Substituted Caffeic and Ferulic Acid Phenethyl Esters: Synthesis, Leukotrienes Biosynthesis Inhibition, and Cytotoxic Activity.
Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a), have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH₃) were designed and synthesized. (CAPE, 1a), but not ferulic acid phenethyl ester (FAPE, 1b), displayed substantial cytotoxicity against two glioma cell lines. Some but not all selected compounds derived from both (CAPE, 1a) and (FAPE, 1b) also displayed cytotoxicity. All CAPE-derived compounds were able to significantly inhibit 5-lipoxygenase (5-LO), however FAPE-derived compounds were largely ineffective 5-LO inhibitors. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds in cancer models and provides additional leads in the development of novel therapeutic strategies in gliomas.


Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca2+ Release in Colonic Smooth Muscle Cells in Rats with Acute Necrotising Pancreatitis.
Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 μg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-β1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-β1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC.


Allyl isothiocyanate, a potent chemopreventive agent targets AhR/Nrf2 signaling pathway in chemically induced mammary carcinogenesis.
In the present study, we investigated the effect of allyl isothiocyanate (AITC) on liver detoxification signaling pathway in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland in Sprague-Dawley rats. DMBA-alone-treated rats show an increased synthesis of phase I detoxification enzymes, lipid peroxidative markers, liver marker enzymes, and lipid profiles whereas, depletion of phase II detoxification enzymes and antioxidants in rat liver tissues. Oral administration of AITC restored the levels of biochemical markers in DMBA-treated rats. Furthermore, histopathological results also confirmed that AITC protects DMBA-mediated hepatocellular damage. We also observed that AITC treatment significantly downregulates AhR and upregulates the expression of Nrf2 in DMBA-treated rats. The binding efficacy of AITC with AhR and Nrf2 analysis by molecular docking studies reveals that AITC has strong interaction with AhR and Nrf2 proteins through hydrogen and hydrophobic interactions. Thus, AITC prevents DMBA-induced mammary carcinogenesis via inhibition of phase I and induction of phase II detoxification enzymes by modulating AhR/Nrf2 signaling pathway.


Corneal vascularization in hydrogel contact lens wearers.
Limbal injection, peripheral corneal edema, and adjacent leukocyte infiltration may all be involved in the neovascularization of corneal tissue. Hydrogel lenses should be made with a minimum average thickness an maximum water content to increase oxygen transmission to the cornea. Lenses should not compress the limbal area in order to decrease the risk of limbal injection and, therefore, possible leukocyte invasion. Following these guidelines will decrease the risk of corneal vascularization in the hydrogel contact lens wearer. Keeping these principles in mind will also help the practitioner evaluate corneal health in all patients.


A multifunctional peptide based on the neutrophil immune defense molecule, CAP37, has antibacterial and wound-healing properties.
CAP37, a protein constitutively expressed in human neutrophils and induced in response to infection in corneal epithelial cells, plays a significant role in host defense against infection. Initially identified through its potent bactericidal activity for Gram-negative bacteria, it is now known that CAP37 regulates numerous host cell functions, including corneal epithelial cell chemotaxis. Our long-term goal is to delineate the domains of CAP37 that define these functions and synthesize bioactive peptides for therapeutic use. We report the novel finding of a multifunctional domain between aa 120 and 146. Peptide analogs 120-146 QR, 120-146 QH, 120-146 WR, and 120-146 WH were synthesized and screened for induction of corneal epithelial cell migration by use of the modified Boyden chamber assay, antibacterial activity, and LPS-binding activity. In vivo activity was demonstrated by use of mouse models of sterile and infected corneal wounds. The identity of the amino acid at position 132 (H vs. R) was important for cell migration and in vivo corneal wound healing. All analogs demonstrated antimicrobial activity. However, analogs containing a W at position 131 showed significantly greater antibacterial activity against the Gram-negative pathogen Pseudomonas aeruginosa. All analogs bound P. aeruginosa LPS. Topical administration of analog 120-146 WH, in addition to accelerating corneal wound healing, effectively cleared a corneal infection as a result of P. aeruginosa. In conclusion, we have identified a multifunctional bioactive peptide, based on CAP37, that induces cell migration, possesses antibacterial and LPS-binding activity, and is effective at healing infected and noninfected corneal wounds in vivo.


[The mechanism of histamine liberation from rat mast cells under the action of x-ray contrast media].
It was demonstrated in rat experiments that a positive direct correlation exists between the decrease in the amount of histamine in rat peritoneal must cells after intravenous infusion of radiopaque agents (ROA) in a dose of 2 ml/kg and the amount of these penetrating from the blood into the peritoneal cavity. The degree of penetration is determined by the chemical structure and/or physiochemical properties of the ROA.


Tracking Fast Neural Adaptation by Globally Adaptive Point Process Estimation for Brain-Machine Interface.
Brain-machine interfaces (BMIs) help the disabled restore body functions by translating neural activity into digital commands to control external devices. Neural adaptation, where the brain signals change in response to external stimuli or movements, plays an important role in BMIs. When subjects purely use neural activity to brain-control a prosthesis, some neurons will actively explore a new tuning property to accomplish the movement task. The prediction of this neural tuning property can help subjects adapt more efficiently to brain control and maintain a good decoding performance. Existing prediction methods track the slow change of the tuning property in the manual control, which is not suitable for the fast neural adaptation in brain control. In order to identify the active neurons in brain control and track their tuning property changes, we propose a globally adaptive point process method (GaPP) to estimate the neural modulation state from spike trains, decompose the states into the hyper preferred direction and reconstruct the kinematics in a dual-model framework. We implement the method on real data from rats performing a two-lever discrimination task under manual control and brain control. The results show our method successfully predicts the neural modulation state and identifies the neurons that become active in brain control. Compared to the existing method, ours tracks the fast changes of the hyper preferred direction from manual control to brain control more accurately and efficiently and reconstructs the kinematics better and faster.


Comparison of two procedures for symptomatic hemorrhoidal disease: Ligation under Vision and Ferguson Hemorrhoidectomy - a retrospective cohort study.
To compare Ligation under Vision (LUV) with Ferguson Hemorrhoidectomy (FH) in patients with Grade II, III and IV hemorrhoidal diseases according to their postoperative outcomes. Between July 2008 and August 2014, 155 patients underwent FH and 120 patients LUV, in Sakarya University Teaching and Research Hospital. Our retrospective analysis focuses on postoperative complications, postoperative pain and rate of recurrence. In LUV procedure, submucosal tissue of the hemorrhoidal pile base was transfixed using absorbable sutures under direct vision through anoscope in the Jackknife position. In a mean postoperative follow-up period of 51.76+/-22.3 months; ectropion, anal fissure, and anal incontinence were the most frequent complications. The overall complication rate was significantly less after LUV than FH, (6.7% vs. 14.2%, P=0.047). The complication rate and need for a second or third surgery did not significantly differ between the two procedures with the increase in affected quadrants (P>0.05). The visual analog scale (VAS) at 24 hours was similar in both groups (P=0.267). LUV is a safe, and practical procedure with similar outcomes compared to FH. LUV may be a better choice than excisional hemorrhoidectomies when three or four quadrants of the anal canal are involved with hemorrhoids as this reduces mucosal defect related possible complications such as ectropion and anal stenosis.


[Proteolysis of human proinsulin catalysed by native, modified, and immobilized trypsin].
Proteolysis of recombinant human proinsulin by the native trypsin, by trypsin modified with a copolymer of vinylpyrrolidone and acrolein, and by the same modified trypsin immobilized on Silochrom 1.5 was studied by RP HPLC and mass spectrometry. Rate constants of the main stages of proinsulin hydrolysis by the native trypsin were estimated. The values of rate constants of the digestions of the most easily hydrolyzable bonds (those formed by the pairs of the basic amino acid residues) in proinsulin were found to be of the same order as those formed by the separate lysine residues (Lys7) and those formed by the four basic amino acid residues of the C-terminal cluster of melittin. It was established that covalent trypsin binding to the copolymer did not change the ratio of the rate constants of the individual stages of proinsulin hydrolysis, whereas after the immobilization of modified trypsin on the Silochrome, the formation of diarginyl insulin-ArgArg, intermediate forms of hydrolyzed insulin, and desThr-insulin proceeds with comparable rates.


METHYSERGIDE (SANSERT) IN THE PREVENTION OF MIGRAINE: A CLINICAL TRIAL.
Methysergide was used as a regular medication to prevent migraine in a series of 87 patients with frequently recurring severe attacks of three types, common, classical and cluster migraine, in a study conducted during a 30-month period. Results were classified as excellent, good, fair and nil. The total reporting excellent and good results was 50.6%. In a few patients the drug appeared to lose effectiveness in long-term treatment. Other investigators have described more favourable results, notably Friedman, who reported improvement in common migraine in 79% of patients and in cluster migraine in 90% of patients. Side effects were noted in 34.2% of patients and led to discontinuing the trial in 10.4%; these promptly subsided when the drug was withdrawn. Methysergide appears to be a useful additional agent for prevention of severe, frequently recurring migraine of common and cluster type. In this small series it had little effect on headaches of combined tension and vascular type.


Interplay of hormones and p53 in modulating gender dimorphism of subventricular zone cell number.
Previous studies have suggested the existence of a gender bias in repair after demyelination. Here we report the existence of gender dimorphism for the regulation of cell number in the subventricular zone (SVZ), an area that has been studied for its repair potential. The number of Sox2(+) multipotential cells in the SVZ of young adult female mice was greater than in age-matched male siblings, but this difference was not evident prior to the surge of sex hormones (i.e., in prepubertal mice). To begin asking whether hormonally derived signals were responsible for these gender-related differences, we analyzed proliferation and survival of cultured male- and female-derived SVZ cells. Estrogen, but not testosterone treatment increased cell proliferation and survival of cultured cells after IFN-gamma treatment or after UV irradiation, regardless of the gender of origin. Because apoptosis in UV-irradiated SVZ cells correlated with the expression of the proapoptotic molecule p53, we postulated that this molecule could be responsible for the gender dimorphism in the SVZ. In agreement with this prediction, no difference in the SVZ cell number was detected in male and female p53 null mice. Together with previous reports, these results implicate p53 as an important component of the mechanism regulating gender dimorphism in the SVZ.


