Comparison of the effect of indoleacetic Acid and fusicoccin on the breakdown of phosphatidylinositol in maize coleoptiles.
The effect of indoleacetic acid (IAA) and fusicoccin (FC) on the breakdown of phosphatidylinositol in maize (Zea mays L.) coleoptiles has been studied. Coleoptiles were able to incorporate [(3)H] myo-inositol into the phospholipid fraction almost linearly for 8 hours. Thin layer chromatography analysis of total phospholipids showed that [(3)H]myo-inositol was incorporated only into phosphatidylinositol. Prelabeled coleoptiles treated with IAA showed a loss of the radioactivity incorporated in the phospholipid fraction, whose level decreased by 34% after 1 hour. Treatment with FC, on the contrary, did not modify the content of labelled phosphatidylinositol with respect to the control. The different effects of IAA and FC and a possible mechanism of IAA action on growth are discussed.


A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice.
Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances.


Effects of an integrated safety system for swivel seat arrangements in frontal crash.
Objective: Autonomous vehicles (Avs) have paved the way for the arrangement of swivel seats in vehicles, which could pose a challenge to traditional safety systems. The integration of automated emergency braking (AEB) and pre-pretension (PPT) seatbelts improves protection for a vehicle's occupant. The objective of this study is to explore the control strategies of an integrated safety system for swiveled seating orientations. Methods: Occupant restraints were examined in various seating configurations using a single-seat model with a seat-mounted seatbelt. Seat orientation was set at different angles, from -45° to 45° with 15° increments. A pretension was used on the shoulder belt to represent an active belt force cooperating with AEB. A generic full frontal vehicle pulse of 20 mph was applied to the sled. The occupant's kinematics response under various integrated safety system control strategies was analyzed by extracting a head pre-crash kinematics envelope. The injury values were calculated for various seating directions with or without an integrated safety system at the collision speed of 20 mph. Results: In a lateral movement, the excursions of the dummy head were 100 mm and 70 mm in the global coordinate system for negative and positive seat orientations, respectively. In the axial movement, the head traveled 150 mm and 180 mm in the global coordinate system for positive and negative seating directions, respectively. The 3-point seatbelt did not restrain the occupant symmetrically. The occupant experienced greater y-axis excursion and smaller x-axis excursion in the negative seat position. Various integrated safety system control strategies led to significant differences in head movement in the y direction. The integrated safety system reduced the occupant's potential injury risks in different seating positions. When the AEB and PPT were activated, the absolute HIC15, brain injury criteria (BrIC), neck injury (Nij), and chest deflection were reduced in most seating directions. However, the pre-crash increased the injury risks at some seating positions. Conclusion: The pre-pretension seatbelt could reduce the occupant's forward movement in the rotating seat positions in a pre-crash period. The occupant's pre-crash motion envelope was generated, which could be beneficial to future restraint systems and vehicle interior design. The integrated safety system could reduce injuries in different seating orientations.


A novel mouse mitochondrial voltage-dependent anion channel gene localizes to chromosome 8.
Voltage-dependent anion channels (VDACs) are small pore-forming channels found in the outer membrane of mitochondria. VDACs translocate adenine nucleotides and are the binding sites for several cytosolic kinases important in intermediary metabolism. Recently two human VDAC cDNAs (HVDAC1 and HVDAC2) were isolated, and possible orthologues of these genes have been isolated from mouse, bovine, and rat tissues. We report the isolation of a novel third VDAC cDNA from the mouse, designated MVDAC3. The deduced MVDAC3 protein is approximately 70% identical to the previously isolated MVDAC1 and MVDAC2 proteins. The MVDAC3 gene was mapped by an interspecies backcross panel to mouse chromosome 8. A database search using the mouse VDACs identified a second yeast VDAC-like gene that retains about 20% amino acid sequence identity with the mouse VDAC genes and 50% identity with the previously isolated yeast VDAC gene. The phylogenetic relationship of the eukaryotic VDAC genes is presented.


Tumor-Penetrating Delivery of siRNA against TNFα to Human Vestibular Schwannomas.
Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine angle, and it typically presents with sensorineural hearing loss. The genomic landscape of schwannoma is complex and many of the molecules implicated in VS pathogenesis represent targets not amenable to antibody-based or small molecule therapeutics. Tumor-targeted delivery of small interfering RNA (siRNA) therapeutics provides a direct and effective means to interrogate targets while minimizing off-target effects. To establish a preclinical model for therapeutic inhibition of putative targets in VS, archived tumor specimens, fresh tumor cells derived from patients with sporadic VS, and an established schwannoma cell line were screened. Nanoparticles directed by the tumor-homing peptide iRGD were selectively taken up by primary VS cultures in vitro via interactions with αvβ3/β5 integrins and neuropilin-1 (NRP-1). Cellular uptake was inhibited by a neutralizing antibody against αv integrin in a dose-dependent manner. When applied to primary VS cultures, iRGD-targeted nanoparticles delivered siRNA directed against TNFα in a receptor-specific fashion to potently silence gene expression and protein secretion. Taken together, our results provide a proof of principle for tumor-targeted, nanoparticle-mediated delivery of siRNA to VS and establish a novel platform for the development and pre-clinical screening of molecular therapeutics against VS.


Newly established regulation in Japan: foods with health claims.
The Japanese government enacted a new regulatory system called 'Foods with health claims' in April 2001, which consists of 'Foods for Specified Health Use' (FOSHU) and 'Foods with Nutrient Function Claims' (FNFC). The FOSHU was set up by the Ministry of Health and Welfare in 1991 to approve descriptions on a label regarding an effect of food on the human body. It was enacted as a part of 'food for specified dietary use' under the Nutrition Improvement Law. There are three important requirements for FOSHU approval. The first is scientific evidence of the efficacy, including clinical testing. The second is safety for consumption. The third is analytical determination of the effective component. At present there are 293 items approved as FOSHU. Most of the descriptions of foods under the FOSHU system are similar to the category of enhanced function claims of Codex. Under FNFC, 12 vitamins (vitamin A, B1, B2, B6, B12, C, E, D, biotin, pantothenic acid, folic acid, and niacin) and two minerals (calcium and iron) are standardized. These claims are similar to the nutrient function claims approved by Codex in 1997. It is desirable that the Japanese administration and the food industry cooperate with ASEAN countries to work together in the development and promotion of nutrition and health claims on foods.


The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC.
Cancer stem cells (CSCs) are a small subpopulation of tumor cells harboring properties that include self-renewal, multi-lineage differentiation, tumor reconstitution, drug resistance and invasiveness, making them key players in tumor relapse. In the present paper, we develop new CSC models and analyze the molecular pathways involved in survival to identify targets for the establishment of novel therapies. Endometrial carcinoma-derived stem-like cells (ECSCs) were isolated from carcinogenic gynecological tissue and analyzed regarding their expression of prominent CSC markers. Further, they were treated with the MYC-signaling inhibitor KJ-Pyr-9, chemotherapeutic agent carboplatin and type II diabetes medication metformin. ECSC populations express common CSC markers, such as Prominin-1 and CD44 antigen as well as epithelial-to-mesenchymal transition markers, Twist, Snail and Slug, and exhibit the ability to form free-floating spheres. The inhibition of MYC signaling and treatment with carboplatin as well as metformin significantly reduced the cell survival of ECSC-like cells. Further, treatment with metformin significantly decreased the mitochondrial membrane potential of ECSC-like cells, while the extracellular lactate concentration was increased. The established ECSC-like populations represent promising in vitro models to further study the contribution of ECSCs to endometrial carcinogenesis. Targeting MYC signaling as well as mitochondrial bioenergetics has shown promising results in the diminishment of ECSCs, although molecular signaling pathways need further investigations.


Recombinant human phenylethanolamine N-methyltransferase: overproduction in Escherichia coli, purification, and characterization.
The gene encoding phenylethanolamine N-methyltransferase (PNMT) has been amplified from a human adrenal medulla cDNA library. Following ligation of the gene into a pET3a-derived expression vector and transformation into Escherichia coli BL21(DE3)pLysS, PNMT was expressed, yielding about 10% of the soluble protein. The enzyme was purified to homogeneity by ammonium sulfate fractionation followed by ion-exchange chromatography and gel filtration. The Km for phenylethanolamine and S-adenosyl-L-methionine were determined to be 130 and 16 microM, respectively. The enzyme could be inhibited by reagents expected to modify cysteine, arginine, tyrosine, and histidine residues, but not by methyl acetimidate, a reagent expected to modify lysine residues.


Direct correlation between methylation status and expression of the human O-6-methylguanine DNA methyltransferase gene.
To assess the role of DNA cytosine methylation in the expression of the O-6-methylguanine DNA methyltransferase (MGMT) gene, the methylation status of selected CpG-containing dinucleotides in and surrounding the coding regions of the gene were examined and correlated with steady state expression of MGMT mRNA in 13 human cell lines. Additionally, tumor cells which exhibited very high levels of MGMT expression were chronically exposed to 5-azacytidine to assess the effects of changes in gene methylation on MGMT expression. Results of these studies demonstrate that the degree of methylation of multiple MGMT gene regions correlates with gene expression, but in a direct rather than an inverse fashion, and that 5-azacytidine-induced demethylation of the MGMT gene correlates with a significant reduction, rather than induction, of MGMT steady-state mRNA expression. These results suggest a unique, potentially alterable methylation-related regulatory mechanism for the MGMT gene.


Identity disclosure between donor families and organ transplant recipients: an integrative review of the international literature.
Anonymity of deceased organ donation is a legal requirement in many international jurisdictions where legislation prohibits health professionals from disclosing identifiable information about donors, recipients or their families. Written correspondence between donor families and transplant recipients that is coordinated by healthcare professionals must remain anonymous. Internationally, an increasing number of donor families and transplant recipients have advocated for law reform and policy amendment to enable the exchange of identifiable written correspondence and/or face-to-face meetings. This paper aims to synthesise and critically evaluate published, peer-reviewed literature on the perceptions, benefits and challenges of identifiable communication or anonymity between donor families and organ transplant recipients in the international context. Analysis of the findings revealed two major themes: (1) views held by donor families, transplant recipients and healthcare professionals towards identity disclosure in the context of organ donation are diverse across and within groups (2) there are benefits and burdens associated with connecting donor families and transplant recipients through written correspondence. Less is known about the impact of face-to-face meetings between donor families and transplant recipients. However, what is known is that for some donor families, meeting with the transplant recipient(s) may provide a range of positive emotions.


