patients, the contribution of study of early nephrograms is less evident. Bacillary non-functioning kidneys have an analogous appearance characterised by the particular frequency of abnormal opacities, calcified ormastic. Thus the aetiological diagnosis of a unilateral nonfunctioning kidney may be obtained in the majority of cases. This permits more judicious selection of those cases requiring angiography or retrograde exploration necessary to pre-operative assessment.


Inflammatory malignant fibrous histiocytoma: distinction from Hodgkin's disease and non-Hodgkin's lymphoma by a panel of leukocyte markers.
Inflammatory malignant fibrous histiocytoma (IMFH), consisting of large, atypical histiocyte-like cells set amidst an inflammatory backdrop of eosinophils, neutrophils, lymphocytes, and xanthoma cells, can be difficult to distinguish from Hodgkin's disease and non-Hodgkin's lymphoma, particularly of the Ki-1 anaplastic large-cell type in small biopsy specimens. This problem is becoming more prevalent with the use of needle biopsies guided by computed tomography for definitive diagnosis. For this reason, we studied the expression of a battery of leukocyte markers in IMFH to evaluate whether they could serve as an independently reliable means of distinguishing amongst the three neoplasms. Eight examples of histologically typical IMFH were stained with a number of leukocyte markers that included CD30 (BerH2), CD15 (leuM1), CD45/ CD45RB (2B11,PD7/26/16), CD43 (leu 22), CD45RO (A6), CD20 (L26), and CD68 (KPI). The large anaplastic tumor cells within IMFH consistently lacked CD30, CD15, CD45/CD45RB, CD43, CD45RO, and CD20. In one case, the anaplastic cells expressed CD68. Benign histiocytes within IMFH expressed CD68 and displayed variable expression of CD15, CD45/CD45RB, and CD43. The reactive lymphocytes consisted mostly of scattered small T cells with a few B cells, mainly within lymphoid aggregates. We conclude that the immunophenotypic profile of the anaplastic cells in IMFH (lack of CD15, CD30, CD43, CD45/CD45RB, CD45RO, CD20) differs from most cases of Hodgkin's disease (ICD30+, CD15+/-) and from Ki-1 anaplastic large cell lymphoma (CD30+, CD45/CD45RB+/-, CD43+/-, CD45RO+/-, CD20-/+). Immunohistochemistry is an important diagnostic adjunct, provided care is taken to exclude benign histiocytes and inflammatory cells from consideration.


Efficacy of antimigrainous therapy in the treatment of migraine-associated dizziness.
To assess the effects of antimigrainous therapy on migraine-associated dizziness/vertigo. We hypothesized that a medication's ability to ameliorate dizziness/vertigo in this patient population would be directly correlated with its efficacy in improving headache symptoms. Patient survey. Patients were entered into the study from the University of California, San Diego (UCSD) Headache Clinic, a tertiary care referral clinic. All patients presenting to the UCSD headache clinic are entered into its comprehensive database. Patients who identified dizziness or vertigo as symptoms were entered into this study and were surveyed. Patients were surveyed as to the nature of their vestibular symptoms, and the therapeutic response of these symptoms and their headaches to various antimigrainous medications. Patients were asked to rank therapeutic efficacy utilizing a numeric scale. These results were then subjected to statistical analysis (Spearman rank correlation) to identify any correlation between the efficacies of the medications in improving headache and dizziness/vertigo. The efficacy of the medications in treating migraine-associated dizziness was directly correlated with their ability to alleviate headaches. We conclude that antimigrainous therapy may offer specific treatment to patients suffering from the spectrum of migraine-associated vestibular disorders. This would include the entity known alternately as vestibular Meniere's disease, benign recurrent vertigo, or recurrent vestibulopathy. Given the potential benefits that may be derived from this therapy, clinicians should be sensitive to a history of migraines in patients complaining of dizziness, particularly in those complaining of recurrent episodic vertigo.