Immunohistochemical expression of immune check point protein PDL-1 in hepatocellular carcinoma denotes its prognostic significance and association with survival.
This study was designed to evaluate the immunohistochemical expression of programmed death ligand-1 (PD-L1) in tumor cells (TCs) and tumor-infiltrating immune cells (TICs) in hepatocellular carcinoma (HCC) and to correlate its expression with clinicopathological parameters. Seventy-two formalin-fixed paraffin-embedded blocks of HCC were collected. The data were collected from the patients' records. The blocks were stained with hematoxylin and eosin. Additionally, they were immunostained with PD-L1. Membranous staining was considered positive expression including the entire membrane or part of it ± cytoplasmic staining, and the percentage of total cancer cells ≥ 5% was evaluated as positive staining for TCs. The TICs were considered positive if they expressed membranous ± cytoplasmic staining of PD-L1 ≥ 1%. Of the total cases, 34.7% expressed PD-L1 positively in TCs and 15.3% expressed PD-L1 positively in TICs. Significant associations were observed between PD-L1 expression in TCs and tumor grade, capsular and/or vascular invasion, tumor stage, nodal metastasis, and the expression of PD-L1 in paracancerous tissue. The cases that positively expressed PD-L1 exhibited reduced overall survival (OS). PD-L1 was expressed in HCC TCs and TICs. Its expression in TCs was associated with higher HCC grades, advanced stages, capsular and/or vascular invasion, and nodal metastasis, and cases that expressed PD-L1 displayed reduced OS. Therefore, PD-L1 might serve as a poor prognostic indicator and a tumor immunotherapy target.


Primary Pulmonary Amebiasis Complicated with Multicystic Empyema.
Amebiasis is a parasitic infection caused by the protozoan Entamoeba histolytica. While most infections are asymptomatic, the disease could manifest clinically as amebic dysentery and/or extraintestinal invasion in the form of amebic liver abscess or other more rare manifestations such as pulmonary, cardiac, or brain involvement. Herein we are reporting a case of a 24-year-old male with history of Down syndrome who presented with severe right side pneumonia complicated with multicystic empyema resistant to regular medical therapy. Further investigation revealed a positive pleural fluid for E. histolytica cysts and trophozoites. The patient was diagnosed with primary pleuropulmonary amebiasis and he responded promptly to surgical drainage and metronidazole therapy. In patients from endemic areas all physicians should keep a high index of suspicion of amebiasis as a cause of pulmonary disease.


The Effectiveness of Psychoeducational Interventions Focused on Sexuality in Cancer.
Although sexual health is a common concern for oncology patients, no practical guidelines to sexual intervention exist, perhaps because of a lack of systematic reviews or meta-analyses. The objectives of this study were to determine the effect size for psychoeducational intervention focused on sexuality and to compare effect sizes according to intervention outcomes and characteristic. We explored quantitative evidence for the effects of sexual intervention for cancer patients or partners by using the electronic databases. Among them, we considered 15 eligible articles. The meta-analysis provided 133 effect sizes from 15 primary studies. The analysis revealed significant improvements after intervention, with a random-effects standardized mean difference of 0.75. Psychoeducational interventions focused on sexuality after cancer diagnosis were effective for compliance (2.40), cognitive aspect (1.29), and psychological aspect (0.83). Individual-based interventions (0.85) were more effective in improving outcomes than group approach and group combined with individual intervention. With regard to intervention providers, registered nurse only (2.22) and team approach including the registered nurse (2.38) had the highest effect size. Face-to-face intervention combined with telephone or the Internet (1.04) demonstrated a higher effect size than face-to-face (0.62) and telephone (0.58) independently. We conducted an analysis of data from various subgroups of preexisting studies, obtained an overall estimate of the effectiveness of the intervention, and compared its effectiveness across variables that affect intervention outcomes. These results provide empirical data for evidence-based practice and inform the development of useful intervention programs through a comprehensive review and meta-analysis of the results.


The molecular basis for water taste in Drosophila.
The detection of water and the regulation of water intake are essential for animals to maintain proper osmotic homeostasis. Drosophila and other insects have gustatory sensory neurons that mediate the recognition of external water sources, but little is known about the underlying molecular mechanism for water taste detection. Here we identify a member of the degenerin/epithelial sodium channel family, PPK28, as an osmosensitive ion channel that mediates the cellular and behavioural response to water. We use molecular, cellular, calcium imaging and electrophysiological approaches to show that ppk28 is expressed in water-sensing neurons, and that loss of ppk28 abolishes water sensitivity. Moreover, ectopic expression of ppk28 confers water sensitivity to bitter-sensing gustatory neurons in the fly and sensitivity to hypo-osmotic solutions when expressed in heterologous cells. These studies link an osmosensitive ion channel to water taste detection and drinking behaviour, providing the framework for examining the molecular basis for water detection in other animals.


Federal civil-service annuitants and social security, December 1975.
This article examines personal and work-related characteristics of a sample of the nearly 1 million Federal civil-service retirees who were receiving annuities based on their own wage records as of December 31, 1975. Employment patterns and subsequent annuities in civil-service careers have been related to corresponding experience in jobs covered under the old-age, survivors, disability, and health insurance (OASDIHI) program. With some exceptions, the review uncovered patterns generally similar to those found in a study of 1967 annuitants. About 2 out of 5 annuitants were entitled to OASDHI cash benefits in 1975. Most of these dual beneficiaries received benefits on the basis of their own OASDHI-covered earnings, but 11 percent were entitled as dependents or survivors of other workers. About two-thirds of the annuitants not currently receiving benefits had some OASDHI-covered employment during their work careers. In general, those with the shortest civil-service careers and lowest annuities were most likely to be entitled to OASDHI cash benefits.


Kras oncogene ablation prevents resistance in advanced lung adenocarcinomas.
KRASG12C inhibitors have revolutionized the clinical management of patients with KRASG12C-mutant lung adenocarcinoma. However, patient exposure to these inhibitors leads to the rapid onset of resistance. In this study, we have used genetically engineered mice to compare the therapeutic efficacy and the emergence of tumor resistance between genetic ablation of mutant Kras expression and pharmacological inhibition of oncogenic KRAS activity. Whereas Kras ablation induces massive tumor regression and prevents the appearance of resistant cells in vivo, treatment of KrasG12C/Trp53-driven lung adenocarcinomas with sotorasib, a selective KRASG12C inhibitor, caused a limited antitumor response similar to that observed in the clinic, including the rapid onset of resistance. Unlike in human tumors, we did not observe mutations in components of the RAS-signaling pathways. Instead, sotorasib-resistant tumors displayed amplification of the mutant Kras allele and activation of xenobiotic metabolism pathways, suggesting that reduction of the on-target activity of KRASG12C inhibitors is the main mechanism responsible for the onset of resistance. In sum, our results suggest that resistance to KRAS inhibitors could be prevented by achieving a more robust inhibition of KRAS signaling mimicking the results obtained upon Kras ablation.


Analysis of flooding-responsive proteins localized in the nucleus of soybean root tips.
Flooding stress has negative impact on soybean cultivation as it severely impairs plant growth and development. To examine whether nuclear function is affected in soybean under flooding stress, abundance of nuclear proteins and their mRNA expression were analyzed. Two-day-old soybean seedlings were treated with flooding for 2 days, and nuclear proteins were purified from root tips. Gel-free proteomics analysis identified a total of 39 flooding-responsive proteins, of which abundance of 8 and 31 was increased and decreased, respectively, in soybean root tips. Among these differentially regulated proteins, the mRNA expression levels of five nuclear-localized proteins were further analyzed. The mRNA levels of four proteins, which are splicing factor PWI domain-containing protein, epsilon2-COP, beta-catenin, and clathrin heavy chain decreased under flooding stress, were also down-regulated. In addition, mRNA level of a receptor for activated protein kinase C1(RACK1) was down-regulated, though its protein was accumulated in the soybean nucleus in response to flooding stress. These results suggest that several nuclear-related proteins are decreased at both the protein and mRNA level in the root tips of soybean under flooding stress. Furthermore, RACK1 might have an important role with accumulation in the soybean nucleus under flooding-stress conditions.


Naturalization fosters the long-term political integration of immigrants.
Does naturalization cause better political integration of immigrants into the host society? Despite heated debates about citizenship policy, there exists almost no evidence that isolates the independent effect of naturalization from the nonrandom selection into naturalization. We provide new evidence from a natural experiment in Switzerland, where some municipalities used referendums as the mechanism to decide naturalization requests. Balance checks suggest that for close naturalization referendums, which are decided by just a few votes, the naturalization decision is as good as random, so that narrowly rejected and narrowly approved immigrant applicants are similar on all confounding characteristics. This allows us to remove selection effects and obtain unbiased estimates of the long-term impacts of citizenship. Our study shows that for the immigrants who faced close referendums, naturalization considerably improved their political integration, including increases in formal political participation, political knowledge, and political efficacy.


Psychological aspects of carcinoma of the breast in the male--two case reports.
Whilst there have been a number of reports about the psychological features of women who develop carcinoma of the breast, there have been no such studies of men. This paper details two reports of men with this unusual condition. In both cases, this illness in the male followed a similar condition which occurred in the breast on the same side in a woman with whom each had an intense relationship. That this could be considered a more than coincidental event is explored. The role of identification with a significant other in determining site and type of illness is discussed, as is a hypothetical mechanism whereby such identification could facilitate the development of the cancers in these cases.


