Safety and efficacy of the new iodinated nonionic low-osmolality contrast medium Iobitridol (Xenetix) in coronary and ventricular angiography.
The aim of this phase-III clinical trial was prospectively to evaluate the clinical safety and diagnostic efficacy as well as the effects on laboratory and electrocardiographic parameters of new iodinated, nonionic, low-osmolality contrast medium, iobitridol(Xenetix 350) during coronary angiography in adults in comparison to an iodinated, nonionic, low-osmolality reference product, iohexol (Omnipaque). This 2-center, comparative, randomized, double-blind trial involved 90 patients, 46 receiving iobitridol and 44 iohexol. Clinical safety was evaluated by recording the adverse events observed during investigation and by the patient's assessments. Electrocardiographic effects on laboratory parameters were evaluated as well as diagnostic efficacy. The age, sex, presence of risk factors and clinical picture ( unstable angina, postinfarction) were not significantly different between the 2 treatment groups. The incidence of significant coronary lesions (stenosis 50%) was also not significantly different between the 2 treatment groups. Clinical safety was good in both groups. Four patients experienced an adverse event, 2 in each group. In the iobitridol group, one patient had an episode of hypertension, followed by hypertension and prolonged chest pain was observed and one patient had sinus tachycardia. In the iohexel group, chest pain was observed in one patient and nausea in another. ECG safety was good in both groups. Transient excitability disorders were observed in 10 and 6 patients, respectively. Moderate conduction abnormalities were noted in one patient in each group and repolarization abnormalities in 10 and 8 cases, respectively. Safety in laboratory parameters was good with no significant changes in either. Diagnostic efficacy was good to excellent in all patients. Diagnostic efficacy and safety of iobitridol 350 in terms of effects on clinical, laboratory and electrocardiographic parameters were comparable to those of the nonionic reference product.


[Therapy of gonarthrosis using chondroprotective substances. Prospective comparative study of glucosamine sulphate and glycosaminoglycan polysulphate].
68 patients with mild or moderate gonarthritis were treated with intra-articular injections of glucosamine sulphate or glycosaminoglycan polysulphate over a period of six weeks. The therapy was successful in two thirds of these patients. "Loading" pain was eliminated or improved in about 80%, "getting-going" pain in about 64%, and signs of synovialitis in about 66%. Gait function and mobility were improved. Glucosamine had a superior effect, in particular in mild arthritis, achieving an improvement of pain in 90%, while glycosaminoglycan polysulphate was successful in advanced cases. The tolerance of the two substances was 94%. The results and the underlying modes of action of the substances are discussed.


Astrobiological implications of dim light phototrophy in deep-sea red clays.
Red clays of Central Indian Basin (CIB) under influence of trace of Rodriguez Triple Junction exhibited chemoautotrophy, low temperature hydrothermal alterations and photoautotrophic potential. Seamount flank TVBC-08, hosting such signatures revealed dominance of aerobic anoxygenic phototroph Erythrobacter, with 93% of total 454 pyrosequencing tags. Subsequently, enrichments for both aerobic (Erythrobacter) and anaerobic anoxygenic phototrophs (green and purple sulphur bacteria) under red and white LED light illumination, with average irradiance 30.66Wm-2, were attempted for three red-clay sediment cores. Successful enrichments were obtained after incubation for c.a. 120 days at 4°± 2°C and 25°± 2°C, representing ambient psychrophilic and low temperature hydrothermal alteration conditions respectively. During hydrothermal cooling, a microbial succession from anaerobic chemolithotrophy to oxygenic photoautotrophy through anaerobic/aerobic anoxygenic phototrophic microbes is indicated. Spectral absorbance patterns of the methanol extracted cell pellets showed peaks corresponding to metal sulphide precipitations, the Soret band of chlorosome absorbance by photosystem II and absence of peaks at Qy transition band. Dendritic nano-structures of metal sulphides are common in these sediments and are comparable with other sulphidic paleo-marine Martian analogues. Significant blue and redshifts have been observed for the experimental samples relative to the un-inoculated medium. These observations indicate the propensity of metal-sulphide deposits contributing to chemiluminiscence supporting the growth of phototrophs at least partially, in the otherwise dark abyss. The effects of other geothermal heat and light sources are also under further consideration. The potential of phototrophic microbial cells to exhibit Doppler shift in absorbance patterns is significant towards understanding planetary microbial habitability. Planetary desiccation could considerably influence Doppler effects and consequently spectral detection techniques exo-planetary microbial life.


Recyclable and Intrinsically Anti-cyanobacterial Polyanionic Membranes.
Cyanobacteria blooms possess serious threats to water resources. Herein, we report the synthesis of polyanionic membranes (PA-M) by in situ photo-crosslinking of a sulfate-based anionic monomer followed by cation-exchange with metal cations, Fe3+ (PA-Fe), Cu2+ (PA-Cu), or Zn2+ (PA-Zn). The effect of cations on the anti-cyanobacterial activities against both Microcystis aeruginosa (M. aeruginosa) and Anabaena flos-aquae (A. flos-aquae) was investigated. All the prepared metal-containing membranes (PA-Fe, PA-Cu, PA-Zn) exhibit high anti-cyanobacterial activities and long-term anti-cyanobacterial stability, demonstrating that the synthesized PA-M membranes can be used as an effective and safe inhibitor to control cyanobacterial blooms.


Functional characterization of LIT1, the Leishmania amazonensis ferrous iron transporter.
Leishmania amazonensis LIT1 was identified based on homology with IRT1, a ferrous iron transporter from Arabidopsis thaliana. Deltalit1L. amazonensis are defective in intracellular replication and lesion formation in vivo, a virulence phenotype attributed to defective intracellular iron acquisition. Here we functionally characterize LIT1, directly demonstrating that it functions as a ferrous iron membrane transporter from the ZIP family. Conserved residues in the predicted transmembrane domains II, IV, V and VII of LIT1 are essential for iron transport in yeast, including histidines that were proposed to function as metal ligands in ZIP transporters. LIT1 also contains two regions within the predicted intracellular loop that are not found in Arabidopsis IRT1. Deletion of region I inhibited LIT1 expression on the surface of Leishmania promastigotes. Deletion of region II did not interfere with LIT1 trafficking to the surface, but abolished its iron transport capacity when expressed in yeast. Mutagenesis revealed two motifs within region II, HGHQH and TPPRDM, that are independently required for iron transport by LIT1. D263 was identified as a key residue required for iron transport within the TPPRDM motif, while P260 and P261 were dispensable. Deletion of proline-rich regions within region I and between regions I and II did not affect iron transport in yeast, but in L. amazonensis were not able to rescue the intracellular growth of Deltalit1 parasites, or their ability to form lesions in mice. These results are consistent with a potential role of the unique intracellular loop of LIT1 in intracellular regulation by Leishmania-specific factors.


A wide-field micro-computed tomography detector: micron resolution at half-centimetre scale.
Ideal three-dimensional imaging of complex samples made up of micron-scale structures extending over mm to cm, such as biological tissues, requires both wide field of view and high resolution. For existing optics and detectors used for micro-CT (computed tomography) imaging, sub-micron pixel resolution can only be achieved for fields of view of <2 mm. This article presents a unique detector system with a 6 mm field-of-view image circle and 0.5 µm pixel size that can be used in micro-CT units utilizing both synchrotron and commercial X-ray sources. A resolution-test pattern with linear microstructures and whole adult Daphnia magna were imaged at beamline 8.3.2 of the Berkeley Advanced Light Source. Volumes of 10000 × 10000 × 7096 isotropic 0.5 µm voxels were reconstructed over a 5.0 mm × 3.5 mm field of view. Measurements in the projection domain confirmed a 0.90 µm measured spatial resolution that is largely Nyquist-limited. This unprecedented combination of field of view and resolution dramatically reduces the need for sectional scans and computational stitching for large samples, ultimately offering the means to elucidate changes in tissue and cellular morphology in the context of larger, whole, intact model organisms and specimens. This system is also anticipated to benefit micro-CT imaging in materials science, microelectronics, agricultural science and biomedical engineering.


The Effect of Bacillus thuringiensis M-exotoxin on Trematode Cercariae
The effect of Bacillus thuringiensis israelensis eluate containing water-soluble exotoxin (M-exotoxin) was observed by its use on cercariae of seven trematode species. To the most sensitive species to the toxic effect of the mentioned toxin belonged schistosome furcocercariae (human species Schistosoma mansoni and avian parasite Trichobilharzia szidati). Under the influence of the toxin, surface syncytial structure (tegument) was separated from underlying tissues, with subsequent disintegration of internal organs connected with disruption of acetabular glands and release of their proteolytic content.


Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells.
The generation and efficient maintenance of antigen-specific memory T cells is essential for long-lasting immunological protection. In this study, we examined the role of interleukin (IL)-15 in the generation and maintenance of virus-specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor alpha chain. Both cytokine- and receptor-deficient mice made potent primary CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV), effectively cleared the virus and generated a pool of antigen-specific memory CD8 T cells that were phenotypically and functionally similar to memory CD8 T cells present in IL-15(+/+) mice. However, longitudinal analysis revealed a slow attrition of virus-specific memory CD8 T cells in the absence of IL-15 signals. This loss of CD8 T cells was due to a severe defect in the proliferative renewal of antigen-specific memory CD8 T cells in IL-15(-/-) mice. Taken together, these results show that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.


Characterization of an internal ribosomal entry segment within the 5' leader of avian reticuloendotheliosis virus type A RNA and development of novel MLV-REV-based retroviral vectors.
The murine leukemia virus (MLV)-related type C viruses constitute a major class of retroviruses that includes numerous endogenous and exogenous mammalian viruses and the related avian spleen necrosis virus (SNV). The MLV-related viruses possess a long and multifunctional 5' untranslated leader involved in key steps of the viral life cycle--splicing, translation, RNA dimerization, encapsidation, and reverse transcription. Recent studies have shown that the 5' leader of Friend murine leukemia virus and Moloney murine leukemia virus can direct cap independent translation of gag precursor proteins (Berlioz et al., 1995; Vagner et al., 1995b). These data, together with structural homology studies (Koning et al., 1992), prompted us to undertake a search for new internal ribosome entry segment (IRES) of retroviral origin. Here we describe an IRES element within the 5' leader of avian reticuloendotheliosis virus type A (REV-A) genomic RNA. Data show that the REV-A 5' IRES element maps downstream of the packaging/dimerization (E/DLS) sequence (Watanabe and Temin, 1982; Darlix et al., 1992) and the minimal IRES sequence appears to be within a 129 nt fragment (nucleotides 452-580) of the 5' leader, immediately upstream of the gag AUG codon. The REV-A IRES has been successfully utilized in the construction of novel high titer MLV-based retroviral vectors, containing one or more IRES elements of retroviral origin. These retroviral constructs, which represent a starting point for the design of novel vectors suitable for gene therapy, are also of interest as a model system of internal translation initiation and its possible regulation during development, cancer, or virus infection.


