Synthesis of terminal uranium(IV) disulfido and diselenido compounds by activation of elemental sulfur and selenium.
Rare stakes: Terminal uranium(IV) disulfido and diselenido compounds, Tp*2U(E2) (E=S, Se), were synthesized by the activation of elemental chalcogens. Structural, spectroscopic, computational and magnetic studies of these species establish their tetravalency and highly polarized U-E bonds.


Histomorphometry and micro-computed tomography of bone augmentation under a titanium membrane.
Bone augmentation underneath an occlusive titanium membrane is evaluated in most cases by means of serial histological sections and histomorphometry. Micro-computed tomography (micro-CT) is a less invasive and dynamic technique to measure bone volume in animals of a size that fits into the gantry. The aim of the present study was to evaluate whether the latter approach could match histomorphometry to assess bone augmentation under a titanium membrane. Pre-formed titanium cups were placed on the skull of 16 rabbits. Bone formation underneath the cups was allowed to occur for 12 weeks. The amount of bone volume assessed by micro-CT was expressed as a numerical unit. One unit volume corresponds to 0.043 mm3. The measurements reveal the volume of bone-like tissue under the membrane, with the same density as that of the original rabbit skull bone. Histological sections were cut along the same plane as the one used for the micro-CT images. The total bone surface was assessed by a digital image system in double-stained undecalcified histological sections and related to the maximum available surface of the titanium cups, which was on average 1366 mm2. The amount of total bone surface found under the titanium membrane varied between 40 and 163 mm2. Measured by micro-CT, the bone detected ranged from 3.7 to 396 numerical units. A highly significant (P<0.001) correlation was found between the total bone volume measured in conventional serial histological sections and by the micro-CT technique (r2=0.72). The total bone volume measured underneath a membrane using the micro-CT when compared with histological sections remained within a 16% error. This is because of the scattering effect of the metallic membrane and the impossibility to distinguish newly formed bone from the original skull bone on the micro-CT images.


The central role of the gut microbiota in chronic inflammatory diseases.
The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.


Metabolism of 14C-estazolam in dogs and humans.
14C-Estazolam (2 mg) administered orally to dogs and human subjects was rapidly and completely absorbed with peak plasma levels occurring within one hour. In humans, plasma levels peaked at 103 +/- 18 ng/ml and declined monoexponentially with a half-life of 14 h. The mean concn. of estazolam in dog plasma at 0.5 h was 186 ng/ml. Six metabolites were found in dog plasma at 0.5 and 8 h, whereas only two metabolites were detected in human plasma up to 18 h. Metabolites common to both species were 1-oxo-estazolam (I) and 4-hydroxy-estazolam (IV). Major metabolites in dog and human plasma were free and conjugated 4-hydroxy-estazolam; the concn. were higher in dogs. After five days, 79% and 87% of the administered radioactivity was excreted in dog and human urine, respectively. Faecal excretion accounted for 19% of the dose in dog and 4% in man. Eleven metabolites were found in the 0-72 h urine of dogs and humans; less than 4% dose was excreted unchanged. Four metabolites were identified as: 1-oxo-estazolam (I), 4'-hydroxy-estazolam (II), 4-hydroxy-estazolam (IV) and the benzophenone (VII), as free metabolites and glucuronides. The major metabolite in dog urine was 4-hydroxy-estazolam (20% of the dose), while the predominant metabolite in human urine (17%) has not been identified, but is likely to be a metabolite of 4-hydroxy-estazolam. The metabolism of estazolam is similar in dog and man.


Multiple sequence alignment with hierarchical clustering.
An algorithm is presented for the multiple alignment of sequences, either proteins or nucleic acids, that is both accurate and easy to use on microcomputers. The approach is based on the conventional dynamic-programming method of pairwise alignment. Initially, a hierarchical clustering of the sequences is performed using the matrix of the pairwise alignment scores. The closest sequences are aligned creating groups of aligned sequences. Then close groups are aligned until all sequences are aligned in one group. The pairwise alignments included in the multiple alignment form a new matrix that is used to produce a hierarchical clustering. If it is different from the first one, iteration of the process can be performed. The method is illustrated by an example: a global alignment of 39 sequences of cytochrome c.


Nutrient Composition of Foods Marketed to Children or Adolescents Sold in the Spanish Market: Are They Any Better?
Healthy eating is essential for the growth and development of children and adolescents. Eating habits established in childhood continue into adulthood. In Spain, the frequent promotion of foods with low nutritional value is already considered a threat to the health of the population, particularly to children and adolescents. In this work, we analyse 3209 foods from the Food Database, BADALI. Foods were classified as marketed to children or adolescents according to the advertising on the packaging, television or internet. We found that 17.5% of foods in the database were marketed to this population and 97% of those were considered unhealthy following the Pan American Health Organization Nutrient Profile Model (PAHO-NPM). In the total of foods for children or adolescents, 61.5% were high in fat, 58.5% in free-sugar, 45.4% in saturated fat and 45% in sodium. Foods marketed to them presented higher amounts of carbohydrates and sugar, while lower protein and fibre content than the rest. There was also considerable variability in levels of the other nutrients found in these products, which depended largely on the food group. According to our findings, there is a tendency for products marketed to children or adolescents to be unhealthy and of a poorer nutritional quality than those not targeted at them.


Dacron velour arteriovenous fistula for hemodialysis access.
Dacron velour arteriovenous fistulas were created in the necks of 12 dogs. Sham dialysis was performed three times per week for one month in six animals, and for six months in an additional six animals. One prosthesis became infected, and perigraft bleeding occurred twice. There were no false aneurysms, and all prostheses remained patent. Dacron velour appears to be a satisfactory prosthetic material for use as an arteriovenous fistula for chronic hemodialysis access. The enhanced fibrous tissue adherence of Dacron velour may account for the few complications encountered.


Pseudomonas aeruginosa strains with lipopolysaccharide defects exhibit reduced intracellular viability after invasion of corneal epithelial cells.
Pseudomonas aeruginosa is a leading cause of infectious keratitis. Many ocular isolates of this bacterium invade corneal epithelial cells in vitro and in vivo. Antibiotic survival assays have shown that a complete core lipopolysaccharide is required for full epithelial invasion by P. aeruginosa. In this study, we show that P. aeruginosa mutants with defects in their lipopolysaccharide core and O antigen exhibited reduced viability after internalization by corneal epithelial cells. Restoration of lipopolysaccharide core and O antigen expression by complementation with the plasmid pLPS1 restored intracellular survival. P. aeruginosa strains with a complete lipopolysaccharide survived and replicated within the cells. The data suggest that lipopolysaccharide is involved in the intracellular survival and/or replication of P. aeruginosa, indicating an additional mechanism by which this important virulence factor may contribute to the pathogenesis of corneal infection.


Spatiotemporal Concurrent Liberation of Cytotoxins from Dual-Prodrug Nanomedicine for Synergistic Antitumor Therapy.
Nanomedicine developed to date by means of directly encapsulating cytotoxins suffers from crucial drawbacks, including premature release and detoxification prior to arrival at pharmaceutics targets. To these respects, redox-responsive polymeric prodrugs of platinum (Pt) and camptothecin (CPT), selectively and concomitantly activated in the cytoplasm, were elaborated in manufacture of dual prodrug nanomedicine. Herein, multiple CPTs were conjugated to poly(lysine) (PLys) segments of block copolymeric poly(ethylene glycol) (PEG)-PLys through the redox responsive disulfide linkage [PEG-PLys(ss-CPT)] followed by reversible conversion of amino groups from PLys into carboxyl groups based on their reaction with cis-aconitic anhydride [PEG-PLys(ss-CPT&CAA)]. On the other hand, Pt(IV) in conjugation with dendritic polyamindoamine [(G3-PAMAM-Pt(IV)] was synthesized for electrostatic complexation with PEG-PLys(ss-CPT&CAA) into dual prodrug nanomedicine. Subsequent investigations proved that the elaborated nanomedicine could sequentially respond to intracellular chemical potentials to overcome a string of predefined biological barriers and facilitate intracellular trafficking. Notably, PEG-PLys(ss-CPT&CAA) capable of responding to the acidic endosomal microenvironment for transformation into endosome-disruptive PEG-PLys(ss-CPT), as well as release of G3-PAMAM-Pt(IV) from nanomedicine, prompted transclocation of therapeutic payloads from endosomes into cytosols. Moreover, concurrent activation and liberation of cytotoxic CPT and Pt(II) owing to their facile responsiveness to the cytoplasmic reducing microenvironment have demonstrated overwhelming cytotoxic potencies. Eventually, systemic administration of the dual prodrug construct exerted potent tumor suppression efficacy in treatment of intractable solid breast adenocarcinoma, as well as an appreciable safety profile. The present study illustrated the first example of nanomedicine with a dual prodrug motif, precisely and concomitantly activated by the same subcellular stimuli before approaching pharmaceutic action targets, thus shedding important implication in development of advanced nanomedicine to seek maximized pharmaceutic outcomes.


Estimating conformation content of a protein using citrate-stabilized Au nanoparticles.
Herein we report the use of the optical properties of citrate-stabilized gold nanoparticles (Au NPs) for estimation of native or denatured conformation content in a mixture of a protein in solution. The UV-vis extinction spectrum of citrate-stabilized Au NPs is known to broaden differently in the presence of native and denatured states of alpha-amylase, bovine serum albumin (BSA) or amyloglucosidase (AMG). On the other hand, herein we show that when a mixture of native and denatured protein was present in the medium, the broadening of the spectrum differed for different fractional content of the conformations. Also, the total area under the extinction spectrum varied linearly with the change in the mole fraction content of a state and for a constant total protein concentration. Transmission electron microscopy (TEM) measurements revealed different levels of agglomeration for different fractional contents of the native or denatured state of a protein. In addition, time-dependent denaturation of a protein could be followed using the present method. The rate constants calculated for denaturation indicated a possible fast change in conformation of a protein before complete thermal denaturation. The observations have been explained based on the changes in extinction coefficient (thereby oscillator strength) upon interaction of citrate-stabilized NPs with proteins being in different states and levels of agglomeration.


Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin.
Because high circulating levels of glucocorticoids impair immunity and predispose to infections, we evaluated whether indices of cortisol (F) production could predict infections in patients with Cushing syndrome (CS) caused by ectopic production of ACTH (EA). Charts of 54 consecutive patients with untreated EA, without underlying diagnosis of small cell carcinoma of the lung, were reviewed, and types of infections, white blood cell (WBC) count, fever, as well as the glucocorticoid indices [0800 h F, daily urine F excretion (UFC), and daily urine 17-hydroxysteroid/g creatinine excretion (17OHS)], were recorded. Thirty-five patients had no or clinically mild infection; the remaining 19 patients had severe, systemic infection (n = 13) and/or sepsis (n = 6), including either bacterial or opportunistic pathogens or both (73.7%, 42.1%, and 13.8%, respectively). The latter group of patients had significantly higher indices of hypercortisolism (F, UFC, and 17OHS) than those with mild or no infections, but these indices did not correlate with temperature or WBC count. Thresholds for identifying severe infection were selected for maximal positive predictive value and were: F, 43.1 microg/dL; UFC, 2000 microg/day; and 17OHS, 35 mg/g creatinine. The most accurate discriminator for severe infection was 17OHS, based on a positive predictive value of 64.7%. Our data strongly suggests that the likelihood for a bacterial or opportunistic infection in CS patients, even without underlying small cell carcinoma of the lung, is greatest in patients with extreme hypercortisolism. The predictive value of total WBC count or the presence of an elevated temperature is not sufficient to identify patients with severe, life-threatening infection.


High performance liquid chromatography purification and amino terminal sequence analysis of the subunits of bovine heart mitochondrial F1-ATPase.
All five subunits of bovine heart mitochondrial F1-ATPase have been isolated by reverse-phase HPLC and NH2-terminal sequences determined by gas phase Edman degradations. Bovine gamma exhibits 16 identities in the first 30 residues compared with the NH2-terminus of gamma from E.coli F1. Bovine delta exhibit about 27% identity with residues 28-59 of precursor delta from N.crassa and in the first six residues is identical with delta from S.cerevisiae. Approximately half of bovine epsilon has been sequenced. Possibly significant sequence similarities exist between bovine gamma and epsilon and kinase-related gene and oncogene products. The bovine alpha subunit has a blocked NH2-terminus.


Comparison of adsorbents for H2S and D4 removal for biogas conversion in a solid oxide fuel cell.
Biogas contains trace compounds detrimental for solid oxide fuel cell (SOFC) application, especially sulphur-containing compounds and volatile organic silicon compounds (VOSiCs). It is therefore necessary to remove these impurities from the biogas for fuelling an SOFC. In this paper, dynamic lab-scale adsorption tests were performed on synthetic polluted gas to evaluate the performance of a polishing treatment to remove hydrogen sulphide (H2S - sulphur compound) and octamethylcyclotetrasiloxane (D4 - VOSiC). Three kinds of adsorbents were tested: an activated carbon, a silica gel (SG) and a zeolite (Z). Z proved to be the best adsorbent for H2S removal, with an adsorbed quantity higher than [Formula: see text] at the SOFC tolerance limit. However, as concerns D4 removal, SG was the most efficient adsorbent, with an adsorbed quantity of about 184 mgD4/gSG at the SOFC tolerance limit. These results could not be explained by structural characteristics of the adsorbents, but they were partly explained by chemical interactions between the adsorbate and the adsorbent. In these experiments, internal diffusion was the controlling step, Knudsen diffusion being predominant to molecular diffusion. As Z was also a good adsorbent for D4 removal, competition phenomena were investigated with Z for the simultaneous removal of H2S and D4. It was shown that H2S retention was dramatically decreased in the presence of D4, probably due to D4 polymerization resulting in pore blocking.


Community-acquired pneumonia.
This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach.


Auxin apical dominance governed by the OsAsp1-OsTIF1 complex determines distinctive rice caryopses development on different branches.
In rice (Oryza sativa), caryopses located on proximal secondary branches (CSBs) have smaller grain size and poorer grain filling than those located on apical primary branches (CPBs), greatly limiting grain yield. However, the molecular mechanism responsible for developmental differences between CPBs and CSBs remains elusive. In this transcriptome-wide expression study, we identified the gene Aspartic Protease 1 (OsAsp1), which reaches an earlier and higher transcriptional peak in CPBs than in CSBs after pollination. Disruption of OsAsp1 expression in the heterozygous T-DNA line asp1-1+/-eliminated developmental differences between CPBs and CSBs. OsAsp1 negatively regulated the transcriptional inhibitor of auxin biosynthesis, OsTAA1 transcriptional inhibition factor 1 (OsTIF1), to preserve indole-3-acetic acid (IAA) apical dominance in CPBs and CSBs. IAA also facilitated OsTIF1 translocation from the endoplasmic reticulum (ER) to the nucleus by releasing the interaction of OsTIF1 with OsAsp1 to regulate caryopses IAA levels via a feedback loop. IAA promoted transcription of OsAsp1 through MADS29 to maintain an OsAsp1 differential between CPBs and CSBs during pollination. Together, these findings provide a mechanistic explanation for the distributed auxin differential between CPBs and CSBs to regulate distinct caryopses development in different rice branches and potential targets for engineering yield improvement in crops.


[Management of acute visual loss in children].
Acute or rapidly progressive visual loss in children needs urgent attention and treatment. It may be unilateral orbilateral. Etiology depends upon the involved areas: eye ball, optic nerve, retro-chiasmatic pathways. Psychogenic origin is quite common in school-age children, however, it has to be considered last. Unilateral visual loss may be overlooked. Acute total transitory visual loss may be due to epilepsy or to migraine. Rapidly progressive visual loss may be due to retinal disease, optic neuritis or cortical blindness. Management of visual loss depends on clinical features, associated symptoms, and aspect of the optic disc. It needs collaboration between ophthalmologist,pediatrician and neuropediatrician. Retinal hemorrhages first call to mind a traumatic origin. Swelling of the optic disc may be due to increased intracranial pressure or due to optic neuritis. When the optic disc is normal it is necessary to rule out organic diseases before establishing the diagnosis of a psychogenic vision disturbance. In emergency, brain neuroimaging is the best way to diagnose intracranial mass and visualize optic pathways.


EEG arousal during laryngoscopy and intubation: comparison of thiopentone or propofol supplemented with nitrous oxide.
We studied EEG arousal after laryngoscopy and intubation with standardized bolus induction of anaesthesia. Twenty patients were prospectively allocated randomly to induction with propofol 3 mg kg-1 (n = 10) or thiopentone (6 mg kg-1 (n = 10) and 50% nitrous oxide in oxygen. Neuromuscular block was produced with vecuronium 0.2 mg kg-1 given 30 s after induction. Three minutes after induction, laryngoscopy was performed for 60 s, with intubation at 3 min 30 s, and study end at 5 min. Nociception to laryngoscopy and intubation was followed by loss of low (relative delta activity change: thiopentone -30%, propofol -7%; P < 0.05) and a shift to higher frequency EEG activity (beta activity change: thiopentone +647%, propofol +61%; P < 0.05). This EEG arousal was greater in the thiopentone group, despite the fact that EEG depression was similar to that produced by propofol before laryngoscopy and intubation. Propofol and thiopentone in combination with nitrous oxide had similar cortical depressant effects, but propofol appeared to depress subcortical nociceptive processing more than thiopentone. While the degree of cortical EEG depression seems less useful for predicting reaction to subsequent nociception, EEG arousal reactions may prove suitable for monitoring intra-anaesthetic nociception and its modulation.


Electrical characterization of single molecule and Langmuir-Blodgett monomolecular films of a pyridine-terminated oligo(phenylene-ethynylene) derivative.
Monolayer Langmuir-Blodgett (LB) films of 1,4-bis(pyridin-4-ylethynyl)benzene (1) together with the "STM touch-to-contact" method have been used to study the nature of metal-monolayer-metal junctions in which the pyridyl group provides the contact at both molecule-surface interfaces. Surface pressure vs area per molecule isotherms and Brewster angle microscopy images indicate that 1 forms true monolayers at the air-water interface. LB films of 1 were fabricated by deposition of the Langmuir films onto solid supports resulting in monolayers with surface coverage of 0.98 × 10(-9) mol·cm(-2). The morphology of the LB films that incorporate compound 1 was studied using atomic force microscopy (AFM). AFM images indicate the formation of homogeneous, monomolecular films at a surface pressure of transference of 16 mN·m(-1). The UV-vis spectra of the Langmuir and LB films reveal that 1 forms two dimensional J-aggregates. Scanning tunneling microscopy (STM), in particular the "STM touch-to-contact" method, was used to determine the electrical properties of LB films of 1. From these STM studies symmetrical I-V curves were obtained. A junction conductance of 5.17 × 10(-5) G 0 results from the analysis of the pseudolinear (ohmic) region of the I-V curves. This value is higher than that of the conductance values of LB films of phenylene-ethynylene derivatives contacted by amines, thiols, carboxylate, trimethylsilylethynyl or acetylide groups. In addition, the single molecule I-V curve of 1 determined using the I(s) method is in good agreement with the I-V curve obtained for the LB film, and both curves fit well with the Simmons model. Together, these results not only indicate that the mechanism of transport through these metal-molecule-metal junctions is non-resonant tunneling, but that lateral interactions between molecules within the LB film do not strongly influence the molecule conductance. The results presented here complement earlier studies of single molecule conductance of 1 using STM-BJ methods, and support the growing evidence that the pyridyl group is an efficient and effective anchoring group in sandwiched metal-monolayer-metal junctions prepared under a number of different conditions.


Robust independent component analysis by iterative maximization of the kurtosis contrast with algebraic optimal step size.
Independent component analysis (ICA) aims at decomposing an observed random vector into statistically independent variables. Deflation-based implementations, such as the popular one-unit FastICA algorithm and its variants, extract the independent components one after another. A novel method for deflationary ICA, referred to as RobustICA, is put forward in this paper. This simple technique consists of performing exact line search optimization of the kurtosis contrast function. The step size leading to the global maximum of the contrast along the search direction is found among the roots of a fourth-degree polynomial. This polynomial rooting can be performed algebraically, and thus at low cost, at each iteration. Among other practical benefits, RobustICA can avoid prewhitening and deals with real- and complex-valued mixtures of possibly noncircular sources alike. The absence of prewhitening improves asymptotic performance. The algorithm is robust to local extrema and shows a very high convergence speed in terms of the computational cost required to reach a given source extraction quality, particularly for short data records. These features are demonstrated by a comparative numerical analysis on synthetic data. RobustICA's capabilities in processing real-world data involving noncircular complex strongly super-Gaussian sources are illustrated by the biomedical problem of atrial activity (AA) extraction in atrial fibrillation (AF) electrocardiograms (ECGs), where it outperforms an alternative ICA-based technique.