Late Obstructive Transcatheter Heart Valve Thrombosis Resolved by Rivaroxaban.
BACKGROUND Although transcatheter aortic valve replacement (TAVR) has become a worldwide and generally accepted treatment of patients with aortic stenosis at high surgical risk, there is a rising concern and debate about the occurrence of transcatheter heart valve (THV) thrombosis and its impact on TAVR outcome. It seems that the incidence of THV thrombosis is higher than first anticipated, but uncertainty remains regarding how to prevent and how to treat it. Hence, there is an urgent need for understanding THV thrombosis and to communicate experiences within the field. CASE REPORT We present a unique case of late occurrence of THV thrombosis that was resolved by switching from clopidogrel to rivaroxaban treatment. CONCLUSIONS As a novel observation, our case demonstrates that THV thrombosis may develop even late after TAVR, and even in such cases may be completely reversed. It also underscores that THV dysfunction should evoke prompt investigation for possible thrombus formation, preferable by multidetector computed tomography. Finally, this case report suggests NOAC as an alternative to warfarin treatment in patients with THV thrombosis.


Structure and reactivity of adsorbed fibronectin films on mica.
Understanding the interactions of adsorbed fibronectin (Fn) with other biomolecules is important for many biomedical applications. Fn is found in almost all body fluids, in the extracellular matrix, and plays a fundamental role in many biological processes. This study found that the structure (conformation, orientation) and reactivity of Fn adsorbed onto mica is dependent on the Fn surface concentration. Atomic force microscopy and x-ray photoelectron spectroscopy were used to determine the surface coverage of adsorbed Fn from isolated molecules at low surface coverage to full monolayers at high surface coverage. Both methods showed that the thickness of Fn film continued to increase after the mica surface was completely covered, consistent with Fn adsorbed in a more upright conformation at the highest surface-Fn concentrations. Time-of-flight secondary ion mass spectrometry showed that relative intensities of both sulfur-containing (cystine, methionine) and hydrophobic (glycine, leucine/isoleucine) amino acids varied with changing Fn surface coverage, indicating that the conformation of adsorbed Fn depended on surface coverage. Single-molecule force spectroscopy with collagen-related peptides immobilized onto the atomic force microscope tip showed that the specific interaction force between the peptide and Fn increases with increasing Fn surface coverage.


Simultaneous occurrence of human antibodies directed against fibrinogen, thrombin, and factor V following exposure to bovine thrombin: effects on blood coagulation, protein C activation and platelet function.
We describe a patient with severe epistaxis, prolonged coagulation tests and decreased plasma factor V following exposure to bovine topical thrombin. Patient IgG, but not normal IgG, showed binding to immobilized thrombin (bovine > human) and fibrinogen, and to factor V by Western blotting; the binding to thrombin was inhibited by hirudin fragment 54-65. Electron microscopy of rotary shadowed preparations showed complexes with IgG molecules attached near the ends of trinodular fibrinogen molecules. Patient IgG inhibited procoagulant, anticoagulant and cell-stimulating functions of thrombin demonstrated by inhibition of fibrinogen clotting, protein C activation and platelet aggregation; thrombin hydrolysis of S-2238 was not inhibited. The results suggest that the antibody is targeted against anion-binding exosite and not catalytic site of thrombin. Antifibrinogen antibodies have not been reported in patients exposed to bovine thrombin. There is a pressing need to re-evaluate the role of bovine thrombin as a therapeutic agent.


Tissue-mimicking phantom materials for narrowband and ultrawideband microwave applications.
We propose and characterize oil-in-gelatin dispersions that approximate the dispersive dielectric properties of a variety of human soft tissues over the microwave frequency range from 500 MHz to 20 GHz. Different tissues are mimicked by selection of an appropriate concentration of oil. The materials possess long-term stability and can be employed in heterogeneous configurations without change in geometry or dielectric properties due to osmotic effects. Thus, these materials can be used to construct heterogeneous phantoms, including anthropomorphic types, for narrowband and ultrawideband microwave technologies, such as breast cancer detection and imaging systems.


Smooth muscle differentiation in scleroderma fibroblastic cells.
Using antibodies to alpha-smooth muscle actin and desmin on paraffin-embedded formalin-fixed tissue sections, the authors demonstrate that fibroblastic cells of localized and systemic scleroderma lesions express features of smooth muscle differentiation. Eleven of eleven skin specimens of systemic sclerosis patients and two of four skin specimens of localized scleroderma displayed the presence of fibroblasts expressing alpha-smooth muscle actin, a cell population that predominated in areas of prominent collagen deposition. A similar fibroblastic phenotype was found in the esophagus, the liver, and the lung specimens obtained from four patients who died of progressive systemic sclerosis. Immunostaining for desmin, performed on adjacent tissue sections, demonstrated that a minority of these fibroblastic cells present in skin and visceral lesions contained this protein. The authors' observations indicate that scleroderma fibroblasts are phenotypically related to the stromal cells previously identified in hypertrophic scars, fibromatoses, and desmoplasia; they might provide novel criteria for the characterization of scleroderma lesions and help to identify the factors responsible for phenotypic modulations in fibroblastic cells.


A new tumor suppressor lncRNA RP11-190D6.2 inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells.
At present, a large number of long noncoding RNAs (lncRNAs) from the human genome have been discovered. Meanwhile, emerging evidence has indicated that lncRNAs could play a critical role in the regulation of cellular processes such as cancer progression and metastasis. However, the functions of some new lncRNAs in the complex transcriptional process are mostly unknown at present. Existing studies suggest that loss of WW domain-containing oxidoreductase (WWOX) expression is linked with poor prognosis in numerous cancers, including epithelial ovarian cancer (EOC). However, the functional role of its antisense transcript RP11-190D6.2 is not clear to date. In this study, WWOX antisense transcript RP11-190D6.2 was analyzed specifically in EOC cells using real-time polymerase chain reaction and gain-/loss-of-function studies. We found that RP11-190D6.2 expression was positively correlated with WWOX expression. The RP11-190D6.2 expression was markedly downregulated in tumor tissues compared with normal tissues, but the RP11-190D6.2 expression was significantly downregu-lated in four EOC cell lines compared with human ovarian surface epithelial cell line. RP11-190D6.2 overexpression resulted in the increase of WWOX expression, whereas its knockdown led to the decrease of WWOX expression. We also found that RP11-190D6.2 was restored by 5-aza-2'-deoxycytidine treatment in EOC. In addition, the RP11-190D6.2 overexpression and knockdown experiments revealed that RP11-190D6.2 overexpression inhibited proliferation, migration, and invasion abilities in HO8910-PM cells, whereas RP11-190D6.2 knockdown in HEY-A8 cells had the opposite effect. The analyses in EOC implicate that RP11-190D6.2 may play a pivotal role in the regulation of tumor metastasis, suggesting that RP11-190D6.2 may serve as a potential biomarker and therapeutic target for EOC.


Mitonuclear sex determination? Empirical evidence from bivalves.
Genetic elements encoded in nuclear DNA determine the sex of an individual in many animals. In bivalves, however, mitochondrial DNA (mtDNA) has been hypothesized to contribute to sex determination in lineages that possess doubly uniparental inheritance (DUI). In these cases, females transmit a female mtDNA (F mtDNA) to all offspring, while male mtDNA (M mtDNA) is transmitted only from fathers to sons. Because M mtDNA is inherited in the same way as Y chromosomes, it has been hypothesized that mtDNA may be responsible for sex determination. However, the role of mitochondrial and nuclear genes in sex determination has yet to be validated in DUI bivalves. In this study, we used DNA, RNA, and mitochondrial short non-coding RNA (sncRNA) sequencing to explore the role of mitochondrial and nuclear elements in the sexual development pathway of the freshwater mussel Potamilus streckersoni (Bivalvia: Unionida). We found that the M mtDNA shed a sncRNA partially within a male-specific mitochondrial gene that targeted pathways hypothesized to be involved in female development and mitophagy. RNA-seq confirmed the gene target was significantly upregulated in females, supporting a direct role of mitochondrial sncRNAs in gene silencing. These findings support the hypothesis that M mtDNA inhibits female development. Genome-wide patterns of genetic differentiation and heterozygosity did not support a nuclear sex determining region, although we cannot reject that nuclear factors are involved with sex determination. Our results provide further evidence that mitochondrial loci contribute to diverse, non-respiratory functions and provide a first glimpse into an unorthodox sex determining system.


Nutraceuticals for treatment of high blood pressure values in patients with metabolic syndrome.
To assess whether the association of a dietary supplement with a correct diet can decrease the incidence of metabolic syndrome. In particular, we studied the effect of a combination of Ortosiphon staminensis, which in rats exerts a diuretic effect, with policosanol, red yeast rice extract, berberine, folic acid and coenzyme Q(10) on the determinants of metabolic syndrome diagnosis. The analysed sample consisted of 21 males and 9 females, who were comparable in age, in order to obtain an adequate comparison between groups with similar demographic characteristics. Thirty patients with metabolic syndrome were divided into two study arms. Both groups received the usual diet recommended by the doctor according to their clinical conditions and placebo for 2 weeks before the beginning of the study, and then they were randomly assigned to two different drug regimens: placebo or the combination of nutraceuticals previously described, and were followed-up for 6 weeks. At baseline, there were no significant differences between the study and control groups for age, sex distribution, waist measurement, body mass index, systolic and diastolic blood pressure, familiarity for cardiovascular events, smoking habit, fasting glucose and lipid profile.At the end of the follow-up, only in the study group was there a significant reduction in systolic and diastolic blood pressure (-19.6±9.7 vs -3.6±8.1 mmHg and -13.6±5.5 vs -2.3±5.3 mmHg; all p < 0.0001) associated with amarked decrease in low-density lipoprotein cholesterol and triglyceride plasma levels. Consequently, 10 of 15 patients in this group no longer satisfied the criteria for metabolic syndrome, while in the control group the ratio was of 2 of 15. The addition of Ortosiphon staminensis to the combination of policosanol, red yeast rice extract, berberine, folic acid and coenzyme Q(10) provides an antihypertensive effect, which allows an effective control of blood pressure in patients with metabolic syndrome.


