Immobilization and hybridization of DNA in a sugar polyacrylate hydrogel.
Using a non-contact microarrayer, amine-terminated probe oligonucleotides representing 20-, 50-, and 70-mer fragments of the fliC gene were covalently coupled into three-dimensional regions in a "sugar polyacrylate" hydrogel based on poly(6-acryloyl-beta-O-methyl galactopyranoside-co-aminopropyl methacrylamide). The arrayer deposited the solution containing ssDNA probes in discrete regions on the surface of the gel (i.e. as a droplet with a ca. 450 microm diameter), allowing penetration and attachment of the ss DNA within the three dimensional region of the gel. The attachment was mediated by the homobifunctional crosslinker bis-succinimidyl suberate. Confocal microscopy showed the density of attached probe DNA was greatest in the interior-most regions of the gel volume. Target ssDNA (20- and 70-mer) was able to diffuse through the gel and undergo successful hybridization with the probes. For target ssDNA in the concentration range 0.19 microM to 6.0 microM, there was a linear correlation between DNA concentration and the fluorescence of the gel region where hybridization occurred.


Plasma-Sprayed Bioactive Ceramic Coatings with High Resorption Resistance Based on Transition Metal-Substituted Calcium Hexaorthophosphates.
Calcium (titanium, zirconium) hexaorthophosphates with a [NZP] (sodium zirconium phosphate) structure belonging to the NaSiCon (Na Superionic Conductor) family were deposited by atmospheric plasma spraying onto the surfaces of Ti6Al4V substrates. (NaSiCon sensu strictu refers to solids with the chemical formula Na1+xZr2SixP3-xO12, 0 < x < 3. In a broader sense, it is also used for similar compounds where Na, Zr and/or Si are replaced by isovalent elements). The microstructure of the coatings revealed the incongruent melting of the precursor material as ascertained by electron probe microanalysis (EPMA). The adhesion of the coatings to the substrate surface was within the limits specified for biomedical coatings. The solubility of the coatings was tested by immersion in 0.2 molar tris-hydroxymethyl-amino-methane-HCl (TRIS-HCl) buffer and found to be at least one order of magnitude lower than that of conventional hydroxylapatite coatings deposited under comparable conditions. In vitro biocompatibility tests with primary rat bone marrow cells (BMCs) showed a substantial cell proliferation in the presence of fetal bovine serum. Animal tests confirmed that coatings based on calcium (titanium, zirconium) hexaorthophosphates applied to Ti6Al4V rods implanted in the femoral medulla of sheep led to the strong neoformation of dense bone at a stable interface implant-bioceramic coating without coating delamination. Hence, based on their multifarious advantageous properties in the biomedical context, CaTi4-xZrx(PO4)6 ceramics may be considered the 'Sleeping Beauty' of osseoconductive coatings for the stem of hip endoprostheses and dental root implants, osteosynthetic fixation devices, and bioelectric devices including bone growth stimulators.


The process of EDC-NHS Cross-linking of reconstituted collagen fibres increases collagen fibrillar order and alignment.
We describe the production of collagen fibre bundles through a multi-strand, semi-continuous extrusion process. Cross-linking using an EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), NHS (N-hydroxysuccinimide) combination was considered. Atomic Force Microscopy (AFM) and Raman spectroscopy focused on how cross-linking affected the collagen fibrillar structure. In the cross-linked fibres, a clear fibrillar structure comparable to native collagen was observed which was not observed in the non-cross-linked fibre. The amide III doublet in the Raman spectra provided additional evidence of alignment in the cross-linked fibres. Raman spectroscopy also indicated no residual polyethylene glycol (from the fibre forming buffer) or water in any of the fibres.


Vismodegib Therapy for Basal Cell Carcinoma in an 8-Year-Old Chinese Boy with Xeroderma Pigmentosum.
Vismodegib is an oral inhibitor of the Hedgehog signaling pathway and has been used to treat basal cell carcinoma (BCC) in adults. This article reports clearance of a nodular BCC of the nasal tip in an 8-year-old boy with xeroderma pigmentosum (XP). BCC can pose therapeutic challenges when located in areas that are not amenable to traditional therapies such as Mohs micrographic surgery or topical agents. Vismodegib was used at a dose of 150 mg/day to treat the boy's BCC. After 4 months of therapy, we achieved complete clinical clearance. During 21 months of follow-up, the patient's nose remained clinically clear of tumor. Vismodegib was successfully used to treat a child with XP and nodular BCC. Our goal in using vismodegib was tumor regression while avoiding cosmetic and functional disfigurement. Vismodegib was effective in clinically clearing the tumor, and the patient has shown no signs of recurrence. Further studies are warranted.


[Cardiovascular risk in patients with renal failure].
Patients with renal failure (RF) have an increased risk of cardiovascular events. The aims of the present study were: a) to evaluate if RF is an independent cardiovascular risk factor, and b) to analyze the predictive capacity of the original Framingham and REGICOR functions charts in patients with RF. A total of 912 patients between 35-74 years old (average: 55.7 years; 56.4% female) with no evidence of cardiovascular disease, were included in the present study. The RF was defined in patients with a glomerular filtration < 60 ml/min (estimated with the equation of Cockroft-Gaukt). 13.5% of the patients presented RF criteria. The final rate of cardiovascular events was higher in the population with RF (21.1% vs 12.0%; p < 0.01; relative risk = 1.76; 95% confidence interval [CI], 1.19-2.59). Statistically significant differences were not found between men and women. The multiple logistic regression analysis showed that cigarette smoking (odds ratio [OR] = 2.17; 95% CI, 1.38-3.35), diabetes (OR = 2.08; 95% CI, 1.37-3.15), RF (OR = 1.83; 95% CI, 1.10-3.06), antihypertensive treatment (OR = 2.03; IC del 95%, 1.32-3.11), and hypertension (OR = 2.06; 95% CI, 1.06-4.05) were important factors for the prediction of coronary and cardiovascular events. The original Framingham function predicted suitably the coronary risk in the population with RF (18.3% versus 17.9%; p = 0.869) whereas REGICOR underestimated it (7.5% versus 17.9%; p < 0.05). The area under the receiver operator characteristic (ROC) curve obtained with the original Framingham function was similar to that of REGICOR function: 0.61 (95% CI, 0.47-0.75) and 0.62 (95% CI, 0.48-0.76), respectively. The RF behaves like an important cardiovascular risk factor. The area under ROC curve obtained with the original Framingham function was similar to that of REGICOR function.


Early environmental factors differentially affect voluntary ethanol consumption in adolescent and adult male rats.
Previous studies using the maternal separation (MS) model have shown that environmental factors early in life affect adult ethanol consumption. Prolonged MS is related to enhanced propensity for high adult ethanol intake when compared to short MS. Less is known about the environmental impact on adolescent ethanol intake. In this study, the aim was to compare establishment of voluntary ethanol consumption in adolescent and adult rats subjected to different rearing conditions. Wistar rat pups were separated from their mother 0 minutes (MS0), 15 minutes (MS15), or 360 minutes (MS360) daily during postnatal days (PNDs) 1 to 20. After weaning, the male rats were divided into two groups; rats were given free access to water, 5 and 20% ethanol at either PND 26 or 68. Ethanol was provided in 24-hour sessions three times per week for 5 weeks. MS resulted in altered ethanol consumption patterns around the pubertal period but otherwise the rearing conditions had little impact on ethanol consumption in adolescents. In adults, the establishment of ethanol consumption was dependent on the rearing condition. The adult MS0 and MS15 rats had a stable ethanol intake, whereas the MS360 rats increased both their ethanol intake and preference over time. With the use of intermittent access to ethanol, new data were provided, which confirm the notion that MS360 represents a risk environment related to higher ethanol intake compared to MS15. The adolescent rats had higher ethanol intake than adult rats but the consumption was independent of rearing condition. Experiences during the first three postnatal weeks thus affect the establishment of voluntary ethanol consumption differently in adolescent and adult rats. Further studies are now warranted to examine the consequences of a combination of early environmental influence and high adolescent ethanol intake.


Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana.
Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Deregulated expression of imprinted genes such as ADMETOS (ADM) underpin the interploidy hybridization barrier in Arabidopsis thaliana; however, the mechanisms of their action remained unknown. In this study, we show that ADM interacts with the AT hook domain protein AHL10 and the SET domain-containing SU(VAR)3-9 homolog SUVH9 and ectopically recruits the heterochromatic mark H3K9me2 to AT-rich transposable elements (TEs), causing deregulated expression of neighboring genes. Several hybrid incompatibility genes identified in Drosophila encode for dosage-sensitive heterochromatin-interacting proteins, which has led to the suggestion that hybrid incompatibilities evolve as a consequence of interspecies divergence of selfish DNA elements and their regulation. Our data show that imbalance of dosage-sensitive chromatin regulators underpins the barrier to interploidy hybridization in Arabidopsis, suggesting that reproductive isolation as a consequence of epigenetic regulation of TEs is a conserved feature in animals and plants.


Crosstalk between the androgen receptor and beta-catenin in castrate-resistant prostate cancer.
The androgen-signaling pathway plays an important role in the development and hormonal progression of prostate cancer to the castrate-resistant stage (also called androgen-independent or hormone refractory). The Wnt pathway and beta-catenin contribute to prostate biology and pathology. Here application of Affymetrix GeneChip analysis revealed the genomic similarity of the LNCaP hollow fiber model to clinical samples and identified genes with differential expression during hormonal progression. The fiber model samples clustered according to the expression profile of androgen-regulated genes to provide genomic evidence for the reactivation of the AR signaling pathway in castrate-resistant prostate cancer. Pathway-based characterization of gene expression identified activation of the Wnt pathway. Together with the increased expression of AR and beta-catenin, there was increased nuclear colocalization and interaction of endogenous AR and beta-catenin in castrate-resistant prostate cancer from castrated mice. Surprisingly, no interaction or colocalization of AR and beta-catenin could be detected in xenografts from noncastrated mice. These studies provide the first in vivo evidence to support aberrant activation of the AR through the Wnt/beta-catenin signaling pathway during progression of prostate cancer to the terminal castrate-resistant stage.


Correlation between polymorphisms in the IL-17A and IL-17F genes and development of coronary artery disease.
A case-control study was conducted to investigate the association between genetic variants of IL-17A rs2275913 and IL-17F rs763780 and the development of coronary artery disease (CAD) in a Chinese population. A total of 306 individuals with CAD and 306 unaffected individuals were enrolled from the Zhengzhou People's Hospital between May 2012 and May 2014. The IL-17A rs2275913 and IL-17F rs763780 genes were genotyped by polymerase chain reaction combined with a restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis revealed that individuals with the AA genotype of rs2275913 were associated with increased risk of CAD, compared to those with the GG genotype in a codominant model [adjusted odds ratio (OR) = 1.96; 95% confidence interval (CI) = 1.10-3.53]. On the other hand, the AA genotype of rs2275913 was correlated with moderately increased risk of CAD compared to the GG + GA genotype (adjusted OR = 1.76; 95%CI = 1.02-3.07) in a recessive model. However, no significant differences were observed between polymorphisms at the IL-17F rs763780 locus and CAD risk, in codominant, dominant, and recessive models. In conclusion, the results of our study suggested that the IL-17A rs2275913 polymorphism may affect the development of CAD; however, no significant association was observed between the IL-17F rs763780 polymorphism and risk of CAD.


Polyethylene glycol-conjugated superoxide dismutase in focal cerebral ischemia-reperfusion.
Generation of free radicals during reperfusion after organ ischemia has been implicated in the pathogenesis of ischemic injury. We have previously shown that a combination of intravenous polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT), at a dose of 10,000 U/kg each, is effective in reducing infarct size in a focal cerebral ischemia model in the rat. It is not clear whether PEG-SOD alone is sufficient to reduce ischemic brain injury. In this study we determined the therapeutic efficacy of PEG-SOD and its dose-response curve. In a range of 1,000-30,000 U/kg, PEG-SOD exhibited a U-shaped dose-response curve. Only 10,000 U/kg significantly reduced infarct size [control 121 +/- 12 mm3 (mean +/- SE), n = 35; PEG-SOD 95 +/- 10 mm3, n = 36, P < 0.05]. PEG-SOD at the doses tested did not have significant acute hemodynamic effects but had a tendency to improve postischemic hypotension. This beneficial effect of PEG-SOD on blood pressure did not appear to fully account for the treatment effect of PEG-SOD on infarct size. The narrow therapeutic dose range of PEG-SOD in this study and similar findings of SOD in other investigations may contribute to the inconsistent protective effects of SOD preparations in ischemia-reperfusion injury in the literature.


Clinical Features of Clonal Cytogenetic Abnormalities in Philadelphia-negative Cells Developed During Tyrosine Kinase Inhibitor Treatment: A Case Series.
Most clonal cytogenetic abnormalities of Philadelphia-negative cells (CCA/Ph-) occurring during tyrosine kinase inhibitor (TKI) treatment are transient, and the development of secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is rare, but the frequency and clinical significance in Japanese patients are still unknown. We herein report four patients who developed CCA/Ph- during TKI therapy and were diagnosed with secondary MDS/AML. The duration from TKI therapy initiation to MDS/AML onset ranged from 3 to 48 months, and the survival ranged from 5 to 84 months. The occurrence of CCA/Ph- with MDS/AML may be associated with a poor prognosis, and careful follow-up is recommended for patients who receive TKI therapy.


Single antibody-antigen interactions monitored via transient ionic current recording using nanopore sensors.
Understanding the single molecular protein-protein interaction has great significance in evaluating the affinity of a specific antibody. Herein, the interaction between single α-fetal protein (AFP) and its antibody was monitored via transient ionic current recording by using the antibody functionalized nanopore sensors. More importantly, the kinetic evaluation was performed at the single molecule level to determine the dissociation constant of this interaction. This method enables the monitoring of the kinetic antigen-antibody interaction in their heterogenetic state without any labelling. Our results provided new insights into the evaluation of the antibody's binding affinity and more into the development of immunoassays for diagnostics.