Herbivory and competition interact to affect reproductive traits and mating system expression in Impatiens capensis.
As a step toward understanding how community context shapes mating system evolution, we investigated the combined role of two plant antagonisms, vegetative herbivory and intraspecific competition, for reproduction and mating system expression (relative production of selfing, cleistogamous and facultatively outcrossing, chasmogamous flowers and fruits) of Impatiens capensis. In a survey of I. capensis populations, we found that vegetative herbivory and intraspecific competition were positively correlated. In a greenhouse experiment where leaf damage and plant density were manipulated, multispecies interactions had dramatic effects on reproductive and mating system traits. Despite having additive effects on growth, herbivory and competition had nonadditive effects for mating system expression, chasmogamous fruit production, flower number and size, and cleistogamous flower production. Our results demonstrate that competitive interactions influence the effect of herbivory (and vice versa) on fitness components and mating system, and thus antagonisms may have unforeseen consequences for mating system evolution, population genetic diversity, and persistence.


[Introduction to biology and control of mosquitoes].
Mosquitoes systematics, life cycle as well as morphology and bionomics of developmental stages, mosquitoes borne diseases, ecology and reemergence, vectorial capacity of some domestic species were presented with regard to mosquitoes control by the integrated methods and ecological prophylaxis.


[Choice and use of antifungal drugs].
During the last decade the incidence of deep mycotic infections has continued to increase dramatically. This new epidemiological feature is mostly due to the expanding population of at risk subjects submitted to intensive and protracted immunosupression. Amphotericin B has a broad spectrum and has remained the drug of choice for these life threatening invasive fungal infections. However adverse events, particularly renal insufficiency, are limiting factors in achieving an effective dose. Since the 1990s the number of oral and parenteral antifungal agents has significantly increased. The use of phospholipid carriers for amphotericin B or cyclodextrine for triazoles improved safety profil and/or pharmacokinetics. New families of drugs with a new target in the fungal cell are under clinical investigation and should be soon available. Comparative studies, consensus on diagnosis criteria and practice guidelines for the treatment of fungal infections will contribute to a better management of the patients and optimize the use of antifungal agents.


Pixelated Vacuum Flat Panel Detector Using ZnS Photoconductor and ZnO Nanowires Cold Cathode.
Vacuum flat panel detectors (VFPDs) using cold cathode have important applications in large-area photoelectric detection. Based on the electron-bombardment-induced photoconductivity (EBIPC) mechanism, the photoconductor-type VFPDs achieved high detection sensitivity. However, pixelated imaging devices have not yet been developed. In this paper, we fabricate a 4 × 7 pixel vacuum flat panel detector array made of ZnS photoconductor and ZnO nanowires cold cathode for an imaging application. The responsivity of the device and the pixel current uniformity are studied, and imaging of the patterned objects is achieved. Our results verify the feasibility of VFPDs for imaging.


Facile Synthesis of Hierarchically Porous Ni-N-C for Efficient CO2 Electroreduction to CO.
The reasonable design of atomically dispersed Ni-Nx sites in porous carbon nanostructures is an efficient strategy to enhance the electrochemical CO2 reduction reaction (CO2RR) catalytic activity. In this work, atomically dispersed Ni-Nx sites on hierarchically porous carbon catalysts (HP-Ni-NC) were fabricated by a facile NaCl template-assisted pyrolysis method. The catalysts exhibit a large specific surface area and a hierarchical porous structure, facilitating the exposure of numerous active sites and the mass/electron transport during the CO2RR. Consequently, the CO Faradaic efficiency maintained over 90% in a wide potential window on the optimized HP-Ni-NC-2 catalyst. The CO partial current achieved 15.2 mA cm-2 at -0.9 V (vs reversible hydrogen electrode) in a H-cell. Furthermore, the current density can achieve 250 mA cm-2 at a cell voltage of 3.11 V in a membrane electrode assembly electrolyzer, demonstrating great promise for commercial-scale application. This study presents a facile approach to synthesizing hierarchically porous structure single-atom catalysts with superior catalytic performance toward CO2RR.


The State Children's Health Insurance Program: successes, shortcomings, and challenges.
This paper examines successes and shortcomings of the State Children's Health Insurance Program (SCHIP). SCHIP is a source of coverage for millions of children, improving their access to health care and sparking innovation in program design and improvements in Medicaid. However, SCHIP adds to the complexity of the insurance system and introduces new inequities in access to insurance; it is imperfectly targeting eligible children who are uninsured; and its financing is problematic because of the block-grant funding structure and use of SCHIP funds to cover adults. These issues need to be addressed during the SCHIP reauthorization process.


Serum Exoglycosidases in Children and Adolescents With Harmful Alcohol Use.
There is a lack of accurate alcohol-use biomarkers in children/adolescents due to a short drinking duration/rapid normalization of elevated markers. We checked if lysosomal exoglycosidases, elevated earlier in binge-drinking young adults, can be applicable in children/adolescents as markers of harmful alcohol use. The serum activities (pKat/mL) of α-fucosidase (FUC), β-galactosidase (GAL), β-glucuronidase (GLU), β-hexosaminidase (HEX; its HEX A and HEX B isoenzymes), and α-mannosidase (MAN) were determined in 20 healthy controls (C) and 25 children/adolescents with harmful alcohol use (intoxicated by alcohol at hospital admission -AI1 and on the next day -AI2). The serum HEX A and alanine aminotransferase (ALT) activity was significantly higher in the AI1 group than in the control. The activities of FUC, GAL, GLU, HEX B, and MAN were lower in the AI group. We found fair and poor accuracy, respectively, for increased enzymes HEX A and ALT. We found fair accuracy for decreased HEX B (AI1) and MAN (AI1), good accuracy for GLU (AI2), FUC (AI2), GAL (AI1, AI2), MAN (AI2), and excellent for FUC (AI1). Correlations were found: ALT with C-reactive protein (CRP), HEX A with white blood cell (WBC) count, blood alcohol concentration with FUC, MAN and HEX B, and WBC with FUC. Decreased FUC, GLU, GAL, MAN values, and especially FUC (AI1) have the potential to be markers of harmful alcohol use in children/adolescents. The raised activity of HEX A and ALT points to the need for further research to check another inflammatory agent as potential alcohol marker in children and adolescents. Samples need to be collected before intravenous fluid therapy.


Identification of hydrophobic tags for the degradation of stabilized proteins.
New HyTs are a knockout: we previously reported that labeling HaloTag proteins with low molecular weight hydrophobic tags (HyTs) leads to targeted degradation of HaloTag fusion proteins. In this report, we employed a chemical approach to extend this hydrophobic tagging methodology to highly stabilized proteins by synthesizing and evaluating a library of HyTs, which led to the identification of HyT36.


Diagnosis of urogenital Chlamydia trachomatis infections by home-obtained, mailed samples: do we need a telephone hotline for information and advice?
This study evaluates the use of dedicated telephone hotlines to provide advice to young individuals who were offered the chance to be tested for Chlamydia trachomatis by means of home-obtained samples that were mailed directly to a testing laboratory. In a school-based screening study, a population-based screening study and a partner-tracing study we established hotlines and registered the calls. The target groups for the 3 studies comprised 8,909, 9,000 and 4,622 individuals and 0.1% (8/8,909), 0.7% (66/9,000) and 2.7% (124/4,622) of the populations, respectively took the opportunity to call anonymously to receive advice. The number of calls per opening hour of the hotlines varied between 0.2 (8 calls/40 opening hours) and 0.4 (124 calls/300 opening hours). Major reasons for calling the hotlines included requests for more information about chlamydial infections, questions relating to the study and emotional concerns (e.g. problems relating to partner tracing, adultery or anxiety concerning infertility). Although only a small fraction of the target populations used the hotlines we conclude that there is a need for advice and counseling in connection with strategies involving home-obtained samples for C. trachomatis testing. The optimal setting for this, however, remains to be determined.


Américo Negrette and Huntington's disease.
The authors present a historical review of the seminal clinical contribution of Professor Américo Negrette, a Venezuelan neurologist, to the evolution of scientific knowledge about Huntington's disease.


What do people who stutter want--fluency or freedom?
In this study, the author examined the following questions: What proportion of adult persons who stutter (PWS) choose fluency and what proportion choose to be free from a need to be fluent in managing their stuttering? What demographic and stuttering-related variables influence their choice, and how consistent are they in their choice? A survey instrument administered over the Internet was used to collect the data. Overall, 8% more of the 216 respondents opted for fluency than freedom. A larger proportion of male PWS and PWS under the age of 30 years preferred fluency. Neither nationality nor language background influenced their preference. Those who received no therapy overwhelmingly chose fluency, and a slight majority of those with fewer than 5 years of therapy preferred fluency. Those with more than 5 years of therapy were evenly divided between the 2 choices. Those who preferred freedom were more consistent in their responses across items than were those who opted for fluency. Based on the consistency of responses, 20% and 23% of the sample decisively opted for fluency and freedom, respectively, and 34% in the fluency group and 23% in the freedom group were ambivalent. A majority of PWS appear to benefit from flexible treatment programs with cafeteria-style choices.


[The rubber dam, a problem for the dentist or the patient?].
Although the advantages of rubber dam use are obvious and rubber dam use is established standard of care in many disciplines, its application in general dental practice is low. To assess whether a negative attitude of patients might be the case, 304 patients were asked by means of a questionnaire comments on their treatment under rubber dam. The majority of the patients experienced no hinder, excepted for rubber dam restricting the communication with the dental practitioner. Women experienced more often than men anxiety, whereas smokers more frequently experienced discomfort.