Combining behavioral and self-help approaches in the inpatient management of dually diagnosed patients.
The combination of a token economy and a self-help model made it feasible to organize and maintain an intensive dual-diagnosis treatment program in a public municipal hospital acute psychiatric ward. The program described here, which integrates the token economy and 12-step approaches, fosters voluntary and active patient participation in the process of simultaneous recovery from mental illness and addiction; it also networks the patient with community resources. Implementation of the clinical program involved addressing multiple clinical and organizational obstacles, including a multihandicapped and often nonmotivated patient population, a lack of psychiatric staff trained in managing substance abuse, and the need to integrate mental health with substance abuse clinical interventions. The program has been operating more than 5 years and has treated more than 1,000 patients. As the token economy became an integral part of the ward routine, violence on the ward declined substantially, and patient participation in group activities increased significantly.


Membrane deterioration in senescing carnation flowers : coordinated effects of phospholipid degradation and the action of membranous lipoxygenase.
The lipid fluidity of microsomal membranes from the petals of cut carnation flowers decreases as the flowers senesce. A comparable change in fluidity was induced by in vitro aging of microsomal membranes from young flowers under conditions in which membranous lipoxygenase-like activity was active. There was no change in fluidity when the membranes were aged in the presence of inhibitors of lipoxygenase or were heat-denatured prior to aging. Membranes from naturally senesced flowers and membranes that had been aged in vitro both sustained an increase in saturated:unsaturated fatty acid ratio that accounted for the decrease in lipid fluidity, and in both instances there was evidence for depletion of the unsaturated fatty acids, linoleic acid, and linolenic acid, which are substrates for lipoxygenase. Loss of lipid phosphate reflecting breakdown of membrane phospholipids preceded the depletion of unsaturated fatty acids attributable to the lipoxygenase-like activity. The data have been interpreted as indicating that fatty acid substrates for membrane-associated lipoxygenase-like activity are made available by the initiation of phospholipid degradation, and that the utilization of these substrates results in a selective depletion of unsaturated fatty acids from the membrane and an ensuing decrease in bulk lipid fluidity.


Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43.
Dominant transmission of multiple uterine and cutaneous smooth-muscle tumors is seen in the disorder multiple leiomyomatosis (ML). We undertook a genomewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype construction and analysis of recombinations permitted the minimal interval containing the locus, which we have designated "MCUL1," to be refined to an approximately 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss studies of tumors indicated that MCUL1 may act as a tumor suppressor. Identification of MCUL1 should have wide interest, since this gene may harbor low-penetrance variants predisposing to the common form of uterine fibroids and/or may undergo somatic mutation in sporadic leiomyomata.


[Study of spectra characteristics of Ca3SiO5 : Eu2+ phosphor].
The Ca3SiO5 : Eu2+ phosphor was synthesized by the sol-gel reaction method. The emission spectrum was measured by a SPEX1404 spectrophotometer, and the excitation spectrum was measured by a SHIMADZU RF-540 ultraviolet spectrophotometer. All the characterization of the phosphors was conducted at room temperature. The results show that the emission spectrum of Ca3SiO5 : Eu2+ phosphor exhibits one asymmetry band centred at 505 nm under the 365 nm excitation, and the excitation spectrum for 505 nm indicates two bands centred at 374 and 397 nm, respectively. The above results indicate that the phosphor used for w-LEDs can be excited by UV light, and emit green light. The effect of synthesis condition, such as synthesis temperature, synthesis time and Eu2+ concentration, on the emission spectrum of Ca3SiO5 : Eu2+ phosphor was investigated. The results show that the emission peak intensity of Ca3SiO5 : Eu2+ phosphor firstly increases, then decreases with the increase in synthesis temperature or synthesis time or Eu2+ concentration, and reaches the maximum value at 1,100 degrees C, for 4 h and 0.5 mol% Eu2+.


M13 cloning of mung bean nuclease digested PCR fragments as a means of gap closure within A/T-rich, genome sequencing projects.
Obtaining the complete DNA sequence of a genome is often not straightforward. After standard shotgun sequencing strategies have been employed there are often gaps remaining and these can be the most intractable regions, frequently containing repeat sequences, "uncloneable" sequences and/or regions of potential secondary structure or differential base composition. In genomes with a high A/T content, such as Plasmodium falciparum and Dictyostelium discoideum, solving these gaps is a particularly difficult problem as the sequences concerned are "fragile" and easily denatured, commonly uncloneable and have a paucity of good oligonucleotide priming sites. Reported here is a simple, yet reliable method for determining the sequence of A/T-rich gap-spanning PCR products. This method relies on the slippage of the specificity of mung bean nuclease so that it digests A/T-rich double-stranded DNA into a set of deletion fragments that can then be cloned into M13, sequenced and the original sequence assembled therefrom.


The age 60 rule: age discrimination in commercial aviation.
The Federal Aviation Administration's Age 60 Rule, promulgated in 1959, prohibits airline pilots from working in Part 121 operations once they have reached the age of 60. The Age 60 Rule remains a most contentious and politically sensitive topic, with challenges to the Rule currently mounted in both legislative and legal arenas. An extensive review of the medical literature was accomplished using MEDLINE. Pertinent Federal Regulations were examined. Legal proceedings and public domain documents were noted. Letters and personal communication were solicited where necessary information could not be ascertained by other means. The Age 60 Rule was not based on any scientific data showing that airline pilots aged 60 and older were any less safe than younger pilots, and there is evidence to indicate that the choice of age 60 was actually based on economic rather than safety considerations. Airline pilots consistently exceed general population norms for longevity, physical health, and mental abilities. Fear of an adverse pilot health event causing a crash in standard multi-crew operations is not justified. For decades, airline pilots under age 60 have been granted the means to demonstrate their fitness for flying by taking medical, cognitive, and performance evaluations that are denied to airline pilots when they reach age 60. Actual flight experience demonstrates that older pilots are as safe as younger pilots. International aviation experience indicates that abolishing the Age 60 Rule will not compromise aviation safety. There appears to be no medical, scientific, or safety justification for the Age 60 Rule. As such, perpetuation of the Age 60 Rule, where age alone is used as the single criterion of older pilot fitness, represents age discrimination in commercial aviation.


[Comparison of radial versus femoral approach for percutaneous coronary intervention in octogenarians with acute coronary syndrome].
To evaluate the prognostic effects of radial artery access (RA) versus femoral artery access (FA) in octogenarians undergoing percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). From January 2008 to January 2013, 279 octogenarians with ACS underwent PCI. PCI was performed through RA in 125 patients and FA in another 154. Clinical and procedural characteristics, combined endpoints including death, acute myocardial infarction, stroke, and major bleeding, and peripheral vascular complications were obtained from both groups. The clinical baseline characteristics of two patient groups, including target vessel location, lesion type, number of implanted stents, fluoroscopy duration and utilization of contrast media had no statistical difference.Femoral approach was associated with a higher rate of ST elevation myocardial infarction (STEMI) than radial approach (27.9% vs 11.2%, χ² = 11.868, P < 0.05). Procedural rate of success, fluoroscopy duration and utilization of contrast media were equivalent with both approaches. Radial approach was associated with a higher crossover rate (10.4% vs 3.9%, χ² = 4.599, P < 0.05) to alternate access site compared with the femoral approach.No difference in combined endpoint during 30 days after PCI including death, acute myocardial infarction, stroke and major bleeding was found between two groups (P > 0.05).However, ambulation time (4.2 ± 0.9 vs 19.3 ± 4.1h, t = 40.381, P < 0.01), incidence of access site bleeding (2.4% vs 7.8%, χ² = 3.943, P < 0.05), hematoma (2.4% vs 9.1%, χ² = 5.398, P < 0.05), pseudoaneurysm (0.0% vs 5.2%, χ² = 4.950, P < 0.05) and vascular complications (4.8% vs 19.5%, χ² = 13.231, P < 0.01) were significantly lowered in radial approach group. Multivariate regression analysis identified radial approach as an independent negative predictor of postprocedural vascular complications (OR = 0.329, 95% CI: 0.124-0.517, P < 0.05).Female gender (OR = 1.955, 95% CI: 1.326-2.248, P < 0.05) and utilization of glycoprotein IIb/IIIa receptor antagonist (OR = 2.787, 95% CI: 2.435-3.071, P < 0.01) were independent predictors of postprocedural vascular complications. Compared with femoral approach, radial approach significantly reduces the vascular complications of PCI in octogenarians with ACS.However, PCI through RA is not associated with reduced combined endpoint at 30 days in octogerians with ACS.


[Diagnosis of pheochromocytoma in Yaoundé (Cameroon): a study of nine cases].
The aim of this study was to describe methods used for diagnosis of pheochromocytoma inYaoundé, Cameroon. This retrospective study was based on analysis of the charts of patients treated in the surgical department of the Yaoundé University Teaching Hospital from 1985 to 2009. Nine patients with histologically confirmed pheochromocytoma were identified. There were 8 women and 1 man with a mean age of 39.5 years (range, 12 and 66). Pheochromocytoma was associated with hypertension in 6 cases. In two women with hypertension, diagnosis was based on palpation of an abdominal tumor after caesarean section following pregnancy associated with arterial hypertension. In another woman, diagnosis was made during laparotomy for a left hypochondrial tumor. In 7 patients, diagnosis was based on laboratory findings showing high urinary levels of vanyl mandelic acid (VMA). In six patients, ultrasound examination allowed topographic diagnosis that was confirmed by CT-scan in 3 cases. Two patients presented extra-renal pheochromocytomas in the abdomen. In three patients, i.e., one third of cases, histology showed malignant features. The findings of this study indicated that diagnosis of pheochromocytoma in Yaoundé be improved with the introduction MRI, scintigraphy, and modern techniques for assaying urinary methoxyderivates.


Carotid Thrombosis in a Crack Cocaine Smoker Woman.
We report a case of stroke in a crack smoker with occlusion of the middle cerebral artery and a large thrombus in the carotid artery. Case Presentation. A 34-year-old female presented with left upper arm weakness, associated with paresthesia with onset of symptoms more than 24 hours before. Angio-RM sequences showed an area of ischemia, with occlusion of the M2 segment of the middle cerebral artery. Carotid ultrasound showed a soft plaque with distal end floating. Anticoagulant treatment was started, and seriated ultrasound evaluations showed its gradual dissolution. In atherothromboembolic stroke from carotid thrombosis, repeated ultrasound studies may be useful for either diagnosis and monitoring the efficacy of anticoagulant therapy.


