Ultrasonography-Based Classification and Reporting System for the Malignant Risk of Thyroid Nodules.
The aim of this study was to test the predictive value of a Thyroid Imaging Reporting and Data System (TI-RADS) for malignant thyroid nodules. Ultrasonographic data was examined for 910 thyroid nodules with histopathologically confirmed diagnoses. Nodules were placed into incomplete (category 0) or complete final categories (1, 2, 3a, 3b, 3c, 4, or 5) based on the presence and number of ultrasonographic features of malignancy, and the predictive value for the malignancy of nodules in categories 2-4 was assessed. The overall rate of malignancy among thyroid nodules included in the study was 59.34%. The rate of malignancy gradually increased according to TI-RADS categories as follows: category 2, 5.4%; category 3 (a-c), 36% to 92%; and category 4, 99.0%. When nodules of category 2 were counted as benign, the reliability of the TI-RADS classification for determining the risk of malignancy was as follows; sensitivity, 98.15%; specificity, 47.84%; positive predictive value, 73.31%; negative predictive value, 94.65%; and odds ratio, 48.61. The TI-RADS classification used in this study is relatively simple and provides a reliable measure of the risk of malignancy of thyroid nodules.


Reversible binding and quantification of heparin and chondroitin sulfate in water using redox-stable biferrocenylene SAMs.
A biferrocenylene (BFD) thiol conjugate was prepared and self-assembled on a gold surface. The resulting SAMs with their extraordinary stability in the monocationic state were used to detect and quantify heparin (3-300 × 10(-5) g L(-1) = 0.003-0.3 U mL(-1)) and chondroitin sulfate (3-250 × 10(-5) g L(-1)) in aqueous buffer by cyclic voltammetry, square wave voltammetry and surface plasmon resonance. As a proof of concept, heparin quantification was performed in a blood plasma sample. Moreover, controlled binding and release of heparin was realised by switching the BFD-SAM between the monocationic and neutral state.


Koilocytosis in dysplastic and reactive cervical squamous epithelium. An ultrastructural study.
Koilocytosis was studied in eight cases of dysplasia and reactive atypia with conventional transmission electron microscopy. The ultrastructural features were compared to the process of maturation of normal cervical epithelium. Koilocytosis was observed as abnormal karyopyknosis as represented by irregular nuclei, coarse chromatin clumping, the less dense ellipsoid perinuclear zone, and the increased tonofilament bundles in the outer zone of the cytoplasm accentuating the margin of the perinuclear zone of the cells.


Immunotherapy for lung cancer: Targeting the PD-1 pathway.
Lung cancer is the third most common cancer in the United States and the top cause of cancer-related mortality in men and women. Despite advances in chemotherapy, molecular therapies, and CT screening, overall survival remains dismal. Additional options and a new treatment paradigm are needed. This article focuses on immunotherapy, a promising new approach targeted at the PD-1 inhibition pathway.


Intermittent chemotherapy of experimental leprosy in mice.
In this study we assess the degree of prolonged bacteriostasis of Mycobacterium leprae after temporary exposure to ehtionamide or thiacetazone, and relate this to their efficacy when administered intermittently to mice with experimental leprosy infections. The results show that temporary exposure of M. leprae to either of these drugs results in a prolonged bacteriostatic effect, but that efficacy is rapidly lost as the interval between doses is increased. Using the mouse foot pad system, growth of M. leprae is not inhibited by thiacetazone when the frequency of administration is less than three times weekly. When ethionamide is administered once weekly, growth of M. leprae is inhibited but bactericidal activity is lost. When ethionamide is administered in combination with continuous dapsone therapy, either continuously or three times weekly, the bactericidal activity of the drug combination is greater than when either drug is administered alone. However, when ethionamide is administered once weekly in combination with continuous dapsone treatment, the bactericidal effect is identical to that when dapsone is given alone: that is, ethionamide makes no contribution to the combination.


Genotypic and developmental evidence for the role of plasmodesmatal regulation in cotton fiber elongation mediated by callose turnover.
Cotton fibers are single-celled hairs that elongate to several centimeters long from the seed coat epidermis of the tetraploid species (Gossypium hirsutum and Gossypium barbadense). Thus, cotton fiber is a unique system to study the mechanisms of rapid cell expansion. Previous work has shown a transient closure of plasmodesmata during fiber elongation (Y.-L. Ruan, D.J. Llewellyn, R.T. Furbank [2001] Plant Cell 13: 47-60). To examine the importance of this closure in fiber elongation, we compared the duration of the plasmodesmata closure among different cotton genotypes differing in fiber length. Confocal imaging of the membrane-impermeant fluorescent molecule carboxyfluorescein revealed a genotypic difference in the duration of the plasmodesmata closure that positively correlates with fiber length among three tetraploid genotypes and two diploid progenitors. In all cases, the closure occurred at the rapid phase of elongation. Aniline blue staining and immunolocalization studies showed that callose deposition and degradation at the fiber base correlates with the timing of plasmodesmata closure and reopening, respectively. Northern analyses showed that the expression of a fiber-specific beta-1,3-glucanase gene, GhGluc1, was undetectable when callose was deposited at the fiber base but became evident at the time of callose degradation. Genotypically, the level of GhGluc1 expression was high in the short fiber genotype and weak in the intermediate and long fiber genotypes. The data provide genotypic and developmental evidence that (1) plasmodesmata closure appears to play an important role in elongating cotton fibers, (2) callose deposition and degradation may be involved in the plasmodesmata closure and reopening, respectively, and (3) the expression of GhGluc1 could play a role in this process by degrading callose, thus opening the plasmodesmata.


Micellar emulsions composed of mPEG-PCL/MCT as novel nanocarriers for systemic delivery of genistein: a comparative study with micelles.
Polymeric micelles receive considerable attention as drug delivery vehicles, depending on the versatility in drug solubilization and targeting therapy. However, their use invariably suffers with poor stability both in in vitro and in vivo conditions. Here, we aimed to develop a novel nanocarrier (micellar emulsions, MEs) for a systemic delivery of genistein (Gen), a poorly soluble anticancer agent. Gen-loaded MEs (Gen-MEs) were prepared from methoxy poly(ethylene glycol)-block-(ε-caprolactone) and medium-chain triglycerides (MCT) by solvent-diffusion technique. Nanocarriers were characterized by dynamic light scattering, transmission electron microscopy, and in vitro release. The resulting Gen-MEs were approximately 46 nm in particle size with a narrow distribution. Gen-MEs produced a different in vitro release profile from the counterpart of Gen-ME. The incorporation of MCT significantly enhanced the stability of nanoparticles against dilution with simulated body fluid. Pharmacokinetic study revealed that MEs could notably extend the mean retention time of Gen, 1.57- and 7.38-fold as long as that of micelles and solution formulation, respectively, following intravenous injection. Furthermore, MEs markedly increased the elimination half-life (t(1/2β)) of Gen, which was 2.63-fold larger than that of Gen solution. Interestingly, Gen distribution in the liver and kidney for MEs group was significantly low relative to the micelle group in the first 2 hours, indicating less perfusion in such two tissues, which well accorded with the elongated mean retention time. Our findings suggested that MEs may be promising carriers as an alternative of micelles to systemically deliver poorly soluble drugs.


The nonmutagenicity of purified 4-amino-2-nitrophenol in Salmonella typhimurium.
Two samples of 4-amino-2-nitrophenol were tested for mutagenicity in Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100. Significant mutagenic activity was detected with a sample of this compound obtained from Aldrich (technical grade (Aldrich), TGA) both in the presence and in the absence of a rat-liver S9 metabolic activation mixture. When toluene-insoluble contaminants of the TGA product were separated and tested for mutagenicity, they were found to be mutagenic in the same strains as the TGA sample. After removal of these major contaminants from the TGA product its mutagenicity was reduced; a nonmutagenic sample was obtained by further purification. The other sample of 4-amino-2-nitrophenol, which was synthesized and purified in our laboratory, was nonmutagenic. H.p.l.c. profiles of the unpurified TGA sample and the purified samples revealed a large number of contaminants in the TGA product. Likewise, t.l.c. revealed the presence of contaminants in the TGA product.


Flow system for automated analysis of maize pollen.
Pollen grains are haploid gametes of uniform shape and size, and can be obtained in large quantity. If appropriate traits are used, they can be an excellent material for investigation of rare but important biological events like intracistronic recombinations or mutations induced by very low level of mutagens. This advantage will be further improved, if the laborious counting and examination can be made automatically. For automation of pollen analysis, techniques of flow analysis and image analysis would be applicable. Flow analysis with a optical detector was tested using maize pollen. Pollen grains were transported by gentle suction through a glass capillary which was placed under a microscope. Interruptions of the light path by pollen grains were detected by a silicon photocell after optical magnification and converted into electric pulses. The frequency distribution of pulse height was examined by a multichannel pulse height analyzer. 10(6) pollen grains would be counted and classified within about 30 min for a pollen suspension dilute enough for separation of each pulse. The flow system tested seems promising for detection of Wx mutant pollen in a wx pollen population after iodine staining if illumination of sample particles is improved.


Myo-inositol deficiency in gerbils: comparative study of the intestinal lipodystrophy in Meriones unguiculatus and Meriones libycus.
Like Mongolian gerbils (Meriones unguiculatus), Meriones libycus develop an intestinal lipodystrophy due to myo-inositol deficiency. Fat accumulation was observed in the intestine of both species when a myo-inositol-deficient diet containing coconut oil was fed to female gerbils. It began in the duodenum and gradually extended to the entire small intestine. Starvation partially removed the accumulated fats. The efficiency of fat absorption was not affected. Most of the accumulated fats were lauric acid-rich triglyceride with the fatty acid composition reflecting the pattern of the intestinal lymph triglyceride during normal transport of absorbed coconut oil. The ratio of oleic acid to linoleic acid in various intestinal lipids was increased. A marked decrease in all plasma lipid and lipoprotein concentrations, including chylomicron, was also observed. It is assumed that the intestinal fat accumulation resulted from a defect in lymphatic transport of dietary fats.