Immediate early gene activity in song control nuclei and brain areas regulating motivation relates positively to singing behavior during, but not outside of, a breeding context.
In some species, such as songbirds, much is known about how the brain regulates vocal learning, production, and perception. What remains a mystery is what regulates the motivation to communicate. European starlings (Sturnus vulgaris) sing throughout most of the year, but the social and environmental factors that motivate singing behavior differ seasonally. Male song is highly sexually motivated during, but not outside of, the breeding season. Brain areas outside the song control system, such as the medial preoptic nucleus (POM) and ventral tegmental area (VTA), have been implicated in regulating sexually motivated behaviors in birds, including song. The present study was designed to explore whether these regions, as well as three song control nuclei [area X, the high vocal center (HVC), and the robust nucleus of the arcopallium (RA)], might be involved differentially in song produced within compared to outside of a breeding context. We recorded the behavioral responses of breeding and nonbreeding condition male starlings to the introduction of a female conspecific. Males did not show context-dependent differences in the overall amount of song sung. However, immunocytochemistry for the protein product of the immediate early gene cFOS revealed a positive linear relationship between the total amount of songs sung and number of cFOS-labeled cells in POM, VTA, HVC, and RA for birds singing during, but not outside of, a breeding context. These results suggest that these regions differentially regulate male song production depending on reproductive context. Overall the data support the hypothesis that the POM and VTA interact with the song control system, specifically HVC and RA, to regulate sexually motivated vocal communication in songbirds.


Primary spinal primitive neuroectodermal tumor: case series and review of the literature.
Primary spinal primitive neuroectodermal tumor (PSPNET) is extremely rare and only 25 cases have been reported in the world literature so far. Three patients of 8, 9 and 18 years of age, who presented with variable grades of neurological deficit were diagnosed as having a dorsal intramedullary lesion, a holocord lesion and cervical extradural tumor with extraspinal extension, respectively, and were operated at our institute. The histopathology of all 3 children revealed PNET. The clinical course, image characteristics and outcome of the 3 children are described, and the relevant literature is reviewed. The following conclusions were drawn from the present study and review of the literature. PNET may manifest itself as a primary lesion of the spine unlike the more common drop metastases from an intracranial lesion. PSPNET may be intramedullary, intradural and extradural with variable extraspinal extension. PSPNET may present as holocord intramedullary lesion, an entity which has not been described earlier. These lesions have a short history, significant neurological deficits and rapid course of illness. PSPNET, though an established entity, did not find a place in the WHO 2000 classification of CNS tumors. Hence its status has to be defined.


It's not what it looks like: atypical rash in cryoglobulinaemic vasculitis.
A 48-year-old man with a history of intravenous drug use and chronic, untreated hepatitis C presented to the emergency room with acute bilateral lower extremity swelling, erythema and maculopapular rash. Serum C4 levels were low, but dermatology felt the rash was due to venous stasis dermatitis. The patient was discharged with compression stockings, but returned to the hospital 5 days later with no improvement in his symptoms. A more extensive laboratory workup revealed hepatitis C viral load of 4 million, elevated serum cryoglobulins, and skin biopsy showing leucocytoclastic vasculitis. He was treated with oral prednisone, with complete resolution of his symptoms after 2 weeks. He was scheduled for follow-up in gastroenterology clinic for treatment of his hepatitis C for definitive cure of his mixed cryoglobulinaemia, but failed to get insurance authorisation to begin treatment with Harvoni. He presented to the hospital 4 months later with diffuse alveolar haemorrhage.