The effect of high resistance weight training on reported pain in older adults.
The present study examined the effect of a progressive, whole- body, high resistance training program on reported pain in older adults. Ninety-eight participants (60 - 83 years) completed the McGill Pain Questionnaire prior to and after an eight week training period. Seventy-nine of the participants completed a progressive, high resistance training program of 11 different exercises on three days a week. At the end of eight weeks, the training group achieved significant strength gains ranging from 62% -119% (p ≤ 0.005). Pain measures for the training and control groups were compared using an analysis of covariance on post-test pain measures after an adjustment by pre-test scores. (p ≤ 0.05). The training group reported less perceived pain than the control group in four pain measures (overall pain intensity, sensory dimension, miscellaneous pain measures, number of pain descriptors selected). There were no differences reported for the affective or evaluative dimensions of perceived pain, the number of painful areas, or the present pain. Results suggest that eight weeks of progressive, whole-body weight training has a positive impact on perception of pain in older adults. Key pointsImproved strength in older adults had a positive effect on the perception of pain.The number of painful areas identified and self-reported pain qualities were diminished following high resistance weight training.The McGill Pain Questionnaire was an effective tool for measuring changes in pain perception as a result of training.


[Effects of C-terminal fragment of substance P-CP 5-11 on the activity of neurons of the dorsal raphe nucleus].
The experiments on Wistar rats showed that microinjection of C-terminal fragment of substance P-CP5-11 (1 microgram) into one of the antinociceptive system structure--dorsal raphe nucleus, caused a prolonged (24 hours of observation) analgetic effect by the hot plate test. Neuronal activity of dorsal raphe nucleus simultaneously enhanced. The CP5-11 antinociceptive activity was higher than the CP1-11 one. The conclusion is that CP1-11 and in particular its C-terminal fragment CP5-11 play a role in activation of antinociceptive system.


1,2,3,4-Tetrasubstituted cyclopentadienes and their applications for metallocenes: efficient synthesis through zirconocene- and CuCl-mediated intermolecular coupling of two alkynes and one diiodomethane.
1,2,3,4-Tetrasubstituted cyclopentadienes and indene derivatives with identical or different substituents were obtained in good to excellent isolated yields through a zirconocene- and CuCl-mediated intermolecular coupling process. This synthetic procedure involved three organic partners, including one CH2 I2 , and two different or identical alkynes. Two alkynes or one diyne undergo Cp2Zr(II)-mediated (Cp = η(5)-C5H5) pair-selective reductive coupling to afford the corresponding zirconacyclopentadiene derivatives, which react, in the presence of CuCl and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone (DMPU), with CH2I2 through intermolecular followed by intramolecular coupling to afford the cyclopentadiene derivatives. An application of the prepared tetrasubstituted cyclopentadiene derivatives was demonstrated by the facile synthesis of the corresponding zirconocene complexes [((4R)Cp)2ZrCl2] and [((4R)Cp)2ZrR'2] (R' = Me, Et, or nBu). The unique 1,2,3,4-tetrasubstituted cyclopentadiene ligands and the corresponding metallocenes are expected to have further applications in organometallic chemistry and organic synthesis.


Intermolecular and intramolecular hydrogen bonds involving fluorine atoms: implications for recognition, selectivity, and chemical properties.
A correlation between 19F NMR isotropic chemical shift and close intermolecular F⋅⋅⋅H-X contacts (with X=N or O) has been identified upon analysis of the X-ray crystal structures of fluorinated molecules listed in the Cambridge Structural Database (CSD). An optimal F⋅⋅⋅X distance involving primary and shielded secondary fluorine atoms in hydrogen-bond formation along with a correlation between F⋅⋅⋅H distance and F⋅⋅⋅H-X angle were also derived from the analysis. The hydrogen bonds involving fluorine are relevant, not only for the recognition mechanism and stabilization of a preferred conformation, but also for improvement in the permeability of the molecules, as shown with examples taken from a proprietary database. Results of an analysis of the small number of fluorine-containing natural products listed in the Protein Data Bank (PDB) appear to strengthen the derived correlation between 19F NMR isotropic chemical shift and interactions involving fluorine (also known as the "rule of shielding") and provides a hypothesis for the recognition mechanism and catalytic activity of specific enzymes. Novel chemical scaffolds, based on the rule of shielding, have been designed for recognizing distinct structural motifs present in proteins. It is envisaged that this approach could find useful applications in drug design for the efficient optimization of chemical fragments or promising compounds by increasing potency and selectivity against the desired biomolecular target.


Route of delivery of fetuses with structural anomalies.
Our ability to diagnose fetuses with congenital anomalies has dramatically increased over the past two decades and with improved surgical treatment for some defects, more women may choose to continue their pregnancies. Antenatal management is thus of increasing relevance. The literature on route of delivery suggests the following conclusions. Babies with neural tube defects presenting by the breech benefit from caesarean section but there is no clear evidence that cesarean improves outcome in those with a vertex presentation. When the size of the sac exceeds 6 cm, cesarean section may be justified to decrease the risk of disruption. Vaginal delivery is desirable in all other cases to reduce maternal morbidity. Cystic hygroma: cesarean section offers optimal conditions for management of large anterior lymphangiomas that can obstruct the airway. Sacrococcygeal teratoma: the current approach is based on the size of the tumor. In a fetus with a tumor of less than 5 cm, vaginal delivery may be attempted. Ventral wall defects: there is no conclusive evidence that cesarean section is beneficial for fetuses with omphalocele. Gastroschisis: because of the heterogeneity of the studies, it is difficult to assess the net impact of mode of delivery. There is no evidence of significant differences in outcome among fetuses delivered by the vaginal versus the abdominal route. Trauma to the abdominal viscera can occur during either route, and careful delivery is thus mandated.


Modular bis(oxazoline) ligands for palladium catalyzed allylic alkylation: unprecedented conformational behaviour of a bis(oxazoline) palladium eta3-1,3-diphenylallyl complex.
New families of enantiopure bis(oxazolines) with 4,5-trans (5 a-g) or 4,5-cis (6 c) stereochemistry at the individual rings have been prepared in high yield. Their eta(3)-allyl palladium complexes (8 a-g, 9 c and 10) have been used as catalytic precursors in allylic alkylation reactions with excellent enantioselectivities (up to 96 %) for the trans oxazoline derivatives, while Pd/6 c system was inactive. NMR studies on palladium eta(3)-1,3-diphenylallyl intermediates (11 a, c and e) showed the presence of syn/syn- and syn/anti-allyl isomers in solution; this resembles the first example of eta(3)-eta(1)-eta(3) isomerism in Pd allylic complexes containing bis(oxazolines) derived from malonic acid.


Cost-effectiveness of IDH testing in diffuse gliomas according to the 2016 WHO classification of tumors of the central nervous system recommendations.
Due to the decreasing prevalence of IDH1 mutations in older patients, the 2016 World Health Organization (WHO) classification of brain tumors proposed not to perform sequencing for isocitrate dehydrogenase (IDH) in glioblastoma patients ≥55 years old. We present a cost-effectiveness analysis to estimate the financial impact of these guidelines. From 2010 to 2015 we performed 1023 IDH tests in gliomas, amounting to ~$1.09 million in direct laboratory test costs. Samples were tested using R132H-specific immunohistochemistry, DNA sequencing validated for detection of noncanonical IDH1/2 mutations, or both methods. In cases tested by DNA sequencing, the fraction of non-R132H mutations was 5.4%, which included only 2 high-grade gliomas in patients ≥55 years (0.9%). When remodeling the optimal age cutoff in our patient population using 5-year age-binning, we found a 10-times higher pretest probability for the presence of a noncanonical IDH1 mutation in the setting of a negative IDH1-R132H immunohistochemistry result in patients <55 years. Applying the independently confirmed age cutoff of 55 years to glioblastoma patients (64%) would result in $403200 saved (43%). By not performing sequencing in patients ≥55 years, the turn-around time to final integrated neuropathological diagnosis is reduced by 53%, allowing these patients to gain earlier benefits from personalized genomic medicine. The negligible prevalence of noncanonical IDH mutations in glioblastoma patients ≥55 years argues against universal IDH sequencing in this population. We predict that adoption of this age-based sequencing cutoff recommendation from the 2016 WHO guidelines will result in significant cost and time savings throughout the global health care system.


Characterization of squamous cell cancers of the vulvar anterior fourchette by human papillomavirus, p16INK4a, and p53.
The incidence of vulvar squamous cell carcinomas located between the clitoris and urethra in young women is rising in distinct geographic regions, but characteristics of the tumors indicating certain carcinogenic mechanisms are unknown. The present study aimed at characterizing these vulvar cancers for their human papillomavirus (HPV), p16(INK4a), and p53 status, revealing potential pathways of carcinogenesis. Squamous cell vulvar cancers of the anterior fourchette were retrospectively collected from 8 German hospitals, with additional squamous cell cancers located at other sites of the vulva from 2 of the hospitals. All tumors were analyzed for HPV DNA by polymerase chain reaction and for p16(INK4a) and p53 expression by immunohistochemistry. Potentially HPV-associated tumors (HPV and p16(INK4a) positive, 21.4% [27/126] of the anterior fourchette and 27.7% [13/47] from other locations), p53-overexpressing tumors (35.7% [45/126] and 29.8% [14/47]), and a third group (HPV/p16(INK4a) negative/p53 not overexpressed, 42.9% [54/126] and 42.6% [20/47]) were observed among tumors from the anterior fourchette as well as among vulvar cancers from other locations. Women with vulvar cancers of the anterior fourchette were of young age irrespective of the HPV/p16(INK4a)/p53 status. Different types of vulvar cancers can be found in squamous cell tumors of the anterior fourchette, similar to the finding in vulvar cancers from other locations and to what has previously been reported for vulvar squamous cell carcinomas in general.


[Systematic lupus erythematosus and antiphospholipid syndrome during pregnancy].
Women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are subject to several complications during pregnancy, including reactivation of SLE, thrombosis, miscarriage, neonatal lupus, pregnancy-induced hypertension, pulmonary hypertension and drug toxicity. Correct management of these patients requires combined medical-obstetric care, close surveillance of baby's growth and well-being, control of SLE activity and correct thromboprophylaxis. With good care, most pregnancies in women with SLE and APS end successfully.