Stigmatization of patients with HIV/AIDS among doctors and nurses in Belize.
This study, conducted from August to September 2007, utilized a population-based survey to investigate stigmatizing attitudes and acts of discrimination against HIV/AIDS patients among doctors and nurses working in public hospitals in Belize. A total of 230 subjects (81.0%) completed the survey. The mean age was 36.8 years; 75% were women; 61% were nurses; 74% were Belizean. Stigmatization was greatest for "attitudes of blame/judgment"; disclosing a patient's HIV/AIDS status to colleagues was the most frequent act of discrimination (29%). Formal HIV/AIDS training was significantly associated with less stigmatization for "attitudes towards imposed measures" (p < .01); "attitudes of blame/judgment" (p < 0.05); and testing without consent (p < 0.05). Doctors showed more stigmatization in "attitudes towards imposed measures," conducted HIV tests without consent and disclosed patient status to colleagues more frequently than nurses (p < 0.05) while nurses gave differential care to patients based on HIV status more frequently (p < 0.01) than doctors. Female and religious health care workers (HCWs) were more stigmatizing in their "attitudes of blame/judgment" than male and nonreligious HCWs (p < 0.05). Cuban HCWs were more stigmatizing in their "attitudes toward imposed measures" and were less comfortable dealing with HIV/AIDS patients than their Belizean counterparts (p < 0.01). Older age was associated with less frequent disclosure of patients' HIV status (p < 0.05). HIV/AIDS training that incorporates stigma reduction strategies tailored to the target groups identified is needed. Additionally, we recommend that the effectiveness of national HIV/AIDS policies be investigated.


Flywheel energy storage for x-ray machines.
X-ray image quality for stop-motion exposures is greatly affected by the system power capability. High power levels are required for adequate resolution, which often precludes the use of mobile x-ray systems for stop-motion exposures. Currently available mobile systems use (1) 90-V nickel-cadmium batteries capable of 120 A, (2) a power line of 220 V ac, 60 Hz capable of about 100 A, or (3) a capacitor discharge unit using 1.0-microF capacitors and limited to 17-mAs equivalent output (compared to three-phase systems at 100 kVp). In each case, instantaneous power is usually limited to 10 kW. An alternative means which now appears to be a practical power source for mobile x-ray systems is the flywheel energy storage system. A 5-kg flywheel has been constructed which runs at 10 000 rpm and stores 25 000 J while drawing only a few hundred watts to bring the system up to speed. When coupled to an aircraft alternator, pulsed power levels of 25 kW have been achieved. The aircraft alternator also has the advantage of high-frequency output which has permitted the use of smaller high-voltage transformers. This system permits the generation of powerful x rays using low-power sources, such as single automobile batteries, common 115-V outlets, or electrical sources of poor regulation such as found in Third World countries.


A possible restriction of ferro- and ferricyanide oxidoreductase activities of rat liver mitochondria by the outer membrane.
In this work, various ferro-ferricyanide oxidoreductase activities of rat liver mitochondria were studied to find conditions under which the outer membrane might restrict the flux of these highly charged non-biological anions. When the isotonic low ionic strength medium was supplemented with 25mM KCl, a several-fold increase in the succinate-ferricyanide reductase activity of mitochondria and in the rate of external NADH oxidation in the presence of ferrocyanide was observed. Mitochondrial respiration with 5mM ferrocyanide was almost completely inhibited after consumption of 3.8-18.5% of the dissolved oxygen, depending on the medium and the presence of 2,4-dinitrophenol. These and other experimental data together with mathematical modeling of the redox-state equilibrium suggest that the measured activities might be restricted by two factors: first, the permeability of the outer mitochondrial membrane and second, a strong influence of the ionic strength of incubation media on the intermembrane space redox reactions.


Self-healing strategies among schizophrenics: attempts at compensation for basic disorders.
New experimental findings show that schizophrenics, as well as some of their non-schizophrenic relatives, manifest basic cognitive disorders defined in terms of variables from the field of experimental psychology. These basic disorders can be regarded as markers--if not, indeed, as psychological manifestations--of vulnerability to schizophrenia. They can be associated with subjectively experienced forms of non-clinically manifest impairments in psychological functioning. It was therefore hypothesised that schizophrenics, as well as non-schizophrenic subjects vulnerable to schizophrenia, will, in the course of learning processes, develop compensatory efforts which may be more or less effective. It is assumed that effective efforts of this kind will take on special significance in stress situations which would tend to elicit the occurrence of a schizophrenic episode. Effective efforts at compensation for basic disorders should be able to act as a 'buffer' against negative stressor effects (moderator function), thus reducing the danger of a psychotic breakdown. These compensation efforts were studied in 40 inpatients in remission after an acute schizophrenic episode. It was found that significant correlations exist between the extent of subjectively experienced basic disorders and the number and kind of conscious compensation attempts. Although the findings to date are of a preliminary and purely descriptive nature they would seem to justify further research.


Genetics of murine craniofacial morphology: diallel analysis of the eight founders of the Collaborative Cross.
Using eight inbred founder strains of the mouse Collaborative Cross (CC) project and their reciprocal F1 hybrids, we quantified variation in craniofacial morphology across mouse strains, explored genetic contributions to craniofacial variation that distinguish the founder strains, and tested whether specific or summary measures of craniofacial shape display stronger additive genetic contributions. This study thus provides critical information about phenotypic diversity among CC founder strains and about the genetic contributions to this phenotypic diversity, which is relevant to understanding the basis of variation in standard laboratory strains and natural populations. Craniofacial shape was quantified as a series of size-adjusted linear dimensions (RDs) and by principal components (PC) analysis of morphological landmarks captured from computed tomography images from 62 of the 64 reciprocal crosses of the CC founder strains. We first identified aspects of skull morphology that vary between these phenotypically 'normal' founder strains and that are defining characteristics of these strains. We estimated the contributions of additive and various non-additive genetic factors to phenotypic variation using diallel analyses of a subset of these strongly differing RDs and the first eight PCs of skull shape variation. We find little difference in the genetic contributions to RD measures and PC scores, suggesting fundamental similarities in the magnitude of genetic contributions to both specific and summary measures of craniofacial phenotypes. Our results indicate that there are stronger additive genetic effects associated with defining phenotypic characteristics of specific founder strains, suggesting these distinguishing measures are good candidates for use in genotype-phenotype association studies of CC mice. Our results add significantly to understanding of genotype-phenotype associations in the skull, which serve as a foundation for modeling the origins of medically and evolutionarily relevant variation.


Francisella tularensis regulates autophagy-related host cell signaling pathways.
The Gram-negative intracellular pathogen Francisella tularensis is known for its ability to dampen host immune responses. We recently performed a microarray analysis comparing human monocyte responses to the highly virulent F. tularensis tularensis Schu S4 strain (F.t.) versus the less virulent F. tularensis novicida (F.n.).(1) Many groups of genes were affected, including those involved with autophagy and with the regulation of autophagy. Here, we discuss the implications in the context of Francisella virulence and host cell response, then conclude with potential future experiments.


Viral metagenomic sequencing in a cohort of international travellers returning with febrile illness.
Diagnosis of infections in returning international travellers can be challenging because of the broad spectrum of potential infectious etiologies potentially involved. Viral metagenomic next-generation sequencing (mNGS) has the potential to detect any virus present in a patient sample and is increasingly being used for difficult to diagnose cases. The aim of this study was to analyze the performance of mNGS for viral pathogen detection in the clinical setting of international travellers returning with febrile illness. Thirty-eight serum samples from international travellers returning with febrile illness and presenting at the outpatient clinic of the Leiden University Medical Center in the Netherlands in the time period 2015-2016 were selected retrospectively. Samples were processed for viral metagenomic sequencing using a probe panel capturing all known vertebrate viruses. Bioinformatic analysis was performed using Genome Detective software for metagenomic virus detection. Metagenomic virus findings were compared with viral pathogen detection using conventional methods. In 8 out of the 38 patients (21%), a pathogenic virus was detected by mNGS. All viral pathogens detected by conventional assays were also detected by mNGS: dengue virus (n=4 patients), Epstein-Barr virus (n=2), hepatitis B virus (n=1). In addition, mNGS resulted in additional pathogenic findings in 2 patients (5%): dengue virus (n=1), and hepatitis C virus (n=1). Non-pathogenic viruses detected were: GB virus C (n=1) and torque teno viruses (n=3). High genome coverage and depth using capture probes enabled typing of the dengue viruses detected. Viral metagenomics has the potential to assist the detection of viral pathogens and co-infections in one step in international travellers with a febrile syndrome. Furthermore, viral enrichment by probes resulted in high genome coverage and depth which enabled dengue virus typing.


Acoustofluidic black holes for multifunctional in-droplet particle manipulation.
Acoustic black holes offer superior capabilities for slowing down and trapping acoustic waves for various applications such as metastructures, energy harvesting, and vibration and noise control. However, no studies have considered the linear and nonlinear effects of acoustic black holes on micro/nanoparticles in fluids. This study presents acoustofluidic black holes (AFBHs) that leverage controlled interactions between AFBH-trapped acoustic wave energy and particles in droplets to enable versatile particle manipulation functionalities, such as translation, concentration, and patterning of particles. We investigated the AFBH-enabled wave energy trapping and wavelength shrinking effects, as well as the trapped wave energy-induced acoustic radiation forces on particles and acoustic streaming in droplets. This study not only fills the gap between the emerging fields of acoustofluidics and acoustic black holes but also leads to a class of AFBH-based in-droplet particle manipulation toolsets with great potential for many applications, such as biosensing, point-of-care testing, and drug screening.


Raltitrexed plus oxaliplatin in the treatment of metastatic colorectal cancer.
As raltitrexed and oxaliplatin (L-OHP) are both effective in the treatment of colorectal cancer but have different mechanisms of action, we studied the antitumoral activity and safety of their combined use in patients with advanced colorectal cancer. A 15-min intravenous infusion of raltitrexed (2.5 mg/m2) and a 180-min infusion of oxaliplatin (100 mg/m2) were administered on day 1 every three weeks for a maximum of six cycles. The study involved 51 patients (27 males and 24 females) with a median age of 65 years (range, 43-78); 28 were aged > or = 65 years. The primary tumor site was the colon in 35 patients and the rectum in 16. Thirty-four patients had received prior chemotherapy: 20 as adjuvant treatment and 14 as pretreatment. The most frequent metastatic sites were liver (18 cases), lung (10 cases), liver + lung (8 cases) and lymph nodes (3 cases). Twenty-four patients completed the entire treatment plan. The most common toxicities were transaminitis (16 patients, grade 3-4), diarrhea (six patients, grade 3), nausea/vomiting (one patient, grade 4), and asthenia (one patient, grade 3). The treatment was stopped in one patient because of prolonged grade 4 transaminitis. The adverse event profile was similar in the patients aged > 65 years and < 65 years. Complete responses were observed in 2 patients, partial responses in 12, stable disease in 23, and progression in 8. The results of the study suggest that the raltitrexed plus oxaliplatin regimen is feasible and clinically active in advanced colorectal cancer.