β-Lactam antibiotics targeting PBP1 selectively enhance daptomycin activity against methicillin-resistant Staphylococcus aureus.
The activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA) is enhanced in the presence of subinhibitory concentrations of antistaphylococcal β-lactam antibiotics by an undefined mechanism. Given the variability in the penicillin-binding protein (PBP)-binding profiles of different β-lactam antibiotics, the purpose of this study was to examine the relative enhancement of DAP activity against MRSA by different β-lactam antibiotics to determine if a specific PBP-binding profile is associated with the ability to enhance the anti-MRSA activity of DAP. We determined that both broad- and narrow-spectrum β-lactam antibiotics known to exhibit PBP1 binding demonstrated potent enhancement of DAP anti-MRSA activity, whereas β-lactam antibiotics with minimal PBP1 binding (cefoxitin, ceftriaxone, cefaclor, and cefotaxime) were less effective. We suspect that PBP1 disruption by β-lactam antibiotics affects pathways of cell division in S. aureus that may be a compensatory response to DAP membrane insertion, resulting in DAP hypersusceptibility.


Olfactory Enrichment in California Sea Lions (Zalophus californianus): An Effective Tool for Captive Welfare?
In the wild, California sea lions (Zalophus californianus) are exposed to a wide variety of sensory information, which cannot be replicated in captive environments. Therefore, unique procedures are necessary for maintaining physiological and psychological health in nonhuman animals in captivity. The effects of introducing natural scents to captive enclosures have been investigated in a variety of species, yet they have not been examined in marine mammals. This project explored the behavioral effect of scent added to the environment, with the goal of improving the welfare of sea lions in captivity. Two scent types were introduced: (a) natural scents, found in their native environment, and (b) non-natural scents, not found in their native environment. This study examined not only scent enrichment but also the possible evolutionary underpinnings of pinniped olfaction. Scent enrichment was found to significantly impact sea lion behavior as demonstrated by a reduction in pattern swimming, an increase in habitat utilization, and a reduction in stereotypical behavior. However, there were no differences in behavior between natural and non-natural scent conditions.


A model 450 million years in the making: zebrafish and vertebrate immunity.
Since its first splash 30 years ago, the use of the zebrafish model has been extended from a tool for genetic dissection of early vertebrate development to the functional interrogation of organogenesis and disease processes such as infection and cancer. In particular, there is recent and growing attention in the scientific community directed at the immune systems of zebrafish. This development is based on the ability to image cell movements and organogenesis in an entire vertebrate organism, complemented by increasing recognition that zebrafish and vertebrate immunity have many aspects in common. Here, we review zebrafish immunity with a particular focus on recent studies that exploit the unique genetic and in vivo imaging advantages available for this organism. These unique advantages are driving forward our study of vertebrate immunity in general, with important consequences for the understanding of mammalian immune function and its role in disease pathogenesis.


Adsorption of small molecules with the hydroxyl group on sodium halide cluster ions.
We have investigated adsorption of molecules with hydroxyl group, ROH, on sodium halide cluster ions, Na(n)X(n-1)(+) (X = F and I, n = 10-17) by mass spectrometry and by theoretical calculations. From analysis of the cluster ion intensities, the adsorption of one water molecule (R = H) is most efficient for Na(13)X(12)(+), whose structure has a NaX defect from a 3 x 3 x 3 cubic structure of n = 14. This result suggests that the defect has an important role in the adsorption reaction. However, it is also found that the reactivity diminishes with increasing bulk size of the R group from H to CH(3), (CH(3))(2)CH, and (CH(3))(3)C. These results imply that the adsorption reactivity is dominated by steric hindrance; the smaller molecules are adsorbed inside the basket structures of Na(13)X(12)(+). Reactivity dependence on the basket size is also discussed by comparing the results of Na(n)F(n-1)(+) and Na(n)I(n-1)(+).


Comparative study of the prevalence and clinical profiles of diarrheas due to Aeromonas and other enteric pathogens.
The prevalence of Aeromonas spp. and other enteric pathogens in stool specimens from diarrheic and non-diarrheic patients was studied over a 12 month period (January to December, 1986). Except for the absence of fever, all the clinical features in Aeromonas diarrhea were comparable to those associated with other diarrheagenic agents. These features included abdominal pain (30%), vomiting (24.5%), fever (31.5%), dehydration (9.5%) and hematochezia (19.5%). Aeromonas spp. were more frequently isolated from patients with gastroenteritis (2.5%) than from control patients (1.0%) (P less than 0.05). Isolates were recovered more often during the dry months (66.7%), than during the wet months (33.3%). Among the enteric pathogens isolated, Aeromonas spp. (2.5%) ranked next to Esch. coli (14.5%) and Shigella spp. (6.3%) in prevalence. Other bacterial isolates included Plesiomonas shigelloides (1.5%) Vibrio spp. (1.0%), Yersinia enterocolitica (1.0%) and Salmonella spp. (1.8%).


Chemical routes to nanocrystalline thermoelectrically relevant AgPb(m)SbTe(m+2) materials.
A direct synthesis of nanoparticles of the thermoelectrically relevant AgPbmSbTem+2 materials (m = 0, 1, 2) was accomplished in reverse micelles. The procedure offers several distinct advantages and opens the field for experimentation of thermoelectric properties for nanoparticle-derived materials.


The Cost-effectiveness of Initial Immunomodulators or Infliximab Using Modern Optimization Strategies for Crohn's Disease in the Biosimilar Era.
Treatment cost, efficacy, and safety are integral considerations when optimizing management of Crohn's disease (CD). This study assessed the cost-effectiveness of initial immunomodulator and anti-tumor necrosis factor (anti-TNF) agents for the treatment of CD from a US third-party perspective, incorporating current treatment algorithms, optimization strategies, and reduced costs availed by biosimilars. A 1-year Markov model was developed to simulate the cost and quality-adjusted life-years (QALYs) of initial azathioprine, infliximab, and combination therapy for moderate to severe CD. Treatment was changed based on tolerability and clinical disease activity at 3-monthly intervals. Efficacy data were based on published literature. Initial azathioprine had the lowest cost and utility ($35,337 and 0.63 QALYs), whereas combination therapy was the costliest yet conferred the highest health benefits ($57,638 and 0.67 QALYs). The incremental cost-effectiveness of infliximab and combination therapy compared with azathioprine were both in excess of $500,000 per QALY gained. Initial azathioprine remained the most cost-effective treatment on sensitivity analysis compared with infliximab and combination therapy, with 90% reductions in anti-TNF therapy costs and a 5-year time horizon, although combination therapy had an acceptable cost-effectiveness when costs were reduced in the extended model. Initial infliximab, ustekinumab, and vedolizumab were dominated by combination therapy. In the biosimilar era, initial azathioprine with escalation to infliximab appeared more cost-effective in the short term compared with infliximab or combination therapy, although initial combination therapy yields acceptable ICERs in the long term with continued reductions in anti-TNF therapy costs and will likely be the preferred treatment strategy in the future.


Temporary transvenous VDD pacing as a bridge to permanent pacemaker implantation in patients with sepsis and haemodynamically significant atrioventricular block.
Permanent pacemaker (PM) implantation is temporarily contraindicated in patients (pts) with sepsis. In patients with symptomatic atrioventricular (AV) block and infection, prolonged VVI pacing is therefore usually ensured by a ventricular pacing lead (PL) connected to an external PM generator. In patients with normal sinus function and heart failure, the VVI mode can exacerbate haemodynamic dysfunction. A single AV PL can be attractive to achieve physiological pacing. This study was designed to assess the efficacy and safety of temporary VDD pacing as a bridge to permanent PM implantation in patients with complete AV block until control of infection. This study included eight patients with complete AV block and sepsis with negative blood culture. Due to the presence of congestive heart failure, a single bipolar AV PL connected to an external VDD PM generator. At VDD implantation, P-wave amplitude was 1.9 ± 1.6 mV and R-wave was 11.3 ± 5.2 mV. The ventricular pacing threshold was 0.53 ± 0.1 V for a 0.5 ms pulse. Antibiotic therapy was instituted in all patients. A permanent VDD or DDD PM was implanted after 8 ± 2.5 days of temporary VDD pacing. At permanent PM implantation, the mean brain natriuretic peptide level had decreased and sepsis was controlled in all patients. No recurrence of sepsis was observed with a mean follow-up of 15.8 ± 5.3 months. Temporary VDD pacing is a safe and effective method to achieve prolonged AV physiological pacing in patients with AV block until infection has been controlled.


Porocarcinoma: a review.
From the first report in 1969 to the present day, diagnosis of eccrine porocarcinoma, also known simply as porocarcinoma (PC), remains a challenge. This review presents a concise update of the history, pathogenesis, epidemiology, diagnosis, management and prognosis of this rare sweat gland neoplasm. PC differentiates towards the intraepidermal spiral ducts in the eccrine gland, is more common in people aged > 60 years and often affects the head, neck and legs. PC presents as a dome-shaped papule, plaque or nodule growing over weeks to months. The exact incidence of PC is unknown but appears to be rising. Diagnosis is difficult because of variable presentations and similar clinical and histological features to cutaneous squamous cell carcinoma. Management involves removal of the tumour, usually using wide local excision or Mohs micrographic surgery. Prognosis is poor, with PC recurring after surgery in 35% of cases. Given the lack of standardized protocols and risk profiles, further studies would help improve the understanding of PC.