AMA Council on Scientific Affairs. Immunization of health care workers with varicella vaccine.
Varicella-zoster virus (VZV) is the etiologic agent of two common diseases: varicella (chickenpox) and herpes zoster (shingles). Groups such as infants under one year of age, the immunocompromised, and adults are at increased risk of developing complications from VZV infection. The transmission of VZV within health care facilities from contact with infected patients, staff, and visitors is a potentially serious problem. Nosocomial outbreaks of varicella can result in significant morbidity and mortality in high-risk patients, particularly in pediatric wards. VZV transmission to susceptible individuals is difficult to prevent because exposures may occur before appropriate infection control procedures can be implemented. In 1995, a varicella vaccine was approved for use in the United States. The vaccine has been shown to be fairly effective in preventing varicella in adults and very effective in preventing severe disease. While current data indicate that the vaccine is safe and poses minimal risks, more research is needed to address concerns about the long-term safety, efficacy, and epidemiological impact of more widespread use of the vaccine. It is important for health care workers, especially those working with high-risk groups, to know their VZV immune status. Unless contraindicated, health care workers who have no history of VZV infection and are serologically negative should be considered a priority for immunization with the varicella vaccine. Administration of the vaccine to health care workers could reduce nosocomial transmission of VZV. Furthermore, significant cost and labor savings could be realized by avoiding expensive and potentially disruptive infection control measures.


Uniportal video assisted thoracoscopic surgery bullectomy and double pleurodesis for primary spontaneous pneumothorax.
Primary spontaneous pneumothorax (PSP) usually occurs in young adults, with higher incidence in smoker, and patients with narrow chest frame and slim body habitus. Surgery is indicated in the cases of recurrence episodes or persistent lung collapse, and failed conservative management by chest drain insertion. Video assisted thoracoscopic surgery (VATS) bullectomy and pleurodesis is the surgical treatment of choice but uniportal approach has been utilised to further minimise surgical trauma, improve cosmesis without compromising the efficacy of the procedure. This video demonstrated the uniportal procedure for bullectomy and double pleurodesis for PSP. A 2.5 cm incision was made at 4th intercostal space, anterior axillary line. Extra small size wound protector was used and CO2 insufflation was not needed. Adhesion divided with diathermy and visible apical bullae was resected using endoscopic stapler. Abrasive pleurodesis performed by using scratch patch mounted on Robert clamp, gently running along the parietal pleura within the chest wall. In addition, 5 grams of pure talc was delivered into pleural space. Single drain inserted via the port and lung fully inflated upon resuming ventilation by anaesthetist. Drain remained for 48 hours under negative pressure of -20 mmHg and patient usually went home on day 3 post-operatively. During the period from 2009 to 2015, over 160 cases of PSP were treated using this method by the author. To date, there is no recurrence reported upon follow up at outpatient clinic. There was no mortality and patients resumed active physical activity 8 weeks after the procedure. Uniportal VATS bullectomy and double pleurodesis is a safe procedure for treating PSP and effective in preventing future recurrence of lung collapse. This simple approach should be encouraged and performed by all enthusiastic VATS thoracic surgeons.


Computational studies and experimental results--an example of excellent teamwork in studying carbocyclization.
In silico veritas? Maybe not the whole truth, but very helpful suggestions and guidelines for the experimental work can be deduced from computational studies on Rh-catalyzed [3+2+1] cycloaddition reactions for the construction of cis-fused bicyclohexenones from alkylidenecyclopropanes and carbon monoxide.


Lack of in vivo effect of vanadium on GLUT4 translocation in white adipose tissue of streptozotocin-diabetic rats.
Vanadium treatment, in vivo, corrects the severe hyperglycemia observed in streptozotocin (STZ)-diabetic rats. A number of metabolic effects of vanadium have been demonstrated in vitro and might contribute importantly to normalization of glucose homeostasis. However, many in vitro effects of vanadium occur at concentrations substantially higher than those achieved in vivo. Effects of vanadium on white adipose tissue have been particularly well characterized in vitro. To examine the relationship between in vitro and in vivo actions of vanadium, we examined the effects of vanadium treatment on acute glucose tolerance and adipose tissue GLUT4 control in vivo. In agreement with previous studies, vanadium treatment of STZ-diabetic rats restored normoglycemia with no appreciable restoration of insulin secretion. GLUT4 expression in white adipose tissue was reduced by 22% in STZ-diabetic rats compared with controls. Vanadium treatment did not significantly alter GLUT4 expression in controls, but completely restored normal expression levels in STZ-diabetic rats. In overnight-fasted control animals, GLUT4 translocation to the plasma membrane (PM) was maximally elevated (by 50%) in adipose tissue within 5 to 10 minutes after an intravenous (IV) glucose challenge. No glucose-induced translocation of GLUT4 was detected in diabetic rats, and peak PM GLUT4 content was 40% lower than in controls. Vanadium treatment did not increase peak PM GLUT4 content in either control or diabetic animals in response to a glucose load. Finally, the suppression of whole-body acute glucose tolerance in diabetic animals was only partially normalized by vanadium treatment. We conclude: (1) that concentrations of vanadium effective for maintaining normoglycemia in vivo (typically below 30 micromol/L) promote normal GLUT4 expression, but do not influence the subcellular localization of GLUT4 in white adipose tissue and (2) that in vivo effects of vanadium may not necessarily reflect the actions observed in vitro at supraphysiologic concentrations.


Bulk-wave and guided-wave photoacoustic evaluation of the mechanical properties of aluminum/silicon nitride double-layer thin films.
The development of devices made of micro- and nano-structured thin film materials has resulted in the need for advanced measurement techniques to characterize their mechanical properties. Photoacoustic techniques, which use pulsed laser irradiation to nondestructively induce very high frequency ultrasound in a test object via rapid thermal expansion, are suitable for nondestructive and non-contact evaluation of thin films. In this paper, we compare two photoacoustic techniques to characterize the mechanical parameters of edge-supported aluminum and silicon nitride double-layer thin films. The elastic properties and residual stresses in such films affect their mechanical performance. In a first set of experiments, a femtosecond transient pump-probe technique is used to investigate the Young's moduli of the aluminum and silicon nitride layers by launching ultra-high frequency bulk acoustic waves in the films. The measured transient signals are compared with simulated transient thermoelastic signals in multi-layer structures, and the elastic moduli are determined. Independent pump-probe tests on silicon substrate-supported region and unsupported region are in good agreement. In a second set of experiments, dispersion curves of the A(0) mode of the Lamb waves that propagate along the unsupported films are measured using a broadband photoacoustic guided-wave method. The residual stresses and flexural rigidities for the same set of double-layer membranes are determined from these dispersion curves. Comparisons of the results obtained by the two photoacoustic techniques are made and discussed.


Role of inverted buttoned device in transcatheter occlusion of atrial septal defects or patent foramen ovale with right-to-left shunting associated with previously operated complex congenital cardiac anomalies.
Feasibility, safety, and effectiveness of transcatheter occlusion of atrial septal defect (ASD) with the buttoned device has been demonstrated. Despite its effectiveness in occluding secundum ASD with left-to-right shunt and patent foramina ovalia, presumably responsible for paradoxic embolism, it has limitations in effectively occluding ASD with evident right-to-left shunts. Therefore, the device was modified so that the square-shaped occluder component of the device is on the right atrial side, the inverted buttoned device. This study determines the feasibility, safety, and effectiveness of inverted buttoned device occlusion of atrial defects with right-to-left shunts. During a 17-month period ending August 1996, 12 patients, aged 1.6 to 39.0 years, underwent occlusion of residual ASD after repair of pulmonary atresia/stenosis with intact ventricular septum (n = 5), modified or fenestrated Fontan for tricuspid or pulmonary atresia (n = 5), and double-inlet left ventricle (n = 2). The systemic arterial oxygen saturation increased (p <0.001) from 82 +/- 7% (range 72% to 90%) to 94 +/- 3% (range 88% to 98%). There was no change in heart rate or cardiac index measured by Fick. Right atrial pressure increased by 1 to 4 mm in 5 of 12 patients (42%). There was trivial (n = 5) or no (n = 7) residual shunt by color Doppler study. Six- to 18-month (median 12) follow-up in all 12 patients revealed stable oxygen saturations (92 +/- 3%) by pulse oximetry. Color Doppler studies revealed small (n = 1), trivial (n = 1), or no (n = 10) residual shunt at follow-up. Based on these data, it is concluded that transcatheter occlusion of ASD with right-to-left shunts with inverted buttoned device is feasible in relieving arterial hypoxemia. Further clinical trials in a larger number of patients and careful evaluation of follow-up results are indicated to examine its safety and longer term effectiveness.


Working in disadvantaged communities: What additional competencies do we need?
Residents of socioeconomically disadvantaged locations are more likely to have poor health than residents of socioeconomically advantaged locations and this has been comprehensively mapped in Australian cities. These inequalities present a challenge for the public health workers based in or responsible for improving the health of people living in disadvantaged localities. The purpose of this study was to develop a generic workforce needs assessment tool and to use it to identify the competencies needed by the public health workforce to work effectively in disadvantaged communities. A two-step mixed method process was used to identify the workforce needs. In step 1 a generic workforce needs assessment tool was developed and applied in three NSW Area Health Services using focus groups, key stakeholder interviews and a staff survey. In step 2 the findings of this needs assessment process were mapped against the existing National Health Training Package (HLT07) competencies, gaps were identified, additional competencies described and modules of training developed to fill identified gaps. There was a high level of agreement among the AHS staff on the nature of the problems to be addressed but less confidence indentifying the work to be done. Processes for needs assessments, community consultations and adapting mainstream programs to local needs were frequently mentioned as points of intervention. Recruiting and retaining experienced staff to work in these communities and ensuring their safety were major concerns. Workforce skill development needs were seen in two ways: higher order planning/epidemiological skills and more effective working relationships with communities and other sectors. Organisational barriers to effective practice were high levels of annual compulsory training, balancing state and national priorities with local needs and giving equal attention to the population groups that are easy to reach and to those that are difficult to engage. A number of additional competency areas were identified and three training modules developed. The generic workforce needs assessment tool was easy to use and interpret. It appears that the public health workforce involved in this study has a high level of understanding of the relationship between the social determinants and health. However there is a skill gap in identifying and undertaking effective intervention.