Classics in Chemical Neuroscience: Aripiprazole.
Aripiprazole was the first antipsychotic developed to possess agonist properties at dopamine D2 autoreceptors, a groundbreaking strategy that presented a new vista for schizophrenia drug discovery. The dopamine D2 receptor is the crucial target of all extant antipsychotics, and all developed prior to aripiprazole were D2 receptor antagonists. Extensive blockade of these receptors, however, typically produces extrapyramidal (movement) side effects, which plagued first-generation antipsychotics, such as haloperidol. Second-generation antipsychotics, such as clozapine, with unique polypharmacology and D2 receptor binding kinetics, have significantly lower risk of movement side effects but can cause myriad additional ones, such as severe weight gain and metabolic dysfunction. Aripiprazole's polypharmacology, characterized by its unique agonist activity at dopamine D2 and D3 and serotonin 5-HT1A receptors, as well as antagonist activity at serotonin 5-HT2A receptors, translates to successful reduction of positive, negative, and cognitive symptoms of schizophrenia, while also mitigating risk of weight gain and movement side effects. New observations, however, link aripiprazole to compulsive behaviors in a small group of patients, an unusual side effect for antipsychotics. In this review, we discuss the chemical synthesis, pharmacology, pharmacogenomics, drug metabolism, and adverse events of aripiprazole, and we present a current understanding of aripiprazole's neurotherapeutic mechanisms, as well as the history and importance of aripiprazole to neuroscience.


A dose-response effect between a sunlight index and age-related cataracts. Italian-American Cataract Study Group.
To explore the existence of a dose-response relationship between sunlight exposure and risk of age-related cataracts, we analyzed data collected from 1008 patients with cataracts and 469 control subjects enrolled in the Italian-American Case-Control Study of Age-Related Cataracts. Fourteen variables related to sunlight exposure history were included in the questionnaire administered to the study participants. A sunlight index was constructed and its relationship to the presence of cataracts was modeled by logistic regression. After adjustments for potential confounding variables and for age and sex, a significant dose-response effect (P = 0.01) was detected between the sunlight exposure index and the presence of pure cortical cataracts. With the exception of corticonuclear cataracts, all the other mixed types of opacity also showed a dose-response association with the sunlight index. These data support the hypothesis that sunlight exposure is a risk factor in the development of cortical cataracts, and demonstrate the existence of a dose-response relationship in this association.


Computing Relative Free Energies of Solvation using Single Reference Thermodynamic Integration Augmented with Hamiltonian Replica Exchange.
This paper introduces an efficient single-topology variant of Thermodynamic Integration (TI) for computing relative transformation free energies in a series of molecules with respect to a single reference state. The presented TI variant that we refer to as Single-Reference TI (SR-TI) combines well-established molecular simulation methodologies into a practical computational tool. Augmented with Hamiltonian Replica Exchange (HREX), the SR-TI variant can deliver enhanced sampling in select degrees of freedom. The utility of the SR-TI variant is demonstrated in calculations of relative solvation free energies for a series of benzene derivatives with increasing complexity. Noteworthy, the SR-TI variant with the HREX option provides converged results in a challenging case of an amide molecule with a high (13-15 kcal/mol) barrier for internal cis/trans interconversion using simulation times of only 1 to 4 ns.


Aldosterone receptors in different types of primary hyperaldosteronism.
The number of mineralocorticoid-binding sites on mononuclear leukocytes and plasma aldosterone (aldo) concentrations were measured in patients with different types of primary hyperaldosteronism. Patients with unilateral adenoma and patients with bilateral adrenal hyperplasia had a significantly lower (P less than 0.001) mean number of binding sites for aldo [144 +/- 36 (+/- SD; n = 6) and 140 +/- 28 sites/cell (n = 4), respectively] compared with normal subjects (292 +/- 110 sites/cell; n = 25). In four patients with dexamethasone-suppressible hyperaldosteronism, mineralocorticoid-binding sites in mononuclear leukocytes were normal (291 +/- 108 sites/cell). In all patients undergoing surgery for unilateral adenoma, the receptors normalized 3 months after the operation. In two patients the reduction in receptors persisted for a short time after surgery even though the plasma aldo level had already normalized. We conclude that mineralocorticoid excess produces down-regulation of mineralocorticoid receptors, which, in turn, might contribute to the genesis of the aldo escape phenomenon.


Assignment of the (13)C NMR spectrum by correlation to dipolar coupled proton-pairs and estimation of order parameters of a thiophene based liquid crystal.
Materials with widely varying molecular topologies and exhibiting liquid crystalline properties have attracted considerable attention in recent years. (13)C NMR spectroscopy is a convenient method for studying such novel systems. In this approach the assignment of the spectrum is the first step which is a non-trivial problem. Towards this end, we propose here a method that enables the carbon skeleton of the different sub-units of the molecule to be traced unambiguously. The proposed method uses a heteronuclear correlation experiment to detect pairs of nearby carbons with attached protons in the liquid crystalline core through correlation of the carbon chemical shifts to the double-quantum coherences of protons generated through the dipolar coupling between them. Supplemented by experiments that identify non-protonated carbons, the method leads to a complete assignment of the spectrum. We initially apply this method for assigning the (13)C spectrum of the liquid crystal 4-n-pentyl-4'-cyanobiphenyl oriented in the magnetic field. We then utilize the method to assign the aromatic carbon signals of a thiophene based liquid crystal thereby enabling the local order-parameters of the molecule to be estimated and the mutual orientation of the different sub-units to be obtained.


The tropical-subtropical coupling in the Southeast Atlantic from the perspective of the northern Benguela upwelling system.
In the Benguela upwelling system, the environmental conditions are determined to a large extent by central water masses advected from remote areas onto the shelf. The origin, spreading pathways and fate of those water masses are investigated with a regional ocean model that is analysed using Eulerian passive tracers and on the basis of Lagrangian trajectories. Two major water masses influencing the Benguela upwelling system are identified: tropical South Atlantic Central Water (SACW) and subtropical Eastern South Atlantic Central Water (ESACW). The spreading of tropical waters into the subtropical Benguela upwelling system is mediated by equatorial currents and their continuation in the Southeast Atlantic. This tropical-subtropical connection has been attributed to signal propagation in the equatorial and coastal waveguides. However, there exists an additional spreading path for tropical central water in the open ocean. This mass transport fluctuates on a seasonal scale around an averaged meridional transport in Sverdrup balance. The inter-annual variability of the advection of tropical waters is related to Benguela Niños, as evidenced by the 2010/2011 event. The northern Benguela upwelling system is a transition zone between SACW and ESACW since they encounter each other at about 20°S. Both water masses have seasonal variable shares in the upwelled water there. To summarise the main pathways of central water mass transport, an enhanced scheme for the subsurface circulation in the Southeast Atlantic is presented.


Characteristics and Outcomes of Patients Receiving Physical Therapy for Low Back Pain with a Nociplastic Pain Presentation: A Secondary Analysis.
Individuals with low back pain (LBP) may be classified based on mechanistic descriptors, such as a nociplastic pain presentation (NPP). The purpose of this secondary analysis was to examine the frequency and characteristics of patients with a NPP referred to physical therapy with LBP. Additionally, we characterized patients with LBP meeting the criteria for NPP by demographic, clinical, psychological, and pain sensitivity variables. Finally, we examined short- and long-term clinical outcomes in patients with a NPP compared to those without a NPP. Patients referred to physical therapy for LBP completed the Patient Self-report Survey for the Assessment of Fibromyalgia. Participants were categorized as "LBP with NPP" or "LBP without NPP" based on the threshold established in this measure. A rank sum test examined for differences in pain-related psychological factors and pressure-pain threshold between groups. Next, a Friedman test examined if LBP intensity and disability trajectories differed by groups at one and six months after initiation of physical therapy. 22.2% of patients referred to physical therapy for LBP met the criteria for a NPP. Patients with a NPP reported significantly greater disability, pain catastrophizing, depression, anxiety, and somatization compared to individuals without a NPP (p < 0.05). Pressure-pain threshold did not differ between groups (p > 0.05). Individuals with LBP with a NPP demonstrated nonsignificant, small to medium reductions in pain and disability at one and six months. Individuals experiencing LBP without a NPP demonstrated significant reductions in pain and disability in the short- and long term. Patients with LBP with a NPP displayed greater negative pain-related psychological factors but similar pain sensitivity compared to LBP without NPP.