A comprehensive DFT investigation of bulk and low-index surfaces of ZrO2 polymorphs.
The bulk structure, the relative stability, and the electronic properties of monoclinic, tetragonal, and cubic ZrO(2) have been studied from a theoretical point of view, through periodic ab initio calculations using different Gaussian basis sets together with Hartree-Fock (HF), pure Density Functional Theory (DFT), and mixed HF/DFT schemes as found in hybrid functionals. The role of a posteriori empirical correction for dispersion, according to the Grimme D2 scheme, has also been investigated. The obtained results show that, among the tested functionals, PBE0 not only provides the best structural description of the three polymorphs, but it also represents the best compromise to accurately describe both the geometric and electronic features of the oxide. The relative stability of the three phases can also be qualitatively reproduced, as long as thermal contributions to the energy are taken into account. Four low-index ZrO(2) surfaces [monoclinic (-111), tetragonal (101 and 111), and cubic (111)] have then been studied at this latter level of theory. Surface energies, atomic relaxations, and electronic properties of these surfaces have been computed. The most stable surface is the cubic one, which is associated to small relaxations confined to the outermost layers. It is followed by the monoclinic (-111) and the tetragonal (101), which have very similar surface energies and atomic displacements. The tetragonal (111) was instead found to be, by far, the less stable with large displacements not only for the outermost but also for deeper layers. Through the comparison of different methods and basis sets, this study allowed us to find a reliable and accurate computational protocol for the investigation of zirconia, both in its bulk and surfaces forms, in view of more complex technological applications, such as ZrO(2) doped with aliovalent oxides as found in solid oxide fuel cells.


Essential role for vav Guanine nucleotide exchange factors in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity.
Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB, regulate a wide range of cellular processes, including dendritic spine formation and functional synapse plasticity. However, the signaling mechanisms that link BDNF-activated TrkB to F-actin remodeling enzymes and dendritic spine morphological plasticity remain poorly understood. We report here that BDNF/TrkB signaling in neurons activates the Vav family of Rac/RhoA guanine nucleotide exchange factors through a novel TrkB-dependent mechanism. We find that Vav is required for BDNF-stimulated Rac-GTP production in cortical and hippocampal neurons. Vav is partially enriched at excitatory synapses in the postnatal hippocampus but does not appear to be required for normal dendritic spine density. Rather, we observe significant reductions in both BDNF-induced, rapid, dendritic spine head growth and in CA3-CA1 theta burst-stimulated long-term potentiation in Vav-deficient mouse hippocampal slices, suggesting that Vav-dependent regulation of dendritic spine morphological plasticity facilitates normal functional synapse plasticity.


A recursive molecular docking coupled with energy-based pose-rescoring and MD simulations to identify hsGC βH-NOX allosteric modulators for cardiovascular dysfunctions.
Modulating the activity of human soluble guanylate cyclase (hsGC) through allosteric regulation of the βH-NOX domain has been considered as an immediate treatment for cardiovascular disorder (CVDs). Currently available βH-NOX domain-specific agonists including cinaciguat are unable to deal with the conundrum raised due to oxidative stress in the case of CVDs and their associated comorbidities. Therefore, the idea of investigating novel compounds for allosteric regulation of hsGC activation has been rekindled to circumvent CVDs. Current study aims to identify novel βH-NOX domain-specific compounds that can selectively turn on sGC functions by modulating the conformational dynamics of the target protein. Through a comprehensive computational drug-discovery approach, we first executed a target-based performance assessment of multiple docking (PLANTS, QVina, LeDock, Vinardo, Smina) scoring functions based on multiple performance metrices. QVina showed the highest capability of selecting true-positive ligands over false positives thus, used to screen 4.8 million ZINC15 compounds against βH-NOX domain. The docked ligands were further probed in terms of contact footprint and pose reassessment through clustering analysis and PLANTS docking, respectively. Subsequently, energy-based AMBER rescoring of top 100 low-energy complexes, per-residue energy decomposition analysis, and ADME-Tox analysis yielded the top three compounds i.e. ZINC000098973660, ZINC001354120371, and ZINC000096022607. The impact of three selected ligands on the internal structural dynamics of the βH-NOX domain was also investigated through molecular dynamics simulations. The study revealed potential electrostatic interactions for better conformational dialogue between βH-NOX domain and allosteric ligands that are critical for the activation of hsGC as compared to the reference compound.


Hormone replacement therapy and coronary artery disease.
The association of estrogen therapy with reduced levels of coronary artery disease in postmenopausal women has resulted in a burst of investigations into the mechanism(s) by which protection is offered. Findings published in the past year suggest that estrogen replacement alters every stage of the disease, from atherogenesis and plaque formation, to vascular responsiveness in already diseased arteries. The lipid metabolic alterations caused by estrogen replacement therapy have been confirmed and appear unaffected by the concurrent use of progestins. Consensus reports have recommended that high cardiovascular disease risk be added to the indications for the use of postmenopausal hormone replacement.


Silibinin loaded inhalable solid lipid nanoparticles for lung targeting.
In the current study, efforts are being made to prepare Inhalable Silibinin loaded solid lipid nanoparticles (SLNs) with narrow size distribution with improved bioavailability. SLNs were formulated by high shear homogenisation method SLNs were characterised, including Differential Scanning Calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR), particle size analysis, entrapment efficiency with Aerodynamic behaviour. The MTT assay was performed against A549 cell line, to measure their anticancer cell activity with In vivo study. Optimized formulation exhibited spherical surface with a mean particle size of 221 ± 1.251 nm, PI of 0.121 ± 0.081, zeta potential of -4.12 ± 0.744. Aerodynamic behaviour such as Mass median aerodynamic diameter (MMAD) and Geometric size distribution (GSD) were found to be 5.487 ± 0.072 and 2.321 ± 0.141 respectively proved formulation is suitable for inhalation. In vitro cellular efficacy against A549 cells, revealed that the optimised formulations were more effective and potent. The Inhalable SLNs approach was successfully engineered and administered to the lungs safely without causing any problems.


The role of BRCA1 gene mutations and apoptosis phenomenon in sporadic breast cancer.
BRCA1 tumor suppressor gene encodes an 1863-amino acid gene product that is implicated in many cellular pathways including transcription, cell-cycle checkpoint control, apoptosis and DNA repair. A role of apoptosis and BRCA1 germ-line mutation in breast cancer appearance was investigated in this study by both apoptosis frequency analysis and mutation screening of BRCA1 among breast cancer cases. Blood was obtained from 40 women with node-negative and node-positive ductal breast carcinomas with uniform tumor size. The blood samples from age matched healthy women (n=42) served as control. BRCA1 gene mutations were determined by PCR-RFLP methods. The apoptotic peripheral blood cells were detected by agarose gel electrophoresis. The apoptotic cells were identified in 30% (12/40) of the patients. There were no significant differences in apoptosis frequencies between patients and controls (P > 0.05). Three mutations of BRCA1 gene were identified in apoptosis positive samples from breast cancer women; one Ex20insC and two ExII17delA. Our study implies that apoptosis may be involved not only in sporadic breast carcinoma without BRCA1 mutations, but also in BRCA1-associated breast carcinoma.


Conditions for successful reflective use of portfolios in undergraduate medical education.
Portfolios are often used as an instrument with which to stimulate students to reflect on their experiences. Research has shown that working with portfolios does not automatically stimulate reflection. In this study we addressed the question: What are the conditions for successful reflective use of portfolios in undergraduate medical education? METHODOLOGY/RESEARCH DESIGN: We designed a portfolio that was aimed at stimulating reflection in early undergraduate medical education, using experiences described in the medical education literature and elsewhere. Conditions for reflective portfolio use were identified through interviews with 13 teachers (mentors), who were experienced in mentoring students in the process of developing their portfolios. The interviews were analysed according to the principles of grounded theory. The conditions for successful reflective use of portfolios that emerged from the interviews fell into 4 categories: coaching; portfolio structure and guidelines; relevant experiences and materials, and summative assessment. According to the mentors, working with a portfolio designed to meet these conditions will stimulate students' reflective abilities. This study shows that portfolios are a potentially valuable method of assessing and developing students' reflective skills in undergraduate medical training, provided certain conditions for effective portfolios are recognised and met. Portfolios have a strong potential for enhancing learning and assessment but they are very vulnerable and may easily lead to disappointment. Before implementing portfolios in education, one should first consider whether the necessary conditions can be fulfilled, including an appropriate portfolio structure, an appropriate assessment procedure, the provision of enough new experiences and materials, and sufficient teacher capacity for adequate coaching and assessment.


The coronary artery disease quality dashboard: a chronic care disease management tool in an electronic health record.
Quality reporting tools, integrated with ambulatory electronic health records (EHRs), may help clinicians understand performance, manage populations, and improve quality. The Coronary Artery Disease Quality Dash board (CAD QD) is a secure web report for performance measurement of a chronic care condition delivered through a central data warehouse and custom-built reporting tool. Pilot evaluation of the CAD Quality Dash board indicates that clinicians prefer a quality report that combines not only structured data from EHRs but one that facilitates actions to be taken on individual patients or on a population, i.e., for case management.


[Clinical examination of challenge test to local anesthetics].
Although adverse reactions to local anesthetics are often diagnosed as local anesthetic allergy, there is evidence that most of these reactions occur via non-allergic mechanisms. To evaluate allergic reactions to local anesthetics, challenge tests were performed in 20 patients who had a history of adverse events to local anesthetics for whom dental treatment was planned. The diagnostic protocol of this challenge test consisted of skin prick and intracutaneous tests, as well as subsequent incremental subcutaneous challenge tests with local anesthetics such as lidocaine. 17 patients (85%) showed no immediate allergic response to lidocaine, which could then be used for dental treatment. Three patients (15%) reacted positively to lidocaine: one had local erythema at the site of the skin prick, and two reacted to subcutaneous challenge. The proportion of immediate-type reactions to local anesthetics is small but not rare in patients suspected of having local anesthetic allergy. This result suggests that the diagnostic approach to confirm allergy to local anesthetics is clinically important and requires further study in a larger population.