Production and biochemical and molecular characterization of a keratinolytic serine protease from chicken feather-degrading Bacillus licheniformis RPk.
A novel feather-degrading bacterium was isolated from a polluted river and identified as Bacillus licheniformis RPk. The isolate exhibited high proteinase production when grown in chicken-feather media. Complete feather degradation was achieved during cultivation. Maximum protease activity (4150 U/mL with casein as a substrate and 37.35 U/mL with keratin as a substrate) was obtained when the strain was grown in a medium containing 7.5 g/L chicken feathers, 2 g/L yeast extract, 0.5 g/L NaCl, 0.1 g/L MgSO4 x 7H2O, 0.7 g/L KH2PO4, and 1.4 g/L K2HPO4 for 48 h with agitation of 200 rev/min at 37 degrees C. The major protease produced by B. licheniformis RPk was purified to homogeneity by a 3-step procedure. The molecular mass of the purified enzyme was estimated to be 32 kDa by SDS-PAGE and gel filtration. The optimum pH and temperature for the caseinolytic activity were around 11.0 and 65 degrees C, respectively. The optimum pH and temperature for the keratinolytic activity were 9.0 and 60 degrees C, respectively. The activity of the enzyme was totally lost in the presence of phenylmethylsulfonyl fluoride, which suggests that the purified enzyme is a serine protease. The thermostability of the enzyme was considerably enhanced in the presence of Ca2+ at temperatures >50 degrees C. The kerRP gene, which encodes the keratinolytic protease, was isolated, and its DNA sequence was determined. The deduced amino acid sequence revealed that the keratinase KerRP differs from KerA of B. licheniformis PWD-1, subtilisin Carlsberg, and keratinase of B. licheniformis by 2, 4, and 62 amino acids, respectively.


Human CYP1A1 gene: cosegregation of the enzyme inducibility phenotype and an RFLP.
The human CYP1A1 (cytochrome P1450) gene encodes an enzyme involved in the activation of procarcinogens, such as benzo[a]pyrene, to the ultimate reactive intermediate. Approximately 10% of the human population exhibit high CYP1A1 inducibility, and Kouri et al. reported that the high-inducibility phenotype might be at greater risk than low-inducibility individuals for cigarette smoke-induced bronchogenic carcinoma. In one 3-generation family of 15 individuals, we show here that the high-CYP1A1-inducibility phenotype segregates concordantly with an infrequent polymorphic site located 450 bases downstream from the CYP1A1 gene. Our findings are consistent with the study of Kawajiri et al., who demonstrated an association between this polymorphism and an increased incidence of squamous-cell lung cancer. Our data suggest that the CYP1A1 structural gene, or a region near this gene, might be correlated with the inducibility phenotype.


Profiles of Community Violence Exposure, Moral Disengagement, and Bullying Perpetration: Evidence from a Sample of Italian Adolescents.
According to the Pathologic Adaptation Model of community violence exposure, repeated experiences of violence within the community lead youth to accept violence as a normative and legitimate strategy to cope with conflict, thus increasing their involvement in aggressive behaviors. This hypothesis has been under-investigated with reference to bullying at school. Using a person-centered analytical approach (latent profile analysis), this study examines the mediating role of moral disengagement as a type of normalizing cognition about violence, in the relationship between profiles of community violence exposure and perpetration of bullying. Eight hundred and two adolescents (11-18 years; 43.4% girls) from two different urban and societal contexts in Italy (Milan vs. Naples) participated in the study. Four profiles of exposure to community violence emerged. Context site and age influenced belonging to the four profiles. Being moderately exposed to violence, both as a victim and as a witness, was significantly associated with higher levels of moral disengagement and bullying perpetration. Being exposed as a witness and as a victim, and being exposed only as a witness were associated with bullying perpetration via the increase of moral disengagement. These findings support the Pathologic Adaptation Model and indicate that adolescents who experience higher levels of community violence, as a witness or both as a witness and a victim, are more likely to develop morally disengaged beliefs about violence, which in turn would increase the likelihood to perpetrate bullying. Results are also discussed in the context of social diversity.


Solvent Effects on Morphology and Electrical Properties of Poly(3-hexylthiophene) Electrospun Nanofibers.
Herein, poly(3-hexylthiophene-2,5-diyl) (P3HT) nanofiber-based organic field-effect transistors were successfully prepared by coaxial electrospinning technique with P3HT as the core polymer and poly(methyl methacrylate) (PMMA) as the shell polymer, followed by extraction of PMMA. Three different solvents for the core polymer, including chloroform, chlorobenzene and 1,2,4-trichlorobenzene, were employed to manipulate the morphologies and electrical properties of P3HT electrospun nanofibers. Through the analyses from dynamic light scattering of P3HT solutions, polarized photoluminescence and X-ray diffraction pattern of P3HT electrospun nanofibers, it is revealed that the P3HT electrospun nanofiber prepared from the chloroform system displays a low crystallinity but highly oriented crystalline grains due to the dominant population of isolated-chain species in solution that greatly facilitates P3HT chain stretching during electrospinning. The resulting high charge-carrier mobility of 3.57 × 10-1 cm2·V-1·s-1 and decent mechanical deformation up to a strain of 80% make the P3HT electrospun nanofiber a promising means for fabricating stretchable optoelectronic devices.


Study on Microstructure of Nb-Ti Based Alloy by Groove Rolling Process.
Niobium-titanium alloy is attractive materials for industrials as a superconducting magnets to high critical magnetic field and supercurrent density at -283 °C. The Nb-Ti alloy has been shown in earlier work to exhibit Van Gosh Sky microstructures. They may also be accentuated by plastic deformation due to work and temperature exposure during deformation. In order to miniaturize the magnet generating the same magnetic field, it is necessary to increase the critical current density of the superconducting wire. When fabricating superconducting wires, it is important to increase critical current density by optimizing processing and annealing conditions. When the α-phase of the Ti rich phase is uniformly precipitated by the heat treatment, the non-superconducting α-phase is dispersed in the superconducting Nb-Ti matrix. It becomes a pinning point that serves to fix the magnetic flux, which improves the critical current density. Also, if the shape of the precipitate is changed by machining, the superconducting and non-superconducting characteristics are further improved. In the present study, we studied the fraction of α-Ti phase of strain amount through groove rolling and heat treatment. The specimens were processed by groove rolling at room temperature and strain of 2.0, 3.16, 4.28 and 5.57. A microstructural analysis of the Nb-Ti alloys was performed by field emission scanning electron microscopy (FESEM).


[Biventricular assist support using centrifugal pump in cardiogenic shock following coronary bypass grafting--a case report of long survival].
Biventricular assist support (BVAS) with centrifugal pump was used for the treatment of 48 y/o male patient with cardiogenic shock following coronary bypass surgery. Assist flow was 2 to 4 l/min in LVAS and 2 to 3 l/min in RVAS. RVAS was weaned in the fourth postoperative day and LVAS in the sixth. Cerebral infarction developed in the weaning period of LVAS. Post operative examination revealed good right and left ventricular function. Patient was well and returned to full work in a two years and two months after surgery. BVAS may be useful for the treatment of severe biventricular failure associated with stunned myocardium.


Ion-specific colloidal aggregation: population balance equations and potential of mean force.
Recently reported colloidal aggregation data obtained for different monovalent salts (NaCl, NaNO(3), and NaSCN) and at high electrolyte concentrations are matched with the stochastic solutions of the master equation to obtain bond average lifetimes and bond formation probabilities. This was done for a cationic and an anionic system of similar particle size and absolute charge. Following the series Cl(-), NO(3)(-), SCN(-), the parameters obtained from the fitting procedure to the kinetic data suggest: (i) The existence of a potential of mean force (PMF) barrier and an increasing trend for it for both lattices. (ii) An increasing trend for the PMF at contact, for the cationic system, and a practically constant value for the anionic system. (iii) A decreasing trend for the depth of the secondary minimum. This complex behavior is in general supported by Monte Carlo simulations, which are implemented to obtain the PMF of a pair of colloidal particles immersed in the corresponding electrolyte solution. All these findings contrast the Derjaguin, Landau, Verwey, and Overbeek theory predictions.


Immobilized hirudin and hirudin-based peptides used for the purification of recombinant human thrombin prepared from recombinant human prothrombin.
A simple and efficient activation-affinity purification system was developed to obtain thrombin from recombinant CHO cells expressing human prothrombin. In this method, a controllable process for the activation of recombinant prothrombin is directly coupled with a purification strategy for the recombinant thrombin generated. At a constant flow rate and with a contact time limited to few seconds, recombinant prothrombin was filtered through immobilized trypsin. In a closed flow system, the recombinant thrombin generated was filtered through newly designed thrombin-specific affinity gels. Hirudin, the most specific thrombin inhibitor, and hirudin-based peptides were covalently immobilized to Sepharose, thus creating thrombin-specific affinity gels that immediately absorb the thrombin generated from the activation mixture. Prothrombin and incompletely activated molecules did not bind to the affinity gel and were recirculated for a further activation cycle. Due to the specificity of the affinity gels for thrombin and the elimination of thrombin from the activation mixture, proteolytic degradation and autocatalytic inactivation of the recombinant thrombin was prevented. Recombinant thrombin was isolated from the hirudin-based affinity gels by chaotrope salt elution, resulting in high yields of highly pure, active thrombin. Affinity purification of thrombin was not deleteriously affected by contamination of the starting material with other proteins. Activation and affinity purification were equally effective for recombinant and human plasma-derived prothrombin as well as for human and recombinant thrombin.


Drug Overdose Deaths with Evidence of Counterfeit Pill Use - United States, July 2019-December 2021.
Using data from CDC's State Unintentional Drug Overdose Reporting System, this report describes trends in overdose deaths with evidence of counterfeit pill use during July 2019-December 2021 in 29 states and the District of Columbia (DC) and characteristics of deaths with and without evidence of counterfeit pill use during 2021 in 34 states and DC. The quarterly percentage of deaths with evidence of counterfeit pill use more than doubled from 2.0% during July-September 2019 to 4.7% during October-December 2021, and more than tripled in western jurisdictions (from 4.7% to 14.7%). Illicitly manufactured fentanyls were the only drugs involved (i.e., caused death) in 41.4% of deaths with evidence of counterfeit pill use and 19.5% of deaths without evidence. Decedents with evidence of counterfeit pill use, compared with those without evidence, were younger (57.1% versus 28.1% were aged <35 years), more often Hispanic or Latino (18.7% versus 9.4%), and more frequently had a history of prescription drug misuse (27.0% versus 9.4%). Smoking was the most common noningestion drug use route among deaths with evidence of counterfeit pill use (39.5%). Overdose prevention messaging that highlights the dangers of pills obtained illicitly or without a prescription (because they might be counterfeit), encourages drug product testing by persons using drugs, and is tailored to persons most at risk (e.g., younger persons) could help prevent overdose deaths.