A Prospective Study on Operation Theater Utilization Time and Most Common Causes of Delays and Cancellations of Scheduled Surgeries in a 1000-Bedded Tertiary Care Rural Hospital with a View to Optimize the Utilization of Operation Theater.
The operation theater (OT) complex is a costly component of a hospital budget expenditure. This area of hospital activity requires maximum utilization to ensure optimum cost benefit. To achieve a high level of utilization in the OT, it is necessary to efficiently coordinate number of activities and personnel. This study was conducted in a 1000-bedded tertiary care teaching hospital in rural maharashtra over aperiod of two months. The OT complex consists of eight major OTs. Normal working hours for routine scheduled cases on all working days except Sundays and public holidays. Total study period consisted of 96 working days. There were a total of eight OT tables of various specialties, and parameters were observed during the routine hours excluding Sundays and holidays. The total procedure time was maximum for ENT followed by orthopedics and least for obstetrics. Room turnover time was maximum for obstetrics followed by general and oncosurgery. Case delays were maximum in general surgery and least for ophthalmology. The most common reason for delay in starting the operation table was patient getting shifted late from the ward and administrative causes. The most prominent reasons for cancellation were lack of operating room time followed by medical reasons of the patient. We concluded that most of the causes of delays and cancellations of surgeries were avoidable with proper preoperative planning and optimization of patients and resources and good communication between surgeon anesthesiologists and the nursing staff.


[Contribution of gene amplification in Mycobacterium ulcerans detection in exudates and cutaneous biopsies in Côte d'Ivoire].
Mycobacterium ulcerans skin ulceration is a major issue of public health in Côte d'Ivoire. The diagnosis of M. ulcerans infection is hampered by the slow growth of the bacterium in culture, implying a delay of several weeks before a specific diagnosis can be obtained. In Côte d'Ivoire the diagnosis of Buruli ulcer is almost based on clinical features. During the last decade, many studies have demonstrated the extremely high capacity of PCR for rapidly and specifically detecting bacteria and genes of interest. That ability has revealed PCR as a powerful tool in clinical microbiology studies. In this study we evaluated the M. ulcerans detection in specimens of exudates and biopsies collected from patients clinically suspected of Buruli ulcer and treated in "Raoul Follereau" centre of Manikro in the North-central region of Côte d'Ivoire. The microscopic research of BAAR in 185 swabs loaded with skin lesions collected from these patients showed a positive rate of 14.6%. The PCR detection in 48 h or 72 h of the M. ulcerans IS2404 and IS2606 in the swabs and in the 26 biopsies, from these patients, showed positive rates of 15.7% and 84.6% respectively and in the same samples. These results obtained with PCR detection of M. ulcerans insertions sequences suggest that this technique performed with exudates and biopsy can be used to confirm a routine specific diagnosis of M. ulcerans and early screening of Buruli ulcer in Côte d'Ivoire.


Zebrafish as an emerging model to study estrogen receptors in neural development.
Estrogens induce several regulatory signals in the nervous system that are mainly mediated through estrogen receptors (ERs). ERs are largely expressed in the nervous system, yet the importance of ERs to neural development has only been elucidated over the last decades. Accumulating evidence shows a fundamental role for estrogens in the development of the central and peripheral nervous systems, hence, the contribution of ERs to neural function is now a growing area of research. The conservation of the structure of the ERs and their response to estrogens make the zebrafish an interesting model to dissect the role of estrogens in the nervous system. In this review, we highlight major findings of ER signaling in embryonic zebrafish neural development and compare the similarities and differences to research in rodents. We also discuss how the recent generation of zebrafish ER mutants, coupled with the availability of several transgenic reporter lines, its amenability to pharmacological studies and in vivo live imaging, could help us explore ER function in embryonic neural development.


Detection of pacific ciguatoxins using liquid chromatography coupled to either low or high resolution mass spectrometry (LC-MS/MS).
Ciguatera Fish Poisoning (CFP) is primarily caused by consumption of tropical and sub-tropical fish contaminated by Ciguatoxins (CTXs). These lipid-soluble, polyether neurotoxins are produced by dinoflagellates in the genera Gambierdiscus and Fukuyoa. While there is no regulatory level in Europe for CTXs, the European Food Safety Authority (EFSA) adopted the United States guidance level of 0.01 μg P-CTX1B eq.kg-1 of fish. This limit is extremely low and requires significant improvement in the detection of CTXs. In this study, we compared analytical protocols based on liquid chromatography coupled to tandem low or high resolution mass spectrometry (LC-LRMS or HRMS) to find the best conditions for sensitivity and/or selectivity. Different approaches such as LC conditions, ion choice and acquisition modes, were evaluated to detect the Pacific-ciguatoxins (P-CTXs) on a triple quadrupole (API4000 Qtrap, Sciex) or a quadrupole time of flight (QTOF 6550, Agilent Technologies) spectrometer. Moreover, matrix effects were calculated using matrix-matched calibration solutions of P-CTX1B and P-CTX3C prepared in purified fish extract. Subsequently, the method performance was assessed on naturally contaminated samples of seafood and phytoplankton. With LRMS, the ammoniated adduct ion used as a precursor ion showed an advantage for selectivity through confirmatory transitions, without affecting signal-to-noise ratios, and hence limits of detection (LODs). As also reported by some studies in the literature, methanol-based mobile phase gave better selectivity and sensitivity for the detection of P-CTXs. While the LOD for P-CTX1B and P-CTX3C met the EFSA recommendation level when using LRMS, the findings suggested careful evaluation of instrumental parameters for determination of CTXs. LODs were significantly higher for HRMS, which currently results in the need for a significantly higher sample intake. Nevertheless, HRMS allowed for the identification of artefacts and may allow for improved confirmation of the identity of P-CTXs analogues. Consequently, LRMS and HRMS are considered complementary to ensure adequate quantitation and identification of P-CTXs.


Effects of lesions of the gustatory necortex on taste aversion learning in the rat.
Normal rats and rats with lesions of the gustatory neocortex (GN) were compared for their ability to learn aversions to taste cues paired with toxicosis. When the taste presentation was followed immediately by toxicosis, normal rats and rats with lesions of the posterior (visual) neocortex learned aversions to sucrose, sodium chloride, quinine hydrochloride, and hydrochloric acid solutions. Rats with GN lesions learned aversions to all solutions except sucrose. In preference tests, all solutions were shown to be discriminable from water by both normal rats and rats with GN lesions. Under conditions in which a 6-hr delay separated taste presentation and toxicosis, normal rats again learned specific aversions to all four solutions, but rats with GN lesions failed to learn specific aversions to sucrose, sodium chloride, and hydrochloric acid solutions. It was shown that the ability of rats with GN lesions to learn aversions to sucrose and quinine depended on stimulus concentration; and it was proposed that the data could be accounted for by postulating a change in the threshold for taste-illness associations following GN lesions.


Gradual dilatation of an occluded transverse sinus associated with dural arteriovenous fistula after balloon angioplasty with sinus packing: A case report.
There is no consensus as to whether balloon angioplasty alone or stent placement is effective for sinus occlusion associated with dural arteriovenous fistula (DAVF). Herein, we first report a case of transverse sinus occlusion associated with DAVF in which gradual sinus dilatation was observed after balloon angioplasty with embolization of the affected sinus with shunt flow. A 69-year-old man presented with executive dysfunction. Magnetic resonance imaging revealed left transverse sinus-sigmoid sinus DAVF with occlusion of the left jugular vein and right transverse sinus. Before endovascular treatment, the patient had symptomatic epilepsy and subarachnoid hemorrhage. Retrograde leptomeningeal venous drainage disappeared with packing of the left transverse sinus-sigmoid sinus. Subsequently, balloon angioplasty of the right occluded transverse sinus was performed to maintain the normal venous drainage and remaining shunt outflow. Dilatation of the right transverse sinus was poor immediately after surgery. However, angiography after 10 days and 6 months revealed gradual dilatation of the right transverse sinus. Sinus occlusion, which is thought to be caused by sinus hypertension associated with DAVF rather than chronic organized thrombosis or thrombophilia, may dilate over time after balloon angioplasty and shunt flow reduction if occluded sinus is necessary for facilitating normal venous drainage.


[Effects of gene transfection at different time on the expression of bone morphogenetic protein-2 during mandibular distraction].
To investgate the expression patterns of bone morphogenetic protein-2 (BMP-2) in the distraction area following plRES-hBMP2-VEGFI65 gene transfection at different time during mandibular distraction osteogenesis in a rabbit model. 48 New-Zeland rabbits were employed to underwent osteotomy and distraction devices implantation on mandible bilaterly. After 3 days of latency period, the devices were activated at the rate of 0. 8 mm per day for 10 days. The rabbits were randomly divided into 4 groups (group A, B, C and D). Group A, B and C were transfected recombinant plasmids pIRES-hBMP2-hVEGF165 via electroporation-mediated approach at latency period, distraction period, consolidation period respectively. Group D was used as control group without gene transfection. Three rabbits in each group were sacrificed at 1, 2, 4 weeks of consolidation respectively. The mandibles were harvested for immunohistochemical staining detection of BMP-2 expression respectively, which were analyzed by CMIAS series multifunction color quantitative analysis of pathological image analysis system. BMP-2 expression was found to be mainly located in the monocyte, fibroblast of the granulation tissue, the osteoblasts, osteocyte on the surface of new formed trabecular, and the connective tissues surrounding the new formed bone. The expression in group B was superior to other groups. Image analysis showed that, at the first week and second week of consolidation, the expression abosordbance A in group B (0. 58 ± 0. 03 and 0. 34 ± 0. 02) was relatively higher, when compared with that in group A (0. 42 ± 0. 02 and. 31 ±0.01), C(0.32 ±0.01 and 0.30 ±0.01)and D(0.27 ±0.01 and 0.23 ±0.02), showing a significant difference(P <0. 05). It was also relatively higher in group A(0. 42 ± 0. 02 and 0. 31 ± 0. 01) and C(0. 32 ± 0.01 and 0.30 ± 0.01), when compared with that in group D(0. 27 ±0.01 and 0.23 ± 0. 02), showing a significant difference( P < 0. 05) , but there was no significant difference ( P > 0. 05) between group A and group C. At the fourth week of consolidation, the expression decreased and there was no significant difference among group A, B, C, D. The electroporation-mediated gene transfection which is transfected at the beginning of traction can promote BMP-2 expression effectively, stimulate bone marrix synthesis and induce proliferation and differentiation of fibroblasts, osteoblasts, endothelial cells, which further effectively promote the new bone formation. It suggests that the distraction stage is the optimal time for gene therapy.