The relative impact of migration type on the reversal of black out-migration from the South.
"In this article historical patterns and recent trends in black migration in the United States are examined. The purpose of the article is two-fold: (1) to examine historical changes in the volume and rates of migration between the southern region and nonsouthern regions; and (2) to determine the relative impact of migration types on the South's changeover to net in-migration during the 1975-1980 migration interval.... The single most important factor influencing the turnaround was a decrease in the number of southern-born blacks migrating out of the region. This finding is contrary to much current speculation about the role of return migrants in influencing the South's changeover to net in-migration for the black population."


Postmarketing surveillance.
Postmarketing drug surveillance refers to the monitoring of drugs once they reach the market after clinical trials. It evaluates drugs taken by individuals under a wide range of circumstances over an extended period of time. Such surveillance is much more likely to detect previously unrecognized positive or negative effects that may be associated with a drug. The majority of postmarketing surveillance concern adverse drug reactions (ADRs) monitoring and evaluation. Other important postmarketing surveillance components include unapproved or off-label drug use, problems with orphan drugs, and lack of paediatric formulations, as well as issues concerning international clinical trials in paediatric population. The process of evaluating and improving the safety of medicines used in paediatric practice is referred to as paediatric pharmacovigilance. It requires special attention. Childhood diseases and disorders may be qualitatively and quantitatively different from their adult equivalents. This may affect either benefit or risk of therapies (or both), with a resulting impact on the risk/benefit balance. In addition, chronic conditions may require chronic treatment and susceptibility to ADRs may change throughout the patient's lifetime according to age and stage of growth and development. Therefore, paediatric pharmacovigillance aspects need to be tailored to a number of variables based on heterogeneity of paediatric population. This chapter will summarize and discuss the key issues.


HUMORAL IMMUNITY IN PATIENTS WITH SARS-COV-2 INFECTION: A REVIEW.
The COVID-19 pandemic caused by SARS-CoV-2 started in China in December, 2019 and has spread across several continents. As at 5th December, 2020, there have been 65,257,767 confirmed cases of COVID-19 worldwide with 1,513,179 deaths (2.31% mortality) Humoral immune responses are highly specific and they provide long-lasting protection against reinfection and the titre of antibodies that persist is directly related to the extent of protection afforded. As research towards generating effective vaccines against SARS-CoV-2 are in advanced stages, there is need for continued robust review of the available data from various studies on the antibody response from natural SARS-COV-2 infection as regards the potential for immunity against re-infection following exposure to the antigens of this virus. Antibodies against RBD of the spike protein of SARS-CoV-2 were detected in majority of patients, appearing within the first week, peaking by 3rd week. IgG antibodies was observed to last beyond 120days and it is predicted seroreversion would happen at about 42.72 months. Antibody response to SARS-CoV-2 correlates with the severity of COVID-19. It was also higher amongst males, hospitalized patients, older people and patients with higher BMI and was lower among smokers, immunosuppressed individuals and patients using anti-inflammatory medications. Persistence of high levels of antiSARS-CoV-2 neutralizing antibodies (IgG) following natural infection is thus likely to be associated with conferment of long term protection against re-infection or attenuate disease severity if reinfection occurs. There is a good potential for development of immunity against SARS-CoV-2 infection in vaccinated individuals.


Clinical significance of co-expression of aberrant antigens in acute leukemia: a retrospective cohort study in Makah Al Mukaramah, Saudi Arabia.
Aberrant phenotypes in acute leukemia have variable frequency and their prognostic and predictive relevance is controversial, despite several reports of clinical significance. To determine the prevalence of aberrant antigen expression in acute leukemia, assess clinical relevance and demonstrate immunophenotype-karyotype correlations. A total of 73 (40 AML and 33 ALL) newly diagnosed acute leukemia cases presenting to KAMC, Kingdom of Saudi Arabia, were included. Diagnosis was based on WHO criteria and FAB classification. Immunophenotyping by flow cytometry, conventional karyotyping and fluorescence in situ hybridization for gene rearrangements were performed. Aberrant antigens were detected in 27/40 (67.5%) of AML and in 14/33 (42.4%) in ALL cases. There were statistically significant higher TLC in Ly+ AML than in Ly-AML (p=0.05) and significant higher blast count in ALL with aberrant antigens at presentation and day 14 (p=0.005, 0.046). There was no significant relation to clinical response, relapse free survival (RFS) or overall survival (p>0.05), but AML cases expressing ≥2 Ly antigens showed a lower median RFS than those expressing a single Ly antigen. In AML, CD 56 was expressed in 11/40. CD7 was expressed in 7/40, having a significant relation with an unfavorable cytogenetic pattern (p=0.046). CD4 was expressed in 5/40. CD19 was detected in 4/40 AML associated with M2 and t (8; 21). In ALL cases, CD33 was expressed in 7/33 and CD13 in 5/33. Regarding T Ag in B-ALL CD2 was expressed in 2 cases and CD56 in 3 cases. Aberrant antigen expression may be associated with adverse clinical data at presentation. AML cases expressing ≥2 Ly antigens may have shorter median RFS. No specific cytogenetic pattern is associated with aberrant antigen expression but individual antigens may be related to particular cytogenetic patterns. Immunophenotype-karyotype correlations need larger studies for confirmation.


Pectic polysaccharide breakdown of cell walls in cucumber roots grown with calcium starvation.
Pectic polysaccharides from the roots of cucumber (Cucumis sativus L.) grown in liquid culture medium with or without calcium (1 mm CaCl(2)) were studied after extraction successively by hot water and Na hexametaphosphate solution. The Ca(2+) starvation-treatment caused a striking reduction in content of extracted pectic polysaccharide; from an equivalent weight of cell walls, only 33.1% of the control level was extracted from root cell walls of plants cultured under Ca(2+) deficiency. The extracted pectic polysaccharides were fractionated into neutral and acidic polymers by a DEAE-Sephadex column. The acidic polymers, which represented more than 76% of the yield, appeared to be a major fraction of extracted pectic polysaccharides. The changes of molecular size and glycosyl residue composition of this fraction were compared for the control and Ca(2+)-deprived samples. The results indicate that Ca(2+) deficiency caused structural changes which could involve both branching pattern and extent of contiguous galacturonosyl units in the water-solubilized pectic polysaccharides. Ca(2+) starvation also led to a notable decrease in molecular size of the hexametaphosphate-solubilized polysaccharides and, to a lesser extent, of the water-solubilized fraction as well. In addition, polygalacturonase activity in tissue homogenates increased remarkably with the Ca(2+) deficiency, whereas beta-galactosidase activity did not undergo a change. Thus, it appears that one major effect of Ca(2+) deprivation was to stimulate polygalacturonase activity, an effect which could be involved in the control of the breakdown of pectic polysaccharides in the cell walls.


A cold environment is a prerequisite for formation of "plastid initials" in winter buds of poplar.
The "plastid initial," the presumed precursor of eoplasts and proplastids, is present in the cells of the apical meristem of winter buds of poplar (Populus euramericana). The formation of the plastid initial in the cells of winter buds is initiated soon after the breaking of the innate or resting stage of dormancy, even in winter under nongrowing conditions in mid-January or early February. From this stage to March, the conglomeration of the plastid initial and the formation of prolamellar bodies is evident. In contrast to the poplar samples kept outdoors, the cells of the apical meristem of the indoor winter buds did not show any indication of the formation of the plastid initial and the buds of the latter sample did not flush even at the end of May. These results suggest that the sequence of reactions involved in the onset of regrowth may be closely related to the formation of the plastid initial.


Effectiveness and predictability of pleurodesis with the Tachosil® surgical patch compared with talc poudrage: an experimental study.
The human fibrinogen/thrombin surgical patch is proposed for videothoracoscopic pleurodesis after recurrent observation in routine clinical practice of site-specific pleuro-pulmonary adhesions. A total of 36 experimental videothoracoscopies were performed on 18 pigs, all of which underwent a bilateral sequential procedure. The right or left side was casually approached and two 4.8 × 4.8 cm Tachosil® patches were placed over the dorsal lung surface in the highest antigravitary position through a double-port thoracoscopy. The contralateral side was subsequently entered by a single-port thoracoscopy to perform talc poudrage in accordance with current recommendations (1 g/18 kg). Thoracoscopy and autopsy were performed after 60 days to evaluate the outcome. Pleurodesis was graded on a predefined three-tier scale (none-moderate-firm); specimens were then submitted to the pathologist. The statistical analyses performed were: frequencies distribution, variables association test and hypothesis testing using binomial distribution. Pleurodesis was firm in 15/18 cases (P = 0.004), moderate in 2/18, and none in 1/18 cases with the sealant matrix. Talc pleurodesis was firm in 7/18 cases and moderate in 11/18. No surgical, medical, behavioural or growth disorders were recorded. There was complete correspondence between lung surface covered by the sealant patch and pleural adhesion topography (P < 0.001) and no other sites of adhesion were found at autopsy, whereas talc effect was commonly found to produce random pleural cavity obliteration, most frequently in declivous places, with inhomogeneous pleural adhesion for tissue density and rough/smooth outline (P < 0.001). The pathologist disclosed that talc creates a variable and unpredictable inflammatory background, sometimes severe, with the development of many granulomas. Fibrin sealant patch pleurodesis is caused by connective tissue irrespective of the pleural and pulmonary anatomy. The fibrin sealant patch is effective in producing localized pleurodesis in swine. The morphology and topography of the adhesions, 2 months after the patch placement, are consistent and more predictable than after talc poudrage. The latter causes a diffuse pleurodesis which is not predictable, with a predominantly gravitational location and produces a much more serious inflammatory response.


A plaster combining diclofenac and heparin: microcirculatory evaluation in 2 models of high-perfusion microangiopathy.
A medicated plaster containing diclofenac epolamine (DHEP) and heparin has been recently proposed for the treatment of local trauma (ie, ankle sprains) accompanied by a clinically significant edema and/or hematoma formation, based on the combined antiinflammatory, hemorheologic, and antiedema properties of diclofenac and heparin. The aim of this study was therefore to compare the effects of a combined DHEP/heparin and DHEP alone in 2 clinical experimental models of microangiopathy, in order to provide a pharmacologic rationale for association of diclofenac and heparin. The microcirculation was evaluated by measuring cutaneous blood flow (laser Doppler) and transcutaneous oxygen and carbon dioxide pressures (TcPO(2) and TcPCO(2)) in 10 healthy volunteers before and after producing 2 microcirculatory models of microangiopathy: the models were based on reactive hyperemia (RH) and on local histamine injection, which both produce a significant increase in skin flux and alterations of TcPO(2) and TcPCO(2). The area of the study was the distal medial leg, treated with placebo, DHEP alone (Flector Tissugel), and DHEP/heparin (Flector Tissugel Heparin). The plasters were applied before producing the microcirculatory models to evaluate the efficacy of DHEP and DHEP/heparin in controlling and limiting vasodilatation and development of microangiopathy. A significant increase in cutaneous flux was obtained with both models. The application of DHEP partially limited the increase in flux and in TcPCO(2), as well as the decrease in TcPO(2) (which were considered signs of microangiopathy), but the combination DHEP/heparin was significantly more effective than DHEP alone. The inclusion of heparin in the plaster thus improved the control of the microcirculation achieved with diclofenac alone, when an experimental model of venous/arterial hyperemia and microangiopathy was used. In conclusion, DHEP in association with heparin modulates microcirculatory changes better than DHEP alone. It should be interesting to investigate the product in comparable clinical conditions in which it may be useful to act pharmacologically both on inflammation and microcirculatory disturbances that delay the recovery of patients.