Econometric estimation of WHO-CHOICE country-specific costs for inpatient and outpatient health service delivery.
Policy makers require information on costs related to inpatient and outpatient health services to inform resource allocation decisions. Country data sets were gathered in 2008-2010 through literature reviews, website searches and a public call for cost data. Multivariate regression analysis was used to explore the determinants of variability in unit costs using data from 30 countries. Two models were designed, with the inpatient and outpatient models drawing upon 3407 and 9028 observations respectively. Cost estimates are produced at country and regional level, with 95% confidence intervals. Inpatient costs across 30 countries are significantly associated with the type of hospital, ownership, as well as bed occupancy rate, average length of stay, and total number of inpatient admissions. Changes in outpatient costs are significantly associated with location, facility ownership and the level of care, as well as to the number of outpatient visits and visits per provider per day. These updated WHO-CHOICE service delivery unit costs are statistically robust and may be used by analysts as inputs for economic analysis. The models can predict country-specific unit costs at different capacity levels and in different settings.


Validation of a Danish version of the Toronto Extremity Salvage Score questionnaire for patients with sarcoma in the extremities.
The Toronto Extremity Salvage Score (TESS) questionnaire is a self-administered questionnaire designed to assess physical disability in patients having undergone surgery of the extremities. The aim of this study was to validate a Danish translation of the TESS. The TESS was translated according to international guidelines. A total of 22 consecutive patients attending the regular outpatient control programme were recruited for the study. To test their understanding of the questionnaires, they were asked to describe the meaning of five randomly selected questions from the TESS. The psychometric properties of the Danish version of TESS were tested for validity and reliability. To assess the test-retest reliability, the patients filled in an extra TESS questionnaire one week after they had completed the first one. Patients showed good understanding of the questionnaire. There was a good internal consistency for both the upper and lower questionnaire measured by Cronbach's alpha. A Bland-Altman plot showed acceptable limits of agreement for both questionnaires in the test-retest. There was also good intraclass correlation coefficients for both questionnaires. The validity expressed as Spearman's rank correlation coefficient comparing the TESS with the QLQ-C30 was 0.89 and 0.90 for the questionnaire on upper and lower extremities, respectively. The psychometric properties of the Danish TESS showed good validity and reliability. not relevant. not relevant.


Electric-Field Emission Mechanism in Q-Carbon Field Emitters.
In this paper, we report the excellent field emission properties of Q-carbon and analyze its field emission characteristics through structural, morphological, and electronic property correlations, supported by density functional theory (DFT) simulation studies. The Q-carbon field emitters show impressive and stable field emission properties, such as a low turn-on electric field of ∼2.38 V/μm, a high emission current density of ∼33 μA/cm2, and a critical field of ∼2.44 V/μm for the transition from a linear region to the saturation region in the F-N plot. The outstanding field emission properties of Q-carbon are attributed to (i) a unique sp2/sp3 mixture in Q-carbon, (ii) sp2-bonded highly conductive amorphous carbon-rich channels inside the Q-carbon cluster, (iii) a large local field enhancement due to the local geometry and microstructure of Q-carbon, and (iv) the presence of sp2-bonded amorphous carbon regions in the composite film. The temperature-dependent field emission properties, such as extreme sensitivity and an enhancement in the emission current density with temperature, can be explained by the local density of states near the Fermi level and the excellent thermal stability of the Q-carbon field emitters. From DFT simulation studies, the computed work function and the field-enhancement factor were determined to be 3.62 eV and ∼2300, respectively, which explains the excellent field emission characteristics of Q-carbon. The obtained field emission properties, in most cases, were superior to those from other carbon/diamond-based field emitters, which will open new frontiers in field emission-based electronic applications.


[Preoperative Evaluation and Arrangements: The Elderly Patient].
With a constantly growing portion of elderly within our population and the advances of modern medicine, surgery on aged and very aged patients has become a daily hospital routine. Due to the physical and mental features of ageing these patients face special perioperative risks. They display a higher rate of complications, morbidity and cognitive deficits which might in the end lead to persisting need of care. Even in the healthy elderly, most organ functions are "physiologically" instable or deficient and the homeostasis of health and disease is fragile. The preoperative evaluation of the aged patient has to be extended towards risk factors and pathologic pre-conditions which derive especially from high age and are so far not determined by a mere "fit-for-anaesthesia?" This includes assessment of frailty and functional status as well as the evaluation of pre-existing cognitive deficits, malnutrition and polypharmacy. Prevention of postoperative cognitive deficits and delirium is an important goal of medical therapy and requires i. a. omission of benzodiazepines, BIS-controlled anaesthesia, focus on patient's comfort and orientation and inclusion of close relatives and confidants in all processes. Considering all this, an elderly patient might require more time than usually given to be well prepared for anaesthesia, surgery and the postoperative course. The altered physiology and the special risk profile of the aged patient demand special attention and time throughout the perioperative phase. With an increasing number of elderly presenting for surgery, it is likely that more age-adapted structures and processes become implemented in our hospitals.


Roles of nibrin and AtM/ATR kinases on the G2 checkpoint under endogenous or radio-induced DNA damage.
Checkpoint response to DNA damage involves the activation of DNA repair and G2 lengthening subpathways. The roles of nibrin (NBS1) and the ATM/ATR kinases in the G2 DNA damage checkpoint, evoked by endogenous and radio-induced DNA damage, were analyzed in control, A-T and NBS lymphoblast cell lines. Short-term responses to G2 treatments were evaluated by recording changes in the yield of chromosomal aberrations in the ensuing mitosis, due to G2 checkpoint adaptation, and also in the duration of G2 itself. The role of ATM/ATR in the G2 checkpoint pathway repairing chromosomal aberrations was unveiled by caffeine inhibition of both kinases in G2. In the control cell lines, nibrin and ATM cooperated to provide optimum G2 repair for endogenous DNA damage. In the A-T cells, ATR kinase substituted successfully for ATM, even though no G2 lengthening occurred. X-ray irradiation (0.4 Gy) in G2 increased chromosomal aberrations and lengthened G2, in both mutant and control cells. However, the repair of radio-induced DNA damage took place only in the controls. It was associated with nibrin-ATM interaction, and ATR did not substitute for ATM. The absence of nibrin prevented the repair of both endogenous and radio-induced DNA damage in the NBS cells and partially affected the induction of G2 lengthening.