Automatic Intensity-based 3D-to-2D Registration of CT Volume and Dual-energy Digital Radiography for the Detection of Cardiac Calcification.
We are investigating three-dimensional (3D) to two-dimensional (2D) registration methods for computed tomography (CT) and dual-energy digital radiography (DR) for the detection of coronary artery calcification. CT is an established tool for the diagnosis of coronary artery diseases (CADs). Dual-energy digital radiography could be a cost-effective alternative for screening coronary artery calcification. In order to utilize CT as the "gold standard" to evaluate the ability of DR images for the detection and localization of calcium, we developed an automatic intensity-based 3D-to-2D registration method for 3D CT volumes and 2D DR images. To generate digital rendering radiographs (DRR) from the CT volumes, we developed three projection methods, i.e. Gaussian-weighted projection, threshold-based projection, and average-based projection. We tested normalized cross correlation (NCC) and normalized mutual information (NMI) as similarity measurement. We used the Downhill Simplex method as the search strategy. Simulated projection images from CT were fused with the corresponding DR images to evaluate the localization of cardiac calcification. The registration method was evaluated by digital phantoms, physical phantoms, and clinical data sets. The results from the digital phantoms show that the success rate is 100% with mean errors of less 0.8 mm and 0.2 degree for both NCC and NMI. The registration accuracy of the physical phantoms is 0.34 ± 0.27 mm. Color overlay and 3D visualization of the clinical data show that the two images are registered well. This is consistent with the improvement of the NMI values from 0.20 ± 0.03 to 0.25 ± 0.03 after registration. The automatic 3D-to-2D registration method is accurate and robust and may provide a useful tool to evaluate the dual-energy DR images for the detection of coronary artery calcification.


Multi-Clinic Quality Improvement Initiative Increases Continuous Glucose Monitoring Use Among Adolescents and Young Adults With Type 1 Diabetes.
Continuous glucose monitoring (CGM) use is associated with improved A1C outcomes and quality of life in adolescents and young adults with diabetes; however, CGM uptake is low. This article reports on a quality improvement (QI) initiative of the T1D Exchange Quality Improvement Collaborative to increase CGM use among patients in this age-group. Ten centers participated in developing a key driver diagram and center-specific interventions that resulted in an increase in CGM use from 34 to 55% in adolescents and young adults over 19-22 months. Sites that performed QI tests of change and documented their interventions had the highest increases in CGM uptake, demonstrating that QI methodology and sharing of learnings can increase CGM uptake.


Interrupted visual searches reveal volatile search memory.
This study investigated memory from interrupted visual searches. Participants conducted a change detection search task on polygons overlaid on scenes. Search was interrupted by various disruptions, including unfilled delay, passive viewing of other scenes, and additional search on new displays. Results showed that performance was unaffected by short intervals of unfilled delay or passive viewing, but it was impaired by additional search tasks. Across delays, memory for the spatial layout of the polygons was retained for future use, but memory for polygon shapes, background scene, and absolute polygon locations was not. The authors suggest that spatial memory aids interrupted visual searches, but the use of this memory is easily disrupted by additional searches.


Short screening tools for risky drinking in Aboriginal and Torres Strait Islander Australians: modified AUDIT-C and a new approach.
Alcohol consumption among Indigenous Australians can involve a stop-start pattern of drinking, with consumption well above recommended guidelines on each occasion. Such intermittent drinking patterns can make screening for risky drinking difficult. This study evaluates the ability of several short alcohol screening tools, contained in the Grog Survey Application, to detect short- or long-term risky drinking as defined by Australian guidelines. Tested tools include a modification of Alcohol Use Disorders Identification Test-Consumption (AUDIT-Cm). Alcohol consumption was assessed in current drinkers in the past year (n = 184) using AUDIT-Cm and using the last four drinking occasions (Finnish method). Sensitivity and specificity were assessed relative to the Finnish method, for how AUDIT-Cm score (3 + for women, 4 + for men), and how subsets of AUDIT-Cm questions (AUDIT-1m and AUDIT-2m; and AUDIT-3mV alone) were able to determine short- or long-term risk from drinking. Responses to AUDIT-Cm were used to calculate the average standard drinks consumed per day, and the frequency at which more than four standard drinks were consumed on single occasions. Finally, shorter versions of the Finnish method (1, 2, or 3 occasions of drinking) were compared to the full Finnish method, by examining the percentage of variance retained by shorter versions. AUDIT-Cm has a high sensitivity in detecting at-risk drinking compared with the Finnish method (sensitivity = 99%, specificity = 67%). The combination of AUDIT-1m and AUDIT-2m was able to classify the drinking risk status for all but four individuals in the same way as the Finnish method did. For the Finnish method, two drinking sessions to calculate drinks per drinking occasion, and four to calculate frequency resulted in nearly identical estimates to data on all four of the most recent drinking occasions (r2 = 0.997). The combination of AUDIT-1m and AUDIT-2m may offer advantages as a short screening tool, over AUDIT-3mV, in groups where intermittent and high per occasion drinking is common. As an alternative to the full Finnish method, the quantity consumed on the last two occasions and timing of the last four occasions may provide a practical short screening tool.