Features of Pharmacodynamics of the Anticoagulant Dabigatran in Secondary Thrombophilia.
One of the crucial risk factors for development of severe postthrombotic disease (PTD) is the recurrence of deep vein thrombosis (DVT). New opportunities for pharmacological thromboprophylaxis of secondary thrombophilia were associated with the direct thrombin inhibitor-Dabigatran (Pradaxa; Boehringer Ingelheim, Germany). We aimed to investigate the daily pharmacodynamics of dabigatran in healthy volunteers and patients with PTD. Treatment with dabigatran in patients with PTD having chronic chronometric hypercoagulation and structural hypocoagulation before the administration of the drug is fraught with excessive anticoagulation and a high risk of clinically significant bleeding. In patients with PTD with detected chronometric and structural hypercoagulability before taking a direct thrombin inhibitor, treatment with dabigatran is fraught with possible inadequate anticoagulation and a high risk of clinically significant relapses of thromboses. According to our data, markers of risk of hemorrhagic complications under Dabigatran are the thromboelastography indicators lying within the reference values of the healthy before the administration of the drug: fibrin-platelet clot formation, maximum amplitude of TEG; total lytic activity of blood, and thrombodynamic potential index . Monitoring the effects of the targeted anticoagulant demonstrated the need for correction of dosage and discrete use of the drug in prevention and treatment for thrombohemorrhagic complications in this category of patients. The results of the study prove the efficiency of the therapy with dabigatran and "behavior" of hemostatic potential in patients being taken into account and controlled. Therapy may be long term but requires dynamic monitoring of patients with timely dose adjustment to achieve and maintain the target level of hemostatic potential.


Effects of adrenalectomy and hypophysectomy on enkephalin content of the rat hypothalamus.
1 Hypothalamic content of enkephalin in rats has been measured by bioassay against methionine-enkephalin on field-stimulated mouse vas deferens after acid extraction and purification using Amberlite XAD-2 resin.2 Surgical stress lowered hypothalamic enkephalin content initially but 6 days after operation the content was higher in sham-operated than in adrenalectomized animals.3 Corticosteroid replacement therapy showed that hypothalamic enkephalin content was not related directly to circulating corticosteroid levels and that it was increased by the stress of handling and injection.4 Hypothalamic enkephalin content of rats that had undergone hypophysectomy 11 days earlier did not differ from that of intact animals but surgical stress, which lowered content in intact rats and had no effect after adrenalectomy, produced a rise in content in these hypophysectomized animals.5 The ingestion of 0.9% saline, in place of water, by sham-adrenalectomized rats altered the effect of surgical stress on hypothalamic enkephalin content without affecting the resting levels.6 Of extracts from adrenalectomized rats, 10% contained a substance that behaved atypically on the mouse vas deferens, showing a slower onset and offset of action. The mol. wt. of the substance and sensitivity to naloxone reversal appeared to be similar to enkephalin, but it was resistant to carboxypeptidase-A and protease treatment.7 It is concluded that the enkephalin content of the hypothalamus is affected by activity in the hypothalamus-pituitary-adrenal system but that it is not related in a simple manner to the levels of corticotrophin releasing hormone, corticotrophin or corticosteroids.


The disease resistance protein SNC1 represses the biogenesis of microRNAs and phased siRNAs.
Plants evolved an array of disease resistance genes (R genes) to fight pathogens. In the absence of pathogen infection, NBS-LRR genes, which comprise a major subfamily of R genes, are suppressed by a small RNA cascade involving microRNAs (miRNAs) that trigger the biogenesis of phased siRNAs (phasiRNAs) from R gene transcripts. However, whether or how R genes influence small RNA biogenesis is unknown. In this study, we isolate a mutant with global defects in the biogenesis of miRNAs and phasiRNAs in Arabidopsis thaliana and trace the defects to the over accumulation and nuclear localization of an R protein SNC1. We show that nuclear SNC1 represses the transcription of miRNA and phasiRNA loci, probably through the transcriptional corepressor TPR1. Intriguingly, nuclear SNC1 reduces the accumulation of phasiRNAs from three source R genes and concomitantly, the expression of a majority of the ~170R genes is up-regulated. Taken together, this study suggests an R gene-miRNA-phasiRNA regulatory module that amplifies plant immune responses.


High air flow-rate electrostatic sampler for the rapid monitoring of airborne coronavirus and influenza viruses.
Capturing virus aerosols in a small volume of liquid is essential when monitoring airborne viruses. As such, aerosol-to-hydrosol enrichment is required to produce a detectable viral sample for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. To meet this requirement, the efficient and non-destructive collection of airborne virus particles is needed, while the incoming air flow rate should be sufficiently high to quickly collect a large number of virus particles. To achieve this, we introduced a high air flow-rate electrostatic sampler (HAFES) that collected virus aerosols (human coronavirus 229E, influenza A virus subtypes H1N1 and H3N2, and bacteriophage MS2) in a continuously flowing liquid. Viral collection efficiency was evaluated using aerosol particle counts, while viral recovery rates were assessed using real-time qRT-PCR and plaque assays. An air sampling period of 20 min was sufficient to produce a sample suitable for use in real-time qRT-PCR in a viral epidemic scenario.


The d4 gene family in the human genome.
The d4 domain, a novel zinc finger-like structural motif, was first revealed in the rat neuro-d4 protein. Here we demonstrate that the d4 domain is conserved in evolution and that three related genes form a d4 family in the human genome. The human neuro-d4 is very similar to rat neuro-d4 at both the amino acid and the nucleotide levels. Moreover, the same splice variants have been detected among rat and human neuro-d4 transcripts. This gene has been localized on chromosome 19, and two other genes, members of the d4 family isolated by screening of the human genomic library at low stringency, have been mapped to chromosomes 11 and 14. The gene on chromosome 11 is the homolog of the ubiquitously expressed mouse gene ubi-d4/requiem, which is required for cell death after deprivation of trophic factors. A gene with a conserved d4 domain has been found in the genome of the nematode Caenorhabditis elegans. The conservation of d4 proteins from nematodes to vertebrates suggests that they have a general importance, but a diversity of d4 proteins expressed in vertebrate nervous systems suggests that some family members have special functions.


Pathophysiological doses of glucagon cause a transient increase of the hepatic vein potassium concentration in man.
In order to evaluate whether glucagon-induced hyperkalemia is due to mobilization of potassium from the splanchnic region, we measured potassium changes in the hepatic veins following a glucagon injection into the ascending aorta. Twenty-seven subjects undergoing routine cardiac catheterization for diagnostic purposes were studied. Hepatic venous and aortic blood samples were withdrawn simultaneously under basal condition and 30, 60, 120, 180, 300, 600 s after a bolus injection of either saline, glucagon (100 ng/kg body weight) or glucagon +somatostatin (100 micrograms). After the intra-aortic injection, plasma glucagon in the hepatic veins reached levels comparable to those observed under pathophysiological conditions. Plasma potassium increased promptly with a peak at 60 s (delta max: 0.79 +/- 0.12 mmol/l, mean +/- SEM; p less than 0.01). The glucose increment peaked at 300 s (delta max: 2.36 +/- 0.20 mmol/l, mean +/- SEM; p less than 0.01). Potassium increment was potentiated by the addition of somatostatin, despite the abolition of insulin and C-peptide rises (potassium delta max: 0.56 +/- 0.10 mmol/l; p less than 0.05). In conclusion, these data demonstrate that glucagon induces a transient mobilization of potassium from the splanchnic region in man. This effect of glucagon on potassium is not antagonized by glucagon-induced insulin secretion.


Assessing the Rhizotoxicity of the Aluminate Ion, Al(OH)(4).
Dissolved aluminum (III) in acidic soils or culture media is often rhizotoxic (inhibitory to root elongation). Alkaline solutions of Al are also sometimes rhizotoxic, and for that reason toxicity has been attributed to the aluminate ion, Al(OH)(4) (-). In the present study, seedlings of wheat (Triticum aestivum L. cv Tyler) and red clover (Trifolium pratense L. cv Kenland) were cultured in aerated aluminate solutions at pH 8.0 to 8.9. The bulk phases of these solutions were free of reactive polynuclear hydroxy-Al (including the extremely toxic species AlO(4)Al(12)[OH](24)[H(2)O](7+) (12) [Al(13)]) according to the ferron (8-hydroxy-7-iodo-5-quinolinesulfonic acid) assay. At an aluminate concentration of 25 micromolar (23 micromolar activity) and a pH of 8, root elongation was less than 40% of Al-free controls, but at pH 8.9 elongation was 100% of controls. The hypothesis is offered that aluminate is nontoxic and that the inhibition at lower pH values is attributable to Al(13) postulated to have formed in the acidic free space of the roots where the ratio /{Al(3+)/}//{H(+)/}(3) may rise above 10(10). At this value hydroxy-Al in over-saturated, alkaline solutions begins to undergo rapid conversion to polynuclear species.