Case-control study of anthropometric measures and breast cancer risk.
A population-based case-control study of 1,233 incident breast cancer cases and 1,241 controls was conducted in Alberta between 1995 and 1997 to examine the influence of anthropometric factors on the risk of breast cancer using several newly derived variables. Data on current height, weight and waist and hip circumference were collected by interviewers using standardized methods. Respondents recalled their body weight at each decade from age 20 to the referent year. Several variables were estimated, and unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No statistically significant associations for any of the estimated variables with breast cancer risk for premenopausal women (462 cases, 475 controls) were found. The results for postmenopausal women (771 cases, 762 controls) in the highest vs. lowest quartiles were, for waist circumference, OR = 1.30 (95% CI 0.97-1.73); waist-hip ratio, OR = 1.43 (95% CI 1.07-1.93); weight gain since age 20, OR = 1.35 (05% CI 1.01-1.81); difference between maximum and minimum weights over adult lifetime, OR = 1.56 (95% CI 1.16-2.08); and the reference weight minus the minimum weight since age 20, OR = 1.47 (95% CI 1.10-1.97). Statistically significant trends in risk were observed for these variables. Effect modification with hormone replacement therapy use was found for most variables assessed for postmenopausal women, with much stronger associations found among never-users compared to ever-users. We found strong evidence that waist-hip ratio and weight gained over lifetime, as assessed by different variables, are postmenopausal breast cancer risk factors. These effects were independent of dietary intake and lifetime total physical activity.


Granulocyte-macrophage colony-stimulating factor induces the expression of the CD11b surface adhesion molecule on human granulocytes in vivo.
The CD11b (Mol) molecule is a member of a family of surface glycoproteins that are essential for adhesion-dependent granulocyte functions. Brief exposure of granulocytes to human granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro increases the surface expression of CD11b and increases granulocyte adhesiveness. To assess the possible in vivo significance of these observations we studied the effect of GM-CSF on CD11b, CD11a (LFA-1), and CD11c (gp 150, 95) expression on granulocytes from nine adult patients with sarcoma who were receiving GM-CSF as part of a phase I trial. GM-CSF was administered as a continuous infusion at a dose of 32 or 64 micrograms/kg/d. Granulocyte CD11b, CD11a, and CD11c expression was determined by indirect immunofluorescence staining of whole blood, thereby minimizing in vitro manipulation. A transient leukopenia developed within 15 minutes of initiation of GM-CSF treatment that was associated with a marked increase in the surface antigen density of CD11b. A mean 1.7-fold increase (P = .001) in the percentage of CD11b-positive granulocytes and a mean 2.1-fold increase (P = .002) in CD11b surface antigen density was noted after 12 hours of treatment. No change in CD11a or CD11c expression was observed over the first 12 hours. The level of CD11b expression was followed in six patients for up to 5 days of treatment with GM-CSF. Compared with the 12-hour value, three of six patients showed a subsequent decrease in CD11b expression, two remained constant, and one showed a continued increase in CD11b surface density. Fluorescence-activated cell sorting of granulocytes into high- and low-density CD11b-positive groups revealed a preponderance of immature myeloid forms in the low-density CD11b fraction, which suggests that the late decrease in CD11b expression in some patients may be related to a greater proportion of circulating immature myeloid forms in the peripheral blood. This study suggests that GM-CSF administered as a continuous infusion rapidly upregulates the expression of granulocyte CD11b in vivo. The influence of this phenomenon on in vivo granulocyte aggregation may be clinically relevant with regard to the toxicity of GM-CSF and deserves further investigation.


Hydroxyl-Boosted Nitrogen Reduction Reaction: The Essential Role of Surface Hydrogen in Functionalized MXenes.
MXenes, an emerging family of two-dimensional (2D) metal carbides and nitrides, have been demonstrated to be effective nitrogen reduction reaction (NRR) catalysts. So far, most of the theoretical studies toward NRR are based on bare MXenes; however, the structural stabilities are questionable. In this work, we studied the NRR process on several synthesized MXenes (Ti2C, V2C, Cr2C, Zr2C, Nb2C, Mo2C, Hf2C, and Ta2C) with hydroxyl (OH) termination since the structures are preferred under NRR operating conditions as per Pourbaix stability diagrams. It is found that OH plays an essential role in tuning the NRR chemistry, as a new surface-hydroxylation mechanism. Different from the widely accepted NRR mechanism where only protons are involved in the reaction, hydrogen (H) atoms from surface hydroxyl could be captured by the intermediate and participate into the NRR, while the remaining H vacancy can subsequently be self-repaired by the protons under the applied potential. The cooperative effect of surface hydroxylation can effectively boost the NRR, while Mo2C(OH)2 stands out with the most favorable limiting potential of -0.62 V and highest selectivity. Moreover, new scaling relationships based on the H vacancy energy are established, elucidating the possibility for structure-activity tuning. This study not only elaborates the essential role of surface OH functionalization in evaluating NRR performance but also affords new insights into advance sustainable NH3 production.


Cytochrome P450 1A1 expression and activity in Caco-2 cells: modulation by apple juice extract and certain apple polyphenols.
Cytochrome P450 (CYP) 1A1 plays a role in drug metabolism of intestinal cells (e.g., by activating certain chemical carcinogens such as polycyclic aromatic hydrocarbons into carcinogenic metabolites). In the human colon carcinoma cell line Caco-2, we investigated the effects of a defined polyphenolic apple juice extract (AJE), the major principle flavonoid/dihydrochalkone constituents quercetin and phloretin, and the corresponding prototype glycosides rutin and phlorizin on CYP1A1 expression and activity. Incubations were carried out with or without the potent aryl hydrocarbon receptor agonist/CYP1A1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AJE and quercetin acted as weak inducers of CYP1A1 mRNA and protein, and AJE, quercetin, and phlorizin led to a slight induction of CYP1A1-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity. However, AJE, quercetin, and phloretin were highly effective in suppressing CYP1A1 induction in co-incubations of the cells with 1 nM TCDD. The antagonistic effects were seen on the levels of mRNA, enzyme protein, and catalytic activity. In contrast, the related glycosides rutin and phlorizin were inactive as inducers or inhibitors. Inhibition of CYP1A1 induction was not related to general cytotoxicity, which could be completely abolished by the addition of ascorbic acid/alpha-tocopherol. AJE, quercetin, and phloretin also antagonized the TCDD-mediated induction of a reporter gene driven by a regulatory sequence of the human CYP1A1 gene promoter. Our findings suggest that apple juice extract can antagonize TCDD-mediated CYP1A1 induction by interfering with AhR-dependent gene transcription and by inhibiting the catalytic activity of CYP1A1. These effects may result in reduced metabolic activation of certain chemical carcinogens, in particular, under conditions of sustained AhR activation.


The impact of the transversus abdominis plane block (TAP) on stress response measured through the complete blood- derived inflammatory markers.
This study aims to evaluate the effect of the transversus abdominis plane (TAP) block on the blood cells and the inflammatory markers neutrophil- to- lymphocyte ratio (NLR), platelet- to- lymphocyte ratio (PLR), and systemic immune- inflammation index (SII) after the laparoscopic ovariectomy (LapOV) in dogs. 72 healthy bitches undergoing LapOV were randomly allocated to the no- TAP group of dogs under inhaled anesthesia (IA), the TAP- S group (IA and TAP with saline), and the TAP- B group (IA and TAP with bupivacaine). The NLR, PLR, and SII were calculated 1 h before ovariectomy (T0) and at 2-3 h (T1), 6-8 h (T2), and 20-24 h (T3) post- surgery. The number of dogs requiring postoperative analgesic rescue with buprenorphine and the doses administered in each group were recorded. Significant changes were observed in all groups' postoperative NLR, PLR, and SII over time. Between groups, no differences were observed in any of the ratios at any control point (NLR at T0-T3: p = 0.17, 0.36, 0.80, and 0.95; PLR at T0-T3: p = 0.70, 0.62, 0.21, 0.87; SII at T0-T3: p = 0.29, 0.65, 0.09, and 0.34). A significantly lower number of dogs required analgesic rescue in the TAP-B group (p = 0.0001) and a lower number of doses were administered (p = 0.001). There is no difference in the inflammatory response measured through the complete blood- derived inflammatory markers after the LapOV in dogs when the postoperative pain is managed entirely with opioids or with the TAP block with bupivacaine. The hydrodissection associated with the TAP block technique does not increase the inflammatory response.


Effect of phenol on ultra structure and plasmid DNA of Xanthomonas oryzae pv. oryzae.
Most phenolic substances of plant origin are toxic to microorganisms and they confer some degree of protection to plants against phytopathogens. Xanthomonas oryzae pv. oryzae, bacterial blight pathogen of rice (Oryza sativa) was treated with phenol (monohydroxy benzene) and its effects on the morphology and cytological changes of the bacterium were studied. Total lysis of cells occurred with 5 mM conc of phenol while at 2 mM conc, the cell walls became rough and cell contents started shrinking. Plasmids isolated from both treated (2 mM) and control cells did not show any marked difference under electron microscope except that they differed in their quantity and might influence pathogenicity.


Contact screen image subtraction technique.
Experimental results have clearly demonstrated that the newly proposed optical contact screen pulse-width modulation image subtraction technique can be used for the evaluation both qualitative and quantitative of the subtle differences between two similar images.


Association of Baseline Neutrophil-to-Lymphocyte Ratio with Clinicopathological Characteristics of Papillary Thyroid Carcinoma.
To investigate the potential association of neutrophil-to-lymphocyte ratio (NLR), a surrogate systemic inflammatory biomarker, with clinical and pathological characteristics of papillary thyroid cancers. 205 patients with papillary carcinoma were identified from the institutional thyroid cancer database between 2006 and 2015 (55 males, 150 females, mean age 51.2 ± 14.7 years). NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count, based on the preoperative complete blood cell counts. NLR was significantly higher in carcinomas with extrathyroidal invasion (2.74 ± 01.24 versus 2.39 ± 0.96, p = 0.04) and bilateral (2.67 ± 1.15 versus 2.35 ± 0.96, p = 0.03) and multifocal tumours (2.65 ± 1.08 versus 2.29 ± 0.96, p = 0.01), as well as lymph node-positive tumours (3.12 ± 1.07 versus 2.41 ± 1.02, p = 0.03). On the other hand, NLR values were not associated with gender, age, tumour size, histologic subtype, the presence of thyroiditis, and TNM staging. As an index of inflammation, NLR is inexpensive, readily available, and easy to extract from routine blood tests. We found increased NLR values in papillary carcinomas with poorer histopathological profile and more aggressive clinical behaviour. Whether this systemic inflammatory response, as expressed by the NLR, represents the inflammatory microenvironment leading to tumourigenesis, or is a tumour-associated phenomenon, remains to be elucidated and warrants further study.