Stress and coping as predictors of children's divorce-related ruminations.
Examined stress and coping variables as predictors of divorce-related ruminations in children whose parents had recently divorced. Simultaneous multiple regression was used to analyze the cross-sectional data of 351 children of divorce. Divorce-related stressful events and threat appraisal were positively related to children's ruminations. A prospective longitudinal design was employed to predict rumination at Time 2 (T2) controlling for Time 1 (T1) rumination. Efficacy of coping was negatively related to T2 rumination after controlling for T1 rumination and all other predictors. This study also provided descriptive data on the frequency of children's divorce-related ruminations.


Long-term oncologic outcomes of laparoscopic surgery for splenic flexure colon cancer are comparable to conventional open surgery.
Few studies about laparoscopic surgery for splenic flexure colon cancer have been published. This study aims to compare the short- and long-term outcomes of laparoscopic surgery for splenic flexure colon cancer with those of conventional open surgery. From January 2004 to December 2010, 51 consecutive patients who underwent curative resection for stages I-III splenic flexure colon cancer were enrolled. Thirty-three patients underwent laparoscopy-assisted colectomy, while 18 patients underwent conventional open colectomy. Short- and long-term outcomes of the 2 groups were compared. There were no differences in baseline characteristics, intra- and postoperative complications. The laparoscopy group showed longer operation time (median [interquartile range, IQR]: 295.0 [255.0-362.5] minutes vs. 180.0 [168.8-206.3] minutes, P < 0.001). In the laparoscopy group, return of bowel function was faster (median [IQR]: 3 [2-4] vs. 4 [3-5], P = 0.007) and postoperative hospital stay was shorter (median [IQR]: 9 [8-11] vs. 10.5 [9-19], P = 0.026). There were no statistically significant differences in overall survival rate (84.3% vs. 76.0%, P = 0.560) or disease-free survival rate (93.8% vs. 74.5%, P = 0.078) between the 2 groups. Laparoscopic surgery for splenic flexure colon cancer has better short-term outcomes than open surgery, as well as acceptable long-term outcomes. Laparoscopic surgery can be a safe and feasible alternative to conventional open surgery for splenic flexure colon cancer.


Validity of the bear tapeworm Diphyllobothrium ursi (Cestoda: Diphyllobothriidae) based on morphological and molecular markers.
The bear tapeworm Diphyllobothrium ursi is described based upon the morphology of adult tapeworms recovered from the brown bear (Ursus arctos middendorffi) and larval plerocercoids found in sockeye salmon (Oncorhynchus nerka) from Kodiak Island in Alaska in 1952. However, in 1987 D. ursi was synonymized with Diphyllobothrium dendriticum, and the taxonomic relationship between both species has not subsequently been revised. In this study mitochondrial cytochrome c oxidase subunit 1 gene (cox1) sequences of holotype and paratype D. ursi specimens that had been preserved in a formalin-acetic acid-alcohol solution since the time the species was initially described approximately 60 yr ago were analyzed. Molecular and phylogenetic analysis of the cox1 sequences revealed that D. ursi is more closely related to D. dendriticum than it is to Diphyllobothrium nihonkaiense and Diphyllobothrium latum. In addition to molecular evidence, differences in the life cycle and ecology of the larval plerocercoids between D. ursi and D. dendriticum also suggest that D. ursi is a distinct species, separate from D. dendriticum and D. nihonkaiense, and also possibly from D. latum .