Anorectal motility and sensation abnormalities and its correlation with anorectal symptoms in patients with systemic sclerosis: a preliminary study.
Gastrointestinal (GI) hypomotility and symptoms are common in Scleroderma (SSc) patients yet so far uncorrelated. Eight SSc patients and matched controls were queried about their GI dysmotility symptoms and quality of life (QoL) and underwent anorectal motility and sensory tests. Specific scoring systems were developed for anorectal symptoms and anorectal dysmotility. We found that (1) the SSc patients showed low QoL and marked overall GI symptoms. The most common anorectal symptom was incomplete bowel movement (50%). (2) Compared to normal controls, SSc patients showed impaired anorectal pressures, sensations, and rectal compliance (P ≤ .01 for each). (3) The anorectal motility/sensation abnormality score was robustly correlated with the total anorectal symptom score (r(s) = .78, P = .02). In conclusion, scleroderma patients have impaired anorectal motor and sensory functions, and the abnormality score of these anorectal functions is correlated with the total anorectal symptoms score. These scoring systems may assist clinicians in predicting dysmotility based on patient symptoms.


Solo surgery--with the aid of a robotic assistant.
In the interests of cost containment this study was performed to compare the cost-effectiveness of utilizing a robotic assistant instead of a human assistant. Twelve patients undergoing laparoscopic bladder neck suspension were studied retrospectively. In six of these cases a human assistant was utilized and in another six a robot arm was utilized to hold and manoeuvre the laparoscope and camera. Evaluations have previously been made showing the improved steadiness and clarity of picture when utilizing the robot rather than a human and in this case the length of surgery was compared and the cost of the equipment and all personnel evaluated. The differences in length of surgery between both groups was not statistically significant. The cost of the robotic arm was less than that of human systems. This depends on the volume of surgery and may vary between institutions. In conclusion, a robotic assistant is seen to be a cost-effective device taking the place of the traditional assistant.


Electrochemical determination of NADH and ethanol based on ionic liquid-functionalized graphene.
It is firstly reported that low-potential NADH detection and biosensing for ethanol are achieved at an ionic liquid-functionalized graphene (IL-graphene) modified electrode. A substantial decrease (440 mV) in the overvoltage of the NADH oxidation was observed using IL-graphene/chitosan coating, with oxidation starting at ca. 0 V (vs. Ag|AgCl). And the NADH amperometric response at such a modified electrode is more stable (95.4% and 90% of the initial activity remaining after 10 min and 30 min at 1 mM NADH solution) than that at bare electrode (68% and 46%). Furthermore, the IL-graphene/chitosan-modified electrode exhibited a good linearity from 0.25 to 2 mM and high sensitivity of 37.43 microA mM(-1)cm(-2). The ability of IL-graphene to promote the electron transfer between NADH and the electrode exhibited a novel and promising biocompatible platform for development of dehydrogenase-based amperometric biosensors. With alcohol dehydrogenase (ADH) as a model, the ADH/IL-graphene/chitosan-modified electrode was constructed through a simple casting method. The resulting biosensor showed rapid and highly sensitive amperometric response to ethanol with a low detection limit (5 microM). Moreover, the proposed biosensor has been used to determine ethanol in real samples and the results were in good agreement with those certified by the supplier.


The role of seven autoantibodies in lung cancer diagnosis.
To investigate the expression and diagnostic value of seven autoantibodies (P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE, and CACE) in lung cancer patients. A total of 370 patients were admitted to the Thoracic Surgery of the First Affiliated Hospital of Suzhou University from 2017 to 2019, including 305 patients with lung cancer and 65 patients with benign lesions. The concentrations of the seven autoantibodies were determined by enzyme linked immunosorbent assay (ELISA).The expression levels of each antibody were compared between the two groups, and the levels of each antibody between lung cancer patients with different pathological types were also compared. We aimed to analyze the diagnostic efficiency of single antibody detection combined with seven antibodies, and also to explore whether there were differences among the positive rates of each antibody in sex, age, smoking history, pathological classification, and clinical stages in the lung cancer group. The expression levels of seven autoantibodies in the lung cancer group were higher than those in the benign lesion group. In the lung cancer group, the expression levels of the seven autoantibodies did not vary statistically among different pathological types. The area under the curve of combined detection of the seven antibodies reached 0.735, and the Y-index reached 0.35, which was higher than that of single antibody detection. P53 exhibited the highest sensitivity and lowest specificity; meanwhile, PGP9.5, SOX2, GAGE7, GBU4-5, and MAGEA1 exhibited low sensitivity and high specificity. The sensitivity and specificity of the CAGE were approximately 60%, respectively. There was no statistical difference in the positive rate of each antibody in age, smoking history, and clinical stage. The positive rate of MAGEA1 and CAGE was statistically different in sex, and the positive rate of MAGEA1 was statistically different in pathological classification. The seven autoantibodies of lung cancer can potentially be used as an auxiliary examination method for the early diagnosis of lung cancer.


Alternative dosing regimens of liposomal amphotericin B (AmBisome) effective in treating murine systemic candidiasis.
This study was done to determine whether high dose AmBisome (4-20 mg/kg), given intermittently, could reduce the frequency of dosing needed to treat murine systemic candidiasis when compared with conventional daily treatment. Mice were immunosuppressed with cyclophosphamide every 3 days, beginning day -3 before challenge with log(10) 5.0 cfu Candida albicans. Treatment was begun 48-72 h post-challenge with daily or intermittent dose regimens of AmBisome, followed by determination of kidney cfu for up to 1 month post-treatment. A single AmBisome dose of 4 mg/kg was as effective as four daily, 1 mg/kg treatments. A total of 8 mg/kg, given as 4 mg/kg on days 2 and 4, or as 5 mg/kg on day 2 followed by 1 mg/kg on days 3, 4, and 5, also produced comparable efficacy. While 20 mg/kg given day 2, 4 and 6 post-challenge as a 1 week loading dose, followed by one 10 mg/kg treatment on day 13, decreased the fungal burden by up to 5 logs compared with controls (log(10) 2.3 cfu/g and log(10) 7.5 cfu/g, respectively), 20 mg/kg given Monday, Wednesday and Friday for 5 weeks, reduced the fungal burden to undetectable levels (i.e. log(10) 1.0 cfu). Significant reduction or clearance of kidney cfu, following intermittent, high dose AmBisome treatment, indicated that non-daily dosing regimens could be successfully used instead of conventional daily dosing to treat established C. albicans infection in immunosuppressed mice.


Crystallization and preliminary X-ray diffraction analysis of the α subdomain of Lon protease from Brevibacillus thermoruber.
DNA-binding ability has previously been reported as a novel function for the thermostable Lon protease from Brevibacillus thermoruber WR-249 (Bt-Lon), and the α subdomain (amino acids 491-605) of Bt-Lon has been identified as being responsible for DNA binding. However, the physiological role and DNA-recognition mode of Bt-Lon still remain unclear. In this study, the crystallization and preliminary crystallographic analysis of the Bt-Lon α subdomain are presented. Native diffraction data to 2.88 Å resolution were obtained from a vitrified crystal at 100 K on the BL13C1 beamline at the NSRRC (National Synchrotron Radiation Research Center), Taiwan. The crystals belonged to space group P23, with unit-cell parameters a = b = c = 94.28 Å. Solvent-content calculations and molecular-replacement results suggest that there are two molecules of Bt-Lon α subdomain per asymmetric unit.


Subcellular localization of calcium release in isolated rat myocardial cells.
Independent determinations of Ca2+ by two indicators showed that subcellular Ca2+ activity (intracellular free calcium concentration) was heterogeneous in rat myocardial cells. Arsenazo III (Az III), a membrane-impermeant absorbance indicator for Ca2+, was loaded into cardiac muscle via liposomes and calcium quantitated at two wavelengths through a focal point diaphragm in 5-100 microns 2 regions by a photometer. Fura-2, a high-affinity fluorescent calcium indicator, was loaded into cells as the ester form, and the light intensity was measured by digital-imaging microscopy using a photon-counting camera. Calcium activity at each picture element was quantitated by division of fluorescence excited by two ultraviolet wavelengths, and corrected for concentration differences in fura-2 by a third, Ca(2+)-insensitive wavelength. Both methods revealed hot spots of Ca2+ release and uptake that could be enlarged, added to, or altered. Addition of 1-10 nM norepinephrine caused up to a 500% increase in Ca2+ in localized regions, although whole cell average Ca2+ increased by only 0-80%, suggesting the importance of localized intracellular Ca2+ release for contraction.


Variation in institutional review board responses to a standard protocol for a multicenter clinical trial.
Multicenter clinical trials require approval by multiple local institutional review boards (IRBs). The Multicenter Airway Research Collaboration mailed a clinical trial protocol to its U.S. investigators and 44 IRBs ultimately reviewed it. To describe IRB responses to one standard protocol and thereby gain insight into the advantages and disadvantages of local IRB review. Two surveys were mailed to participants, with telephone follow-up of nonrespondents. Survey 1 was mailed to 82 investigators across North AMERICA: Survey 2 was mailed to investigators from 44 medical centers in 17 U.S. states. Survey 1 asked about each investigator's local IRB (e.g., frequency of meetings, membership), whereas survey 2 asked about IRB queries and concerns related to the submitted clinical trial. Both surveys had 100% response rate. Investigators submitted applications a median of 58 days (interquartile range [IQR], 40--83) after receipt of the protocol, and IRB approval took an additional 38 days (IQR, 26--62). Although eight applications were approved with little or no changes, IRBs requested an average of 3.5 changes per site. Changes involved study logistics and supervision for 45%, the research process for 43%, and the consent form for 91%. Despite these numerous requests, all eventually approved the basic protocol, including inclusion criteria, intervention, and data collection. The IRBs showed extreme variability in their initial responses to a standard protocol, but ultimately all gave approval. Almost all IRBs changed the consent form. A national, multicenter IRB process might streamline ethical review and warrants further consideration.