Changes in energy-regulated molecules in the trophocytes and fat cells of young and old worker honeybees (Apis mellifera).
Trophocytes and fat cells of honeybees (Apis mellifera) have been used for cellular senescence studies, but the changes in the expression, concentration, and activity of cellular energy-regulated molecules that occur with aging in worker bees is unknown. In this study, energy-regulated molecules were evaluated in the trophocytes and fat cells of young and old workers. The results showed that (i) adenosine monophosphate-activated protein kinase-α2 (AMPK-α2) expression increased with aging, whereas phosphorylated AMPK-α2 expression, the phosphorylated AMPK/AMPK ratio, and AMPK activity decreased with aging; (ii) adenosine diphosphate and adenosine triphosphate concentrations decreased with aging, the AMP concentration was unchanged, the adenosine diphosphate/adenosine triphosphate ratio did not change with aging, and the AMP/adenosine triphosphate ratio increased with aging; (iii) the cyclic AMP concentration decreased with aging, and cyclic AMP-specific phosphodiesterases activity increased with aging; (iv) silent information regulator 2 (Sir2) expression increased with aging, whereas its activity decreased with aging; and (v) peroxisome proliferator-activated receptor-α expression decreased with aging. These results show that the trophocytes and fat cells of young workers have higher cellular energy status and express higher levels of energy-regulated molecules than those of old workers and that aging results in a decline in the energy status of trophocytes and fat cells in worker honeybees.


Cardioscopic tricuspid valve repair in a beating ovine heart.
Open heart surgery is commonly associated with cardiopulmonary bypass and cardioplegic arrest. The attendant risks of cardiopulmonary bypass may be prohibitive in high-risk patients. We present a novel endoscopic technique of performing tricuspid valve repair without cardiopulmonary bypass in a beating ovine heart. Six sheep underwent sternotomy and creation of a right heart shunt to eliminate right atrial and right ventricular blood for clear visualization. The superior vena cava, inferior vena cava, pulmonary artery, and coronary sinus were cannulated, and the blood flow from these vessels was shunted into the pulmonary artery via a roller pump. The posterior leaflet of the tricuspid valve was partially excised to create tricuspid regurgitation, which was confirmed by Doppler echocardiography. A 7.0-mm fiberoptic videoscope was inserted into the right atrium to visualize the tricuspid valve. Under cardioscopic vision, an endoscopic needle driver was inserted into the right atrium, and a concentric stitch was placed along the posterior annulus to bicuspidize the tricuspid valve. Doppler echocardiography confirmed reduction of tricuspid regurgitation. All animals successfully underwent and tolerated the surgical procedure. The right heart shunt generated a bloodless field, facilitating cardioscopic tricuspid valve visualization. The endoscopic stitch resulted in annular plication and functional tricuspid valve bicuspidization, significantly reducing the degree of tricuspid regurgitation. Cardioscopy enables less invasive, beating-heart tricuspid valve surgery in an ovine model. This technique may be useful in performing right heart surgery without cardiopulmonary bypass in high-risk patients.


Alterations to DNMT3A in Hematologic Malignancies.
In the last decade, large-scale genomic studies in patients with hematologic malignancies identified recurrent somatic alterations in epigenetic modifier genes. Among these, the de novo DNA methyltransferase DNMT3A has emerged as one of the most frequently mutated genes in adult myeloid as well as lymphoid malignancies and in clonal hematopoiesis. In this review, we discuss recent advances in our understanding of the biochemical and structural consequences of DNMT3A mutations on DNA methylation catalysis and binding interactions and summarize their effects on epigenetic patterns and gene expression changes implicated in the pathogenesis of hematologic malignancies. We then review the role played by mutant DNMT3A in clonal hematopoiesis, accompanied by its effect on immune cell function and inflammatory responses. Finally, we discuss how this knowledge informs therapeutic approaches for hematologic malignancies with mutant DNMT3A.


Additive Manufacturing of Micro-Electro-Mechanical Systems (MEMS).
Recently, additive manufacturing (AM) processes applied to the micrometer range are subjected to intense development motivated by the influence of the consolidated methods for the macroscale and by the attraction for digital design and freeform fabrication. The integration of AM with the other steps of conventional micro-electro-mechanical systems (MEMS) fabrication processes is still in progress and, furthermore, the development of dedicated design methods for this field is under development. The large variety of AM processes and materials is leading to an abundance of documentation about process attempts, setup details, and case studies. However, the fast and multi-technological development of AM methods for microstructures will require organized analysis of the specific and comparative advantages, constraints, and limitations of the processes. The goal of this paper is to provide an up-to-date overall view on the AM processes at the microscale and also to organize and disambiguate the related performances, capabilities, and resolutions.


Redox modulatory protective effects of ω-3 fatty acids rich fish oil against experimental colitis.
Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is an immune-modulated disorder characterized by chronic and recurring inflammatory episodes. Oxidative stress and COX pathway of prostaglandin (PG) biosynthesis are indispensable to pathogenesis of UC. Any imbalance between PGs can compromise the mucosal homeostasis, leading to mucosal damage and chronic inflammation. However, blocking these PGs using classical Cox inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs) can instead aggravate signs of IBD. Therefore, realizing the need for safer and well tolerable alterative treatment approaches, currently, we evaluated the efficacy of n-3 fatty acids rich fish oil (FO) in the resolution of UC. Using a dextran sodium sulfate (DSS) model of experimental colitis, we have demonstrated that supplementation of FO containing 180 mg EPA and 120 mg DHA for 1 month relieved the signs (diarrhea, bloody stools, weight loss) of colitis-associated inflammation. To understand the biophysical changes associated with FO mediated inflammatory regulation, impedance measurement and Fourier transform infrared spectroscopy (FTIR) were done. These changes were also correlated with oxidative stress through markers such as GST, glutathione peroxidase (GPx), LPO, catalase, protein carbonyl content, GR, etc. in colonic mucosa. The modulation of COX mediated pathways in UC-associated inflammation was observed by protein expressions of various pro-inflammatory cytokines such as TNF-α and enzymes of PG synthesis such as COX-2, PGES, TXAS, and anti-inflammatory PGDS. Refuting the earlier reports that suggested the contradictory effects of FO, in the current study, we evidently demonstrated that the protective effects of FO are mediated through molecular mechanisms involving the redox-regulation of metabolism of key lipid metabolites.


Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease.
Ceramides, composed of a sphingosine and a fatty acid, are bioactive lipid molecules involved in many key cellular pathways (e.g., apoptosis, oxidative stress and inflammation). There is much evidence on the relationship between ceramide species and cardiometabolic disease, especially in relationship with the onset and development of diabetes and acute and chronic coronary artery disease. This review reports available evidence on ceramide structure and generation, and discusses their role in cardiometabolic disease, as well as current translational chances and difficulties for ceramide application in the cardiometabolic clinical settings.


Development and validation of a questionnaire measuring knowledge, attitudes, and practices (KAP) to healthy eating and activity patterns in school children (HEAPS).
Development of culturally appropriate and psychometrically sound instruments that measure knowledge and health behaviors of children will help to inform appropriate interventions. To develop and test the validity and reliability of a questionnaire measuring knowledge, attitudes, and practices to healthy eating and activity patterns in school children in India. Review of literature, focus-group discussions, and theoretical constructs of the Health Belief Model guided the development of an item pool. Face and content validity were assessed by children and a panel of experts and the item content validity, item difficulty, and discrimination indices were calculated. Construct validity was determined using the principal axis method of exploratory factor analysis among a cross-sectional sample of children (n=252). Internal consistency (Cronbach α values >0.7) and test-retest reliability (intraclass correlation coefficient values >0.75) were estimated. Item content validity index for clarity and relevance were satisfactory (>0.80) and internal consistency for knowledge (Kuder-Richardson 20 = 0.832), attitude (Cronbach's α = 0.912), and practice items (Cronbach's α = 0.769) were good. Four factors (children's eating habits, family dietary practices, and consumption of healthy and unhealthy foods) and two factors (moderate to vigorous activities and sedentary activities) explained 67.7% and 48.2% of the total variance in practice items. Intraclass correlation coefficient estimates ranged from good to excellent (0.72-0.99). The results of the validity and reliability of the 84-item knowledge, attitudes, and practices to healthy eating and activity patterns in schoolchildren questionnaire were promising. The detailed description of the methodology employed may prove useful to researchers conducting similar studies in children.


Promoting practice-based policy.
When service providers participating in the Archstone Foundation's Elder Abuse and Neglect Initiative met to discuss common concerns, they highlighted the need for a sustained and proactive approach to improving California's response to elder abuse. The Advocacy Work Group formed to identify unmet needs and barriers, including the shortage of mental health services for vulnerable older adults, the need for alternatives to guardianship, and insufficient coordination with other constituencies. The Work Group is currently developing a blueprint for promoting dynamic partnerships among stakeholders, facilitating the exchange of information, and advancing informed public policy and service development.


Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children.
To establish a reference range in the paediatric population for the new glomerular filtration rate (GFR) marker, cystatin C, and to compare it with that of creatinine. Cystatin C and creatinine were measured by particle enhanced nephelometric immunoassay (PENIA) and fixed interval Jaff¿e methods, respectively, in 291 children aged 1 day to 17 years, including 30 premature infants with gestational ages ranging from 24 to 36 weeks. In the premature infants, concentrations of both cystatin C and creatinine were significantly raised compared with term infants, with cystatin C concentrations being between 1.10 and 2.06 mg/litre and creatinine between 32 and 135 micromol/litre. In premature infants, there was no significant relation between gestational age and cystatin C or creatinine concentration. Creatinine concentrations fell to a nadir at 4 months of age, rising gradually to adult values by about 15-17 years of age, in contrast to cystatin C, which fell to a mean concentration of 0.80 mg/litre by the 1st year of life, and remained constant throughout adulthood up to the age of 50 years. Neither analyte showed any influence of sex. The measurement of cystatin C, rather than creatinine, is more practical for monitoring GFR changes in the paediatric population.