[Bibliometric analysis of Zhonghua Nan Ke Xue (National Journal of Andrology)].
To identify the characteristics of the articles published in Zhonghua Nan Ke Xue (National Journal of Andrology, NJA) and the distribution of the authors in the andrological world. Articles published in NJA between 2009 to 2012 were collected and analyzed using statistic and bibliometric methods. The indicators include cooperation degree, core authors, distribution of grant articles, and geographical distribution of authors. During the 4 years, 1064 articles were published in NJA, of which 998 (93.80%) were coauthored, with a cooperation degree of 4.72. Totally, 909 authors, including 792 (87.13%) of the first authors, published 1 article each; 272 (25.56%) papers were written by 117 (12.87%) core authors, and 396 granted by 619 foundations. There were 13 high-productivity institutions, which published a total number of 257 (24.15%) articles. As for geographical distribution, Jiangshu, Guangdong and Beijing ranked as the top three, contributing 215 (20.21%), 105 (9.87%) and 102 (9.59%) of the published papers, respectively. Among the published papers, 132 were cited for 185 times by 119 journals in SCI, and another 418 cited for 701 times by 94 journals in CSCD. NJA has a high cooperation degree and a wide geographical distribution of authors, with Jiangshu, Guangdong and Beijing as the top three areas in andrological research, though the overall geographical distribution is not well balanced. NJA is receiving more and more attention from both domestic and international researchers.


Reticuloendothelial function in renal allograft recipients.
The phagocytic capacity of the reticuloendothelial system (R.E.S.) was assessed in patients with chronic renal failure and in renal transplant recipients. R.E.S. phagocytosis was increased in the former group. Soon after transplantation R.E.S. phagocytosis was moderately reduced (through levels were comparable with those of normal controls) but was particularly reduced after high-dose corticosteroid treatment for rejection. In long-term allograft recipients R.E.S. phagocytosis was also depressed though steroid maintenance doses were small.


Recurrent acute suppurative thyroiditis due to pyriform sinus fistula in an adult--case report.
We present a case study of acute suppurative thyroiditis (AST) with frequent recurrence due to anatomical malformation described as pyriform sinus fistula (PSF). Difficulty in diagnosis and treatment may be explained by the rarity of the disease in adult patients. AST had been observed in our patient five times before a radical surgery treatment was performed. The most typical symptoms and signs in our patient include: fever, difficulty in swallowing and tender tumour in the left side of the neck. Computed tomography (CT), barium swallow study and endoscopic examination gave us an opportunity to confirm the presence of an anatomical abnormality. After fistulectomy, we have not observed AST up to the date of this publication.


Effectiveness of disinsertion-resection and tucking of the inferior oblique muscle in patients with unilateral long-standing superior oblique muscle palsy.
To investigate the effectiveness and safety of disinsertion-resection and tucking of the inferior oblique muscle in patients with unilateral long-standing superior oblique muscle palsy and secondary inferior oblique muscle overaction. Between April 2000 and January 2005, the records of 31 patients who underwent disinsertion-resection and tucking of the inferior oblique muscle for treatment of unilateral long-standing (> 6 months) superior oblique muscle palsy were retrospectively reviewed. A comprehensive ocular examination including best-corrected visual acuity measurements, ductions, versions, and deviations at near and distance in the diagnostic positions of gaze, head tilt test, abnormal head position, dilated fundus, field of binocular fixation, and Lee screen test was performed prior to and after surgery. All patients had Knapp's class I unilateral superior oblique muscle palsy. The mean preoperative score of inferior oblique muscle overaction was +3.03 and the mean vertical deviation was 15.9 PD in primary position. The follow-up period ranged from 4 to 82 months. Inferior oblique muscle overaction diminished in 29 patients, and 2 patients had +1.0 overaction in adduction of the affected eye. The vertical deviation in these patients had some residual but smaller hypertropia. Disinsertion-resection and tucking of the inferior oblique muscle was safe, simple, and effective in eliminating inferior oblique muscle overaction and abnormal head posture, and in reducing the hyperdeviation in patients with unilateral long-standing superior oblique muscle palsy.


Deviation from the planarity--a large Dy3N cluster encapsulated in an Ih-C80 cage: an X-ray crystallographic and vibrational spectroscopic study.
The high-yield synthesis of Dy3N@C80 (I) opens the possibility of characterizing its molecular and vibrational structures. We report on the structure determination of Dy3N@C80 (I) by X-ray crystallographic study of single crystal of email@example.com(OEP).2C6H6, revealing a nearly planar Dy3N cluster encapsulated in an Ih-C80 cage. The vibrational structure of Dy3N@C80 (I) is studied by Fourier transform infrared (FTIR) and Raman spectroscopy in combination with force-field calculations. A correlation was found between the antisymmetric metal-nitrogen stretching vibration and the structure of the M3N cluster of M3N@C80 (I) (M = Y, Gd, Tb, Dy, Ho, Er, Tm). Moreover, a stronger interaction between the encaged nitride cluster and the C80 carbon cage was found in the class II M3N@C80 (I) (M = Y, Gd, Tb, Dy, Ho, Er, Tm) than in Sc3N@C80 (I). This study demonstrates that the cluster size plays the dominating role in the structure of the M3N cluster in M3N@C80 (I).


Functional outcome following direct repair or intervertebral fusion for adolescent spondylolysis: a systematic review.
A systematic review of the literature was performed to establish whether direct repair of the pars defect or intervertebral fusion achieves better Oswestry Disability Index scores in adolescent spondylolysis or low-grade spondylolisthesis. Nine studies fulfilled the inclusion criteria, reporting a minimum total of 80 direct repairs and 108 fusions because of presumed replication of data between studies. Little statistically or clinically significant difference could be established between the two interventions. The only comparative study showed improved long-term outcome with fusion. Further well-designed prospective comparative studies are required to establish the optimum treatment for this condition.


Application of built-in adjuvants for epitope-based vaccines.
Several studies have shown that epitope vaccines exhibit substantial advantages over conventional vaccines. However, epitope vaccines are associated with limited immunity, which can be overcome by conjugating antigenic epitopes with built-in adjuvants (e.g., some carrier proteins or new biomaterials) with special properties, including immunologic specificity, good biosecurity and biocompatibility, and the ability to vastly improve the immune response of epitope vaccines. When designing epitope vaccines, the following types of built-in adjuvants are typically considered: (1) pattern recognition receptor ligands (i.e., toll-like receptors); (2) virus-like particle carrier platforms; (3) bacterial toxin proteins; and (4) novel potential delivery systems (e.g., self-assembled peptide nanoparticles, lipid core peptides, and polymeric or inorganic nanoparticles). This review primarily discusses the current and prospective applications of these built-in adjuvants (i.e., biological carriers) to provide some references for the future design of epitope-based vaccines.


Widespread adoption of evidence-based practices is essential for a growing Medicare population.
When providers move from employing traditional practices to new methods that are steeped in evidence, this benefits patient health. The result is higher-quality, more affordable care, often stemming from lower rates of hospital infections, readmissions, and, in general, improved outcomes.