[Qualitative und quantitative salmonella investigations and their hygienic valuation in connection with the E. coli titre, demonstrated with examples from the coastal waters of Kiel bight (Western Baltic Sea) (author's transl)].
Qualitative salmonella investigations and E. coli titre determinations were carried out in about 4,000 water samples taken from the coastal region of Kiel Bight (Western Baltic) in 1972 and 1973, and evaluated in connection with epidemiological data. Further, about 100 samples were determined quantitatively by the MPN method and set in relation to the E. coli titre. The significance to be attributed to positive salmonella findings particularly in relation to the assessment of risk of infection and as impurity indicators was investigated with reference to this material. A comparison of salmonella findings and E. coli titre showed that with increasing E. coli contamination the proportion of positive salmonella findings also increased (paraboloid curve). Salmonella frequencies and the frequency with which the limiting values of the E. coli titre is exceeded run approximately parallel; the frequency of exceeding a limiting value of E. coli titre of 1.0 and the frequency of salmonella (determination in 100 ml) in sewage laden areas largely coincide. The quantitative salmonella investigations (MPN method) also showed that up to an E. coli titre of 1.0 extremely low salmonella counts only are to be expected (on the average, less than 2/100 ml). With an E. coli titre of 0.1, a marked increase can be seen. A limiting value of 1.0 is proposed for the E. coli titre in coastal waters. Epidemiological data have also shown that an increased risk of infection could not be deduced from positive salmonella findings. According to the present investigations, the value of the information obtained from salmonella findings is small compared with the E. coli titre. Considering the great expense of laboratory investigations, tests for salmonella should be dispensed with in routine examination of water.


Babesia infection through blood transfusions: reports received by the US Food and Drug Administration, 1997-2007.
Human babesiosis is an illness with clinical manifestations that range from asymptomatic to fatal. Although babesiosis is not nationally notifiable, the US incidence appears to be increasing. Babesia infection is a transfusion-transmissable disease. An estimated 70 cases were reported during 1979-2007; most of these cases were reported during the past decade. We queried the 3 following US Food and Drug Administration safety surveillance systems to assess trends in babesiosis reporting since 1997: fatality reports for blood donors and transfusion recipients, the Adverse Event Reporting System (which includes MedWatch), and the Biological Product Deviations Reporting system.We analyzed fatality reports for time frames, clinical presentations, and patient and donor demographic characteristics. Eight of 9 deaths due to transfusion-transmitted babesiosis that were reported since 1997 occurred within the past 3 years (2005-2007). Four implicated donors and 5 patients lived in areas where Babesia infection is not endemic. Increasing numbers of Biological Product Deviations Reports were submitted to the US Food and Drug Administration over the past decade; the Adverse Event Reporting System received no reports. After nearly a decade with no reported death due to transfusion-transmitted babesiosis, the US Food and Drug Administration received 8 reports from November 2005 onward. The increased numbers of deaths reported and Biological Product Deviations Reports suggest an increasing incidence of transfusion-transmitted babesiosis. Physicians should consider babesiosis in the differential diagnosis in immunocompromised, febrile patients with a history of recent transfusion, even in areas where Babesia infection is not endemic. Accurate and timely reporting of babesiosis-related donor and transfusion events assists the US Food and Drug Administration in developing appropriate public health-control measures.


Rural initiatives at the James Cook University School of Medicine: a vertically integrated regional/rural/remote medical education provider.
Building on the success of the former North Queensland Clinical School/Royal Australian College of General Practitioners collaboration in North Queensland, the James Cook University School of Medicine continues to develop a model of close collaboration with stakeholder groups that provides medical education services to dispersed communities in northern Australia. The flagship themes of the programme (rural & remote, Indigenous and tropical health) are essential to the regional mission to improve the health care of people in northern Australia. Selection processes target regional and rural background students and Aboriginal and Torres Strait Islander students. An innovative curriculum design reinforces interest in and relevance to regional health needs. The present paper provides an overview of the roles and early progress of the new School of Medicine, with the aim of keeping rural doctors informed about the continuing development of a successful 'national standards/local collaboration and control' model of education service delivery.


Cicatricial alopecia.
Cicatricial alopecias (CAs) are clinical pathological conditions that result in the complete destruction of hair follicles, which are replaced by fibrotic structures. Clinically they are characterized by different inflammatory conditions resulting in the end stage in the complete disappearance of hair follicle and follicular ostia. CAs are classified in primary cicatricial alopecia (PCA) and secondary cicatricial alopecia (SCA). PCA include multiple inflammatory diseases with distinctive clinical and histopathologic features that primarily affect and destroy the hair follicle. On the other way, diseases classified as SCA include inflammatory and neoplastic conditions and physical traumas usually primarily affecting the dermis and causing secondary follicular destruction.


Inhaled nickel nanoparticles alter vascular reactivity in C57BL/6 mice.
The use of nanoparticles (NPs) in technological applications is rapidly expanding, but the potential health effects associated with NP exposure are still largely unknown. Given epidemiological evidence indicating an association between inhaled ambient ultrafine particles and increased risk of cardiovascular disease morbidity and mortality, it has been suggested that exposure to NPs via inhalation may induce similar cardiovascular responses. Male C57BL/6 mice were exposed via whole-body inhalation to either filtered air (FA) or nickel hydroxide (NH) NPs (100, 150, or 900 µg/m(3)) for 1, 3, or 5 consecutive days (5 h/day). At 24-h post-exposure, vascular function in response to a vasoconstrictor, phenylephrine (PE), and a vasodilator, acetylcholine (ACh), was measured in the carotid artery. Carotid arteries from mice exposed to all concentrations of NH-NPs showed statistically significant differences in graded doses of PE-induced contractile responses compared with those from FA mice. Similarly, vessels from NH-NP-exposed mice also demonstrated impaired vasorelaxation following graded doses of ACh as compared with FA mice. These results suggest that short-term exposure to NH-NPs can induce acute endothelial disruption and alter vasoconstriction and vasorelaxation. These findings are consistent with other studies assessing vascular tone and function in the aorta, coronary, and mesenteric vessels from mice exposed to motor vehicular exhaust and concentrated ambient particles.


'I think my future will be better than my past': examining support group influence on the mental health of HIV-infected Rwandan women.
Urgent need exists for improved psychological services among HIV-infected women in post-genocide Rwanda. Psychological problems associated with trauma and sexual violence (i.e., depression, posttraumatic stress disorder [PTSD]) place women at increased risk for sexual risk behaviour, low health-seeking behaviour, delay of antiretroviral therapy (ART) and reduced ART adherence. We explored experiences of HIV-infected Rwandan women attending psychosocial support groups and their narratives about how participation affected their mental health and HIV treatment. Focus group discussions examined participants' reasons for support group attendance, perceived psychological benefit of support groups, influence on ART adherence, and other influences on health behaviors and attitudes. Rwandan women (aged 18-65) were randomly selected from 10 health clinic-facilitated support groups for HIV-infected trauma survivors in Kigali. Results identified positive psychological and physical changes as well as behaviour changes in relationships with men, which participants attributed to support group attendance. Data showed significant improvement in mental health, ART adherence and HIV serostatus disclosure resulting from group attendance. Participants acknowledged limitations of support groups with respect to addressing poverty and hunger. Implementing psychosocial support groups may leverage clinical outcomes and rejuvenate the well-being of HIV-infected women with interpersonal trauma and/or PTSD and depressive symptoms, particularly those from post-conflict countries.


Aggregated gene co-expression networks predict transcription factor regulatory landscapes in grapevine.
Gene co-expression networks (GCNs) have not been extensively studied in non-model plants. However, the rapid accumulation of transcriptome datasets in certain species represents an opportunity to explore underutilized network aggregation approaches. In fact, aggregated GCNs (aggGCNs) highlight robust co-expression interactions and improve functional connectivity. We applied and evaluated two different aggregation methods on public grapevine RNA-Seq datasets from three different tissues (leaf, berry, and 'all organs'). Our results show that co-occurrence-based aggregation generally yielded the best-performing networks. We applied aggGCNs to study several transcription factor gene families, showing their capacity for detecting both already-described and novel regulatory relationships between R2R3-MYBs, bHLH/MYC, and multiple specialized metabolic pathways. Specifically, transcription factor gene- and pathway-centered network analyses successfully ascertained the previously established role of VviMYBPA1 in controlling the accumulation of proanthocyanidins while providing insights into its novel role as a regulator of p-coumaroyl-CoA biosynthesis as well as the shikimate and aromatic amino acid pathways. This network was validated using DNA affinity purification sequencing data, demonstrating that co-expression networks of transcriptional activators can serve as a proxy of gene regulatory networks. This study presents an open repository to reproduce networks in other crops and a GCN application within the Vitviz platform, a user-friendly tool for exploring co-expression relationships.


Helical lanthanide(III) complexes with chiral nonaaza macrocycle.
The chiral nonaazamacrocyclic amine L, which is a reduction product of the 3 + 3 Schiff base macrocycle, wraps around the lanthanide(III) ions to form enantiopure helical complexes. These Ce(III), Pr(III), Nd(III), Eu(III), Gd(III), Tb(III), Er(III), Yb(III) and Lu(III) complexes have been isolated in enantiopure form and have been characterized by spectroscopic methods. X-ray crystal structures of the Ln(III) complexes with L show that the thermodynamic product of the complexation of the RRRRRR-isomer of the macrocycle is the (M)-helical complex in the case of Ce(III), Pr(III), Nd(III) and Eu(III). In contrast, the (P)-helical complex is the thermodynamic product in the case of Yb(III) and Lu(III). The NMR and CD spectra show that the (M)-helicity for the kinetic complexation product of the RRRRRR-isomer of the macrocycle is preferred for all investigated lanthanide(III) ions, while the preferred helicity of the thermodynamic product is (M) for the early lanthanide(III) ions and (P) for the late lanthanide(III) ions. In the case of the late lanthanide(III) ions, a slow inversion of helicity between the kinetic (M)-helical product and the thermodynamic (P)-helical product is observed in solution. For Er(III), Yb(III) and Lu(III) both forms have been isolated in pure form and characterized by NMR and CD. The analysis of 2D NMR spectra of the Lu(III) complex reveals the NOE correlations that prove that the helical structure is retained in solution. The NMR spectra also reveal large isotopic effect on the 1H NMR shifts of paramagnetic Ln(III) complexes, related to NH/ND exchange. Photophysical measurements show that L(RRRRRR) appears to favor an efficient 3pipi*-to-Ln energy transfer process taking place for Eu(III) and Tb(III), but these Eu(III)- and Tb(III)-containing complexes with L(RRRRRR) lead to small luminescent quantum yields due to an incomplete intersystem crossing (isc) transfer, a weak efficiency of the luminescence sensitization by the ligand, and/or efficient nonradiative deactivation processes. Circularly polarized luminescence on the MeOH solutions of Eu(III) and Tb(III) complexes confirms the presence of stable chiral emitting species and the observation of almost perfect mirror-image CPL spectra for these compounds with both enantiomeric forms of L.