Towards high performance computing for molecular structure prediction using IBM Cell Broadband Engine--an implementation perspective.
RNA structure prediction problem is a computationally complex task, especially with pseudo-knots. The problem is well-studied in existing literature and predominantly uses highly coupled Dynamic Programming (DP) solutions. The problem scale and complexity become embarrassingly humungous to handle as sequence size increases. This makes the case for parallelization. Parallelization can be achieved by way of networked platforms (clusters, grids, etc) as well as using modern day multi-core chips. In this paper, we exploit the parallelism capabilities of the IBM Cell Broadband Engine to parallelize an existing Dynamic Programming (DP) algorithm for RNA secondary structure prediction. We design three different implementation strategies that exploit the inherent data, code and/or hybrid parallelism, referred to as C-Par, D-Par and H-Par, and analyze their performances. Our approach attempts to introduce parallelism in critical sections of the algorithm. We ran our experiments on SONY Play Station 3 (PS3), which is based on the IBM Cell chip. Our results suggest that introducing parallelism in DP algorithm allows it to easily handle longer sequences which otherwise would consume a large amount of time in single core computers. The results further demonstrate the speed-up gain achieved in exploiting the inherent parallelism in the problem and also elicits the advantages of using multi-core platforms towards designing more sophisticated methodologies for handling a fairly long sequence of RNA. The speed-up performance reported here is promising, especially when sequence length is long. To the best of our literature survey, the work reported in this paper is probably the first-of-its-kind to utilize the IBM Cell Broadband Engine (a heterogeneous multi-core chip) to implement a DP. The results also encourage using multi-core platforms towards designing more sophisticated methodologies for handling a fairly long sequence of RNA to predict its secondary structure.


Treatment options in pediatric femoral shaft fractures.
Fracture of the femur in a pediatric patient presents special problems, and a variety of treatment options. Child abuse and neglect should be considered and evaluated. Fractures in infants (0-18 months) may be treated successfully in a Pavlik Harness. Spica casting is safe and effective in children up to about 6 years or 100 pounds, although complications can occur and careful attention to technique is important. Surgical treatment is superior in most older or larger children or adolescents, and in cases of multiple trauma, soft tissue injury, obesity or head injury. External fixation is minimally invasive, but carries a risk of malunion and refracture. Rigid antegrade intramedully nailing is possible in adolescents of acceptable size, but has a risk of avascular necrosis. Flexible nailing is minimally invasive and well suited to fractures of the central 2/3 of the diaphysis. In comminuted fractures, it may require supplemental external support. Plate fixation is stable and addresses the entire length of the femur. Soft tissue concerns due to surgical exposure can be minimized by the use of submuscular placement technique.


Heterogeneous bond percolation on multitype networks with an application to epidemic dynamics.
Considerable attention has been paid, in recent years, to the use of networks in modeling complex real-world systems. Among the many dynamical processes involving networks, propagation processes-in which the final state can be obtained by studying the underlying network percolation properties-have raised formidable interest. In this paper, we present a bond percolation model of multitype networks with an arbitrary joint degree distribution that allows heterogeneity in the edge occupation probability. As previously demonstrated, the multitype approach allows many nontrivial mixing patterns such as assortativity and clustering between nodes. We derive a number of useful statistical properties of multitype networks as well as a general phase transition criterion. We also demonstrate that a number of previous models based on probability generating functions are special cases of the proposed formalism. We further show that the multitype approach, by naturally allowing heterogeneity in the bond occupation probability, overcomes some of the correlation issues encountered by previous models. We illustrate this point in the context of contact network epidemiology.


Decomposition of Microbial Necromass Is Divergent at the Individual Taxonomic Level in Soil.
The turnover of microbial biomass plays an important part in providing a significant source of carbon (C) to soil organic C. However, whether the decomposition of microbial necromass (non-living microbial biomass) in the soil varies at the individual taxa level remains largely unknown. To fill up these gaps, we compared the necromass decomposition of bacterial and archaeal taxa by separating live microbial biomass with 18O-stable isotope probing from dead microbial biomass in soil. Our results showed that most of the microbial necromass at the operational taxonomic unit level (88.51%), which mainly belong to Acidobacteria, Actinobacteria, Gemmatimonadetes, and Proteobacteria, decomposed significantly after 30 days. In addition, there were great variations in necromass decomposition within each phylum, such as the decomposition of operational taxonomic units in Proteobacteria that ranged from 51% (Beijerinckia) to 92% (Nitrosospira). More importantly, the necromass decomposition was not related to the chemical composition of the cell wall but might positively correlate with the guanine-cytosine content of DNA and negatively correlated with genome size. This study provided a new insight that the decomposition of microbial necromass in soil was divergent at the individual taxonomic level and could not be fully explained by previously proposed mechanisms.


Long non-coding RNA OR3A4 promotes metastasis of ovarian cancer via inhibiting KLF6.
Recently, long noncoding RNAs (lncRNAs) have attracted much attention for their roles in tumor progression. The aim of this study was to investigate the exact role of lncRNA OR3A4 in the development of ovarian cancer (OC), and to explore the possible underlying mechanism. OR3A4 expression in OC tissue samples was detected by Real-time quantitative polymerase chain reaction (qRT-PCR). Moreover, wound healing assay and transwell assay were performed to evaluate the effect of OR3A4 on the metastasis of OC. Furthermore, the underlying mechanism was explored by RT-qPCR and Western blot assay. The expression level of OR3A4 in OC samples was significantly higher than that of adjacent tissues. Moreover, cell migration and invasion were significantly repressed after OR3A4 knockdown in vitro. Moreover, the mRNA and protein expressions of kruppel-like factor 6 (KLF6) were remarkably upregulated after knockdown of OR3A4. Furthermore, the expression level of KLF6 was negatively correlated with the expression of OR3A4 in OC tissues. Our results showed that OR3A4 could enhance OC cell metastasis and invasion via suppressing KLF6. Moreover, OR3A4 might be a potential therapeutic target for OC.


Intra- and post-operative blood loss and haemodynamics in total hip replacement when performed under lumbar epidural versus general anaesthesia.
The effects of lumbar epidural anaesthesia and two types of general anaesthesia on blood loss and haemodynamics during and after hip replacement were compared in three groups of patients. One group (n = 14) received continuous lumbar epidural anaesthesia, another group (n = 10) was given inhalational anaesthesia and spontaneous breathing after endotracheal intubation, and the third group (n = 14) received artificial ventilation after intubation and pancuronium and fentanyl intermittently i.v. Intra-operative blood loss in patients under epidural anaesthesia was 950 +/- 300 ml (mean +/- SD) and blood loss during the following 24 h-i.e. as long as the epidural anaesthesia was maintained-was 370 +/- 80 ml. These figures were significantly lower than the intra- and post-operative blood losses in patients under general anaesthesia with narcotics as post-operative pain treatment: 1140 +/- 200 ml (inhalational anaesthesia) followed by 480 +/- 70 ml and 1540 +/- 340 ml (artificial ventilation) followed by 500 +/- 110 ml. The intra-operative blood loss in the general anaesthesia group with spontaneous breathing was significantly smaller than the blood loss in the artificially ventilated group, whereas the post-operative blood loss in the two general anaesthetic groups was similar. Haemodynamic differences explain these differences in blood loss. Thus epidural anaesthesia induced hypotension on the arterial and venous sides. Intra-operatively, inhalational anaesthesia also induced hypotension on the arterial and venous sides compared with general anaesthesia using artificial ventilation. Post-operatively, the general anaesthesia groups behaved haemodynamically similarly and no differences in blood loss were seen. The reduction in blood loss, notably associated with lumbar epidural anaesthesia, is beneficial in decreasing the hazard and cost of blood transfusion.


Self-Assembly of Double Hydrophilic Poly(2-ethyl-2-oxazoline)-b-poly(N-vinylpyrrolidone) Block Copolymers in Aqueous Solution.
The self-assembly of a novel combination of hydrophilic blocks in water is presented, namely poly(2-ethyl-2-oxazoline)-b-poly(N-vinylpyrrolidone) (PEtOx-b-PVP). The completely water-soluble double hydrophilic block copolymer (DHBC) is formed via copper-catalyzed polymer conjugation, whereas the molecular weight of the PVP is varied in order to study the effect of block ratio on the self-assembly process. Studies via dynamic light scattering, static light scattering as well as microscopy techniques, e.g., cryo scanning electron microscopy or laser scanning confocal microscopy, show the formation of spherical particles in an aqueous solution with sizes between 300 and 400 nm. Particles of the DHBCs are formed without the influence of external stimuli. Moreover, the efficiency of self-assembly formation relies significantly on the molar ratio of the utilized blocks. The nature of the formed structures relies further on the concentration, and indications of particular and vesicular structures are found.


Psychosocial aspects of the functional gastrointestinal disorders.
This report reviews recent research on the psychosocial aspects of the functional gastrointestinal disorders (FGIDs). A review and evaluation of existing literature was conducted by a multidisciplinary committee of experts in this field. This report is a synopsis of a chapter published in the Rome III book. The committee reached consensus in finding considerable evidence supporting the association between psychological distress, childhood trauma and recent environmental stress, and several of the FGIDs but noted that this association is not specific to FGIDs. There is also considerable evidence that psychosocial variables are important determinants of the outcomes of global well-being, health-related quality of life, and health care seeking. In line with these descriptive findings, there is now increasing evidence that a number of psychological treatments and antidepressants are helpful in reducing symptoms and other consequences of the FGIDs in children and adults. The FGIDs are a result of complex interactions between biological, psychological, and social factors, and they can only be treated satisfactorily when all these factors are considered and addressed. Therefore, knowledge about the psychosocial aspects of FGIDs is fundamental and critical to the understanding, assessment, and treatment of these disorders. More extensive physician training is needed if these aspects of treatment are to be used effectively and widely in clinical practice.