Thickness of plantar fascia is not predictive of functional outcome in plantar fasciitis treatment.
The aim of this study was to define a quantitative parameter to indicate which cases of plantar fasciitis will benefit from local corticosteroid injection or ESWT and to compare the efficacy of two different treatment modalities. Seventy patients (mean age: 49.10; range: 41-58) with chronic plantar fasciitis unresponsive to conservative treatment for 3 months were treated with either betamethasone injection or extracorporeal shock wave therapy (ESWT). Correlation between AOFAS scores, fascia thickness, duration of symptoms, age and calcaneal spur length were assessed. Degree of fascial thickening (mean 4.6 mm for all patients) did not influence baseline AOFAS scores (r = -0.054). Plantar fascia thickness significantly decreased in both groups after treatment (1.2 mm for steroid, 1.2 mm for ESWT) (p < 0.01 for both groups). Percentage of change in AOFAS scores (68% for steroid and 79% for ESWT, p = 0.069) and fascial thickness (24% for steroid and 26% for ESWT, p = 0.344) were similar between two groups. Functional recovery was not correlated with baseline fascial thickness (r = 0.047) or degree of fascial thinning after treatment (r = -0.099). Percentage of change in AOFAS scores was correlated only with baseline AOFAS scores (r = -0.943). Plantar fascia thickness increases significantly in plantar fasciitis and responds to treatment. Both ESWT and betamethasone injection are effective in alleviating symptoms and reducing plantar fascia thickness in chronic plantar fasciitis. However, the only predictive factor for functional recovery in terms of AOFAS scores is patients' functional status prior to treatment. Measuring of plantar fascia is not helpful as a diagnostic or prognostic tool and MRI imaging should be reserved for differential diagnosis. Level III, Therapeutic study.


[Possibilities of the use of the Converse scalp flap in maxillofacial surgery. Review of 13 cases].
13 Converse scalping flaps have been done in the past 3 years. 11 cases were for nasal reconstruction, at least half nose which is its main indication including 4 after gun shot wounds and 7 for invasive skin cancers. The preference of this flap is discussed versus the other processes for reconstruction: median forehead flap whatever its design, Washio or orther fronto-auricular flaps, free flaps. Lining and framework repair are done in the same operation than cover when usefull. 2 other clinical cases illustrate other areas than nose where the Converse flap can be employed.


[Heat debt and thermal insulation in women exposed to cold : contribution of direct calorimetry to the study of a mathematical model (author's transl)].
1. Measurements of total heat losses by direct calorimetry, metabolic heat production by indirect calorimetry, body temperatures by thermometry, and thickness of subcutaneous fat with skin-fold calipers were made in four groups of subjects (anorexic, controls, trend to obesity, and obesity) at ambient temperatures of 28 degrees C and 20 degrees C. 2. At 28 degrees C, the four groups of subjects reached thermal equilibrium after 30 min. 3. Both metabolic heat production and total heat losses were lower in the anorexic group than in the control group. 4. Body thermal insulation was not simply related to the thickness of subcutaneous fat (passive insulation), but was actively regulated in such a way that thermal balance was attained by all subjects at 28 degrees C. Body tissues underlying the subcutaneous fat contributed to the thermal insulation of the subjects at both 28 degrees C and 20 degrees C. 5. At 28 degrees C, total body thermal insulation was higher in anorexic subjects than in controls. 6. At 20 degrees C, heat debt was similar in three of the four groups : the anorexic subjects showed a higher debt. 7. A highly significant correlation between subcutaneous fat and weight/area ratio, was found. 8. The heat exchange coefficient of radiation and convection was found to be 6,47 Wm-2 degrees C-1. 9. By combining our measured values with those of various tissue physical characteristics, it was possible to produce a mathematical model. With this model one can calculate the penetration of the thermal gradient into the body, and estimate the mean temperature of each tissue participating in the thermal insulation for moderately cold ambient temperatures.


The experience of therapeutic reading.
This article describes a qualitative study of therapeutic reading intended to provide understanding of bibliotherapy. Using the Colaizzi method, interviews with eight participants were analyzed and the structure of the experience of therapeutic reading identified. The structure of the experience of therapeutic reading was recognition of self evolving into ways of feeling and ways of knowing. A discussion of the implications of results is presented.


ZHOUPI and KERBEROS Mediate Embryo/Endosperm Separation by Promoting the Formation of an Extracuticular Sheath at the Embryo Surface.
Arabidopsis thaliana seed development requires the concomitant development of two zygotic compartments, the embryo and the endosperm. Following fertilization, the endosperm expands and the embryo grows invasively through the endosperm, which breaks down. Here, we describe a structure we refer to as the embryo sheath that forms on the surface of the embryo as it starts to elongate. The sheath is deposited outside the embryonic cuticle and incorporates endosperm-derived material rich in extensin-like molecules. Sheath production is dependent upon the activity of ZHOUPI, an endosperm-specific transcription factor necessary for endosperm degradation, embryo growth, embryo-endosperm separation, and normal embryo cuticle formation. We show that the peptide KERBEROS, whose expression is ZHOUPI dependent, is necessary both for the formation of a normal embryo sheath and for embryo-endosperm separation. Finally, we show that the receptor-like kinases GSO1 and GSO2 are required for sheath deposition at the embryo surface but not for production of sheath material in the endosperm. We present a model in which sheath formation depends on the coordinated production of material in the endosperm and signaling within the embryo, highlighting the complex molecular interaction between these two tissues during early seed development.


Endophytic bacterial diversity in banana 'Prata Anã' (Musa spp.) roots.
The genetic diversity of endophytic bacteria in banana 'Prata Anã' roots was characterized. Two hundred and one endophytic bacteria were isolated, 151 of which were classified as Gram-positive and 50 as Gram-negative. No hypersensitivity response was observed in any of the isolates. The rep-PCR technique generated different molecular profiles for each primer set (REP, ERIC and BOX). Fifty readable loci were obtained and all of the fragments were polymorphic. Amplified ribosomal DNA restriction analysis (ARDRA) of the isolates based on cleavage with four restriction enzymes yielded 45 polymorphic bands and no monomorphic bands. PCR amplified the nifH gene in 24 isolates. 16S rDNA sequencing of the 201 bacterial isolates yielded 102 high-quality sequences. Sequence analyses revealed that the isolates were distributed among ten bacterial genera (Agrobacterium, Aneurinibacillus, Bacillus, Enterobacter, Klebsiella, Lysinibacillus, Micrococcus, Paenibacillus, Rhizobium and Sporolactobacillus) and included 15 species. The greatest number of isolates belonged to the genus Bacillus. The bacteria identified in this study may be involved in promoting growth, phosphate solubilization, biological control and nitrogen fixation in bananas.


Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons.
Self-injection of 12 sedative-anxiolytics was examined in baboons. Intravenous injections and initiation of a 3-h time-out were dependent upon completion of a fixed-ratio schedule requirement, permitting eight injections per day. Before testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. At some doses, all five of the benzodiazepines examined (alprazolam, bromazepam, chlordiazepoxide, lorazepam, triazolam) maintained rates (number of injections per day) of drug self-injection above vehicle control in each of the baboons tested. Maximum rates of benzodiazepine self-injection were generally submaximal. Of the benzodiazepines examined, triazolam maintained the highest rates of self-injection. Among the three barbiturates tested, methohexital generally maintained high rates of self-injection in contrast to hexobarbital and phenobarbital, which only maintained low rates. Of the four non-benzodiazepine non-barbiturate sedatives examined, both chloral hydrate and methyprylon occasionally maintained high rates of self-injection. Although there were differences within and across animals, baclofen maintained intermediate rates of self-injection. The novel anxiolytic buspirone maintained only low rates of self-injection that were not different from vehicle. This study further validates the self-injection methodology for assessing sedative-anxiolytic abuse liability and provides new information about drug elimination rate as a determinant of drug self-administration.