Promoting photocatalytic H2 evolution by tuning cation deficiency in La and Cr co-doped SrTiO3.
Cation defects in La and Cr co-doped SrTiO3 have been specifically studied for elucidating correlations between defect concentration, electronic properties, structural properties and photocatalytic activity for H2 production. A moderate cation deficiency can promote the photocatalytic activity by ca. 3 fold, which can be mainly linked to the enhancement of the charge carrier mobility.


The downregulation of miR-144 is associated with the growth and invasion of osteosarcoma cells through the regulation of TAGLN expression.
Alterations in the expression of microRNAs (miRNAs or miRS) have been implicated in the pathogenesis of the majority of human malignancies, and the dysregulation of microRNA-144 (miR-144) has been associated with several diseases. However, the potential involvement of miR-144 in osteosarcoma, a common malignant bone tumor in children and adolescents with a high risk of relapse and metastasis, has not yet been fully investigated. In the present study, we examined the expression and roles of miRNAs in osteosarcoma as potential diagnostic markers and therapeutic targets, and we focused on miR-144 due to its known involvement in osteogenesis. We demonstrate that miR-144 is downregulated in osteosarcoma cell lines and primary human osteosarcoma tissue samples and that its ectopic expression inhibits osteosarcoma cell proliferation and invasion. We identified TAGLN as a downstream target of miR-144 and demonstrated that its expression is upregulated in osteosarcoma cell lines and tumor tissue and is inversely correlated with miR-144 expression. Our results indicate that miR-144 may regulate osteosarcoma cell proliferation and invasion by downregulating its target gene, TAGLN, suggesting that miR-144 may be a potential therapeutic target for the treatment of osteosarcoma.


Cellular immune function in mice tolerant to or abstinent from l-trans-delta 9-tetrahydrocannabinol.
The effects of tolerance to l-trans-delta 9-tetrahydrocannabinol (THC) following repeated administration and of subsequent abstinence following drug withdrawal on the cellular immune function were determined in female B6C3F1 mice. Mice were injected with THC (10 mg/kg s.c.) twice daily for 4 days. On day 5, analgesic response to various doses of THC was determined using the tail flick test. Similarly, hypothermic response to THC was also determined. Multiple injections of THC resulted in the development of tolerance to both the analgesic and hypothermic effects of THC. Immune function studies were performed on mice rendered tolerant to or abstinent from THC by these procedures. Neither tolerance nor abstinence subsequent to a 4-day THC administration had any effect on either body weight or thymus weight and cellularity, although both spleen weight and cellularity were decreased in THC-abstinent animals. Likewise, no significant effects on B cell proliferation were observed in either tolerant or abstinent mice. The production of the cytokine interleukin-2 by T helper cells was markedly suppressed in both tolerant and abstinent mice, whereas the production of interleukin-4 was significantly suppressed only in THC-abstinent mice. Significant suppression of tumor cell cytolysis mediated by cytotoxic T cells and natural killer cells was only observed in THC-abstinent mice. These results suggest that THC-mediated modulation of the immune response may result from a differential effect on cellular populations.


The Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties: A Pilot Study.
Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis were employed to study two groups of male Sprague-Dawley rats: control (11 weeks) and aging (80 weeks). Aging was associated with increases in RV peak pressures (+17%, p = 0.017), RV contractility (+52%, p = 0.004), and RV wall thickness (+38%, p = 0.001). Longitudinal realignment of RV collagen (16.4°, p = 0.013) and myofibers (14.6°, p = 0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. Aging led to increased RV myofiber stiffness (+141%, p = 0.003), in addition to a bimodal alteration in the biaxial biomechanical properties of the RV free wall, resulting in increased tissue-level stiffness in the low-strain region, while progressing into decreased stiffness at higher strains. Our results demonstrate that healthy aging may modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fibrosis, fiber reorientation, and altered mechanical properties in male Sprague-Dawley rats. Similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload. These findings may help our understanding of age-related changes in the cardiovascular fitness and response to disease.


Oligofuranosides containing conformationally restricted residues: synthesis and conformational analysis.
The synthesis of a panel of arabinofuranosyl oligosaccharide analogues (5-13) in which one ring is locked into either the E(3) or OE conformation is described. The E(3)-locked scaffolds 15 and 16 required for the synthesis of 5-10 were prepared in one step from known 1,5-anhydroalditols. A number of routes were explored for the preparation of the OE-locked monosaccharide derivative 17 needed for the preparation of 11-13. The successful synthesis of 17 was achieved in 17 steps from D-arabinose. Subsequent analysis of 5-13 by 1H NMR spectroscopy demonstrated that the locked residue does not exert any detectable influence upon the conformers populated by adjacent conformationally unrestricted furanose rings.


Cyclin-Dependent Kinases (CDKs) and the Human Cytomegalovirus-Encoded CDK Ortholog pUL97 Represent Highly Attractive Targets for Synergistic Drug Combinations.
Human cytomegalovirus (HCMV) is a pathogenic human herpesvirus associated with serious, potentially life-threatening symptoms in the immunocompromised or immunonaïve host. The limitations encountered by antiviral therapy options currently available include a narrow panel of accessible targets, the induction of viral drug resistance as well as severe drug dosage-mediated side-effects. Improved drug-targeting strategies to resolve these issues are the focus of our investigations. In particular, pharmaceutical kinase inhibitors (PKIs), either directed to host kinases or directed to the viral protein kinase pUL97, have been considered to overcome these restrictions. Recently, we reported the identification of a synergistic combination of two PKIs directed to host cyclin-dependent kinase 7 (CDK7) and viral CDK ortholog pUL97. Here, we substantiate these findings with the following results: (i) true drug synergy was exhibited by various chemical classes of PKI pairs directed to pUL97 and CDK7; (ii) no putative amplification of cytotoxicity by these drug combinations was observed; (iii) a reduction in drug dosage levels for synergistic combinations was defined on a quantitative basis and compared to monotreatments; (iv) the quantities of target proteins CDK7 and pUL97 expressed in HCMV-infected cells were assessed by confocal imaging, indicating a strong down-modulation of CDK7 levels as a result of synergistic drug treatment; (v) the functional importance of these target kinases, both binding to cyclin H, was illustrated by assessing HCMV replication under the viral genomic deletion of ORF-UL97 or cellular cyclin knock-out; (vi) new combinations of HCMV-specific drug synergy were demonstrated for solely host-directed treatments using PKIs against CDK2, CDK7, CDK8 and/or CDK9 and (vii) a triple PKI combination provided further support for the synergy approach. With these combined findings, this study highlights the potential of therapeutic drug combinations of approved, developmental and preclinical PKIs for expanding future options for anti-HCMV therapy.


Human alpha-globin genes demonstrate autonomous developmental regulation in transgenic mice.
Recent studies have demonstrated that transcriptional activation of the human adult beta-globin transgene in mice by coinsertion of the beta-globin cluster locus control region (beta-LCR) results in loss of its adult restricted pattern of expression. Normal developmental control is reestablished by coinsertion of the fetal gamma-globin transgene in cis to the adult beta-globin gene. To test the generality of this interdependence of two globin genes for their proper developmental control, we generated transgenic mice in which the human adult alpha-globin genes are transcriptionally activated by the beta-LCR either alone or in cis to their corresponding embryonic zeta-globin gene. In both cases, the human globin transgenes were expressed at the appropriate developmental period. In contrast to the beta-globin gene, developmental control of the human adult alpha-globin transgenes appears to be autonomous and maintained even when activated by an adjacent locus control region.


Protégé-2000: an open-source ontology-development and knowledge-acquisition environment.
Protégé-2000 is an open-source tool that assists users in the construction of large electronic knowledge bases. It has an intuitive user interface that enables developers to create and edit domain ontologies. Numerous plugins provide alternative visualization mechanisms, enable management of multiple ontologies, allow the use of interference engines and problem solvers with Protégé ontologies, and provide other functionality. The Protégé user community has more than 7000 members.


Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade.
DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. In the current study, the mode of action of DCP-001 was further characterized by static and dynamic analysis of the interaction between labelled DCP-001 and host antigen-presenting cells (APCs). Direct cell-cell interactions and uptake of DCP-001 cellular content by APCs were shown to depend on DCP-001 cell surface expression of calreticulin and phosphatidylserine, while blockade of CD47 enhanced the process. Injection of DCP-001 in an ex vivo human skin model led to its uptake by activated skin-emigrating DCs. These data suggest that, following intradermal DCP-001 vaccination, local and recruited host APCs capture tumor-associated antigens from the vaccine, become activated and migrate to the draining lymph nodes to subsequently (re)activate tumor-reactive T-cells. The improved uptake of DCP-001 by blocking CD47 rationalizes the possible combination of DCP-001 vaccination with CD47 blocking therapies.


Blinded by headlights.
Target identification is impaired when targets are presented during the planning or execution of a compatible response (e.g., right-pointing arrow during a right keypress) relative to an incompatible response (Müsseler & Hommel, 1997 a, b). Examinations of this blindness to response-compatible stimuli have typically used arrowheads as targets ("<" and ">"). The importance of the target symbol was examined by manipulating subjects' interpretation of that symbol (i.e., ">" interpreted as a right-pointing arrow or as a headlight shining to the left). Targets were presented at varying times during the planning or execution of a response in order to examine the time-course of the effect. Results showed that the interpretation, and not the physical identity, of the target was important for the blindness effect. Although the blindness effect was largest during the planning and execution of a response, it was not always confined to that temporal interval.


Managed care, medical technology, and the well-being of society.
The growth of managed care could have widespread effects on the structure and functioning of the health care delivery system, potentially influencing all patients, even those not enrolled in managed care plans. One important mechanism by which managed care could have such broad effects is by influencing technology development and adoption. This article examines available literature on the effects of managed care activity on technology adoption and the implications of any effects on patient care, outcomes, and health care costs. Existing literature supports the view that managed care has contributed to slowing the adoption of new technologies, particularly the high-cost, high-profile technologies that have been the focus of the most attention. The literature outlining the effects of managed-care-induced changes in technology adoption on patient care and outcomes is not large, but what literature there is tends not to find negative effects on patient care and outcomes. Specific evidence about costs also is somewhat sparse, but it suggests that managed care has contributed to some reduction in health care spending, although the extent to which savings will persist over time is unclear. Although evidence thus far does not suggest important detrimental effects of managed care on care or outcomes and even indicates some benefit through savings, it should be noted that existing literature has only explored a small number of the many technologies and services that might have been influenced, and there remain issues for the future that deserve vigilance.