Ranking Support Vector Machine with Kernel Approximation.
Learning to rank algorithm has become important in recent years due to its successful application in information retrieval, recommender system, and computational biology, and so forth. Ranking support vector machine (RankSVM) is one of the state-of-art ranking models and has been favorably used. Nonlinear RankSVM (RankSVM with nonlinear kernels) can give higher accuracy than linear RankSVM (RankSVM with a linear kernel) for complex nonlinear ranking problem. However, the learning methods for nonlinear RankSVM are still time-consuming because of the calculation of kernel matrix. In this paper, we propose a fast ranking algorithm based on kernel approximation to avoid computing the kernel matrix. We explore two types of kernel approximation methods, namely, the Nyström method and random Fourier features. Primal truncated Newton method is used to optimize the pairwise L2-loss (squared Hinge-loss) objective function of the ranking model after the nonlinear kernel approximation. Experimental results demonstrate that our proposed method gets a much faster training speed than kernel RankSVM and achieves comparable or better performance over state-of-the-art ranking algorithms.


Boosting the adsorptive and photocatalytic performance of MIL-101(Fe) against methylene blue dye through a thermal post-synthesis modification.
Photocatalytic degradation under ultra-low powered light is a viable advanced oxidation process technique against extensive emerging contaminants. As a new and remarkable class of nanoporous materials, metal-organic frameworks (MOFs), attract interest for the supreme adsorptive and photocatalytic functionalities. An outstanding MOF, MIL-101(Fe) chosen as a photocatalyst template for the synthesis of α-Fe2O3 by a simple thermal modification to improve the structural properties toward methylene blue (MB) eradication. Octahedron-like α-Fe2O3 photocatalyst (Modified MIL-101(Fe), M-MIL-101(Fe)) was superior in dispersion and separation properties in aqueous medium. Moreover, the adsorptive and catalytic performance was increased for modified form by ~ 7.3% and ~ 17.1% compared to pristine MIL-101(Fe), respectively. Synergistic improvement of MB removal achieved by simultaneous adsorption/degradation under 5-W LED irradiation. Parametric study indicated an 18.1% and 44.5% improvement in MB removal was observed by increasing pH from 4 to 10, and M-MIL-101(Fe) dose from 0.2 to 1 g L-1, respectively. MB removal followed the pseudo-second-order kinetics model and the process efficiency dropped by 38% as MB concentration increased from 5 to 20 mg L-1. Radical trapping tests revealed the significant role of [Formula: see text] and electron radicals as the major participants in dye degradation. A significant loss in the efficiency of M-MIL-101(Fe) was observed in the reusability tests that is good to study further. In conclusion, a simple thermal post-synthesis modification on MIL-101(Fe) improved its structural, catalytic, and adsorptive properties against MB.


[A retrospective analysis of fluid resuscitation in 94 patients with extensive burns].
To analyze the clinical data of adult patients with total burn surface area (TBSA) greater than 50% in Guangzhou and explore the optimal fluid resuscitation protocols for these patients. The clinical data of 94 adult patients with a TBSA over 50% treated in our center during 1991-2010 were reviewed. and the former decade. Fluid resuscitation volume of various components in shock stage, urine volume, occurrence of visceral complications and mortality rate within 10 days after injury were compared between patients treated in 1991-1999 and those in 2000-2010. The first 24-h crystalline colloidal fluid ratio, first 24-h infusion volume and the second 24-h crystalloid fluid coefficients were significantly greater in the patients treated in 2000-2010 than in those treated in 1991-1999. The visceral complications and mortality rate were significantly lower in the latter than in the former patients (7.69% vs 27.3% and 2.56% vs 18.18%, respectively, P<0.05). For patients with extensive burns, an individualized fluid resuscitation regimen, an adequately high colloid/crystal rehydration ratio, and a greater total infusion volume according to the local climate of Guangzhou can be beneficial to reduce the incidence of visceral complications and the mortality rate.