Plasticity in nitrogen uptake among plant species with contrasting nutrient acquisition strategies in a tropical forest.
Nitrogen (N) availability influences the productivity and distribution of plants in tropical montane forests. Strategies to acquire soil N, such as direct uptake of organic compounds or associations with root symbionts to enhance N acquisition in exchange for carbon (C), may facilitate plant species coexistence and ecosystem N retention. Alternatively, rapid microbial turnover of soil N forms in tropical soils might promote flexible plant N-uptake strategies and mediate species coexistence. We tested whether sympatric plant species with different root symbiont associations, and therefore potentially different nutrient acquisition strategies, partition chemical forms of N or show plasticity in N uptake in a tropical pre-montane forest in Panama. We traced the movement of three 15 N forms into soil pools, microbes, and seedlings of eleven species differing in root traits. Seedlings were grown in a split-plot field transplant experiment, with plots receiving equimolar mixtures of ammonium, nitrate, and glycine, with one form isotopically labeled in each block. After 48 h, more 15 N was recovered in microbes than in plants, while all pools (extractable organic and inorganic N, microbial biomass, and leaves) contained greater amounts of 15 N from nitrate than from ammonium or glycine. Furthermore, 13 C from dual-labeled glycine was not recovered in the leaves of any seedling, suggesting the studied species do not directly take up organic N or transform organic N prior to translocation to leaves. Nitrogen uptake differed by root symbiont group only for nitrate, with greater 15 N recovery in plants with arbuscular mycorrhizal (AM) associations or proteoid roots compared to orchids. Some root trait groups differed in 15 N recovery among N forms, with greater nitrate uptake than ammonium or glycine by AM-associated and N2 -fixing plants. However, only five of eleven species showed differences in uptake among N forms. These results indicate flexibility in uptake of N forms in tropical plants across root trait groups, with only a few species displaying weak preferences for a specific N form.


Deviated mechanism of wound healing in diabetic corneas.
We examined phenotypic changes during the wound healing process in the corneal epithelium of Goto-Kakizaki (GK) rats, a spontaneous model of type 2 diabetes mellitus. In this article, we provide an overview of our and other groups' research and describe the clinical features of diabetic keratopathy. We observed that the rate of corneal epithelial wound closure was decreased in GK rats compared with Wistar rats. Immunoreactivity for Cx43, K14, and Ki-67 was detected in the 2 layers of cells adjacent to the basement membrane in the corneal epithelium of GK rats, whereas only the single basal layer of cells was positive for these proteins in the corneal epithelium of Wistar rats. The frequency of Ki-67-positive cells was greater in GK rats than in Wistar rats in the intact corneal epithelium and during wound healing. The GK rat represents delayed corneal epithelial wound closure as well as that which is observed in human diabetic keratopathy. Furthermore, these results indicate a possibility of functional deviation in corneal epithelial cells with diabetes mellitus.


Construction of 8-Azabicyclo[3.2.1]octanes via Sequential DDQ-Mediated Oxidative Mannich Reactions of N-Aryl Pyrrolidines.
A concise synthesis of 8-azabicyclo[3.2.1]octanes via sequential oxidative Mannich reactions is described. This approach involves an intermolecular oxidative Mannich coupling reaction between N-aryl pyrrolidines with TMS enol ether and a subsequent intramolecular oxidative Mannich cyclization of the corresponding silyl enol ether. DDQ is used as a key oxidant for both reactions.


Acetyltanshinone IIA is more potent than lapatinib in inhibiting cell growth and degrading HER2 protein in drug-resistant HER2-positive breast cancer cells.
High expression of human epidermal factor receptor 2 (HER2) is directly related to tumor progression, malignancy and drug resistance in HER2-positive breast cancer (HER2-PBC). The major limitation of current anti-HER2 therapies is that they cannot reduce the levels of HER2 protein. Here, we investigated the effect of acetyltanshinone IIA (ATA) in lapatinib-resistant HER2-PBC cells. Our data showed that ATA exhibited more potent effects than lapatinib against drug-resistant HER2-PBC cells in terms of (1) inhibiting cell growth, (2) reducing phosphorylated and total HER2 levels, (3) inhibiting tumor xenograft growth in nude mice, and (4) reducing HER2 protein levels in tumor xenografts. A mechanistic study revealed that ATA promoted HER2 degradation via increasing c-Cbl and CHIP-mediated HER2 ubiquitination and subsequent HER2 degradation by the proteasome or lysosome. ATA also reduced the levels of other tyrosine kinase receptors (TKRs), such as HER3, IGF-1R and MET, in lapatinib-resistant cells. Our findings suggest that direct degradation of HER2 and other TKRs can be an effective strategy for combatting drug resistance. They also indicate the potential utilization of ATA in treating breast cancer that is resistant or nonresponsive to current HER2-targeted therapies.


Effects of bile acid oxazolines on gallstone formation in prairie dogs.
The effects of 2 bile acid analogs, chenodeoxy-oxazoline [2-(3 alpha, 7 alpha-dihydroxy-24-nor-5 beta-cholanyl)-4,4-dimethyl-2-oxazoline] and ursodeoxy-oxazoline [2-(3 alpha, 7 beta-dihydroxy-24-nor-5 beta-cholanyl)-4,4-dimethyl-2-oxazoline] were examined in the prairie dog model of cholesterol cholelithiasis. Gallstones and biliary cholesterol crystals were induced in 5 out of 6 male prairie dogs fed a semisynthetic diet containing 0.4% cholesterol for 8 weeks. Six animals maintained on a low cholesterol control diet (0.08% cholesterol) exhibited neither gallstones nor biliary cholesterol crystals. The addition of 0.06% chenodeoxy-oxazoline to the lithogenic diet did not prevent induced cholelithiasis or the appearance of cholesterol crystals in bile. In contrast, 0.06% dietary ursodeoxy-oxazoline prevented gallstones in 5 out of 6 prairie dogs (but cholesterol crystals were present in the bile of 4 of these animals). Histologically, most of the livers from the prairie dogs fed the cholesterol-supplemented semisynthetic diet showed bile duct proliferation, inflammatory infiltration and fibrosis along the portal tracts. These pathologic changes were generally not ameliorated by adding chenodeoxy-oxazoline or chenodeoxy-oxazoline plus chenodeoxycholic acid to the diet. Portal tract pathology was markedly reduced in most animals by adding ursodeoxy-oxazoline to the cholesterol-supplemented diet. The pathologic changes overall could best be correlated with the presence of gallstones, but not with the incidence of biliary cholesterol crystals.


Association between polymorphisms in CTR1, CTR2, ATP7A, and ATP7B and platinum resistance in epithelial ovarian cancer.
The copper transporters <italic>CTR1</italic>, <italic>CTR2</italic>, <italic>ATP7A</italic>, and <italic>ATP7B</italic> regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in <italic>CTR1</italic>, <italic>CTR2</italic>, <italic>ATP7A</italic>, and <italic>ATP7B</italic> on platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) in <italic>CTR1, CTR2, ATP7A</italic>, and <italic>ATP7B</italic> were genotyped in these patients. The <italic>CTR1</italic> rs10981694 polymorphism was observed to be associated with carboplatin resistance, while patients with the rs10981694 G allele showed a significantly higher rate of carboplatin resistance (OR = 4.00, 95% CI 1.309 - 12.23, p < 0.01). In addition, we found that <italic>ATP7A</italic> rs2227291 was associated with cisplatin resistance and that carriers of the C allele were more sensitive to cisplatin (OR = 0.40, 95% CI: 0.17 - 0.94, p = 0.03). Our findings suggest that the <italic>CTR1</italic> and <italic>ATP7A</italic> genetic polymorphisms could affect platinum resistance. The <italic>CTR1</italic> and <italic>ATP7A</italic> genes might be considered a predictive marker for carboplatin and cisplatin resistance, respectively. .