Requirements for more effective prevention of work-related musculoskeletal disorders.
Exposures to occupational hazards substantially increase workers' risk of developing musculoskeletal disorders (MSDs) and can exacerbate pre-existing disorders. The effects on MSD risk of the physical requirements of work performance are well recognised, but there is now ample evidence that work-related psychosocial hazards can also have substantial effects; further, some hazards may be additive or interactive. This evidence is not reflected in current workplace risk management practices. Barriers to more effective workplace management of MSD risk include: the widespread belief that risk arises largely or entirely from physical hazard exposures; regulatory and guidance documents targeting MSDs, most of which reflect this belief; risk assessment tools that focus narrowly on subsets of mainly physical hazards and yet generate outputs in the form of MSD risk indicators; and the conventional occupational health and safety (OHS) risk management paradigm, which is ill-suited to manage MSD risk. It is argued that improved workplace management of MSD risk requires a systems-based management framework and more holistic risk assessment and control procedures that address risk from all types of hazard together rather than in isolation from each other, and that support participation by workers themselves. New MSD risk management tools are needed to meet these requirements. Further, successful implementation of such changes is likely to require some restructuring of workplace responsibilities for MSD risk management. Line managers and supervisors often play key roles in generating hazards, both physical and psychosocial, so there is a need for their more active participation, along with OHS personnel and workers themselves, in routine risk assessment and control procedures. MSDs are one of our largest OHS problems, but workplace risk management procedures do not reflect current evidence concerning their work-related causes. Inadequate attention is given to assessing and controlling risk from psychosocial hazards, and the conventional risk management paradigm focuses too narrowly on risk from individual hazards rather than promoting the more holistic approach needed to manage the combined effects of all relevant hazards. Achievement of such changes requires new MSD risk management tools and better integration of the roles of OHS personnel with those of line managers.


Pleiotropic effects of the Arabidopsis cryptochrome 2 allelic variation underlie fruit trait-related QTL.
The previous molecular identification of a flowering time QTL segregating in the Arabidopsis L er x Cvi cross, demonstrated that natural allelic variation at the blue light photoreceptor CRY2 gene affects flowering time (El-Assal et al., 2001). In addition, previous works on the same cross have mapped several QTL affecting other unrelated life history traits in the CRY2 genomic region. In the present report, we have used a set of Arabidopsis L er transgenic plants carrying four different functional CRY2 transgenes for phenotypic analyses, with the aim of exploring the extent of pleiotropy of CRY2 allelic variation. It is concluded that previously identified QTL affecting fruit length, ovule number per fruit, and percentage of unfertilized ovules are caused by this same Ler/Cvi CRY2 allelic variation. In addition, dose effects of the CRY2-L er allele are detected for fruit length. A seed weight QTL at the map position of CRY2 could not be confirmed and also no effect on seed dormancy was observed. Thus, it is shown that transgenic plants carrying different alleles can be a useful tool to attribute QTL for different complex traits to a specific locus, even when the relationship among the traits has not been previously suggested.


Surgical technique and operative mortality in coronary artery bypass. A postmortem analysis with castangiography.
Post-mortem analysis with castangiography was performed on 54 patients who died within 30 days of coronary artery bypass surgery. Myocardial failure was the cause of 85% of the deaths. There were 215 coronary anastomoses (4.0 +/- 1.1/patient), 24% of which were non-functioning. Most of the occlusions were due to various technical failures. The most striking features were 1) high occlusion rate (25%) in sequential vein grafts and 2) disastrous complications of coronary endarterectomies. Compared with preoperative angiographic data, only 15 (28%) of the 54 patients were found to have 'complete' revascularization, with patent grafts and all stenosed coronary arteries bypassed. The need for recognition and avoidance of technical complications is stressed: Failures of surgical technique constitute a major risk factor in coronary artery surgery.


Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthase.
We have determined the crystal structure of dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Cryptosporidium hominis, revealing a unique linker domain containing an 11-residue alpha-helix that has extensive interactions with the opposite DHFR-TS monomer of the homodimeric enzyme. Analysis of the structure of DHFR-TS from C. hominis and of previously solved structures of DHFR-TS from Plasmodium falciparum and Leishmania major reveals that the linker domain primarily controls the relative orientation of the DHFR and TS domains. Using the tertiary structure of the linker domains, we have been able to place a number of protozoa in two distinct and dissimilar structural families corresponding to two evolutionary families and provide the first structural evidence validating the use of DHFR-TS as a tool of phylogenetic classification. Furthermore, the structure of C. hominis DHFR-TS calls into question surface electrostatic channeling as the universal means of dihydrofolate transport between TS and DHFR in the bifunctional enzyme.


Portal hypertension and hypersplenism in pregnancy secondary to chronic schistosomiasis. A case report.
In this country, Schistosoma mansoni infections are seen rarely since the distribution of schistosomes in humans is governed by the range of their molluscan hosts. The snail hosts of S. mansoni reside in fresh waters of tropical zones. A native of Brazil was seen in her second trimester of pregnancy with marked splenomegaly and hypersplenism. Thirteen years before she had been treated for schistosomiasis, and she had been well until her pregnancy. Studies were done to rule out other causes of splenomegaly and hypersplenism. Esophageal endoscopy confirmed the presence of esophageal varices. The main risk to these patients is severe, sometimes fatal gastrointestinal bleeding. In our patient this risk was compounded by marked thrombocytopenia. Splenectomy was performed, and a liver biopsy confirmed the presence of S. mansoni eggs.


Reproductive fitness and survivorship of Aedes aegypti (Diptera: Culicidae) maintained on blood, with field observations from Thailand.
Daily survivorship and fecundity of Aedes aegypti mosquitoes were monitored for cohorts provided with five nutritional treatments: water, 2% sucrose, blood from a live chicken plus water, blood plus 2% sucrose, and blood alone. The median mortality time (LT50) for these females was 6, 54, 16, 12, and 29 d, respectively. There was no significant difference in the number of eggs laid by females in any of the treatments containing a host. Females maintained on blood alone laid as many or more eggs during their lifetime as females with access to sugar who had a greater life expectancy. Males maintained on sugar alone survived significantly longer than those in any of the other treatments. Large- and small-bodied, sugar-starved Ae. aegypti females that were marked, released, and recaptured in a Thai village survived as well as the replicate cohorts that received sugar or sugar plus blood during the 36 +/- 12 h period from emergence until their release. These results indicate that Ae. aegypti females live longer in the laboratory if they are provided a source of carbohydrate, but the increased survival associated with sugar feeding does not increase reproductive success.


Acute restraint stress enhances calcium mobilization and proliferative response in splenic lymphocytes from mice.
Calcium (Ca2+ ) plays an essential role in lymphocyte activation and maturation. Acute and chronic stress has been shown to modulate the lymphocyte immune response; but the relationship between cytosolic free Ca2+ concentration ([Ca2+ ]i) and the immune response in lymphocytes following exposure to stress has not been examined. In the present study, we investigated the effects of acute restraint stress on [Ca2+ ]i and the proliferation of splenic lymphocytes from mice. We observed that 2 h of restraint significantly increased plasma corticosterone levels in mice. On examining [Ca2+ ]i and the proliferation ex vivo of splenic lymphocytes isolated from restraint-stressed mice using fura-2 and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, respectively, we found that acute restraint stress caused a significant increase in resting [Ca2+ ]i and significantly enhanced the ability of concanavalin A (Con A; a T-cell-selective mitogen) to increase [Ca2+ ]i but not that of lipopolysaccharide (LPS; a B-cell-selective mitogen). In addition, acute restraint stress significantly enhanced Con A-stimulated but not LPS-stimulated lymphocyte proliferation. Overall, there was a positive correlation between [Ca2+ ]i and T-cell proliferation following acute restraint stress. The enhancements of [Ca2+ ]i and T-cell proliferation were completely suppressed by verapamil (a Ca2+ channel blocker). These results suggest that acute restraint stress enhances Con A-stimulated T-cell proliferation by increasing [Ca2+ ]i via stimulation of Ca2+ entry.


Paradoxical embolism-in-transit: diagnosis and surgical treatment.
Paradoxical embolism-in-transit is an uncommon presentation of the thromboembolism complex. The advent of echocardiography has permitted its antemortem diagnosis and serves to guide treatment; this is illustrated by the case of a 51-year-old female who presented with paradoxical embolism-in-transit and pulmonary embolism following craniotomy. Echocardiography demonstrated mobile clot straddling the atrial septum and embolus in the right pulmonary artery. Surgery successfully removed all clots as demonstrated by intraoperative echocardiography, and the patient had an uneventful recovery.


Scabies in a Patient with Rheumatoid Arthritis Treated with Adalimumab - A Case Report.
Rheumatoid arthritis is a chronic systemic inflammatory disease characterized by synovitis, erosions, and destruction of affected joints. If untreated, it leads to severe disability and premature mortality. Tumor necrosis factor alpha (TNF-α) inhibitors are biological drugs used in treatment of rheumatoid arthritis. Possible side effects include skin allergic reactions, which, if generalized, are the reason for discontinuation of the drug. We report the case of a 46-year-old female patient with rheumatoid arthritis who presented with pruritus and erythematous papular exanthema after administration of the second dose of adalimumab. At first, we suspected a drug hypersensitivity reaction. As the signs and symptoms persisted for 2 months after discontinuation of adalimumab and despite continuous administration of antihistamines and glucocorticoids, further work-up was performed, and scabies was diagnosed. The patient was treated with topical 10% crotamiton. The symptoms were persistent and additional applications of the preparation were needed. After clinical remission of scabies, treatment of active rheumatoid arthritis with adalimumab was restarted without any complications.