The human dioxin-inducible NAD(P)H: quinone oxidoreductase cDNA-encoded protein expressed in COS-1 cells is identical to diaphorase 4.
NAD(P)H: quinone oxidoreductase (NQO1) is believed to be protective against cancer and toxicity caused by exposure to quinones and their metabolic precursors. This enzyme catalyzes the two-electron reduction of compounds, compared with one-electron reduction mediated by NADPH: cytochrome-P450 oxidoreductase which produces toxic and mutagenic free radicals. Recently we cloned and sequenced the cDNA encoding human 2.3,7,8-tetrachlorodibenzo-p-dioxin (dioxin)-inducible cytosolic NQO1 [Jaiswal et al. (1988) J. Biol. Chem. 263, 13572-13578] and provided preliminary evidence that this enzyme may correspond to diaphorase 4, an enzymatic activity present in various tissues that catalyzes the reduction of a variety of quinones by both NADH and NADPH [Edwards et al. (1980) Biochem. J. 187, 429-436]. In the present report we characterize the catalytic properties of the protein encoded by the NQO1 cDNA. The enzyme was synthesized in monkey kidney COS-1 cells transfected with a pMT2-based expression plasmid containing the NQO1 cDNA. Western blot analysis of the transfected cells using an antibody against rat liver cytosolic NQO1 revealed a 31-kDa band that was not detected in nontransfected cells. This band corresponded to a polypeptide with the same electrophoretic mobility as the endogenous NQO1 protein detected in the human hepatoblastoma (Hep-G2) cells with the same antibody. The immunoreactive protein detected in human Hep-G2 cells was induced approximately fourfold by exposure of the cultures to dioxin, an increase commensurate with the increased in quinone oxidoreductase activity. These studies suggest that the protein encoded by NQO1 cDNA is indeed similar, if not identical, to the dioxin-inducible protein band detected in human Hep-G2 cells. Further characterization of the product of NQO1 cDNA, which was present at approximately 20-30-fold higher levels in transfected COS cells than the endogenous product in uninduced human Hep-G2 cells indicated that it had very high capacity (greater than 1000-fold over background) to catalyze the reduction of 2.6-dichloroindophenol and menadione. Besides these two commonly used substrates for quinone reductase, the expressed NQO1 protein also effectively metabolized 2,6-dimethylbenzoquinone, methylene blue, p-benzoquinone, 1,4-naphthoquinone, 2-methyl-1,4-benzoquinone, with the latter being the most potent electron acceptor at 50 microM concentration of the substrate.


Efficacy and safety of current drug therapies for invasive aspergillosis.
Invasive aspergillosis (IA) is a potentially lethal infection that affects mostly immunocompromised patients. The therapeutic goals are to restore leucocyte function and to reduce the fungal burden by effective antifungal agents and, contingently, by surgery. Several drugs for the treatment of IA are currently licensed. The longest known among them is amphotericin B (AmB). In well-performed clinical trials, approximately 30-50% of participants treated with AmB showed complete or partial response. However, this drug is associated with considerable acute and chronic toxicity which was somewhat mitigated by the development of lipid-based formulations. In contrast, voriconazole (VRC) is better tolerated, penetrates well into the central nervous system and may be given intravenously and orally in a sequential manner. The overall rates of favourable response to VRC were similar to that for AmB. Most notably, double-digit rates of complete remission were observed in studies including extraordinarily high proportions of patients with proven IA and specific risk factors. Disadvantages of VRC include the genetically determined interindividual variability of pharmacokinetics and the potential for drug-drug interactions that may require therapeutic drug monitoring. The recently introduced caspofungin (CPF) offers an excellent safety profile, but underperformed in terms of efficacy against mold infections. Other antifungals such as itraconazole and posaconazole are presently recommended as second-line option for the therapy or prophylaxis of (non-)IA. The value of micafungin and anidulafungin remains to be investigated in randomized clinical trials. In guidelines released by relevant medical societies, VRC is recommended as the first choice in the treatment of IA. AmB, preferably given as a liposomal preparation, or combinatory antifungal regimens combining VRC or liposomal AmB with CPF are stated as alternative options.


Oxygen and Hydrogen Isotope Ratios of Water from Photosynthetic Tissues of CAM and C(3) Plants.
Water samples from photosynthetic tissues of C(3) and Crassulacean acid metabolism (CAM) plants that grew together in the field were extracted and the stable oxygen and hydrogen isotope ratios determined. During the day, (18)O/(16)O and deuterium/hydrogen (D/H) ratios of water from CAM plants were lower than those observed in water from C(3) plants. The patterns of diurnal variation (or lack thereof) in isotope ratios of plant water are consistent with the gross anatomical and physiological characteristics of the plants studied here. Our observations support the previously advanced hypothesis that high D/H ratios in cellulose nitrate prepared from CAM plants relative to those for C(3) plants are not caused by greater deuterium enrichment in the water in CAM plants, but rather by isotopic fractionations associated with different biochemical reactions in the two types of plants.


[Well-being among children and the aged in the aging society].
The age structure of Japan and the well-being of the aged as compared to that of children are discussed in light of Samuel Preston's thesis that the increase in the number of elderly people contributes to their well-being. The author evaluates "three-year comparisons of Japanese expenditure data by age on the basis of special tabulations of the Social Survey for Health and Welfare Administration.... An attempt has been made to retabulate and analyze the latest available income data from...the Statistics Bureau. The results of both surveys seem to generally support the relevance [of] Preston's [argument]." (SUMMARY IN ENG)


Role of SHP2 protein tyrosine phosphatase in SERT inhibition by enteropathogenic E. coli (EPEC).
Enteropathogenic Escherichia coli (EPEC), one of the diarrheagenic E. coli pathotypes, is among the most important food-borne pathogens infecting children worldwide. Inhibition of serotonin transporter (SERT), which regulates extracellular availability of serotonin (5-HT), has been implicated previously in EPEC-associated diarrhea. EPEC was shown to inhibit SERT via activation of protein tyrosine phosphatase (PTPase), albeit the specific PTPase involved is not known. Current studies aimed to identify EPEC-activated PTPase and its role in SERT inhibition. Infection of Caco-2 monolayers with EPEC strain E2348/69 for 30 min increased the activity of Src-homology-2 domain containing PTPase (SHP2) but not SHP1 or PTPase 1B. Similarly, Western blot studies showed increased tyrosine phosphorylation of (p-tyrosine) SHP2, indicative of its activation. Concomitantly, EPEC infection decreased SERT p-tyrosine levels. This was associated with increased interaction of SHP2 with SERT, as evidenced by coimmunoprecipitation studies. To examine whether SHP2 directly influences SERT phosphorylation status or function, SHP2 cDNA plasmid constructs (wild type, constitutively active, or dominant negative) were overexpressed in Caco-2 cells by Amaxa electroporation. In the cells overexpressing constitutively active SHP2, SERT polypeptide showed complete loss of p-tyrosine. In addition, there was a decrease in SERT function, as measured by Na+Cl--sensitive [3H]5-HT uptake, and an increase in association of SERT with SHP2 in Caco-2 cells expressing constitutively active SHP2 compared with dominant-negative SHP2. Our data demonstrate that intestinal SERT is a target of SHP2 and reveal a novel mechanism by which a common food-borne pathogen uses cellular SHP2 to inhibit SERT.NEW & NOTEWORTHY The data presented in the current study reveal that intestinal serotonin transporter (SERT) is a target of the tyrosine phosphatase SHP2 and show a novel mechanism by which a common diarrheagenic pathogen, EPEC, activates cellular SHP2 to inhibit SERT function. These studies highlight host-pathogen interactions, which may be of therapeutic relevance in the management of diarrhea associated with enteric infections.


Task-related electroencephalographic deviances in adults with attention deficit hyperactivity disorder.
This study aimed to provide more insight into the functional significance of electroencephalographic (EEG) deviances in attention-deficit/hyperactivity disorder (ADHD) by evaluating quantitative EEG during performance on a task with a low activation level and a task tapping top-down executive control. Behavioral performance and EEG activity were compared between 24 adults with ADHD and 20 typically developing adults during a simple slow-paced 2-choice reaction time (2-CRT) task and a moderately paced flanker task. During the slow 2-CRT task, adults with ADHD responded slower, more variably, and tended to make more errors of commission. Although being slower, adults with ADHD showed equally large congruency effects during flanker task performance, indicating intact interference inhibition. In the slow 2-CRT task, (midline) theta and beta power were higher in the ADHD group than in the control group, whereas no significant EEG group differences were observed in the flanker task. A moderate positive correlation between theta power and errors of commission was found in the 2-CRT task for adults with ADHD. Adults with ADHD performed worse on a task inducing a low activation level but showed intact interference inhibition. The EEG findings are in accord with this, showing an abnormal EEG pattern in ADHD only when a low activation level was induced, not when top-down executive control load was high. Time-on-task effects could not explain the group deviances. The findings indicate that EEG deviances in ADHD are task-dependent and may be related to a suboptimal energetic state, rather than impaired top-down executive control.


Structural characterization of polypeptides and proteins by combination of capillary electrophoresis and (252)Cf plasma desorption mass spectrometry.
An efficient and sensitive method for the isolation and transfer of peptides and proteins from capillary zone electrophoresis separation for subsequent analysis by 252Cf plasma desorption mass spectrometry was developed. Sample isolation on to nitrocellulose-coated targets for mass spectrometric analysis is performed by using a stainless-steel microtube pre-filled with aqueous buffer solution, to which the capillary end is connected, and the peptide is collected by applying a suitable transfer voltage according to the separation voltage. Low-and sub-picomolar sample amounts were isolated with high transfer efficiency and reproducibility, without the necessity for independent determination of electroosmotic flow-rates. Plasma desorption mass spectra of several peptides and proteins showed predominantly intact molecular ions; however, for several peptides partial oxidative modification was found which can be accounted for by the electrophoretic separation and/or transfer conditions. First applications to peptides and proteins show the feasibility of this off-line combination for primary structure characterization, such as by in situ chemical modification and enzymatic proteolysis reactions on the sample target prior to mass spectrometric analysis.


Viral-like characteristics of particle aggregates in a lymphoblastic cell line.
A lymphoblastic cell line (K45) established from a child with acute lymphoblastic leukemia (ALL) is characterized by a profusion of intracytoplasmic particle aggregates (PA) similar in morphology to those occurring in fresh childhood ALL cells. The PA in K45 cells were examined for morphology and capacity for nucleic acid synthesis to test the hypothesis that they are identical to those in fresh ALL cells, and also to identify characteristics which might distinguish PA from cell organelles and which might determine if they are viral-like. In contrast to cell organelles, the PA in both K45 and ALL cells were found to be characterized by a localized thickening of the particle wall. Furthermore, autoradiography of K45 cells showed uptake by PA of 3H uridine rather than 3H thymidine indicating an RNA composition. The presence of PA in profusion was associated with, but preceded necrotic death of K45 cells. These combined features suggest that the PA in K45 and in ALL cells are identical, that they are distinct from cell organelles, are not formed as a consequence of the initiation of cell death and that, while their exact nature remains unknown, a viral origin cannot be excluded.