Temporal Pattern of Pain and Disability Following the Administration of a Selective Nerve Root Block in Lumbar Disc Herniation With Radiculopathy.
Lumbar disc herniation with radiculopathy has a favorable natural history, and a selective nerve root block (SNRB) is an accepted treatment modality. This study aims to ascertain the temporal pattern of pain and disability following the administration of an SNRB in the management of lumbar disc herniation with radiculopathy because there is limited evidence regarding this issue in the published literature. This prospective study included 50 patients who underwent an SNRB and were followed for 3 months. Numerical Rating Scale (NRS) for back and leg pain and Oswestry Disability Index (ODI) and Depression Anxiety Stress Scales-21 (DASS-21) scores were collected. At the final follow-up at 3 months, the number of patients who underwent surgery was ascertained. Forty-two of 50 (84%) patients avoided the surgery with a reduction in mean preinjection NRS for back and leg pain from 7.5 (SD 1.33) and 7.7 (SD 1.35) to 3.1 (SD 1.69) and 2.3 (SD 1.14) (P < 0.001), respectively, within the 30 minutes after injection. The pain relief was sustained until the last follow-up. The ODI score also decreased from a mean preinjection level of 59.4 (SD 14.69) to 26.3 (SD 9.43) (P < 0.001) at 3 months. The mean preinjection depression score was higher in patients who had recurrence of pain and eventually underwent surgery. Early administration of an SNRB in the course of lumbar radiculopathy is recommended as it provides instantaneous and sustained relief of back and leg pain and disability in a majority of patients. SNRB should be administered early in the course of management of lumbar radiculopathy and should not be delayed until after other non-surgical modalities have failed. 2.


Association of hyperhomocysteinemia in Alzheimer disease with elevated neopterin levels.
In patients with dementias including Alzheimer disease (AD), elevated blood concentrations of homocysteine are common, often going along with low normal folate and vitamin B12. Immune activation leading to oxidative stress also seems to play an important role in the pathogenesis of AD. To find out a possible relationship between immune activation and the development of moderate hyperhomocysteinemia, we determined serum concentrations of homocysteine, folate, vitamin B12 and immune activation markers 75 kD soluble TNF receptor (sTNF-R75) and neopterin in 38 patients with clinically diagnosed AD. A subgroup of patients (45%) presented with increased homocysteine concentrations in comparison to reference ranges in healthy controls of similar age. Also, concentrations of immune activation markers were elevated in a significant proportion of patients. In 17 patients with moderate hyperhomocysteinemia, concentrations of neopterin were higher than in those with lower homocysteine (p < 0.001). Homocysteine correlated with folate (rs= -0.43; p < 0.01) and neopterin (rs= 0.506; p < 0.001). The data suggest that immune activation and concomitant production of reactive oxygen species in patients with AD could be involved in the development of hyperhomocysteinemia via an enhanced decomposition of folate.


Comparison of the fouling release properties of hydrophobic fluorinated and hydrophilic PEGylated block copolymer surfaces: attachment strength of the diatom Navicula and the green alga Ulva.
To understand the role of surface wettability in adhesion of cells, the attachment of two different marine algae was studied on hydrophobic and hydrophilic polymer surfaces. Adhesion of cells of the diatom Navicula and sporelings (young plants) of the green macroalga Ulva to an underwater surface is mainly by interactions between the surface and the adhesive exopolymers, which the cells secrete upon settlement and during subsequent colonization and growth. Two types of block copolymers, one with poly(ethylene glycol) side-chains and the other with liquid crystalline, fluorinated side-chains, were used to prepare the hydrophilic and hydrophobic surfaces, respectively. The formation of a liquid crystalline smectic phase in the latter inhibited molecular reorganization at the surface, which is generally an issue when a highly hydrophobic surface is in contact with water. The adhesion strength was assessed by the fraction of settled cells (Navicula) or biomass (Ulva) that detached from the surface in a water flow channel with a wall shear stress of 53 Pa. The two species exhibited opposite adhesion behavior on the same sets of surfaces. While Navicula cells released more easily from hydrophilic surfaces, Ulva sporelings showed higher removal from hydrophobic surfaces. This highlights the importance of differences in cell-surface interactions in determining the strength of adhesion of cells to substrates.


Study of the teratogenicity of the vaccine strain of the Rubella virus «Orlov-V» (Matonaviridae: Rubivirus: Rubella virus) in experience on rhesus macaques.
Rubella virus has pronounced teratogenic properties that can cause generalized and persistent intrauterine infection of the fetus. As a result, the control of the loss of teratogenicity inherent in «wild-type» virus strains is a necessary stage of a preclinical study of the vaccine strain for a live attenuated rubella vaccine.The purpose of the study is to comprehensively study the teratogenic properties of the vaccine strain of rubella virus «Orlov-V» in the experiment on rhesus macaques. Seronegative to rubella virus female rhesus macaques in early pregnancy at the age of 4-7 years (n = 13) were used in the experiment. Animals of the experimental group (n = 9) received single immunization intramuscularly with a preparation from the «Orlov-V» strain. The control group of the monkeys (n = 3) were immunized with a commercial vaccine containing Wistar RA27/3 strain. The female of the control group (n = 1) was injected with a solvent used in the rubella vaccine. Study of possible teratogenic properties of vaccine strains of rubella virus was carried out using a complex of clinical, immunological, pathomorphological and virological methods. Clinical observations were made within 3 months after the monkeys' birth. Determination of antibody titers in the blood serum of immunized monkeys was performed in HI test on the 28th-30th day after infection. The ELISA method was applied to determine IgM antibodies in the blood serum of newborns within the first month of life. Detection of rubella virus RNA was performed by PCR with electrophoretic detection of amplicons. No markers of congenital rubella infection were found in infants born from monkeys vaccinated during the pregnancy. It is shown that PCR can be an informative method to confirm the absence of teratogenic properties of vaccine strains of rubella virus. The obtained data demonstrated that vaccine strains of the «Orlov-V» rubella virus and Wistar RA27/3 have lost their teratogenic properties. The possibility of using an alternative strategy for preclinical assessment of specific safety of antiviral vaccines including a complex of clinical, immunological, pathologic and virological methods instead of the classical pathologic method is discussed. The results obtained in this study showed the absence of teratogenic properties and high immunogenic activity of the vaccine strain of rubella virus «Orlov-V».


Gross vs. net income: How plant toughness affects performance of an insect herbivore.
Leaf biomechanical properties are thought to impose a significant obstacle to herbivores and as such influence patterns of herbivory more than leaf chemistry. However, evidence for the role of structural traits in influencing herbivore food choice and performance has come from correlative studies, whereas the underlying mechanisms have been given little attention. By manipulating the biomechanical properties of a host grass species through a combination of lyophilization and milling, and providing water separately, we were able to compare behavioral, physiological, and developmental responses of the Australian plague locust, Chortoicetes terminifera, to the biomechanical properties of plant food (exemplified by toughness) independently of the food's macronutrient content and the insect's demand for water. Increasing leaf toughness was associated with reduced rates of locust growth and prolonged development, with potential ecological consequences. Poorer performance on the tougher foods was primarily a consequence of a reduced rate of nutrient supply, which occurred as a result of (1) smaller meals being eaten more slowly, (2) slowed gut passage rates, which limited how quickly the next meal could be taken, and (3) reduced efficiency of assimilation of nutrients from food in the gut. In addition, there were deleterious changes in the ratio of protein to carbohydrate assimilated from the gut. Prolonged development time was associated with increased total nutrient demands throughout the extended developmental period. Because these demands could not be met by increased consumption, there was a decreased efficiency of conversion of assimilated nutrients to growth. By disentangling the effects of biomechanical properties from macronutrient and water content we have shown that leaf biomechanical traits can influence chewing herbivores independently of leaf chemical traits.


Current concepts in adult respiratory distress syndrome in children.
Acute respiratory distress syndrome (ARDS) is an acute form of severe alveolar-capillary injury that evolves after a direct or indirect lung insult. It begins as noncardiogenic pulmonary edema and develops into a neutrophilic alveolitis, and, later, pulmonary fibrosis. Mortality remains high among children with ARDS, particularly when serious underlying conditions co-exist, sepsis occurs, and when there is multi-organ failure. Lung function improves with time among survivors, but pulmonary fibrosis may persist. Advances in the care of children with ARDS include the use of lung-protective ventilator strategies, permissive hypercapnia, inhaled nitric oxide, high-frequency ventilation, and extra-corporeal life support. These approaches reduce ventilator-associated lung injury and may improve survival when used in combination with one another. Interventions that reduce alveolar inflammation, enhance alveolar fluid removal, and reduce pulmonary fibrosis will further improve survival and recovery from ARDS in the future.


Decreased plasma apolipoprotein A-IV levels in patients with acute coronary syndrome.
The purpose of this study was to evaluate the relationship between apolipoprotein A-IV (apoA-IV) plasma concentrations and acute coronary syndrome (ACS). Plasma apoA-IV concentrations were measured in 115 patients with different types of ACS and in 68 gender- and age-matched control subjects using Enzyme-Linked Immunosorbent Assay (ELISA) kits. The clinical data were collected by an internist, who was blinded to plasma apoA-IV concentrations. Plasma apoA-IV levels in ACS patients were significantly decreased compared to the levels in control subjects (437.0±157.5 μg/mL vs. 590.2±183.7 μg/mL, P<0.001). An statistically significant decreasing trend of plasma apoA-IV levels from the control subjects, to patients with unstable angina pectoris (UAP) (457.3±152.9 μg/mL), to patients with acute myocardial infarction (AMI) (311.7±127.8 μg/mL), was observed. Moreover, plasma apoA-IV level was negatively associated with New York Heart Association (NYHA) functional class. NYHA class II (467.2±142.1 μg/mL, P<0.001) and class III/IV (368.1±170.8 μg/mL, P<0.001) patients had statistically decreased levels of plasma apoA-IV when compared to the control subjects. A stepwise multivariate regression analysis identified types of ACS, NYHA classes, and plasma fibrinogen levels as the most important determinants of plasma apoA-IV levels in ACS patients. Low plasma apoA-IV levels are associated with ACS, and plasma apoA-IV levels may be a potential treatment target for ACS patients.