Morphological Development of Eggs, Larvae and Juveniles of the Far Eastern Catfish, Silurus asotus in Korea (Pisces: Siluridae).
This study was conducted to investigate egg development and larvae morphological development of catfish and to provide basic data to clarify the genetic relationship with Siluriformes fish. The mother fish that was used in this study was caught in the stream of Nakdong River in Uiseong-gun, Gyeongbuk. The temperature range of the breeding was 23.0-25.0℃ (mean 24.0±1.0℃) and egg size was 1.62-1.70 mm (mean 1.66±0.05, n=30). Eggs of catfish began hatching at 54 hours and 40 minutes after fertilization. Immediately after hatching, the total length of larvae was 3.60-3.65 mm (mean 3.62±0.03, n=5) and had an egg yolk without swimming ability. On the third day after hatching, the larvae at the medium stage was 8.00-8.65 mm (mean 8.32±0.45) in total length, and two pairs of whiskers formed around the mouth were elongated. On the 12th day after hatching, the larvae at the juvenile stage was 16.5-17.0 mm (mean 16.7±0.35) in total length, and the stem of each fin was in the range, and the juvenile at this period was morphologically similar to the mother fish.


Chronic Helicobacter pylori infection results in gastric hypoacidity and hypergastrinemia in wild-type mice but vagally induced hypersecretion in gastrin-deficient mice.
Helicobacter pylori infection is a causal factor of gastric cancer (which is associated with low gastric acid secretion) or duodenal ulcer (high acid secretion). Parietal cells and ECL cells in the stomach are controlled by gastrin, which plays a crucial role in the regulation of acid secretion. The present study was undertaken to identify a possible role of gastrin in determining the different responses of the parietal cells and ECL cells to chronic H. pylori infection. Wild-type (C57BL/6J) gastrin(+/+) mice and gastrin(-/-) knockout mice, generated through targeted gene disruption and backcrossed eight times to C57BL/6J, were infected with H. pylori for 9 months. The acid output was measured 4 h after pylorus ligation (known to cause vagal excitation). The gastric mucosa was examined by immunocytochemistry with antisera to alpha-subunit of H+/K(+)-ATPase for the parietal cells, and to histamine and vesicle monoamine transporter-2 for the ECL cells, and by quantitative electron microscopy. In infected gastrin(+/+) mice, the acid output and the percentage of secreting parietal cells (freely fed state) were 20-30% of the values in uninfected controls, while the density and ultrastructure of parietal cells were normal. The infected mice had hypergastrinemia and displayed hypertrophy and hyperplasia of ECL cells. Although uninfected gastrin(-/-) mice had lower the acid output than uninfected gastrin(+/+) mice, there was a higher acid output (approximately 3 times) in infected gastrin(-/-) mice than their uninfected homologues. The numbers of parietal cells and ECL cells remained unchanged in infected gastrin(-/-) mice. In conclusion, chronic H. pylori infection results to impaired parietal-cell function (acid hyposecretion), hypergastrinemia and hyperplasia of ECL cells in wild-type mice but leads to vagally induced hypersecretion in gastrin-deficient mice.


Forward-backward asymmetry in electron impact ionization of CO.
We experimentally investigate the molecular-orientation dependence of high-energy electron-impact ionization of CO. The direction of the molecular-axis with respect to the momentum transfer vector K is deduced from the angular correlation between the fragment ion and the scattered electron. The experimental results on the 3 2Π ionization reveal that at small momentum transfer, the ionization probability near the threshold is higher when K points toward the C atom along the molecular axis than when it is in the opposite direction. Such a forward-backward asymmetry does not appear in single-photon ionization and requires non-dipole contributions. It is also shown that the {4 2Σ+ + 5 2Σ+ + 6 2Σ+} ionization preferentially takes place in the vicinity of the molecular orientation parallel to K at small momentum transfer, while non-dipole contributions cause the decrease in the relative intensity of the parallel direction.


FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin.
DNA segments that actively regulate transcription in vivo are typically characterized by eviction of nucleosomes from chromatin and are experimentally identified by their hypersensitivity to nucleases. Here we demonstrate a simple procedure for the isolation of nucleosome-depleted DNA from human chromatin, termed FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements). To perform FAIRE, chromatin is crosslinked with formaldehyde in vivo, sheared by sonication, and phenol-chloroform extracted. The DNA recovered in the aqueous phase is fluorescently labeled and hybridized to a DNA microarray. FAIRE performed in human cells strongly enriches DNA coincident with the location of DNaseI hypersensitive sites, transcriptional start sites, and active promoters. Evidence for cell-type-specific patterns of FAIRE enrichment is also presented. FAIRE has utility as a positive selection for genomic regions associated with regulatory activity, including regions traditionally detected by nuclease hypersensitivity assays.


Increased Echogenicity and Radiodense Foci on Echocardiogram and MicroCT in Murine Myocarditis.
To address the question as to whether echocardiographic and/or microcomputed tomography (microCT) analysis can be utilized to assess the extent of Coxsackie B virus (CVB) induced myocarditis in the absence of left ventricular dysfunction in the mouse. Viral myocarditis is a significant clinical problem with associated inflammation of the myocardium and myocardial injury. Murine models of myocarditis are commonly used to study the pathophysiology of the disease, but methods for imaging the mouse myocardium have been limited to echocardiographic assessment of ventricular dysfunction and, to a lesser extent, MRI imaging. Using a murine model of myocarditis, we used both echocardiography and microCT to assess the extent of myocardial involvement in murine myocarditis using both wild-type mice and CVB cleavage-resistant dystrophin knock-in mice. Areas of increased echogenicity were only observed in the myocardium of Coxsackie B virus infected mice. These echocardiographic abnormalities correlated with the extent of von Kossa staining (a marker of membrane permeability), inflammation, and fibrosis. Given that calcium phosphate uptake as imaged by von Kossa staining might also be visualized using microCT, we utilized microCT imaging which allowed for high-resolution, 3-dimensional images of radiodensities that likely represent calcium phosphate uptake. As with echocardiography, only mice infected with Coxsackie B virus displayed abnormal accumulation of calcium within individual myocytes indicating increased membrane permeability only upon exposure to virus. These studies demonstrate new, quantitative, and semi-quantitative imaging approaches for the assessment of myocardial involvement in the setting of viral myocarditis in the commonly utilized mouse model of viral myocarditis.


A human herpesvirus 6A-encoded microRNA: role in viral lytic replication.
Human herpesvirus 6A (HHV-6A), a member of the betaherpesvirus family, is associated with several human diseases. Like all herpesviruses, HHV-6A establishes a lifelong, latent infection in its host. Reactivation of HHV-6A is frequent within the immunosuppressed and immunocompromised populations and results in lytic viral replication within multiple organs, often leading to severe disease. MicroRNAs (miRNAs) are key regulators of multiple cellular processes that regulate the translation of specific transcripts. miRNAs carried by herpesviruses play important roles in modulating the host cell, thereby facilitating a suitable environment for productive viral infection and/or latency. Currently, there are approximately 150 known human herpesvirus-encoded miRNAs, although an miRNA(s) encoded by HHV-6A has yet to be reported. We hypothesized that HHV-6A, like other members of the human herpesvirus family, encodes miRNAs, which function to promote viral infection. We utilized deep sequencing of small RNA species isolated from cells harboring HHV-6A to identify five novel small noncoding RNA species that originate from the viral genome, one of which has the characteristics of a viral miRNA. These RNAs are expressed during productive infection by either bacterial artificial chromosome (BAC)-derived virus in Jjhan cells or wild-type HHV-6A strain U1102 virus in HSB2 cells and are associated with the RNA induced silencing complex (RISC) machinery. Growth analyses of mutant viruses that lack each individual miRNA revealed that a viral miRNA candidate (miR-U86) targets the HHV-6A IE gene U86, thereby regulating lytic replication. The identification and biological characterization of this HHV-6A-specific miRNA is the first step to defining how the virus regulates its life cycle. A majority of the human population is infected with human herpesvirus 6A (HHV-6A), a betaherpesvirus family member. Infections usually occur in young children, and upon resolution, the virus remains in a latent state within the host. Importantly, during times of weakened immune responses, the virus can reactivate and is correlated with significant disease states. Viruses encode many different types of factors that both undermine the host antiviral response and regulate viral replication, including small RNA species called microRNAs (miRNAs). Here we report that HHV-6A encodes at least one miRNA, which we named miR-U86. We have characterized the requirement of this viral miRNA and its impact on the viral life cycle and found that it functions to regulate a viral protein important for efficient viral replication. Our data suggest that viral miRNAs are important for HHV-6A and that they may serve as an important therapeutic target to inhibit the virus.


Physical growth patterns and dental caries in thalassemia.
This study was conducted to assess the effect of age, ferritin level, hemoglobin level and chelating agents on the physical growth in thalassemic children and to determine the prevalence of dental caries in thalassemic children. Weight, standing height, sitting height and subischial leg length were measured in 65 children attending the Thalassemia day care center at a tertiary hospital in Delhi. Their mean pre transfusion hemoglobin and ferritin levels over the previous two years were calculated. Dental caries indices, DMFT and DMFS were measured and compared with age matched controls. Weight, standing height, sitting height and subischial leg length expressed as percentage for age in children >or=10 y were significantly lower than those of children < 6 y, and those 6 to 10 y. Mean hemoglobin and ferritin did not affect growth significantly. Sitting height for age in children receiving Desferrioxamine alone or Desferrioxamine with Deferiprone was significantly lower than that of children receiving Deferiprone alone or no chelating agent. Dental caries were significantly higher in thalassemics.