Physically Compatible Machine Learning Study on the Pt-Ni Nanoclusters.
Pt-Ni alloy nanoclusters are essential for high-performance catalysis, and the full description for the finite temperature properties is highly desired. Here we developed an efficient machine learning method to evaluate the accurate structure-stability correspondence in a Pt(85-x)-Nix nanocluster over the structural space with a dimension of 3.84 × 1025. On the basis of the physical model and big-data analysis, for the first time, we demonstrated that the segregation-extent bond order parameter (BOP) and the shell-resolved undercoordination ratio play the key roles in the structural stability. This a priori knowledge extremely reduced the computational costs and enhanced the accuracies. With the 500-sample train data set generated by density functional theory (DFT)-level geometry optimizations, we fit the machine-learning excess energy potential and verified the mean-square-error is <0.13. Our physically niche genetic-machine learning program (PNG-ML) searched 2.5 × 105 structures and predicted precisely the most stable Pt43-Ni42 (x = 42). The structural space dimension was reduced by 1020 fold using our PNG-ML method. The Pt/Ni ratio of the most stable nanocluster is 1.02, which is highly consistent with the experimental observation of 1.0. The above results provide reliable theoretical references for the realistic applications of Pt-Ni nanoclusters and suggest feature engineering for future studies on binary alloys nanostructures.


Inelastic helium atom scattering from Sb2Te3(111): phonon dispersion, focusing effects and surfing.
We present an experimental study of inelastic scattering processes on the (111) surface of the topological insulator Sb2Te3 using helium atom scattering. In contrast to other binary topological insulators such as Bi2Se3 and Bi2Te3, Sb2Te3 is much less studied and the as-grown Sb2Te3 sample turns out to be p-doped, with the Fermi-level located below the Dirac-point as confirmed by angle-resolved photoemission spectroscopy. We report the surface phonon dispersion along both high symmetry directions in the energy region below 11 meV, where the Rayleigh mode exhibits the strongest intensity. The experimental data is compared with a study based on density functional perturbation theory calculations, providing good agreement except for a set of additional peculiar inelastic events below the Rayleigh mode. In addition, an analysis of angular scans with respect to a number of additional inelastic events is presented, including resonance enhancement, kinematical focusing, focused inelastic resonance and surfing. In the latter case, phonon-assisted adsorption of the incident helium atom gives rise to a bound state where the helium atom rides the created Rayleigh wave.


Purification and Properties of UDP-GlcNAc:Dolichyl-Pyrophosphoryl-GlcNAc GlcNAc Transferase from Mung Bean Seedling.
The N-acetylglucosamine (GlcNAc) transferase that catalyzes the formation of dolichyl-pyrophosphoryl-GlcNAc-GlcNAc from UDP-GlcNAc and dolichyl-pyrophosphoryl-GlcNAc was solubilized from the microsomal enzyme fraction of mung beans with 1.5% Triton X-100, and was purified 140-fold on columns of DE-52 and hydroxylapatite. The partially purified enzyme preparation was quite stable when stored in 20% glycerol and 0.5 millimolar dithiothreitol, and was free of GlcNAc-1-P transferase and mannosyl transferases. The GlcNAc transferase had a sharp pH optimum of 7.4 to 7.6 and the K(m) for dolichyl-pyrophosphoryl-GlcNAc was 2.2 micromolar and that for UDP-GlcNAc, 0.25 micromolar. The enzyme showed a strong requirement for the detergent Triton X-100 and was stimulated somewhat by the divalent cation Mg(2+). Uridine nucleotides, especially UDP and UDP-glucose inhibited the enzyme as did the antibiotic, diumycin. However, a variety of other antibiotics including tunicamycin were without effect. The product of the reaction was characterized as dolichyl-pyrophosphoryl-GlcNAc-GlcNAc.


Quantum chemistry investigation of secondary reaction kinetics in acrylate-based copolymers.
Recently, a growing amount of attention has been focused on the influence of secondary reactions on the free radical polymerization features and the properties and microstructure of the final polymer, particularly in the context of acrylate copolymers. One of the most challenging aspects of this research is the accurate determination of the corresponding reaction kinetics. In this paper, this problem is addressed using quantum chemistry. The reaction rate coefficients of various backbiting, propagation, and β-scission steps are estimated considering different chain configurations of a terpolymer system composed of methyl acrylate, styrene, and methyl methacrylate. The replacement of methyl acrylate radical units with styrene and methyl methacrylate globally decreases the backbiting probability and shifts the equilibrium toward the reactants, while the effect of replacing adjacent units is weaker and more dependent upon the specific substituting monomer. Propagation kinetics is affected primarily by the replacement of the radical units, while this effect appears to be particularly effective on midchain radical reactivity. The overall results clarify the different physicochemical behavior of chain-end, midchain, and short-branch radicals as a function of copolymer composition, providing new insights into free radical polymerization kinetics.


Cost-Effectiveness of One-Time Hepatitis C Screening Strategies Among Adolescents and Young Adults in Primary Care Settings.
High hepatitis C virus (HCV) rates have been reported in young people who inject drugs (PWID). We evaluated the clinical benefit and cost-effectiveness of testing among youth seen in communities with a high overall number of reported HCV cases. We developed a decision analytic model to project quality-adjusted life years (QALYs), costs (2016 US$), and incremental cost-effectiveness ratios (ICERs) of 9 strategies for 1-time testing among 15- to 30-year-olds seen at urban community health centers. Strategies differed in 3 ways: targeted vs routine testing, rapid finger stick vs standard venipuncture, and ordered by physician vs by counselor/tester using standing orders. We performed deterministic and probabilistic sensitivity analyses (PSA) to evaluate uncertainty. Compared to targeted risk-based testing (current standard of care), routine testing increased the lifetime medical cost by $80 and discounted QALYs by 0.0013 per person. Across all strategies, rapid testing provided higher QALYs at a lower cost per QALY gained and was always preferred. Counselor-initiated routine rapid testing was associated with an ICER of $71000/QALY gained. Results were sensitive to offer and result receipt rates. Counselor-initiated routine rapid testing was cost-effective (ICER <$100000/QALY) unless the prevalence of PWID was <0.59%, HCV prevalence among PWID was <16%, reinfection rate was >26 cases per 100 person-years, or reflex confirmatory testing followed all reactive venipuncture diagnostics. In PSA, routine rapid testing was the optimal strategy in 90% of simulations. Routine rapid HCV testing among 15- to 30-year-olds may be cost-effective when the prevalence of PWID is >0.59%.


Development and Validation of a Predictive Model for Coronary Artery Disease Using Machine Learning.
Early identification of coronary artery disease (CAD) can prevent the progress of CAD and effectually lower the mortality rate, so we intended to construct and validate a machine learning model to predict the risk of CAD based on conventional risk factors and lab test data. There were 3,112 CAD patients and 3,182 controls enrolled from three centers in China. We compared the baseline and clinical characteristics between two groups. Then, Random Forest algorithm was used to construct a model to predict CAD and the model was assessed by receiver operating characteristic (ROC) curve. In the development cohort, the Random Forest model showed a good AUC 0.948 (95%CI: 0.941-0.954) to identify CAD patients from controls, with a sensitivity of 90%, a specificity of 85.4%, a positive predictive value of 0.863 and a negative predictive value of 0.894. Validation of the model also yielded a favorable discriminatory ability with the AUC, sensitivity, specificity, positive predictive value, and negative predictive value of 0.944 (95%CI: 0.934-0.955), 89.5%, 85.8%, 0.868, and 0.886 in the validation cohort 1, respectively, and 0.940 (95%CI: 0.922-0.960), 79.5%, 94.3%, 0.932, and 0.823 in the validation cohort 2, respectively. An easy-to-use tool that combined 15 indexes to assess the CAD risk was constructed and validated using Random Forest algorithm, which showed favorable predictive capability (http://220.127.116.11:3000/randomforest). Our model is extremely valuable for clinical practice, which will be helpful for the management and primary prevention of CAD patients.


Need and duration of antibiotic therapy in clean and clean contaminated operations.
To define the need and duration of prophylactic antibiotic administration in clean and clean contaminated surgery in the prevailing operating theatre environment in Karachi. Surgical Department of Hamdard University Hospital and three other private hospitals in Karachi. One hundred consecutive patients undergoing elective clean and clean contaminated surgery were recruited from October 2000 to October 2001. Patients were admitted either a day prior to surgery or on the day of surgery, depending on the nature of procedure. Prophylaxis was provided by single dose of antibiotic at induction. The rest of the pre-operative preparation was done in standard way. Patients were discharged home as dictated by the nature of the operation and social circumstances. Wounds were examined for Surgical Site Infection (SSI) on day 4 and day 11. Patients who had post-operative pyrexia or signs of SSI were given extended antibiotic treatment for 5 days or until resolution of infection. Four out of 8 patients who developed SSI required extended antibiotic treatment. Single dose prophylactic antibiotic therapy is satisfactory in our surgical environment. This practice would be efficient, cost effective and prevent the emergence of nosocomial infections in a developing country such as Pakistan with extremely limited health care resources.


Roasting conditions for preserving cocoa flavan-3-ol monomers and oligomers: interesting behaviour of Criollo clones.
Cocoa bean roasting is important for creating the typical chocolate aroma through Maillard reactions, but it is also a key step deleterious to the polyphenol content and profile. Compared with usual roasting at 150 °C, keeping the beans for 30 min at 120 °C or for 1 h at 90 °C proved much better for preventing strong degradation of native P1, P2 and P3 flavan-3-ols in cocoa (shown for Forastero, Trinitatio and Criollo cultivars). Surprisingly, Cuban, Mexican and Malagasy white-seeded beans behaved atypically when roasted for 30 min at 150 °C, releasing a pool of catechin. Enantiomeric chromatographic separation proved that this pool contained mainly (-)-catechin issued from (-)-epicatechin by epimerisation. As the (-)-epicatechin content remained relatively constant through Criollo bean roasting, flavan-3-ol monomers must have been regenerated from oligomers. This emergence of (-)-catechin in Criollo beans only, reported here for the first time, could be due to increased flavan-3-ol monomer stability in the absence of anthocyanidin-derived products. The degradation rate of flavan-3-ols through roasting is higher in cocoa beans containing anthocyani(di)ns. The liberation of a pool of (-)-catechin when submitted to roasting at 150 °C allows to distinguish white-seeded cultivars. © 2017 Society of Chemical Industry.