The challenge of osteo-articular tuberculosis in the twenty-first century: a 15-year population-based study.
Serbia, an intermediate tuberculosis (TB) incidence country in socio-economic transition. To examine the epidemiological and clinical pattern of osteo-articular TB (OATB) in Serbia over 15 years. This retrospective observational study included OATB cases diagnosed between 1 January 1993 and 31 December 2007, according to the National Referral Institute of Lung Diseases and TB in Belgrade and the Central TB Register. Population estimates with extrapolations were based on 1991 and 2002 census data. The 295 OATB cases represented 10.9% (range 5.3-20.2) of all extra-pulmonary TB cases notified in Serbia over the period. One tenth of these were relapses. The incidence rate showed a significant increasing trend (y = 0.1167 + 0.0175x, R(2) = 0.3196), with an average age-specific incidence rate of 0.26 per 100 000 population. The peak number of cases was in the 45-64 year age group for both men and women. The average male:female ratio was 0.85. The outcome was favourable for 279 of the 295 patients (94.6%). In addition to a standardised chemotherapy regimen, 25.4% patients underwent surgery. The increasing time trend of OATB is caused by increased morbidity, a higher TB detection rate and better notification. Although rare in children, OATB remains a challenge in clinical practice.


Changes of Marginal Bone Level in Patients with "Progressive Bone Loss" at Brånemark System® Implants: A Radiographic Follow-Up Study over an Average of 9 Years.
Patients have in many studies been identified with progressive bone loss and peri-implantitis problems, but few studies are available where these groups of patients have been followed up. The purpose of this paper is to study further progression of bone loss in a cohort of 182 patients that have been reported to suffer from "progressive" bone loss and peri-implantitis. Altogether, 182 patients that have earlier been identified to suffer from "progressive" bone loss formed the present study group. Data from patients' files have been retrieved, and intraoral radiographs have been analyzed for further bone level changes. Bone loss has been measured from time of inclusion into the present group to last available radiographs. Within each patient, one or several implants were diagnosed to suffer from "progressive" bone loss (affected), whereas others are not (unaffected). Altogether, 145 patients (80%) were radiographically followed up on an average of 9.1 years (SD 3.77) after inclusion. Twenty-four implants (3.1%) were lost in 16 patients (11%). Marginal bone loss was on an average 0.3 mm (SD 0.75) at stable implants with only small differences between "affected" and "unaffected" implants. In total, 67 implants (8.6%) presented an annual bone loss of >0.2 mm. Oral hygienist treatment and/or peri-implantitis surgery did not neither reduce implant failure rate nor marginal bone loss in 88 treated patients as compared with untreated patients. Less than one-third of the patients identified with "progressive bone loss" showed one or more implants as failures or with high annual bone loss (>0.2 mm) during follow-up (11.6% of implants). Treated patients (oral hygienist and/or surgery) did not perform better than untreated patients with regard to bone loss or implant failure.


Photodissociation of nitromethane cluster anions.
Three types of anionic fragments are observed in the photodissociation of nitromethane cluster anions, (CH(3)NO(2))(n)(-), n=1-6, at 355 nm: NO(2)(-)(CH(3)NO(2))(k), (CH(3)NO(2))(k)(-), and OH(-) (k<n). The fragmentation trends are consistent with the parent clusters containing a monomer-anion core, CH(3)NO(2)(-), solvated by n-1 neutral nitromethane molecules. The NO(2)(-)(CH(3)NO(2))(k) and OH(-) fragments formed from these clusters are described as core-dissociation products, while the (CH(3)NO(2))(k)(-) fragments are attributed to energy transfer from excited CH(3)NO(2)(-) into the solvent network or a core-dissociation-recombination (caging) mechanism. As with other cluster families, the fraction of caged photofragments shows an overall increase with increasing cluster size. The low-lying A(2)A' and/or B(2)A' electronic states of CH(3)NO(2)(-) are believed responsible for photoabsorption leading to dissociation to NO(2)(-) based fragments, while the C(2)A" state is a candidate for the OH(-) pathway. Compared to neutral nitromethane, the photodissociation of CH(3)NO(2)(-) requires lower energy photons because the photochemically active electron occupies a high energy pi* orbital (which is vacant in the neutral). Although the electronic states in the photodissociation of CH(3)NO(2) and CH(3)NO(2)(-) are different, the major fragments, CH(3)+NO(2) and CH(3)+NO(2)(-), respectively, both form via C-N bond cleavage.


Gender, apolipoprotein E genotype, and mesial temporal atrophy: 2-year follow-up in patients with stable mild cognitive impairment and with progression from mild cognitive impairment to Alzheimer's disease.
This study aimed to examine the relationship between gender, apolipoprotein E (APOE) genotype, and mesial temporal atrophy in mild cognitive impairment (MCI) with and without progression to Alzheimer's disease (AD). We evaluated 236 MCI patients with (n = 121) and without (n = 115) AD progression. Longitudinal MRI-based hippocampal volumes (HV) and entorhinal cortex (ERC) thickness were obtained. The Clinical Dementia Rating Sum of Boxes (CDR-SB) score was used to assess disease severity. We found a significant effect of APOE, gender, and clinical course (stable MCI versus MCI-AD progression) on HV. There was a significant effect of clinical course and APOE, but not gender, on ERC. Baseline HV and APOE4 status predicted MCI-AD progression in women. Baseline ERC and APOE4 status predicted MCI-AD progression in men. There were significant differences in CDR-SB scores between patients with and without MCI-AD progression, but not between males and females, or APOE4 carriers and non-carriers. HV, but not ERC, is strongly influenced by gender in MCI. The effects of gender and APOE4 on neuroimaging biomarkers have potentially important implications in the prediction of MCI-AD progression and should be taken into account in clinical trials.


Taxonomic characterization of Haloferax sp. (" H. alicantei") strain Aa 2.2: description of Haloferax lucentensis sp. nov.
An extremely halophilic archaeon, previously named as Haloferax sp. strain Aa 2.2 or "Haloferax alicantei" that has been extensively used for genetic studies with halobacteria, was taxonomically characterized by using phenotypic tests (including morphological, physiological, biochemical and nutritional features), DNA-DNA hybridization and 16S rRNA sequence phylogenetic analysis. This organism was isolated in 1986 by Torreblanca et al. from a pond of a Spanish saltern located in Alicante. The cells were pleomorphic, Gram negative and grew optimally at 25% NaCl. The polar lipid composition was similar to that of species of the genus Haloferax. The DNA G+C content of this strain was 64.5 mol%. Phylogenetic analysis based on 16S rRNA sequence comparison confirmed that this archaeon is a member of the genus Haloferax and was most closely related to Haloferax volcanii. DNA-DNA hybridization between strain Aa 2.2 and the type strain of all named species of the genus Haloferax revealed low levels of relatedness (25-2%), supporting the placement of this organism in a new species. On the basis of the phenotypic characteristics, molecular data and phylogenetic analysis we propose to name strain Aa 2.2 as a new species, Haloferax lucentensis sp. nov. The type strain is Aa 2.2 (=JCM 9276=NCIMB 13854=CIP 107410=DSM 14919=CECT 5871=CCM 7023).


The effect of diet on ontogenic development of the digestive tract in juvenile reared long snout seahorse Hippocampus guttulatus.
Ontogenetic development of the digestive tract and associated organs in long snout seahorse Hippocampus guttulatus juveniles was morphologically and histologically examined from the time of release from the male's pouch until 72 h after the first meal. When released from the male's pouch, juvenile seahorses are small adult replicates. This means that unlike other teleost fish larvae, the first developmental phase has already taken place, and juveniles are morphologically prepared and able to feed on live prey immediately following parturition. At this stage, the buccopharynx, oesophagus, and intestine already appear to be fully developed. The intestine is divided into the midgut and hindgut by an intestinal valve, and intestinal villi are visible in the midgut. When fed with DHA-Selco(®) enriched Artemia, H. guttulatus juveniles developed a severe condition of overinflation of the gas bladder. The continuous overinflation of the gas bladder forced air into the gut (48 h after the first meal), resulting in overinflation of both the gut and the gas bladder (72 h after the first meal), and death occurred within 120 h after the first meal. When fed natural copepods, H. guttulatus juveniles continued a normal feeding activity with no signs of intestinal disorders, and the gas bladder and intestine maintained their normal shape. This is the first study to positively associate gas bladder overinflation of juvenile seahorses with nutritionally unbalanced diets, and not to gas supersaturation alone. It is therefore necessary to develop more adequate feed and/or enrichment products to improve the survival of juvenile seahorses in captivity.


Ultrasound enhancement of thrombolytic therapy: observations and mechanisms.
Fibrinolytic therapy is a proven approach for achieving reperfusion of occluded coronary arteries during myocardial infarction, resulting in reduced mortality and preservation of ventricular function. The amount of myocardial muscle loss is proportional to the duration of ischemia. Bleeding complications are not infrequent. Adjuvant therapy by ultrasound might enhance the rate of fibrinolysis and reduce the concentrations of lytic agents required to achieve an equivalent degree of clot lysis. Noninvasive ultrasound at low intensities and high frequencies, parameters that potentially could be applied and tolerated in vivo, have been proven to significantly accelerate the rate of fibrinolysis in both in vitro and in vivo models, in pure fibrin as well as whole blood clots. Such enhancement is not drug-specific. These effects were achieved by nonthermal mechanism. Ultrasound exposure did not cause mechanical fragmentation of the clot, did not alter the size of plasmatic derivates and degradation products. Ultrasound caused increased flow rate through thrombi, probably by cavitation-induced changes in fibrin ultrastructure; disaggregation of uncrosslinked fibrin fibers into smaller fibers has been shown. This resulted in increased transport of the lytic agent into the clot, alteration of binding affinity and increased maximum binding. Presence of echo-contrast agent induced further acceleration of thrombolysis by ultrasound.