Japanese Encephalitis: Estimating Future Trends in Asia.
Limited surveillance programs and lack of diagnostic laboratory testing capacity in many low and middle income Asian countries have made it difficult to validate epidemiological patterns and anticipate future changes in disease risk. In this study, we consider the case of Japanese Encephalitis in Asia and examine how populations of human hosts and animal reservoirs are expected to change over the next three decades. Growth was modelled at the sub-national level for rural and urban areas to estimate where high-density, susceptible populations will potentially overlap with populations of the virus' amplifying host. High-risk areas based on these projections were compared to the current distribution of Japanese Encephalitis, and known immunization activities in order to identify areas of highest priority for concern. Results indicated that mapping JE risk factors at the sub-national level is an effective way to contextualize and supplement JE surveillance data. New patterns of risk factor change occurring in Southeast Asia were identified, including around major urban areas experiencing both urbanization and growth in pig populations. A hotspot analysis of pig-to-population ratio found a significant spatial cluster extending northward through Southeast Asia and interior China. Mapping forecasted changes in risk factors for JE highlights regions vulnerable to emerging zoonoses and may be an important tool for developing effecting transnational health policies.


Platelet Count in First Trimester of Pregnancy as a Predictor of Perinatal Outcome.
To rule out maternal and pregnancy factors that may contribute to platelet count (PLT) changes in the first trimester of gestation and examine if there is any association between its levels and adverse perinatal outcome. The study population included all patients from the first-trimester visit between 2013-2015 with pregnancy results. Linear multiple regression was constructed to rule out variables that may have a significant contribution to PLT. For each adverse outcome at birth, multiple logistic regression analysis was implemented to estimate the PLT effect. PLT was measured in 6092 patients. There was the significant contribution on PLT in the first trimester from maternal weight, the presence of rheumatologic disease, BHCG levels and MPV. There was a significant association between PLT and abnormal cardiotocography at delivery (OR 1.004; IC95% 1.001 to 1.007) and C-Section due to abnormal CTG (OR 1.005; IC95% 1.002 to 1.008). When adjusted for factors that interact with PLT there was also a significant association with pH at birth < 7.10 and gestational diabetes. Maternal and pregnancy factors can poorly predict relevant changes in PLT at the first trimester of gestation. PLT at first trimester of pregnancy might predict adverse perinatal outcome in combination with other markers.


Thermal Dynamics of Charge Density Wave Pinning in ZrTe_{3}.
Impurity pinning has long been discussed to have a profound effect on the dynamics of an incommensurate charge density wave (CDW), which would otherwise slide through the lattice without resistance. Here, we visualize the impurity pinning evolution of the CDW in ZrTe_{3} using the variable temperature scanning tunneling microscopy. At low temperatures, we observe a quasi-1D incommensurate CDW modulation moderately correlated to the impurity positions, indicating a weak impurity pinning. As we raise the sample temperature, the CDW modulation gets progressively weakened and distorted, while the correlation with the impurities becomes stronger. Above the CDW transition temperature, short-range modulations persist with the phase almost all pinned by impurities. The evolution from weak to strong impurity pinning through the CDW transition can be understood as a result of losing phase rigidity.


[Clinical study of percutaneous transhepatic intrahepatic portosystemic shunt].
To introduce an innovative procedure for portal hypertension with preliminary results and assess the technical feasibility and efficacy of portosystemic shunt creation through percutaneous transhepatic approach with its potential clinical significance. Between November 2009 and January 2011, 8 patients with complicated portal hypertension underwent percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS). The severity of liver disease was Child's A (n = 2), Child's B (n = 3) and Child's C (n = 3). Under fluoroscopic guidance, portal vein (PV) was punctured with a 22-gauge Chiba needle. A 0.018-inch guidewire was advanced through the needle into PV lumen. The needle was exchanged and a 7-French sheath inserted over the wire. Then retrohepatic inferior vena cava (RIVC) or hepatic vein (HV) was punctured with a 20-gauge, 20-cm Chiba needle through sheath. Another 0.018-inch guidewire was advanced through the needle into right internal jugular vein and then snared out of body. A 0.035-inch, 260-cm-long stiff shaft wire was then introduced through the transjugular sheath and manipulated into main portal vein (MPV) and then into superior mesenteric vein (SMV). Afterward the PTIPS procedure was completed in the standard transjugular fashion. The procedure was technically successful in all patients. And effective portal decompression and free antegrade shunt flow were achieved. The mean portal pressure gradient decreased from 31.0 ± 4.3 to 18.9 ± 2.7 mm Hg before and after PTIPS creation respectively and the difference was significant statistically (P < 0.01). Among 8 patients, 1 developed hepatic coma and died after 5 days while the other 7 patients survived. The median follow-up period was 9 months (range: 2 - 20). Among 5 patients with PTIPS created for bleeding varices, no recurrent bleeding occurred during the follow-up period. For the patient with diffuse portal vein thrombosis, the clinical symptoms disappeared after PTIPS and computed tomography (CT) showed the shunt was occluded after 4 months. One patient with refractory ascites had a recurrence of abdominal distention after 2 months. There was a stenotic shunt on CT. Cure was achieved by replanting a stent in MPV. PTIPS is both safe and effective for the treatment of portal hypertension with exceptionally challenging anatomy. It is an available supplement for transjugular intrahepatic portosystemic shunt.


Cyclomodulins in urosepsis strains of Escherichia coli.
Determinants of urosepsis in Escherichia coli remain incompletely defined. Cyclomodulins (CMs) are a growing functional family of toxins that hijack the eukaryotic cell cycle. Four cyclomodulin types are actually known in E. coli: cytotoxic necrotizing factors (CNFs), cycle-inhibiting factor (Cif), cytolethal distending toxins (CDTs), and the pks-encoded toxin. In the present study, the distribution of CM-encoding genes and the functionality of these toxins were investigated in 197 E. coli strains isolated from patients with community-acquired urosepsis (n = 146) and from uninfected subjects (n = 51). This distribution was analyzed in relation to the phylogenetic background, clinical origin, and antibiotic resistance of the strains. It emerged from this study that strains harboring the pks island and the cnf1 gene (i) were strongly associated with the B2 phylogroup (P, <0.001), (ii) frequently harbored both toxin-encoded genes in phylogroup B2 (33%), and (iii) were predictive of a urosepsis origin (P, <0.001 to 0.005). However, the prevalences of the pks island among phylogroup B2 strains, in contrast to those of the cnf1 gene, were not significantly different between fecal and urosepsis groups, suggesting that the pks island is more important for the colonization process and the cnf1 gene for virulence. pks- or cnf1-harboring strains were significantly associated with susceptibility to antibiotics (amoxicillin, cotrimoxazole, and quinolones [P, <0.001 to 0.043]). Otherwise, only 6% and 1% of all strains harbored the cdtB and cif genes, respectively, with no particular distribution by phylogenetic background, antimicrobial susceptibility, or clinical origin.


Investigation of SCCmec types I-IV in clinical isolates of methicillin-resistant coagulase-negative staphylococci in Ahvaz, Southwest Iran.
Today methicillin resistant coagulase-negative staphylococci (MR-CoNS) are important in terms of causing significant nosocomial infections. Besides, MR-CoNS are confirmed as the reservoir of SCCmec elements that carry mecA (methicillin-resistant) gene. Hence, the present study was designed to evaluate the susceptibility pattern, prevalence and diversity of SCCmec types I, II, III, and IV in MR-CoNS strains. In this cross-sectional study, 44 clinical isolates of MR-CoNS were identified using the cefoxitin disc method and further confirmation by polymerase chain reaction (PCR) amplification of the mecA gene. Antimicrobial susceptibility of isolates was investigated by disc diffusion. The identification of CoNS was done by amplification and sequencing of the tuf gene. Multiplex PCR method was done for the determination of SCCmec types. In the present study, the Staphylococcus epidermidis and Staphylococcus haemolyticus were the most predominant isolates with a prevalence of 45.4%. The highest resistance rates were observed against erythromycin (84.1%) and clindamycin (75%). Multiplex PCR revealed the SCCmec type I as the predominant type in the present study. Our study showed that there was no significant relationship between the presence of different types of SCCmec elements and resistance to antibiotics. The present study highlighted a frequent prevalence of MR-CoNS harboring SCCmec type genes in Ahvaz, southwest of Iran. Thus, the molecular typing and periodical monitoring of their drug resistance pattern should be considered in national stewardship programs to designing useful antibiotic prescription strategies.


Involvement of interleukin-1 genotypes in the association of coronary heart disease with periodontitis.
Epidemiologic studies demonstrated an association between periodontitis (PE) and coronary heart disease (CHD). The coexistence of the two disease entities could be dependent on mutual risk factors, and polymorphism of the interleukin (IL)-1 gene cluster associated with the severity of PE might also be involved in the pathogenesis of CHD. The study consisted of 225 dentate white subjects, including 97 patients with CHD and 128 controls. Patients with confirmed diagnoses of CHD were recruited after being discharged from a cardiology department, and controls without CHD were recruited consecutively from the Copenhagen City Heart Study. Mean alveolar bone level (ABL) was measured on radiographs. ABL was stratified into ABL1 (ABL < or = 2 mm), ABL2 (2 mm <ABL < or = 4 mm), and ABL3 (ABL >4 mm). Genotypes were analyzed by amplifying the polymorphic regions of the IL-1 gene cluster using polymerase chain reaction, followed by restriction digestion and gel electrophoresis. In the univariate analysis, allele 2 of IL-1B+3954 and IL-1B-511 was associated with ABL (P = 0.040 and P = 0.039, respectively), whereas no association was found with allele 2 of IL-1A+4845 or IL-1RN variable number tandem repeat (VNTR) (P = 0.445 and P = 0.375, respectively). A lower ABL was associated with the occurrence of allele 2 of IL-1B-511. The multiple logistic regression analysis also showed a significant association of allele 1 of IL-1B-511 with high ABL (P = 0.049) and of allele 2 of IL-1A+4845 with high ABL among individuals with CHD (P = 0.050). There was no association between any of the polymorphisms of IL-1 and CHD in the univariate or multiple analyses. However, in a binary multiple logistic regression model, carriage of allele 1 of IL-1RN VNTR was found to be associated with the occurrence of both CHD and ABL3 (P = 0.016). Allele 1 of IL-1RN VNTR may be associated with the coexistence of CHD and PE in a multiple regression model.


Using basic approaches to address applied problems in dairy reproduction.
Poor reproductive efficiency is a worldwide problem affecting the dairy industry. There is substantial evidence for an association between high milk production and lower conception rates observed in cows compared to heifers. However, whether the decline in fertility is due directly to the level of milk production or other factors associated with lactation is unclear. There are various checkpoints along the developmental axis which could, in part, contribute to reduced fertility including suboptimal follicle development associated with poor oestrus exhibition, suboptimal oocyte quality, altered sperm transport and fertilization and/or a suboptimal reproductive tract environment incapable of supporting normal embryo development. The challenge is deciphering where the major problems lie. Evidence for the relative contributions of oocyte quality, embryo quality and the reproductive tract environment is discussed in this paper.