Pattern of the evolution of HIV-1 enν gene in Côte d׳Ivoire.
Cête d׳Ivoire continues to have the highest HIV-1 prevalence rate in West Africa, although the infection number is in constant decline. The external envelope protein of the viruses is a likely site of selection, and responsible for receptor binding and entry into host cells, and therefore constitutes an ideal region with which to investigate the evolutionary processes acting on HIV-1. In this study, we analyse 189 envelope glycoprotein V3 loop region sequences of viruse isolates from 1995 to 2009, from HIV-1 untreated patients living in Cête d׳Ivoire, to decipher the temporal relationship between disease diversity, divergence and selection. Our analyses show that the nonsynonymous and synonymous ratio (dN/dS) was lower than 1 for viral populations analysed within 15 years, which showed the sequences did not undergo adequate immune pressure. The phylogenetic tree of the sequences analysed demonstrated distinctly long internal branches and short external branches, suggesting that only a small number of viruses infected the new host cell at each transmission. In addition to identifying sites under purifying selection, we also identified neutral sites that can cause false positive inference of selection. These sites presented form a resource for future studies of selection pressures acting on HIV-1 enν gene in Cête d׳Ivoire and other West African countries.


Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity.
The phagocyte respiratory burst is crucial for innate immunity. The transfer of electrons to oxygen is mediated by a membrane-bound heterodimer, comprising gp91phox and p22phox subunits. Deficiency of either subunit leads to severe immunodeficiency. We describe Eros (essential for reactive oxygen species), a protein encoded by the previously undefined mouse gene bc017643, and show that it is essential for host defense via the phagocyte NAPDH oxidase. Eros is required for expression of the NADPH oxidase components, gp91phox and p22phox Consequently, Eros-deficient mice quickly succumb to infection. Eros also contributes to the formation of neutrophil extracellular traps (NETS) and impacts on the immune response to melanoma metastases. Eros is an ortholog of the plant protein Ycf4, which is necessary for expression of proteins of the photosynthetic photosystem 1 complex, itself also an NADPH oxio-reductase. We thus describe the key role of the previously uncharacterized protein Eros in host defense.


Giant cell arteritis.
Giant cell arteritis is a form of vasculitis affecting medium- and large-size arteries, with a predilection for vessels arising from the aortic arch. The origins of giant cell arteritis are unknown. However, ethnic affinities are prominent, with the majority of cases involving white, elderly patients. In addition, there is evidence of a familial pattern and an association with HLA-DR4, suggesting a genetic predisposition in select cases. With an increase in the elderly population, clinicians must become cognizant of this age-related malady and its treatment to ensure quality care for elderly patients.


Gastro-floating bilayer tablets for the sustained release of metformin and immediate release of pioglitazone: preparation and in vitro/in vivo evaluation.
Owing to the complementary mechanisms of action of metformin hydrochloride (MH) and pioglitazone hydrochloride (PG), combination therapy for type 2 diabetes mellitus using the two drugs is highly desired; on the other hand, MH is not well absorbed in lower gastrointestinal tract and has a short half-life, therefore compromising the therapeutic effects. Herein, the present study was to develop gastro-floating bilayer matrix tablets in which the two drugs were incorporated into two separate layers, aiming at sustaining MH release with enhanced absorption and achieving immediate release of PG. The tablets of the optimized formulation floated on the test medium for more than 24 h with 5 min of floating lag time, and sustained MH release for 12 h via a diffusion-dependent manner; and complete release of PG within 5 min were achieved. Moreover, a steady plasma concentration of MH with a 1.5-fold increase in bioavailability, decreased C(max) and reduced T(max) was obtained, and the in vivo behavior of PG was similar to the marked product. Summarily, sustained MH release with improved absorption and immediate release of PG were obtained simultaneously using the gastro-floating bilayer tablet, allowing strengthened combination therapy for diabetes mellitus.


Comparison between Slow Freezing and Vitrification in Terms of Ovarian Tissue Viability in a Bovine Model.
Objective To assess the viability of bovine ovarian tissue after cryopreservation through either slow freezing or vitrification, and to compare it to that of control tissue by performing morphological analyses. Methods The study included 20 bovine ovarian cortex fragments that were divided into control, vitrification, and slow freezing groups. Each group consisted of four fragments of the same ovary, two fixed without cultivation, and two fixed with cultivation. Tissues were evaluated based on follicular morphology immediately after heating and after 7 days of culture, and compared with the control group. Results A total of 240 fragments were analyzed, generating a sample of 1,344 follicles without cultivation and 552 with cultivation. When the non-cultivated samples were classified as non-atretic follicles, 572 were found in the control group, 289 in the vitrification group, and 373 in the slow freezing group, showing no significant differences. When classified as atretic, 46 follicles were found in the control group, 23 in the vitrification group, and 41 in the slow freezing group, also showing no statistical difference. In the post-culture sample, an evolution of the follicular stages could be observed. This finding was important to support that the follicles considered non-atretic in the non-cultivated group were actually viable in the morphological evaluation. Conclusion With no differences between the protocols, vitrification was shown to be an advanced and alternative method for patients who will undergo treatments that carry the risk of ovarian failure, as the method is less expensive, faster, and more adaptable to laboratory routine.


Contrast-enhanced dynamic and diffusion-weighted magnetic resonance imaging at 3.0 T to assess early-stage nasopharyngeal carcinoma.
The present study aimed to assess early-stage nasopharyngeal carcinoma (NPC) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) at 3.0 T. A total of 44 patients newly diagnosed with NPC were included in the present study. All patients underwent MR examination at 3.0 T using DCE-MRI and DWI. The volume transfer constant (Ktrans ), flux rate constant between extravascular extracellular space and plasma (Kep ), the volume of extravascular extracellular space per unit volume of tissue (Ve ) and the apparent diffusion coefficient (ADC) of tumours were investigated. Furthermore, the correlation between clinical stages and ADC value and Ktrans were analysed. The diagnostic accuracy of Ktrans and ADC were estimated using receiver operating characteristic curves. NPC stage correlated positively with Ktrans and negatively with ADC values. Additionally, tumour Ktrans negatively correlated with ADC value. The sensitivity and accuracy of combined Ktrans and ADC in distinguishing between stage II and stage III and stage III and IV were higher than the values of either measurement used separately. The present study suggested that Ktrans and ADC derived from DCE-MRI and DWI may be useful to detect stage early NPC accurately. Ktrans and ADC in combination were superior than either alone.


IMGT ® Nomenclature of Engineered IGHG Variants Involved in Antibody Effector Properties and Formats.
The constant region of the immunoglobulin (IG) or antibody heavy gamma chain is frequently engineered to modify the effector properties of the therapeutic monoclonal antibodies. These variants are classified in regards to their effects on effector functions, antibody-dependent cytotoxicity (ADCC), antibody-dependent phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) enhancement or reduction, B cell inhibition by the coengagement of antigen and FcγR on the same cell, on half-life increase, and/or on structure such as prevention of IgG4 half-IG exchange, hexamerisation, knobs-into-holes and the heteropairing H-H of bispecific antibodies, absence of disulfide bridge inter H-L, absence of glycosylation site, and site-specific drug attachment engineered cysteine. The IMGT engineered variant identifier is comprised of the species and gene name (and eventually allele), the letter 'v' followed by a number (assigned chronologically), and for each concerned domain (e.g, CH1, h, CH2 and CH3), the novel AA (single letter abbreviation) and IMGT position according to the IMGT unique numbering for the C-domain and between parentheses, the Eu numbering. IMGT engineered variants are described with detailed amino acid changes, visualized in motifs based on the IMGT numbering bridging genes, sequences, and structures for higher order description.


Correlation between Mcl-1 and pAKT protein expression in colorectal cancer.
Mcl-1 inhibits apoptosis in well-differentiated cells by sequestering BAD, BID, and BAX and other apoptotic molecules. pAKT blocks apoptotsis by facilitating the interaction of BAD with BCL-XL. Expression of pAKT and Mcl-1 have been described in colon cancer, however, the relationship between pAKT and Mcl-1 has not. Mcl-1 and pAKT immunohistochemistry was performed using colorectal cancer tissue microarray (TMA). The Holm step-down method was used to adjust for multiple testing. Mcl-1 and pAKT scores, stage, and grade were compared using Spearman's correlation coefficient. Metastasis and no metastasis groups were compared using the Wilcoxon rank sum test. Mcl-1 and pAKT scores were compared for normal colorectal mucosa (NR), adenoma (AD), and colorectal cancer (CRC) cohorts. The mean (SD) pAKT expression in NR (14) was 2.0 (1.4), in AD (8) was 3.0 (1.7), and in CRC (101) was 5.6 (2.4). These differences were statistically significant. For Mcl-1 the mean (SD) expression was 4.1 (1.7) in NR, 3.2 (1.2) in AD, and 3.3 (2.6) in CRC. Mcl-1 and pAKT scores were directly correlated during various stages of colon car-cinogenesis (p = 0.04). Mcl-1 showed direct correlation with tumor grade (p = 0.001) and tumor stage (p = 0.02) and with presence of metastasis (p = 0.008). We report the correlation of Mcl-1 protein expression with higher grade and stage in colorectal cancer. Mcl-1 correlated also with pAKT expression. We also report the up regulation of pAKT during the transition from NR to CRC.


Living "anyway:" stories of access.
Elana Dykewomon's 1974 novel, Riverfinger Women, was among the first lesbian books with a "happy ending." Her seven books of fiction and poetry include the Lambda Award winner Beyond the Pale (now an audio and e-book) and Lambda nominee, Risk. She was an editor of the lesbian-feminist journal, Sinister Wisdom, for eight years. Her literary work foregrounds the lesbian heroic as integral to women's communities. As a social justice activist, she has organized and participated in anti-war, anti-racist, anti-classist, fat and disability rights work since the 1970s. She is now working with Old Lesbians Organizing for Change. She is happy to live embedded in dyke community as a lesbian radical committed to a loving justice. While she suffered psychiatric abuse at 13 (and acknowledges long-term adaptive behavior on that account), she has not experienced disabling mental illness since. Her primary disabilities are mobility impairment through severe, progressive arthritis and constant low-to-powerful pain, sometimes diagnosed as fibromyalgia. Her acute illnesses include pancreatitis and a rare-in-adults kidney disease currently in remission.