The efficacy of mycophenolate mofetil in treating Takayasu arteritis: a systematic review and meta-analysis.
The purpose of this study is to assess the effectiveness of mycophenolate mofetil (MMF) in treating Takayasu arteritis (TA) patients. Embase, Cochrane Library, Pubmed, Clinicaltrials. Gov and three Chinese literature databases (VIP, CNKI, WanFang) were searched; randomized-controlled trials and observational studies that compared the efficacy before and after treatment with MMF were included. The efficacy outcomes were disease activity, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) values and steroid dosage. The results were expressed as mean differences with 95% confidence intervals. Compared with the baseline, there were significant reductions in the ESR (-14.92 [25.35, -4.48]), CRP values (-12.99 [-23.29, -2.68]) and the steroid dosage (-17.64 [-24.89, -10.4]) after the addition of MMF, and the disease tended to stabilize. Therefore, MMF might be an alternative immunosuppressive drug for TA for the control of disease activity and to taper the steroid dosage.


Large clones with PNH-type phenotype are not common in patients presenting with intra-abdominal thrombosis--a prospective study.
Intra-abdominal thrombosis is a complication of paroxysmal nocturnal hemoglobinuria (PNH). There is scarcity of data on cases presenting with thrombosis in whom PNH is the predisposing factor. We assessed the role of PNH defect in 81 patients with intra-abdominal thrombosis, 44 patients of Budd Chiari syndrome and 37 patients of extra hepatic venous obstruction. Flowcytometry with glycosylphosphatidyl inositol-anchored proteins (GPI-AP)-CD55, -CD59, and -CD16 was performed on all patients and controls to assess the prevalence of deficiencies and PNH-type phenotype clone size. Deficiencies of individual GPI-AP were seen in 17.3% cases versus 3.4% controls. This was due to CD55 deficiency on red blood cells and CD16 deficiency on the granulocytes. Deficiency of multiple GPI-APs was less frequent (3.7% cases). Data of this study indicate that the PNH defect as detected with CD55, CD59, and CD16 is not an important cause of intra-abdominal thrombosis in northwestern India.


[Epilepsy-acquired aphasia syndrome with psychosis. Report of a case ].
We report the case of a boy whose development was normal until the age of three when regression with loss of speech occurred. Other anomalies included eating and sleep disorders, sterotyped behavior disorders, suggesting infantile psychosis. The electroencephalogram evidenced paroxysmal anomalies, particularly during sleep, with no clinical seizures. The diagnosis of epilepsia-acquired aphasia syndrome (Landau-Kleffner syndrome) was made. The psychotic disorders were not considered as a differential diagnosis but rather as intertwined with the elements of the syndrome. The relationship between acquired aphasia and psychosis are discussed.


Effectiveness of five-day-old 10% bleach in a student microbiology laboratory setting.
In the student laboratory, 10% bleach (sodium hypochlorite) is used to disinfect benches before and after work, and when a spill occurs. Centers for Disease Control and Prevention (CDC) Guidelines recommend diluting bleach daily. In a student laboratory setting, the organisms in use are known and may include only selected standard bacteria. Diluting bleach daily is time consuming and wastes bleach. We hypothesized that 10% bleach stored in low density polyethylene (LDPE) wash bottles would maintain sufficient chlorine concentration to be effective against the organisms used in the student laboratory for five days, so that bleach could be diluted weekly instead of daily. Approximately 3 x 10(6) CFU of each bacterium were spotted to a laboratory bench surface in duplicate and allowed to air dry. One spot was individually cleaned with five-day old 10% bleach following the same protocol as student laboratories. The second spot was uncleaned and sampled as a control. Contact plates containing D/E Neutralizing agar were touched to the spots, incubated overnight at 35 degrees C and examined for growth. An uninoculated spot was also sampled as a background control. A total of 22 different organisms were tested, representing the major groups of organisms used in the student laboratories. All organisms tested were eliminated by the five-day old bleach. All uncleaned spots showed dense growth. The background control had no growth. Reducing the dilution of bleach to once a week rather than daily will save time and money, which can then be devoted to more teaching and curriculum responsibilities, while still maintaining laboratory safety.