Prospecting for novel biocatalysts in a soil metagenome.
The metagenomes of complex microbial communities are rich sources of novel biocatalysts. We exploited the metagenome of a mixed microbial population for isolation of more than 15 different genes encoding novel biocatalysts by using a combined cultivation and direct cloning strategy. A 16S rRNA sequence analysis revealed the presence of hitherto uncultured microbes closely related to the genera Pseudomonas, Agrobacterium, Xanthomonas, Microbulbifer, and Janthinobacterium. Total genomic DNA from this bacterial community was used to construct cosmid DNA libraries, which were functionally searched for novel enzymes of biotechnological value. Our searches in combination with cosmid sequencing resulted in identification of four clones encoding 12 putative agarase genes, most of which were organized in clusters consisting of two or three genes. Interestingly, nine of these agarase genes probably originated from gene duplications. Furthermore, we identified by DNA sequencing several other biocatalyst-encoding genes, including genes encoding a putative stereoselective amidase (amiA), two cellulases (gnuB and uvs080), an alpha-amylase (amyA), a 1,4-alpha-glucan branching enzyme (amyB), and two pectate lyases (pelA and uvs119). Also, a conserved cluster of two lipase genes was identified, which was linked to genes encoding a type I secretion system. The novel gene aguB was overexpressed in Escherichia coli, and the enzyme activities were determined. Finally, we describe more than 162 kb of DNA sequence that provides a strong platform for further characterization of this microbial consortium.


Role of purified β-1, 3 glucan binding protein (β-GBP) from Paratelphusa hydrodromus and their anti-inflammatory, antioxidant and antibiofilm properties.
β- 1, 3-glucan binding protein (β-GBP), a pattern recognition protein (PRP), plays a critical role in triggering the innate immune response by detecting β-glucan found on the surface of microbes. In the present study, β-GBP was purified from the haemolymph of rice field crab Paratelphusa hydrodromus by affinity column chromatography. The monomeric protein Ph-β-GBP appeared as a single band with a molecular weight of approximately 95 kDa in SDS-PAGE analysis and its purity was determined to be 89% by HPLC. MALDI-TOF/TOF analysis revealed that, the purified 95 kDa protein display 36% similarity with β-GBP of crayfish Astacus lepidodactylus. Purified Ph-β-GBP exhibited increased agglutination, phagocytic activity and encapsulation in a dose-dependent manner, indicating the involvement of Ph-β-GBP in cellular immune response against pathogens in crustaceans. Moreover, addition of Ph-β-GBP increased the prophenoloxidase (proPO) and serine protease activity, possibly contributing to the clearance of pathogens. The antioxidant activity of Ph-β-GBP was determined by DPPH radical scavenging activity demonstrates maximum scavenging activity of 78.4%. In addition, RBC membrane stabilization and inhibition of protein (albumin) denaturation proved anti-inflammatory property of Ph-β-GBP. Furthermore, light microscopic and confocal laser scanning microscopic analysis revealed that the reactive compound (laminarin and Ph-β-GBP) reduced the biofilm thickness of Gram-positive (Enterococcus faecalis) and Gram-negative (Vibrio parahaemolyticus) bacteria at the concentration of 25 μg/ml. Taken together, our results demonstrate that, the β-GBP triggers proPO activating system in rice field crab P. hydrodromus and plays a vital role in innate defense mechanism against invading pathogens.


Factors that influence CNSs' decision about specialization.
Few studies have explored nurses' decision making relative to advanced practice. The purposes of this study were to determine when the decision to prepare as a CNS in a particular specialty is made and to identify the factors that influence that decision. A survey was completed by 257 CNSs. Results indicated that more than half (69%) decided on their specialty after graduation from a basic nursing program. The factors that influenced choice of specialty included experience in first position (47%), clinical role model (37%), and student experience (35%). Critical care was rated the most desirable specialty and psychiatric nursing the least preferred.


The efficiency of design-based stereology in estimating spiral ganglion populations in mice.
Accurate quantification of cell populations is essential in assessing and evaluating neural survival and degeneration in experimental groups. Estimates obtained through traditional two-dimensional counting methods are heavily biased by the counting parameters in relation to the size and shape of the neurons to be counted, resulting in a large range of inaccurate counts. In contrast, counting every cell in a population can be extremely labor-intensive. The present study hypothesizes that design-based stereology provides estimates of the total number of cochlear spiral ganglion neurons (SGNs) in mice that are comparable to those obtained by other accurate cell-counting methods, such as a serial reconstruction, while being a more efficient method. SGNs are indispensable for relaying auditory information from hair cells to the auditory brainstem, and investigating factors affecting their degeneration provides insight into the physiological basis for the progression of hearing dysfunction. Stereological quantification techniques offer the benefits of efficient sampling that is independent of the size and shape of the SGNs. Population estimates of SGNs in cochleae from young C57 mice with normal-hearing and C57 mice with age-related hearing loss were obtained using the optical fractionator probe and traditional two-dimensional counting methods. The average estimated population of SGNs in normal-hearing mice was 7009, whereas the average estimated population in mice with age-related hearing loss was 5096. The estimated population of SGNs in normal-hearing mice fell within the range of values previously reported in the literature. The reduction in the SGN population in animals with age-related hearing loss was statistically significant. Stereological measurements required less time per section compared to two-dimensional methods while optimizing the amount of cochlear tissue analyzed. These findings demonstrate that design-based stereology provides a practical alternative to other counting methods such as the Abercrombie correction method, which has been shown to notably underestimate cell populations, and labor-intensive protocols that account for every cell individually.


Intermittent long-term shedding and induction of carrier birds after infection of chickens early posthatch with a low or high dose of Salmonella enteritidis.
Poultry are very likely to become infected with Salmonella in the early posthatch period, due to environmental contamination. The purpose of this study was to evaluate the effect of infection dose on the risk of persistent infection in laying hens. In this study, young layer chicks were orally infected with a low (10(2) at 1 d posthatch) or a high dose (10(9) cfu at 1 wk posthatch) of Salmonella Enteritidis. The pattern and duration of fecal shedding was studied for 18 wk. All chickens shed Salmonella early after infection and shed Salmonella intermittently during the whole study period. There were more positive birds in the high-dose group than in the low-dose group in the first weeks following Salmonella exposure. From 10 wk postinfection onwards, however, birds that were orally infected with the low dose of Salmonella Enteritidis shed more Salmonella than the birds that received the high dose. At 18 wk of age, there was no difference in cecal colonization between the treatment groups. It can be concluded that infection of newly hatched chicks with a low dose of Salmonella Enteritidis can lead to persistent infection until onset of lay, hereby excreting Salmonella bacteria intermittently.


Development of a multivariable prediction model for patient-adjusted aortic risk morphology.
Preventing type A aortic dissection requires reliable prediction. We developed and validated a multivariable prediction model based on anthropometry to define patient-adjusted thresholds for aortic diameter and length. We analysed computed tomography angiographies and clinical data from 510 control patients, 143 subjects for model validation, 125 individuals with ascending aorta ectasia (45-54 mm), 58 patients with aneurysm (≥55 mm), 206 patients with type A aortic dissection and 19 patients who had received a computed tomography angiography ≤2 years before they suffered from a type A aortic dissection. Computed tomography angiographies were analysed using curved planar reformations. In the control group, the mean ascending aortic diameter was 33.8 mm [standard deviation (SD) ±5.2 mm], and the length, measured from the aortic valve to the brachiocephalic trunk, was 91.9 mm (SD ±12.2 mm); both diameter and length were correlated with anthropometric parameters and were smaller than the respective values in all pathological groups (P < 0.001). Multivariable linear regression analysis of the control group revealed that age, sex and body surface area were predictors of ascending aorta diameter (R2 = 0.40) and length (R2 = 0.26). Bicuspidity of the aortic valve was not included in the model; its prevalence was only 3.2% in the control group but >25% in the ectasia and aneurysm groups. The regression model provides a patient-adjusted prediction of the thresholds for aortic diameter and length. In our retrospective data, the model resulted in better identification of aortas at the risk of dissection than the conventional 55-mm diameter threshold. The model is available as an Internet calculator (www.aorticcalculator.com).


Understanding Nitrilotris(methylenephosphonic acid) reactions with ferric hydroxide.
Phosphonate compounds are used in a wide variety of industrial and agricultural applications, and are commonly found in surface and ground waters. Adsorption to ferric hydroxide can have a significant effect on the transport and fate of phosphonate compounds in the environment. This research used density functional theory modeling to investigate the adsorption mechanisms of nitrilotris(methylenephosphonic acid) (NTMP) on ferric hydroxide. Standard Gibbs free energies of reaction (ΔGro) and reaction activation barriers (Ea) were calculated for different possible adsorption mechanisms. Physical adsorption of NTMP to ferric hydroxide was promoted by negative charge assisted hydrogen bonding, and had ΔGro ranging from -2.7 to -7.4 kcal/mol. NTMP was found to form three different types of inner sphere complexes, monodentate, bidentate mononuclear and bidentate binuclear. For the monodentate complexes, ΔGro ranged from -8.0 to -13.7 kcal/mol, for the bidentate complexes ΔGro ranged from -15.3 to -28.9 kcal/mol. Complexation with Ca2+ decreased the energy for physical adsorption but increased the binding energies for mono- and bidentate complexes. Complexation with Ca2+ also allowed formation of a tridentate ternary surface complex, whereby the Ca2+ ion formed a bridge between three FeO- and three PO- groups. Physical adsorption had Ea = 0, but mono- and bidentate complex formation had Ea values ranging from 36 to 53 kcal/mol. Formation of tridentate ternary surface complexes involving Ca2+ had the lowest activation barriers of 8 and 10 kcal/mol. The different activation barriers for different modes of adsorption may explain previous experimental observations of unusual kinetic behavior for adsorption and desorption of NTMP.