Detachment of colloids from a solid surface by a moving air-water interface.
Colloid attachment to liquid-gas interfaces is an important process used in industrial applications to separate suspended colloids from the fluid phase. Moving gas bubbles can also be used to remove colloidal dust from surfaces. Similarly, moving liquid-gas interfaces lead to colloid mobilization in the natural subsurface environment, such as in soils and sediments. The objective of this study was to quantify the effect of moving air-water interfaces on the detachment of colloids deposited on an air-dried glass surface, as a function of colloidal properties and interface velocity. We selected four types of polystyrene colloids (positive and negative surface charge, hydrophilic and hydrophobic). The colloids were deposited on clean microscope glass slides using a flow-through deposition chamber. Air-water interfaces were passed over the colloid-deposited glass slides, and we varied the number of passages and the interface velocity. The amounts of colloids deposited on the glass slides were visualized using confocal laser scanning microscopy and quantified by image analysis. Our results showed that colloids attached under unfavorable conditions were removed in significantly greater amounts than those attached under favorable conditions. Hydrophobic colloids were detached more than hydrophilic colloids. The effect of the air-water interface on colloid removal was most pronounced for the first two passages of the air-water interface. Subsequent passages of air-water interfaces over the colloid-deposited glass slides did not cause significant additional colloid removal. Increasing interface velocity led to decreased colloid removal. The force balances, calculated from theory, supported the experimental findings, and highlight the dominance of detachment forces (surface tension forces) over the attachment forces (DLVO forces).


Simulation of Constrained Musculoskeletal Systems in Task Space.
This paper proposes an operational task space formalization of constrained musculoskeletal systems, motivated by its promising results in the field of robotics. The change of representation requires different algorithms for solving the inverse and forward dynamics simulation in the task space domain. We propose an extension to the direct marker control and an adaptation of the computed muscle control algorithms for solving the inverse kinematics and muscle redundancy problems, respectively. Experimental evaluation demonstrates that this framework is not only successful in dealing with the inverse dynamics problem, but also provides an intuitive way of studying and designing simulations, facilitating assessment prior to any experimental data collection. The incorporation of constraints in the derivation unveils an important extension of this framework toward addressing systems that use absolute coordinates and topologies that contain closed kinematic chains. Task space projection reveals a more intuitive encoding of the motion planning problem, allows for better correspondence between observed and estimated variables, provides the means to effectively study the role of kinematic redundancy, and most importantly, offers an abstract point of view and control, which can be advantageous toward further integration with high level models of the precommand level. Task-based approaches could be adopted in the design of simulation related to the study of constrained musculoskeletal systems.


Health Games: A Key Component for the Evolution of Wellness Programs.
Healthcare cost growth has been a major concern for both governments and employers. Considerable efforts have been made to "bend the trend" or find ways to control costs. At the highest levels, this has been the move from indemnity care models to managed care and then to consumer-directed health models using Healthcare Reimbursement Accounts and Healthcare Spending Accounts in plan designs. Accompanying this move in plan design has been an effort to get the consumer/patient/employee more engaged and responsible for his or her health expenditures, health decision-making, and activities. Consumers have gone through the phases of health being doctor-centric (indemnity care model), to health plan-centric (managed care models), to consumer-centric (consumer-directed health models). There is currently a need to incorporate wellness into the equation. Simply put, wellness is intended to keep people out of the health system by reducing the risk factors that would put them into the system in the first place. This includes things like smoking cessation, exercise, weight management, nutrition, and other factors over which individuals have a significant level of control over, as well as condition management such as medication adherence, and condition monitoring (such as glucose monitoring for diabetics). Wellness will become increasingly more common for major buyers, initially large self-funded employers and then health plans that will offer it as a part of their overall Plan Design and Administration services. Wellness initiatives will also be offered by Federal and State governments and will include programs for the elderly and at-risk populations as well as for the general population. The measure of success of wellness programs to actually "bend the trend" will be engagement. How large a piece of the population can be captured and retained will be the critical metric for success…and metrics require real data and will be used by the entire healthcare value-chain to measure efficacy and efficiency of "wellness spending."


The evolution of dental education as a profession, 1936-2011, and the role of the journal of dental education.
This article describes selected changes in dental education from 1936 to 2011 and describes how the Journal of Dental Education (JDE) has assisted in both reporting and, at times, championing change. The review provides a series of selective contextual milestones as a backdrop and running commentary for the changing profession of dental education. An assessment of the current state of knowledge in this field is articulated, as are some of the drivers of change. The article poses a series of questions in seven categories that define the extraordinary opportunities ahead. A vision of the future of the JDE and dental education is described including the use of the journal as a futurist forum to educate, cajole, and advocate for continuous movement toward realizing an enlightened destiny.


Value of a single Widal test in the diagnosis of typhoid fever.
Results of a single Widal test in patients with bacteriologically confirmed typhoid fever (116), clinically suggestive but culture negative fever (170) and non-typhoidal febrile illness (98) and in normal control children (54) were analysed. Positive Widal test (antibody titre against S. typhi O antigen of 1:160) was recorded in 61.2 per cent of patients with bacteriologically confirmed typhoid fever and in 58.8 per cent with culture negative but clinically suggestive typhoid fever. In contrast, the same titre was observed in 10.2 per cent patients with other febrile illnesses of known etiology and in 1.8 per cent of normal children. Differences in the positivity of Widal test in patients with bacteriologically confirmed typhoid fever and clinically suggestive but culture negative fever were highly significant (P < 0.000001) when compared to that of patients with non-typhoidal febrile illnesses and normal controls. High specificity and positive predictive value in 1:160 dilution makes the Widal test acceptable as a diagnostic tool.


Facilitation of bottom-up feature detection following rTMS-interference of the right parietal cortex.
In visual search tasks the optimal strategy should utilize relevant information ignoring irrelevant one. When the information at the feature and object levels are in conflict, un-necessary processing at higher level of object shape can interfere with detection of lower level orientation feature. We explored the effects of inhibitory trains of transcranial magnetic stimulation (rTMS) on the right and left parietal cortex in healthy subjects performing two visual search tasks. One task (Task A) was characterised by an object-to-feature interference. The other task (Task B) was without such interference. We found that rTMS of the right parietal cortex significantly reduced reaction times (RTs) in Task A, where object recognition interferes with detection of orientation. This significant RT reduction was present only for the first 10 trials. Interestingly, right parietal rTMS had no effect on Task B. Moreover, rTMS of the left parietal cortex did not modify subjects' RTs in either task. Subjects' accuracy was equally affected by rTMS in both tasks over time. We suggest that inhibition of the right parietal cortex by means of rTMS facilitates feature-based visual search by inhibiting the interfering feature binding and spatial attentional processes. This allows subjects to accomplish Task A faster.


Recent EULEP dosimetry intercomparisons for whole body irradiation of mice. European Late Effects Project group.
To foster quality assurance of dosimetry among the institutes involved in joint studies on late effects of ionizing radiation. The participants in the dosimetry intercomparison received for each facility two mouse phantoms loaded with LiF thermoluminescent dosemeters (TLD) and a control badge. The participants were requested to irradiate the test phantoms in the actual arrangement used for whole body irradiation of mice, such that the dose in the centre of the test phantoms was 2 Gy and the dose distribution was uniform. The readout of the TLD and the dose evaluation were made at the organizing institute. Ten institutes operating 14 exposure facilities in four countries took part in the intercomparison. For one facility a dose deviation between 5 and 10% was found, whereas for two others the deviation exceeded 10%. The requirement for uniform dose distribution in a mouse phantom was not fulfilled by six exposure facilities. The causes for the dose discrepancies were found for two participants whereas for one participant the problems were only partly resolved. Non-uniform dose distributions are mainly related to unilateral irradiations. The seven EULEP dosimetry intercomparisons clearly show the need for quality assurance of dosimetry in radiobiology.


Preliminary results of a prospective trial using three dimensional radiotherapy for lung cancer.
To evaluate the preliminary results of a prospective trial using three-dimensional (3D) treatment for lung cancer. Seventy patients with inoperable Stage I through IIIB lung cancer were treated with three-dimensional thoracic irradiation with or without chemotherapy (35% received chemotherapy). Total prescribed dose to the tumor ranged from 60-74 Gy (uncorrected for lung density). All patients were evaluated for local control, survival, and development of pneumonitis. These parameters were evaluated in respect to and compared with three-dimensional parameters used in their treatment planning. With a minimum follow-up of 6 to 30 months, the 2-year cause-specific survival rate for Stages I and II was 90% and 53% for Stage III (no difference between Stages IIIA and IIIB). Patients with local tumor control had a better 2-year overall survival rate (47%) than those with local failure (31%). Volumetrically heterogeneously calculated doses were important to the accurate delineation of dose-volume coverage as there was a wide range of discrepancies between a homogeneously prescribed point dose calculation and the heterogeneously calculated volume coverage of that prescription. High-grade pneumonitis was correlated with the location of the tumor with lower lobe tumors having a much higher risk than those with upper lobe tumors. A critical volume effect and threshold dose were apparent in the development of high-grade pneumonitis. Three-dimensional therapy for lung cancer has been practically implemented at the Mallinckrodt Institute of Radiology and shows promising results in our preliminary analysis. The incidence of high-grade pneumonitis, however, warrants careful selection of patients for future dose escalation. Future dose escalation trials in lung cancer should be directed to volumes that limit the amount of elective nodal irradiation. However, the volume of necessary elective nodal irradiation remains unknown and should be studied prospectively. Dose escalation trials are indicated and may be facilitated by smaller target volumes.