Low normal alpha-1-antitrypsin serum concentrations and MZ-phenotype are associated with byssinosis and familial allergy in cotton mill workers.
Recent studies have shown a close association between byssinosis and airborne endotoxin concentrations. Endotoxin might induce byssinosis through the release of biochemical mediators as the broncheoalveolar surface. Alpha-1-antitrypsin (alpha-1-A) which neutralizes enzymes released by granulocytes is known to be important. This study evaluates the possible importance of alpha-1-A concentration and the heterozygosity (Pi-S and Pi-Z alleles), in the prevalence of byssinosis and familial allergy. 253 cotton workers were interviewed and clinically studied to identify persons with the cotton lung disease, byssinosis, and atopic disease. Serum was available for alpha-1-A concentration determination in 226 individuals, and for Pi phenotyping in 206. The overall prevalence of byssinosis was 30/226 (13%). In the group with alpha-1-A < or = 35 mumol l-1 the prevalence was 5/18 (28%), versus the prevalence 25/208 (12%) in the group with alpha-1-A > 35 mumol l-1 (p < 0.1, Fishers exact test). MZ phenotype was associated with an increased prevalence of byssinosis compared with the MM-group: 3/8 (38%) and 25/187 (13%), p < 0.1, Fishers exact test. An association between MZ-phenotype and familial allergy was found: 4/8 (50%) contra 23/187 (12%), p < 0.05, Fishers exact test. In a logistic regression model controlling for confounding by endotoxin, tobacco exposure, sex, and age, the odds ratio for byssinosis in the MZ-phenotype group was significantly elevated 5.8 (1.1-30.3). Odds ratio for familial allergy was also significantly elevated in the MZ-group 2.8 (1.3-5.9).(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis.
Chronic pancreatitis is a progressive inflammatory disorder leading to irreversible exocrine and/or endocrine impairment. It is well documented that mutations in the cationic trypsinogen (PRSS1) gene can cause hereditary pancreatitis. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) and the serine protease inhibitor Kazal type 1 (SPINK1) genes are also associated with pancreatitis. We analyzed 381 patients with a primary diagnosis of chronic or recurrent pancreatitis using the Ambry Test: Pancreatitis to obtain comprehensive genetic information for the CFTR, SPINK1, and PRSS1 genes. The results identified 32% (122/381) of patients with 166 mutant CFTR alleles, including 12 novel CFTR variants: 4375-20 A>G, F575Y, K598E, L1260P, G194R, F834L, S573C, 2789 + 17 C>T, 621+83 A>G, T164S, 621+25 A>G, and 3500-19 G>A. Of 122 patients with CFTR mutations, 5.5% (21/381) also carried a SPINK1 mutation, and 1.8% (7/381) carried a PRSS1 mutation. In addition, 8.9% (34/381) of all patients had 1 of 11 different SPINK1 mutations. Another 6.3% (24/381) of the patients had 1 of 8 different PRSS1 mutations. Moreover, 1.3% of the patients (5/381) had 1 PRSS1 and 1 SPINK1 mutation. A total 49% (185/381) of the patients carried one or more mutations. Comprehensive testing of the CFTR, PRSS1, and SPINK1 genes identified genetic variants in nearly half of all subjects considered by their physicians as candidates for genetic testing. Comprehensive test identified numerous novel variants that would not be identified by standard clinical screening panels.