Manganese-Based Nanoplatform As Metal Ion-Enhanced ROS Generator for Combined Chemodynamic/Photodynamic Therapy.
Reactive oxygen species (ROS) with strong oxidizing and high activity have been regarded as an effective "weapon" for antitumor therapy, since it can induce organelle injury, oxidative damage, and cell death. Herein, hollow structured manganese carbonate (MnCO3) nanocubes are fabricated and loaded with photosensitizer (chlorin e6, Ce6), obtaining a responsive nanoplatform H-MnCO3/Ce6-PEG (HMCP NCs). Two different approaches to upregulate intracellular ROS level were realized by HMCP NCs. On one hand, with irradiation of external laser, Ce6 could generate singlet oxygen (1O2) through a multistep photochemical process applied in photodynamic therapy (PDT). On the other hand, MnCO3 could be specifically degraded into Mn2+ in an acidic tumor microenvironment (TME), triggering Mn2+-activated Fenton-like reaction to convert endogenous H2O2 into hydroxyl radical (•OH). In vitro combined chemodynamic therapy (CDT) and PDT showed that the metal ion-enhanced ROS production could break the intracellular redox equilibrium, thus leading to cell death. In vivo combined CDT/PDT with HMCP NCs exhibited remarkably enhanced therapeutic efficacy in inhibiting tumor growth, without resulting in noticeable damage to normal tissues. This work presents a unique type of manganese-based nanoplatform for efficiently generating ROS in solid tumors, favorable for ROS-involved therapeutic strategies.


Digital vascular imaging: two years of clinical experience.
Over 2000 digital vascular imaging studies have been performed at the University of Cincinnati Hospital. During this period, methods and techniques for the performance of these examinations were established. The results of these efforts are reported and compared to angiography. Additionally, the advantages and disadvantages of digital vascular imaging, as well as the future of digital vascular imaging at the University of Cincinnati, are discussed.


Alpha-type phospholipase A2 inhibitors from snake blood.
It is of popular and scientific knowledge that toxins from snake venom (among them the PLA2 and myotoxins) are neutralized by various compounds, such as antibodies and proteins purified from animal blood. Venomous and nonvenomous snakes have PLA2 inhibitory proteins, called PLIs, in their blood serum. One hypothesis that could explain the presence of these PLIs in the serum of venomous snakes would be self-protection against the enzymes of their own venom, which eventually could reach the circulatory system. However, the presence of PLIs in non-venomous snakes suggests that their physiological role might not be restricted to protection against PLA2 toxins, but could be extended to other functions, as in the innate immune system and local regulation of PLA2s. The present study aimed to review the currently available literature on PLA2 and myotoxin alpha inhibitors present in snake plasma, thus helping to improve the research on these molecules. Furthermore, this review includes current information regarding the mechanism of action of these inhibitors in an attempt to better understand their application, and proposes the use of these molecules as new models in snakebite therapy. These molecules may help in the neutralization of different types of phospholipases A2 and myotoxins, complementing the conventional serum therapy.


Structural basis for targeting avian sarcoma virus Gag polyprotein to the plasma membrane for virus assembly.
For most retroviruses, including HIV-1, binding of the Gag polyprotein to the plasma membrane (PM) is mediated by interactions between Gag's N-terminal myristoylated matrix (MA) domain and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the PM. The Gag protein of avian sarcoma virus (ASV) lacks the N-myristoylation signal but contains structural domains having functions similar to those of HIV-1 Gag. The molecular mechanism by which ASV Gag binds to the PM is incompletely understood. Here, we employed NMR techniques to elucidate the molecular determinants of the membrane-binding domain of ASV MA (MA87) to lipids and liposomes. We report that MA87 binds to the polar head of phosphoinositides such as PI(4,5)P2 We found that MA87 binding to inositol phosphates (IPs) is significantly enhanced by increasing the number of phosphate groups, indicating that the MA87-IP binding is governed by charge-charge interactions. Using a sensitive NMR-based liposome-binding assay, we show that binding of MA87 to liposomes is enhanced by incorporation of PI(4,5)P2 and phosphatidylserine. We also show that membrane binding is mediated by a basic surface formed by Lys-6, Lys-13, Lys-23, and Lys-24. Substitution of these residues to glutamate abolished binding of MA87 to both IPs and liposomes. In an accompanying paper, we further report that mutation of these lysine residues diminishes Gag assembly on the PM and inhibits ASV particle release. These findings provide a molecular basis for ASV Gag binding to the inner leaflet of the PM and advance our understanding of the basic mechanisms of retroviral assembly.


Residence close to high traffic and prevalence of coronary heart disease.
Long-term exposure to urban air pollution may accelerate atherogenesis and increase cardiopulmonary mortality. We aim to examine the relationship between the long-term residential exposure to traffic and prevalence of coronary heart disease (CHD). We used baseline data from the German Heinz Nixdorf RECALL study, a population-based, prospective cohort study. For 3399 participants from two cities, we assessed the long-term personal traffic exposure and background air pollution, comparing residents living within 150 m of major roads with those living further away. The principal outcome variable was clinically manifest CHD. We evaluated the association with multivariable logistic regression, controlling for background air pollution and individual level risk factors. Of 3399 participants, 242 (7.1%) had CHD. The crude odds ratio (OR) for prevalence of CHD at high traffic exposure was significantly elevated (1.62, 95%CI 1.12-2.34) and rose to 1.85 (95%CI 1.21-2.84) after adjusting for cardiovascular risk factors and background air pollution. Subgroup analysis showed stronger effects for men (OR 2.33, 95%CI 1.44-3.78), participants younger than 60 years (OR 2.67, 95%CI 1.24-5.74) and never-smokers (OR 2.72, 95%CI 1.40-5.29). This study provides epidemiological evidence that the long-term exposure to traffic-related emissions may be an important risk factor for CHD.


Pericardial mesothelioma presenting as systemic lupus erythematosus.
A case of mesothelioma of the pericardium with many features of systemic lupus erythematosus (SLE) is described. We stress that satisfaction of the American Rheumatism Association's classification criteria for SLE does not confirm the diagnosis, even though their diagnostic sensitivity and specificity has recently been improved.


Effects of (D-ala2, met5)-enkephalinamide and naloxone on ACTH and corticosterone secretion.
An intravenous administration of (D-ala2, met5)-enkephalinamide (DALA) caused a significant elevation of plasma ACTH and corticosterone at 10 to 20 min after injection in unanesthetized freely moving rats. An intraperitoneal administration of cyproheptadine tended to reduce plasma ACTH and corticosterone levels at 60 min after injection, but it did not attenuate the DALA-induced ACTH and corticosterone elevation. A large dose of naloxone (1-10 mg/kg body weight) caused a significant elevation in plasma corticosterone, but naloxone at 10 mg/kg body weight reduced the basal ACTH level and DALA-induced ACTH elevation. When both DALA and naloxone were injected, the steroidogenic effect was attenuated. Neither DALA nor naloxone affected the basal ACTH release and CRF-induced ACTH stimulation in rat anterior pituitary cell cultures. These results suggest that DALA acts at the extra-hypophyseal level to stimulate ACTH and corticosterone and that the naloxone stimulatory effect on steroidogenesis acts on the adrenal gland or is mediated by stimulating corticosterone stimulating factors other than ACTH.


[What nurses with a bachelor of nursing degree know about the effects of alcohol on blood pressure and risk of arterial hypertension].
Alcohol abuse is one of the main causes of arterial hypertension. Alcohol is responsible for a few to more than ten percent of all cases of primary hypertension, particularly in persons consuming more than 20-30 g of alcohol per day. The aim of this study was to find out what Bachelor of Nursing degree holders know about alcohol consumption styles and the effects of alcohol on blood pressure, as well as on the risk of arterial hypertension in adults. The study group comprised 116 qualified nurses (112 females, 4 males; age 21-50 years; work seniority 0-29 years). The study was done between June 2007 and January 2008 with the use of the diagnostic poll technique based on a questionnaire developed by the authors. We found that 8.62% of participants were informed about screening tools used for evaluating styles of alcohol consumption while 41.38% gave the correct definition of the standard portion of alcohol. The alcohol consumption threshold above which the risk of hypertension becomes significant was known to 58.62% of respondents. The influence of alcohol (drunk directly before blood pressure measurement) on blood pressure was known to 89.66% of the nurses. We observed a statistically significant effect of work experience (p = 0.002), place of work (p < 0.001), and position held (p < 0.001) on the number of correct answers. No statistically significant differences depending on age, place of residence, family status or type of postgraduate education were noted. It is necessary to increase awareness among nurses regarding the risk of arterial hypertension associated with alcohol consumption and to improve the effectiveness of undergraduate and postgraduate education aimed at early recognition of problems caused by alcohol consumption which are important for the prevention of arterial hypertension.


25-hydroxycholesterol acts in the Golgi compartment to induce degradation of tyrosinase.
Oxysterols play a significant role in cholesterol homeostasis. 25-Hydroxycholesterol (25HC) in particular has been demonstrated to regulate cholesterol homeostasis via oxysterol-binding protein and oxysterol-related proteins, the sterol regulatory element binding protein, and the rate-limiting enzyme of cholesterol biosynthesis, hydroxymethylglutaryl coenzyme A reductase. We have examined the effect of 25HC on pigmentation of cultured murine melanocytes and demonstrated a decrease in pigmentation with an IC(50) of 0.34 microM and a significant diminution in levels of melanogenic protein tyrosinase. Pulse-chase studies of 25HC-treated cells demonstrated enhanced degradation of tyrosinase, the rate-limiting enzyme of melanin synthesis, following endoplasmic reticulum (ER) and Golgi maturation. Protein levels of GS28, a member of an ER/cis-Golgi SNARE protein complex, were also diminished in 25HC-treated melanocytes, however levels of the ER chaperone calnexin and the cis-Golgi matrix protein GM130 were unaffected. Effects of 25HC on tyrosinase were completely reversed by 4 alpha-allylcholestan-3 alpha-ol, a sterol identified by its ability to reverse effects of 25HC on cholesterol homeostasis. Finally, the addition of 25HC to lipid deficient serum inhibited correct processing of tyrosinase. We conclude that 25HC acts in the Golgi compartment to regulate pigmentation by a mechanism shared with cholesterol homeostasis.


The characterization of the neutralizing bovine viral diarrhea virus monoclonal antibodies and antigenic diversity of E2 glycoprotein.
Bovine viral diarrhea virus (BVDV) is associated with a range of economically important diseases of cattle including reproductive disorders and an acute fatal hemorrhagic disease. Neutralizing antibodies that bind to the E2 glycoprotein are important predictors of vaccinal immunity. Neutralization tests using the NADL strain of BVDV and five anti-E2 monoclonal antibodies showed one, Wb163, neutralized the NADL strain of BVDV in an unexpected manner. Its titer was 10,000 compared to <35 as reported previously. The present stock of NADL differed from that of the earlier study in that the amino acid at position 79 of E2 was Valine instead of Glutamic acid. MAb Wb163 may, however, recognize a less important neutralizing epitope than another mAb Wb166, because it was less cross reactive than mAb Wb166, had a neutralizing titer 50-fold lower than Wb166 and was of lower relative affinity than Wb166. Variations in the amino terminus of E2 will be discussed in the context of vaccinal immunity.