Lysis and biological control of Aspergillus niger by Bacillus subtilis AF 1.
A biocontrol rhizobacterial strain of Bacillus subtilis AF 1 grown for 6 h was coinoculated with Aspergillus niger at different time intervals and microscopic observations revealed adherence of bacterial cells to the fungal mycelium. Bacterial cells multiplied in situ and colonized the mycelial surface. Growth of AF 1 resulted in damage to the cell wall, followed by lysis. AF 1 inoculation into media containing A. niger at 0, 6, and 12 h suppressed > 90% fungal growth, while in 18- and 24-h cultures fungal growth inhibition was 70 and 56%, respectively, in terms of dry weight. In dual culture the fungal growth was not accompanied by formation of spores. The mycelial preparation of A. niger as principal carbon source supported the growth of B. subtilis, as much as chitin. Extracellular protein precipitate from B. subtilis culture filtrate had a significant growth-retarding effect on A. niger. Groundnut seeds bacterized with B. subtilis showed a reduced incidence of crown rot in a niger infested soil, suggesting a possible role of A. subtilis in biological control of A. niger.


Amelioration of drought tolerance in wheat by the interaction of plant growth-promoting rhizobacteria.
Drought stress adversely affects the growth and yield of wheat. The present study was planned to investigate the effect of inoculation of plant-growth promoting rhizobacteria (PGPR) strains IG 3 (Klebsiella sp.), IG 10 (Enterobacter ludwigii) and IG 15 (Flavobacterium sp.) in improving drought tolerance in wheat. These PGPR strains were screened for drought tolerance in nutrient broth supplemented with different concentrations (0-25%) of polyethylene glycol (PEG6000). Effect of PGPR inoculation on various physiological, biochemical parameters and gene expression of stress responsive genes were studied under drought stress. Root colonization at the surface and interiors of roots was demonstrated using scanning electron microscopy (SEM) and tetrazolium staining, respectively. Drought stress significantly affected various growth parameters, water status, membrane integrity, osmolyte accumulation and stress-responsive gene expressions, which were positively altered by PGPR-inoculation in wheat. Quantitative real-time (qRT)-PCR analysis revealed the up regulation of some stress-related genes (DREB2A and CAT1) in un-inoculated wheat plants exposed to drought stress. PGPR-inoculated plants showed attenuated transcript levels suggesting improved drought tolerance due to interaction of PGPRs. The PGPR strain IG 3 was found to be the best in terms of influencing biochemical and physiological status of the seedlings under drought stress. Our report demonstrates the role of PGPRs Enterobacter ludwigii and Flavobacterium sp. in plant growth promotion of wheat plants under drought stress. The study reports the potential of PGPR in alleviating drought stress in wheat which could be used as potent biofertilizers.


Photophysics of delocalized excitons in carbazole dendrimers.
The photophysical properties in solution of three generations of carbazole-based dendrons and dendrimers with fluorenyl surface groups were studied using steady-state, time-resolved femtosecond transient absorption and anisotropy, and coherent two-dimensional ultraviolet spectroscopy. It was found that increasing the generation caused a switch in the nature of the emissive state between the first-generation compounds and the second- and third-generation dendrimers. Time-resolved anisotropy measurements revealed low initial anisotropies that decreased with increasing dendrimer generation consistent with increasing intradendrimer interchromophore coupling. Two-dimensional UV spectroscopy showed that the signal from the second- and third-generation dendrimers is the product of multiple chromophores interacting. The maximum number of interacting chromophores is reached by the second generation.


[Monoclonal antibodies directed against the beta hCG subunit and against a synthetic peptide analog of the carboxyl-terminal end. Clinical use in vivo and in vitro].
In order to detect specifically the beta-hCG, we have produced monoclonal antibodies (Mabs), using as immunogens hCG, beta hCG or a totally synthetic molecule (109-145 peptide) analogous to the beta-subunit carboxyl terminus. 34 fusion experiments were performed and led to 8 Mabs which presented a high reactivity to 125I beta hCG in the screening test. Mab D1E8 was directed to the 1-115 region of beta hCG and was cross reactive with hLH (greater than 60%). Mabs 702, 1032, and 1211 were directed against three different epitopes located in the 109-145 region and were specific for the beta hCG. The in vivo localization of tumors containing beta hCG ty tomoscintigraphy (SPECT) was evaluated in 5 patients by injecting 131I-Mab D1E8, selected for imaging because of its high affinity to beta hCG (Ka = 1.9 X 10(9)). SPECT was performed 48 h and 96 h after injection: 2 patients with proven tumor sites had positive "immunoscintigraphy" results. One patient, simultaneously injected with 125I non-specific IgG, had a tumor resection: the count ratio between normal and tumoral tissues revealed a low specific uptake. Two and three-site immunoradiometric assays (IRMA) were performed with monoclonal antibodies purified from nude mice ascitic fluids. IRMA were based upon two or three Mabs, with D1E8 on a solid phase and 125I Mab 702 or a mixing of 125I-702 and 125I-1032 as tracer. The specificity of IRMA was demonstrated by the absence of binding with increasing amount of hLH, hFSH and hTSH up to 5000 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison and analysis on sheep meat quality and flavor under pasture-based fattening contrast to intensive pasture-based feeding system.
The objective of this study was to investigate the effect of 4-month intensive feeding on the meat quality, fatty acid profile, flavor, and growth performance of grazing Hulunbuir sheep (HBS). The HBS were selected 4-months after birth in a pasture rearing system as the experimental animals (n = 44, female, average body weight 23.8±2.2 kg) then divided equally into pasture-based grazing fattening (PAS) and concentrate-included intensive fattening (CON) groups for another 4-month finishing. When finished fattening, all animals were slaughtered to collect musculus longissimus dorsi subcutaneous adipose tissue and to investigate the influences on meat quality, fatty acid profile, flavor and growth performance. The results showed lambs in CON group got significantly higher live weight, hot carcass weight, and dressing percentage. The CON group had significantly higher value of redness (a*), lightness (L*) and water holding capacity (p<0.05), significantly lower value of Warner-Bratzler shear force than the PAS group (p<0.05). The subcutaneous fat from CON group lambs demonstrated a significantly higher content of C18:1 and C18:2 (p<0.05), but lower C14:0 and C16:0, indicating an increased degree of unsaturated fatty acid. The content of 4-methyloctanoic acid, 4-ethyloctanoic acid and 4-methylnonanoic acid had increased 2 to 4 times, representing a more intense odor in the CON group. However, the values were still lower than most sheep breeds reported, indicating the indoor feeding system could not fundamentally deteriorate the excellent meat characteristic of HBS. It was evident that lambs in CON group exhibited a better meat production performance, improved in meat color, texture and healthier fatty acid profile through pastureweaned concentrate included intensive fattening system, which offers a good alternative regimen for lamb finishing and has a wide prospection in the HBS meat industry.


[Effects of Chinese wild rice on lipid metabolism and lipotoxicity in rats fed with high fat/cholesterol diet].
To study the effects of four kinds of experimental diet, including high fat/cholesterol diet, Chinese wild rice diet, white rice-flour diet and basal diet on the lipotoxicity and disordered lipid metabolism in rats. 44 male SD rats were divided into four groups, the basal group, high fat/cholesterol diet group, white rice-flour group and Chinese wild rice group. All rats of four groups were given different diets. Body weights were measured every week, serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), free fatty acids (FFA) and leptin concentrations were measured, and liver pathology were observed. When compared with the basal diet group, the hyperlipidemic rat model was successfully made in high fat/cholesterol diet group. When compared with the high fat/cholesterol diet group and white rice-flour diet group, the serum TG and TC contents were significantly decreased (P < 0.05), and HDL-C concentration significantly increased (P < 0.05) in Chinese wild rice group. Moreover, Chinese wild rice group had lower contents of serum and liver FFA than those of the high fat/cholesterol diet group and white rice-flour diet group (P < 0.05). Although Chinese wild rice group had a lower serum leptin level than the high fat/cholesterol diet group and white rice-flour diet group, there was no significant differences among the three groups (P > 0.05). The conditions of liver cell fatty degeneration in Chinese wild rice group were slight. Compared to the white rice-flour diet, Chinese wild rice could improve the lipid metabolism and liver lipotoxicity of hyperlipidemic rats induced by high fat/cholesterol diet.


Asymmetry between excitatory and inhibitory learning.
Five experiments investigated how learning about the added feature in a feature-positive discrimination or feature-negative discrimination is related to the change in reinforcement rate that the feature signals. Rats were trained in a magazine-approach paradigm with 2 concurrent discriminations between A versus AX and B versus BY. In 2 experiments (1 and 3), X and Y signaled an increase of 0.3 in the probability of reinforcement, from 0.1 to 0.4 (A vs. AX), or from 0.6 to 0.9 (B vs. BY). After extended training, each session included probe test trials in which X and Y were presented alone (Experiment 1) or in compound with another excitatory conditional stimulus (CS), C (Experiment 3). There was no difference in response rate between the 2 types of test trial (X vs. Y; XC vs. YC), consistent with the fact that X and Y signaled the same absolute change in reinforcement. In Experiments 2 and 4, X and Y signaled a decrease of 0.3 in the probability of reinforcement, from 0.4 to 0.1 (A vs. AX) or from 0.9 to 0.6 (B vs. BY). Test trials in which X or Y was presented with C showed that X had greater inhibitory strength than Y, consistent with the fact that X signaled a larger relative change in reinforcement. This was confirmed in Experiment 5, in which X and Y had the same inhibitory strength on test after training in which they signaled the same relative change in reinforcement but different absolute changes (0.3 to 0.1 for A vs. AX; 0.9 to 0.3 for B vs. BY). The results show that excitatory conditioning is linearly related to the increase in reinforcement rate, whereas inhibitory learning is not linearly related to the decrease in reinforcement rate. Implications of this for theories of associative learning are discussed. (PsycINFO Database Record


Public health is every nurse's responsibility.
Nurses in all specialties and midwives can influence the public health of individuals, the wider community and the population as a whole. From theory to evidence, education to practice, and implementation to evaluation, there is a clear cycle by which nurses and midwives can have a demonstrable impact on the public's health. Public health is no longer the preserve of a few professionals and can and should be core to all nursing practice.