Lack of health maintenance examinations and risk in myeloma patients.
Health maintenance (HM) practices are essential to prevent illness, promote well-being, and maximize health. Patients with multiple myeloma (MM) are at increased risk for cardiovascular disease and cancers, yet, research on HM practices and preventative care of MM survivors has limited report. The study comprised a descriptive, correlational, and cross-sectional online survey design. Survey of patients with MM was carried out through the International Myeloma Foundation (IMF) and the Association of Cancer Online Resources (ACOR) e-mail list services. The members of the IMF and ACOR e-mail list services were surveyed, of which 237 patients responded. The modified Medical Expenditure Preventive Survey-Preventive Care questionnaire was used; it included items that ask patients regarding their healthcare practices that relate to dental care, cancer prevention, addiction, lifestyles, sensory screening, immunizations, cardiovascular, endocrine, psychosocial, and bone health. Descriptive statistics, Pearson's chi-square, and Spearman's rho correlation coefficient were obtained. In this study, men had statistically significant inferior global health maintenance scores than women (P = 0.002). Being employed (P = 0.054) and married or partnered (P = 0.017) were significantly correlated with better health maintenance patterns among male respondents. In contrast, no statistically significant correlations between sociodemographic factors and health maintenance patterns were found in women. Patients with MM, particularly men, require continued education and close monitoring of health maintenance practices. These findings are consistent with publications looking at gender disparities in healthcare utilization in the United States. Studies show that men, in general, are less likely to seek preventative healthcare screenings. Healthcare providers must incorporate health maintenance promotion during clinic visits.


Assessment of difference in dimensions of sexual orientation: implications for substance use research in a college-age population.
The present research examines the associations between three distinct dimensions of sexual orientation and substance use in a random sample of undergraduate students. A Web-based survey was administered to students attending a large, midwestern research university in the spring of 2003. The sample consisted of 9,161 undergraduate students: 56% female, 68% white, 13% Asian, 6% black, 4% Hispanic and 9% other racial categories. Using multivariate logistic regression analyses, several measures of alcohol and other drug use were compared across three dimensions of sexual orientation: sexual identity, sexual attraction and sexual behavior. All three dimensions of sexual orientation were associated with substance use, including heavy episodic drinking, cigarette smoking and illicit drug use. Consistent with results of several other recent studies, "nonheterosexual" identity, attraction or behavior was associated with a more pronounced and consistent risk of substance use in women than in men. Study findings suggest substantial variability in substance use across the three dimensions of sexual orientation and reinforce the importance of stratifying by gender and using multiple measures to assess sexual orientation. Study results have implications for future research and for interventions aimed at reducing substance use among college students.


Adenosine triphosphate-competitive mTOR inhibitors: a new class of immunosuppressive agents that inhibit allograft rejection.
The mechanistic/mammalian target of rapamycin (mTOR) is inhibited clinically to suppress T cell function and prevent allograft rejection. mTOR is the kinase subunit of two mTOR-containing complexes, mTOR complex (mTORC) 1 and 2. Although mTORC1 is inhibited by the macrolide immunosuppressant rapamycin (RAPA), its efficacy may be limited by its inability to block mTORC1 completely and its limited effect on mTORC2. Adenosine triphosphate (ATP)-competitive mTOR inhibitors are an emerging class of mTOR inhibitors that compete with ATP at the mTOR active site and inhibit any mTOR-containing complex. Since this class of compounds has not been investigated for their immunosuppressive potential, our goal was to determine the influence of a prototypic ATP-competitive mTOR inhibitor on allograft survival. AZD8055 proved to be a potent suppressor of T cell proliferation. Moreover, a short, 10-day course of the agent successfully prolonged murine MHC-mismatched, vascularized heart transplant survival. This therapeutic effect was associated with increased graft-infiltrating regulatory T cells and reduced CD4(+) and CD8(+) T cell interferon-γ production. These studies establish for the first time, that ATP-competitive mTOR inhibition can prolong organ allograft survival and warrant further investigation of this next generation mTOR inhibitors.


What Are the Factors Affecting Total Sleep Time During Video Polysomnography in Infants?
The aim of the study is to investigate factors affecting total sleep time (TST) during infant polysomnography (PSG) and assess if <4 hours of TST is sufficient for accurate interpretation. Overall, 242 PSGs performed in 194 infants <6 months of chronological age between March 2013 and December 2015 were reviewed to identify factors that affect TST, including age of infant, location and timing of study, presence of medical complexity, and presence of nasal tubes. A continuum of apnea-hypopnea index (AHI) in relation to TST was reviewed. Data were examined in infants who had TST <4 hours and low AHI. Greater TST (p < 0.001) was noted among infants during nocturnal PSGs, at older chronological and post-menstrual ages, and without medical complexity. The presence of nasogastric/impedance probes reduced TST (p = 0.002). Elevated AHIs were identified even in PSGs with TST <4 hours. Short TST may have affected interpretation and delayed initial management in one infant without any inadvertent complications. Clinical factors such as PMA and medical complexity, and potentially modifiable factors such as time of day and location of study appeared to affect TST during infant PSGs. TST < 4 hours can be sufficient to identify high AHI allowing physician interpretation. · Less than 4 hours of TST is enough for interpretation of infant polysomnography.. · Shorter TST appears related to infant age, medical complexity, and higher apnea-hypopnea index.. · Modifiable factors seen with higher TST were time of day, environment, and presence of nasal tubes..


Multiple pathways of angiotensin I conversion and their functional role in the canine penile corpus cavernosum.
Multiple pathways of angiotensin (Ang) I conversion and their functional role in the canine penile corpus cavernosum were investigated. Biochemical analysis revealed high activities of angiotensin-converting enzyme (ACE) (6.9 +/- 1.7 mU/mg of protein, mean +/- S.E.M., n = 8) and chymase-like enzyme (4.0 +/- 1.4 mU/mg of protein). Functional recording of isometric tension showed that Ang I (3 x 10(-7) M) induced a tension of 0.17 +/- 0.05 g (n = 5), which was reduced to about 60% by pretreatment with an ACE inhibitor, lisinopril (10(-6) M), and almost completely blocked by lisinopril in combination with a chymase inhibitor, chymostatin (10(-4) M). Binding sites for ACE and Ang II receptors were studied by in vitro autoradiography using 125I-351A and 125I-[Sar1, Ile8]Ang II as ligands, respectively. Dense binding of ACE appeared in the endothelial layer of the corpus cavernosum penis, and Ang II receptors were localized in the trabecular smooth muscle layer. An AT1 receptor antagonist, CV-11974 (10(-6) M), markedly displaced 125I-[Sar1, Ile8]Ang II bindings, indicating that the corpus cavernosum penis contains AT1 receptors exclusively. Immunohistochemical studies demonstrated ACE in the endothelium of the corpus cavernosum penis. Mast cells that produce chymase were present mainly in the cavernosal area. These results demonstrate that chymase, in addition to ACE, is involved in the contraction of canine penile corpus cavernosum through local Ang II formation.


Introducing the rotavirus vaccine in the UK.
Rotavirus accounts for more than 1.3 million deaths per year around the world. In many countries, vaccination against it is already part of childhood immunisation schedules. The vaccine's use in the UK is being extended to the primary immunisation schedule and health professionals will be expected to administer it. This article explores the benefits, challenges and contraindications of administering rotavirus immunisation to children.


Consumer experiences of community-based residential mental health rehabilitation for severe and persistent mental illness: A pragmatic grounded theory analysis.
Semi-structured interviews were used to explore the consumer experience of community-based residential mental health rehabilitation support at Community Care Units in Australia. These clinical services provide recovery-oriented residential rehabilitation to people affected by severe and persistent mental illness. Typically, nurses occupy the majority of staff roles. However, two of the three sites in the study were trialling a novel integrated staffing model where the majority of staff were people with a lived experience of mental illness employed as peer support workers (PSWs). The interviews explored consumers' experiences of care 12-18 months after admission. Fifteen interviews were completed with an independent interviewer. Most participants were diagnosed with schizophrenia or a related psychotic disorder. The analysis followed a pragmatic approach to grounded theory. Consumers viewed the CCU favourably, emphasizing the value of the relationships formed with staff and co-residents. No major differences in consumers' experience under the traditional versus integrated staffing models were identified; however, those from the integrated staffing model sites valued the contributions of the peer support workers. The understanding of the consumer experience emerging through this study aligned with their expectations of the service at the time of commencement.


Induced pluripotent stem cells from highly endangered species.
For some highly endangered species there are too few reproductively capable animals to maintain adequate genetic diversity, and extraordinary measures are necessary to prevent extinction. We report generation of induced pluripotent stem cells (iPSCs) from two endangered species: a primate, the drill, Mandrillus leucophaeus and the nearly extinct northern white rhinoceros, Ceratotherium simum cottoni. iPSCs may eventually facilitate reintroduction of genetic material into breeding populations.


Augmentation of the antibody response of Atlantic salmon by oral administration of alginate-encapsulated IPNV antigens.
The objective of the present study was to assess the effect of alginate-encapsulated infectious pancreatic necrosis virus antigens in inducing the immune response of Atlantic salmon as booster vaccines. One year after intraperitoneal injection with an oil-adjuvanted vaccine, post-smolts were orally boosted either by 1) alginate-encapsulated IPNV antigens (ENCAP); 2) soluble antigens (UNENCAP) or 3) untreated feed (control). This was done twice, seven weeks apart. Sampling was done twice, firstly at 7 weeks post 1st oral boost and the 2nd, at 4 weeks after the 2nd oral boost. Samples included serum, head kidney, spleen and hindgut. Serum antibodies were analyzed by ELISA while tissues were used to assess the expression of IgM, IgT, CD4, GATA3, FOXP3, TGF-β and IL-10 genes by quantitative PCR. Compared to controls, fish fed with ENCAP had a significant increase (p<0.04) in serum antibodies following the 1st boost but not after the 2nd boost. This coincided with significant up-regulation of CD4 and GATA3 genes. In contrast, serum antibodies in the UNENCAP group decreased both after the 1st and 2nd oral boosts. This was associated with significant up-regulation of FOXP3, TGF-β and IL-10 genes. The expression of IgT was not induced in the hindgut after the 1st oral boost but was significantly up-regulated following the 2nd one. CD4 and GATA3 mRNA expressions exhibited a similar pattern to IgT in the hindgut. IgM mRNA expression on the other hand was not differentially regulated at any of the times examined. Our findings suggest that 1) Parenteral prime with oil-adjuvanted vaccines followed by oral boost with ENCAP results in augmentation of the systemic immune response; 2) Symmetrical prime and boost (mucosal) with ENCAP results in augmentation of mucosal immune response and 3) Symmetrical priming and boosting (mucosal) with soluble antigens results in the induction of systemic immune tolerance.