The Influence of Memorable Message Receipt on Dietary and Exercise Behavior among Self-Identified Black Women.
Guided by Control Theory and the memorable messages framework, the current investigation examined the relationship between receipt of a health-related memorable message and self-reported diet and exercise behavior. A cross-sectional survey methodology was utilized to evaluate the relationship between receipt of a memorable message and dietary and exercise behaviors in a sample of Black women. Over 80% of the research sample (N = 121) reported receiving a memorable health message regarding diet and/or exercise. Women receiving a memorable message reported a significantly higher number of days engaging in healthy eating and exercise behaviors each week. Messages from medical professionals had the greatest impact on healthy dietary practices, while media-based messages were most influential on the enactment of exercise behavior. Additional research is warranted to determine how the utilization and reinforcement of memorable messages impacts health outcomes among Black women.


A gene coexpression network for bovine skeletal muscle inferred from microarray data.
We present the application of large-scale multivariate mixed-model equations to the joint analysis of nine gene expression experiments in beef cattle muscle and fat tissues with a total of 147 hybridizations, and we explore 47 experimental conditions or treatments. Using a correlation-based method, we constructed a gene network for 822 genes. Modules of muscle structural proteins and enzymes, extracellular matrix, fat metabolism, and protein synthesis were clearly evident. Detailed analysis of the network identified groupings of proteins on the basis of physical association. For example, expression of three components of the z-disk, MYOZ1, TCAP, and PDLIM3, was significantly correlated. In contrast, expression of these z-disk proteins was not highly correlated with the expression of a cluster of thick (myosins) and thin (actin and tropomyosins) filament proteins or of titin, the third major filament system. However, expression of titin was itself not significantly correlated with the cluster of thick and thin filament proteins and enzymes. Correlation in expression of many fast-twitch muscle structural proteins and enzymes was observed, but slow-twitch-specific proteins were not correlated with the fast-twitch proteins or with each other. In addition, a number of significant associations between genes and transcription factors were also identified. Our results not only recapitulate the known biology of muscle but have also started to reveal some of the underlying associations between and within the structural components of skeletal muscle.


Nonhuman primates at the intersection of aging biology, chronic disease, and health: An introduction to the American Journal of Primatology Special Issue on aging, cognitive decline, and neuropathology in nonhuman primates.
Aging across the Primate Order is poorly understood because ages of individuals are often unknown, there is a dearth of aged animals available for study, and because aging is best characterized by longitudinal studies which are difficult to carry out in long-lived species. The human population is aging rapidly, and advanced age is a primary risk factor for several chronic diseases and conditions that impact healthspan. As lifespan has increased, diseases and disorders of the central nervous system (CNS) have become more prevalent, and Alzheimer's disease and related dementias have become epidemic. Nonhuman primate (NHP) models are key to understanding the aging primate CNS. This Special Issue presents a review of current knowledge about NHP CNS aging across the Primate Order. Similarities and differences to human aging, and their implications for the validity of NHP models of aging are considered. Topics include aging-related brain structure and function, neuropathologies, cognitive performance, social behavior and social network characteristics, and physical, sensory, and motor function. Challenges to primate CNS aging research are discussed. Together, this collection of articles demonstrates the value of studying aging in a breadth of NHP models to advance our understanding of human and nonhuman primate aging and healthspan.


[Pathogenesis and therapy of Hodgkin lymphoma].
Although the pathogenesis of Hodgkin's disease is not clear, molecular analyses reveal characteristic features. EBV infection can be demonstrated in more than 50% of cases at the DNA or protein level. Recently, immunoglobulin gene rearrangements were found in single Hodgkin and Reed-Sternberg cells. Sequence analyses revealed that the rearranged Ig genes have frequently somatic mutations, which indicate that the cells are derived from the germinal center. These rearrangements may be used as defined markers to detect residual disease after chemotherapy. Modern polychemotherapy regimen and radiotherapy are very effective, and 60-90% of patients, depending on stage of the disease and risk factors, can be cured. Salvage therapy for relapsed patients including high-dose chemotherapy with autologous stem cell support frequently results in remission although duration is frequently short. New immunotherapy strategies with immunotoxins or bispecific antibodies are currently analysed in clinical studies.


Effectiveness and safety of carotid endarterectomy under remifentanil.
The aim of this study was to evaluate the effectiveness and safety of carotid endarterectomy (CEA) with conscious sedation under remifentanil (Remifentanil anesthesia - RA) vs conventional loco-regional anesthesia (Conventional-LRA) in the current practice of a vascular surgery unit. We introduced the ''Remifentanil-RA'' in our practice according to a two-step protocol. In the first step we performed a pilot prospective study to assess the procedure's safety and reproducibility in our setting on 60 consecutive patients with symptomatic and/or high-grade (>70%) internal carotid artery stenosis and alternately assigning them either to ''Remifentanil-RA'' or ''Conventional-LRA'' CEA. In the second step we analysed our routine operative records as to effectiveness and safety on 533 patients who consecutively underwent ''Remifentanil-RA'' CEA. We compared them with 533 age- and sex-matched historical controls who underwent ''Conventional-LRA'' CEA. The patients' mean age was 71.2+/-6.8 vs 71.8+/-6.1 (''Remifentanil-RA'' vs ''Conventional-LRA''). About 73% of them were male and 56% had a symptomatic carotid stenosis. Neither the pilot study nor second step comparison showed differences in outcome measures. We found only higher peri-operative nausea/ vomit (3.6% vs 0.4% ''Remifentanil-RA'' vs ''Conventional-LRA'', P<0.0002) and fewer re-operations for post-operative hematomas (3% vs 5.4% respectively, P=0.048). We found that ''Remifentanil-RA'' CEA was safe, effective and satisfactory. Nevertheless, with the potential problems of intubation and those already found with side effects, a randomized control trial (RCT) is needed in order to prove that this method is superior to ''Conventional-LRA'' CEA.


The potential of Mid-Infrared spectroscopy for prediction of wood density and vulnerability to embolism in woody angiosperms.
Xylem resistance to embolism formation determines the species-specific drought tolerance and the survival prospects of plants under extreme climatic conditions. Fourier Transform-Infrared (FTIR) spectroscopy is a cost-effective and rapid analytical tool with potential beyond its current use in plant physiology. We tested the use of FTIR spectroscopy as a method for estimating wood density (WD) and xylem resistance to embolism formation (P50) in 24 angiosperm species. Higher WD was associated with more negative P50 (r2 = 0.41). Partial least squares regression was applied to establish models of FTIR spectra and the reference data. They showed a high predictive quality for WD (r2 = 0.73), whereas the prediction of P50 was weaker (r2 = 0.49). By including WD in the model as an additional factor influencing P50, its predictive power significantly increased (r2 = 0.59). The spectral range in the model elaboration has been also narrowed (bands of lignin, cellulose, hemicellulose), but this did not influence the model descriptors, suggesting that for P50 prediction broad spectral range is more informative than narrow band regions reflecting main wood constituents. In conclusion, FTIR spectroscopy associated with WD measurements has proven to be a promising alternative to traditional methods for screening of individual- or species-specific resistance to embolism in angiosperms.


Computed Tomography and Magnetic Resonance Imaging Parameters Associated with Poor Clinical Outcome in Spondylodiscitis.
Prognostic factors for the disease course of patients with spondylodiscitis have not been well studied. The prognostic value of initial magnetic resonance imaging (MRI) and computed tomography imaging parameters was analyzed in 62 patients (47% women; mean age ± SD, 71.6 ± 9.6 years) with a confirmed diagnosis of spondylodiscitis. The disease course was separately evaluated during initial treatment response during hospitalization, relapse, and clinical short-term follow-up at 3 months. Overall CT findings graded as definitely inflammatory (P = 0.006), reduced disc height on MRI (P = 0.044) and fluid-equivalent hyperintensity of discs on T2 short tau inversion recovery-weighted sequences (P = 0.047) were associated with poor initial treatment response. High initial C-reactive protein value (>10.1 mg/dL) was associated with a higher relapse rate (P = 0.038). Risk factors for poor outcome were infection with low-virulence bacteria (P = 0.040) and overall MRI findings atypical for infection (P = 0.027). Compared with MRI, CT imaging parameters have a higher prognostic value regarding the disease course. Patients infected with low-virulence bacteria and atypical MRI findings are at higher risk for poor clinical outcome and thus warrant closer monitoring.


[Pubertal decompensation in the clinical picture of schizoid psychopathy].
The author examined 30 patients in whom the psychic condition in adolescence was characterized by "metaphysical (philosophical) intoxication". This phenomenon was qualified as an adolescent variant of over-valued ideas. It was established as well that these traits develop in personalities of a schizoid character. The conditions as a whole was considered as pubertal decompensation in schizoid psychopathy. The report contains criteria for a differentiation of these conditons with slowly progressive forms of schizophrenic process.


Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double-blind, multicenter study.
For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids, addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines. To compare montelukast, a once-daily leukotriene receptor antagonist, and salmeterol, a twice-daily, long-acting beta-agonist, concomitantly administered with inhaled fluticasone, according to the percentage of patients without an asthma attack for 1 year. A randomized, double-blind, double-dummy, multicenter study was conducted. Adult patients with moderate-to-severe persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 microg/d) who remained symptomatic during a 4-week run-in period were randomized to the addition of salmeterol (84 microg/d) or montelukast (10 mg/d) for 48 weeks. Of the 1,473 randomized patients, 743 were randomized to montelukast and 730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients in the montelukast group and 83.3% of patients in the salmeterol group remained attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts compared with salmeterol, whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second, asthma-specific quality of life, morning peak expiratory flow rate, and decreased nocturnal awakenings compared with montelukast. Differences between treatments were small, and both treatments were generally well tolerated. Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period, but, based on noninferiority limits, the study was inconclusive with regard to a difference between treatment groups.


Learning Microbial Interaction Networks from Metagenomic Count Data.
Many microbes associate with higher eukaryotes and impact their vitality. To engineer microbiomes for host benefit, we must understand the rules of community assembly and maintenance that, in large part, demand an understanding of the direct interactions among community members. Toward this end, we have developed a Poisson-multivariate normal hierarchical model to learn direct interactions from the count-based output of standard metagenomics sequencing experiments. Our model controls for confounding predictors at the Poisson layer and captures direct taxon-taxon interactions at the multivariate normal layer using an ℓ1 penalized precision matrix. We show in a synthetic experiment that our method handily outperforms state-of-the-art methods such as SparCC and the graphical lasso (glasso). In a real in planta perturbation experiment of a nine-member bacterial community, we show our model, but not SparCC or glasso, correctly resolves a direct interaction structure among three community members that associates with Arabidopsis thaliana roots. We conclude that our method provides a structured, accurate, and distributionally reasonable way of modeling correlated count-based random variables and capturing direct interactions among them.


A new smart healthcare framework for real-time heart disease detection based on deep and machine learning.
Cardiovascular diseases (CVDs) are the most critical heart diseases. Accurate analytics for real-time heart disease is significant. This paper sought to develop a smart healthcare framework (SHDML) by using deep and machine learning techniques based on optimization stochastic gradient descent (SGD) to predict the presence of heart disease. The SHDML framework consists of two stage, the first stage of SHDML is able to monitor the heart beat rate condition of a patient. The SHDML framework to monitor patients in real-time has been developed using an ATmega32 Microcontroller to determine heartbeat rate per minute pulse rate sensors. The developed SHDML framework is able to broadcast the acquired sensor data to a Firebase Cloud database every 20 seconds. The smart application is infectious in regard to displaying the sensor data. The second stage of SHDML has been used in medical decision support systems to predict and diagnose heart diseases. Deep or machine learning techniques were ported to the smart application to analyze user data and predict CVDs in real-time. Two different methods of deep and machine learning techniques were checked for their performances. The deep and machine learning techniques were trained and tested using widely used open-access dataset. The proposed SHDML framework had very good performance with an accuracy of 0.99, sensitivity of 0.94, specificity of 0.85, and F1-score of 0.87.


Working memory updating occurs independently of the need to maintain task-context: accounting for triggering updating in the AX-CPT paradigm.
Theoretical models suggest that maintenance and updating are two functional states of working memory (WM), which are controlled by a gate between perceptual information and WM representations. Opening the gate enables updating WM with input, while closing it enables keeping the maintained information shielded from interference. However, it is still unclear when gate opening takes place, and what is the external signal that triggers it. A version of the AX-CPT paradigm was used to examine a recent proposal in the literature, suggesting that updating is triggered whenever the maintenance of the context is necessary for task performance (context-dependent tasks). In four experiments using this paradigm, we show that (1) a task-switching cost takes place in both context-dependent and context-independent trials; (2) task-switching is additive to the dependency effect, and (3) unlike switching cost, the dependency effect is not affected by preparation and, therefore, does not reflect context-updating. We suggest that WM updating is likely to be triggered by a simple mechanism that occurs in each trial of the task regardless of whether maintaining the context is needed or not. The implications for WM updating and its relationship to task-switching are discussed.


Rethinking traditional methods for measuring intellectual capital.
Historically, approaches to measuring intellectual capital have included both conventional accounting-based measures, such as variants of the market-to-book ratio, and more progressive measures, such as the measurement of intangible assets found in approaches such as the Balanced Scorecard and Human Resource Accounting. As greater emphasis is placed on intellectual capital and its various aspects in the continually growing service and knowledge economy, the use of assessment instruments to inventory the alignment, balance, and variety of intellectual capacities and metrics that assess the effectiveness of succession planning may represent new directions in which organizations can head in the measurement of this important construct.


Mesothelioma in Scotland.
In a retrospective study of the incidence of mesothelioma in Scotland for 1950-67 80 cases were traced from pathological reports and biopsy material of malignant tumours invading the pleura and peritoneum. These cases were matched with two sets of controls. Detailed histories of residence, occupation, and degree of exposure to asbestos confirmed that the incidence of mesothelioma in Scotland is similar to that in other parts of Britain.


Stable association of viral protein VP1 with simian virus 40 DNA.
Mild dissociation of simian virus 40 particles releases a 110S virion core nucleoprotein complex containing histones and the three viral proteins VP1, VP2, and VP3. The association of viral protein VP1 within this nucleoprotein complex is mediated at least partially through a strong interaction with the viral DNA. Treatment of the virion-derived 110S nucleoprotein complex with 0.25% Sarkosyl dissociated VP2, VP3, and histones, leaving a stable VP1-DNA complex. The VP1-DNA complex had a sedimentation value of 30S and a density of 1.460 g/cm3. The calculated molecular weight of the complex was 7.9 x 10(6), with an average of 100 VP1 molecules per DNA. Agarose gel electrophoresis of the VP1-DNA complex demonstrated that VP1 is associated not only with form I and form II simian virus 40 DNAs but also with form III simian virus 40 DNA generated by cleavage with EcoRI.


Death of solid tumor cells induced by Fas ligand expressing primary myoblasts.
Anticancer therapy for solid tumors suffers from inadequate methods for the localized administration of cytotoxic agents. Fas ligand (FasL) has been reported to be cytotoxic to a variety of cells, including certain tumor cell lines. We therefore postulated that myoblasts could serve as non-transformed gene therapy vehicles for the continuous localized delivery of cytotoxic anticancer agents such as FasL. However, contrary to previous reports, fluorescence activated cell sorting (FACS) analyses revealed that both primary mouse and human myoblasts express Fas, the receptor for FasL. To avoid self-destruction and test the cytotoxic potential of myoblasts, the cells were isolated from mice deficient in Fas (lpr/lpr), the mouse counterpart of human autoimmune lymphoproliferative syndrome (ALPS). These primary mouse myoblasts were transduced with a retroviral vector encoding mouse FasL and expression of a biologically active and soluble form of the molecule was confirmed by the apoptotic demise of cocultured Fas-expressing Jurkat cells, the standard in the field. To test whether the lpr myoblasts expressing FasL could be used in anticancer therapy, human rhabdomyosarcoma derived cell lines were assayed for Fas and then tested in the apoptosis coculture assay. The majority of Fas-expressing muscle tumor cells were rapidly killed. Moreover, FasL expressing myoblasts were remarkably potent; indeed well characterized cytotoxic antibodies to Fas were only 20% as efficient at killing rhabdomyosarcoma cells as FasL expressing myoblasts. These findings together with previous findings suggest that primary myoblasts, defective in Fas but genetically engineered to express FasL, could function as potent anticancer agents for use in the localized destruction of solid tumors in vivo by three synergistic mechanisms: (1) directly via Fas/FasL mediated apoptosis, (2) indirectly via neutrophil infiltration and immunodestruction, and (3) as allogeneic inducers of a bystander effect via B and T cells.


Effect of increasing dietary canola meal inclusion on lactation performance, milk composition, and nutrient digestibility of lactating sows.
The aim was to determine the effects of increasing dietary canola meal in substitution for soybean meal in lactation sow diets. Forty-five sows with an average parity of 1.8 (SD = 0.83) were randomly assigned to 1 of 3 dietary treatments ( = 15) consisting of a corn-based control diet and 2 diets with 15% and 30% canola meal formulated by replacing soybean meal with canola meal. Diets were formulated to be similar in standardized ileal digestible AA content and NE value and to meet or exceed nutrient recommendations for lactating sows. Sows were moved to farrowing on d 111 of gestation and fed the experimental diets until weaning on d 21. Sows were fed 3.0 kg/d from d 111 of gestation until parturition. After farrowing, feed was gradually increased through d 6 after which the diets were offered on an ad libitum basis until weaning. Sows were weighed and backfat thickness measured on d 111 of gestation and also on d 0, 7, and 21 postfarrowing. Litters were weighed on d 0, 7, and 21. Weaning to estrus interval in sows was also recorded. Blood and milk samples were collected 2 h postfeeding from sows on d 0, 7, and 21 and analyzed for plasma urea nitrogen (PUN) and milk composition. Fecal samples were collected on d 10, 11, and 12 postfarrowing to determine energy and nutrient digestibility. There were no dietary effects on lactation feed intake, sow BW and backfat change, weaning to estrus interval, and milk fat, protein, lactose, and urea composition. Also, there were no dietary effects on piglet ADG ( 0.10). Sows fed diets containing 15% and 30% canola meal had lower (linear, < 0.05) PUN values compared with those fed the control diet on d 0, 7, and 21 postfarrowing. Apparent total tract digestibility of DM, GE, CP, and P were reduced linearly ( < 0.05) with increasing canola meal inclusion. In conclusion, up to 30% canola meal in lactation diet can support satisfactory sow and suckling piglet performance.


Pilot studies for proficiency testing using fluorescence in situ hybridization with chromosome-specific DNA probes: a College of American Pathologists/American College of Medical Genetics Program.
Fluorescence in situ hybridization using chromosome-specific DNA probes is rapidly becoming part of clinical laboratory practice for certain congenital and neoplastic disorders. Current legislation requires proficiency testing for clinical laboratory studies. To evaluate the efficacy of fluorescence in situ hybridization proficiency testing, we invited 19 representative institutions to participate in three pilot studies. One study used probes for the X and Y chromosomes to evaluate metaphase spreads and interphase nuclei. Another study used probes for bcr and abl to detect bcr/abl fusion in interphase nuclei in chronic myelogenous leukemia. The third study used a D22S75 probe to detect microdeletions in metaphase spreads from a patient with velocardiofacial syndrome. The results of these studies demonstrate that proficiency testing with fluorescence in situ hybridization is attainable using either metaphase or interphase preparations, and that either microscope slides or fixed cell pellets are suitable.


Reactions to alcohol in sons of alcoholics and controls.
This paper synthesizes some major findings coming from our laboratory over the last decade. The data focuses on our search for mechanisms that might contribute to the elevated risk for alcoholism in sons of alcoholic fathers. Consistent results corroborated by several additional groups indicate that the higher risk sons of alcoholics demonstrate less intense reactions to ethanol as measured by their subjective self-reports, measures of body sway, changes in several hormones after drinking, and the intensity or persistence of ethanol-related changes on two electrophysiological measures. The potential implications of these results as they might relate to an enhanced vulnerability to alcoholism, and some possible future research directions, are discussed.