The effect of flow on vascular endothelial cells grown in tissue culture on polytetrafluoroethylene grafts.
Vascular grafts lined with endothelial cells (EC) grown to confluence in culture before implantation may provide a thromboresistant flow surface. Growth of EC on and their adherence to currently available prosthetic materials under conditions of flow are two impediments remaining in the development of such a graft. To address these problems, 22 polytetrafluoroethylene grafts (PTFE) (5 cm by 4 mm inside diameter) were pretreated with collagen and fibronectin, seeded with 2 to 3 X 10(6) bovine aortic EC per graft, and placed in tissue culture (seeded grafts). Twenty-two grafts pretreated with collagen and fibronectin alone served as controls. After 2 weeks morphologic studies revealed that 20/22 seeded grafts were lined with a confluent endothelial layer. Indium 111-oxine was then used to label the EC-seeded grafts. After exposure to either low (25 ml/min) or high (200 ml/min) flow rates for 60 minutes in an in vitro circuit, examination of the luminal surface of the graft by light microscopy and scanning electron microscopy revealed minimal loss of EC. These findings were corroborated by radionuclide scans that showed an insignificant loss of the EC-associated indium label during exposure to flow (7% low flow, 11% high flow). Pretreatment of PTFE grafts with collagen and fibronectin thus promotes both attachment and adherence of EC even under flow conditions.


Investigation on preventive inerting approach of coal spontaneous combustion in gob considering adsorption effect.
Coal spontaneous combustion in the gob poses a significant threat to coal mining operations. Designing optimal process parameters for nitrogen injection to prevent and control fires efficiently is crucial. To achieve this, a multi-field coupling equation was established, considering the adsorption of coal to gas. The model's accuracy was verified on-site, and the effects of nitrogen injection at different locations and flow rates were simulated. The optimal injection parameters were determined by analyzing temperature and inerting time. The results showed that the coal spontaneous combustion hazardous zone in the gob tested on-site was consistent with the simulation from the perspective of physisorption. Nitrogen injection had three stages: gas expansion, rapid oxygen dilution, and complete inerting. The nitrogen injection effect presented a nonlinear change in injection location and flow rate. The optimal nitrogen injection location for the Tingnan Coal Mine in Shaanxi was determined to be 90 m behind the working face on the inlet side, with an optimal flow rate of 800 m3/min. This study focused on gas adsorption and offered valuable insights for creating high-efficiency fire-fighting techniques that involve inserting in the gob.


Development of peptide mimics of a protective epitope of Vibrio cholerae Ogawa O-antigen and investigation of the structural basis of peptide mimicry.
As an alternative approach toward the development of a cholera vaccine, the potential of peptide mimics of Vibrio cholerae lipopolysaccharide (LPS) to elicit cross-reactive immune responses against LPS was investigated. Two closely related protective monoclonal antibodies, S-20-4 and A-20-6, which are specific for Ogawa O-antigen (O-specific polysaccharide; O-SP) of V. cholerae O1, were used as the target antibodies (Abs) to pan phage display libraries under different elution conditions. Six phage clones identified from S-20-4 panning showed significant binding to both S-20-4 and A-20-6. Thus, it is likely that these phage-displayed peptides mimic an important conformational epitope of Ogawa antigens and are not simply functionally recognized by S-20-4. Each of the six phage clones that could bind to both monoclonal antibodies also competed with LPS for binding to S-20-4, suggesting that the peptides bind close to the paratope of the Ab. In order to predict how these peptide mimics interact with S-20-4 compared with its carbohydrate counterpart, one peptide mimic, 4P-8, which is one of the highest affinity binders and shares motifs with several other peptide mimics, was selected for further studies using computer modeling methods and site-directed mutagenesis. These studies suggest that 4P-8 is recognized as a hairpin structure that mimics some O-SP interactions with S-20-4 and also makes unique ligand interactions with S-20-4. In addition, 4P-8-KLH was able to elicit anti-LPS Abs in mice, but the immune response was not vibriocidal or protective. However, boosting with 4P-8-KLH after immunizing with LPS prolonged the LPS-reactive IgG and IgM Ab responses as well as vibriocidal titers and provided a much greater degree of protection than priming with LPS alone.


E-learning, dual-task, and cognitive load: The anatomy of a failed experiment.
The rising popularity of commercial anatomy e-learning tools has been sustained, in part, due to increased annual enrollment and a reduction in laboratory hours across educational institutions. While e-learning tools continue to gain popularity, the research methodologies used to investigate their impact on learning remain imprecise. As new user interfaces are introduced, it is critical to understand how functionality can influence the load placed on a student's memory resources, also known as cognitive load. To study cognitive load, a dual-task paradigm wherein a learner performs two tasks simultaneously is often used, however, its application within educational research remains uncommon. Using previous paradigms as a guide, a dual-task methodology was developed to assess the cognitive load imposed by two commercial anatomical e-learning tools. Results indicate that the standard dual-task paradigm, as described in the literature, is insensitive to the cognitive load disparities across e-learning tool interfaces. Confounding variables included automation of responses, task performance tradeoff, and poor understanding of primary task cognitive load requirements, leading to unreliable quantitative results. By modifying the secondary task from a basic visual response to a more cognitively demanding task, such as a modified Stroop test, the automation of secondary task responses can be reduced. Furthermore, by recording baseline measures for the primary task as well as the secondary task, it is possible for task performance tradeoff to be detected. Lastly, it is imperative that the cognitive load of the primary task be designed such that it does not overwhelm the individual's ability to learn new material.


Effects of water movement and temperature on Rhizophydium infection of Planktothrix in a shallow hypereutrophic lake.
Grand Lake St. Marys (GLSM) is a popular recreational lake located in western Ohio, United States, generating nearly $150 million in annual revenue. However, recurring algal blooms dominated by Planktothrix agardhii, which can produce harmful microcystin toxins, have raised concerns about water safety and negatively impacted the local economy. Planktothrix agardhii is host to a number of parasites and pathogens, including an obligate fungal parasite in the Chytridiomycota (chytrids). In this study, we investigated the potential of these chytrid (Rhizophydium sp.) to infect P. agardhii blooms in the environment by modifying certain environmental conditions thought to limit infection prevalence in the wild. With a focus on temperature and water mixing, mesocosms were designed to either increase or decrease water flow compared to the control (water outside the mesocosm). In the control and water circulation mesocosms, infections were found infrequently and were found on less than 0.75% of the Planktothrix population. On the other hand, by decreasing the water flow to stagnation, chytrid infections were more frequent (found in nearly 3x as many samples) and more prevalent, reaching a maximum infection rate of 4.12%. In addition, qPCR coupled with 16S-18S sequencing was utilized to confirm the genetic presence of both host and parasite, as well as to better understand the effect of water circulation on the community composition. Statistical analysis of the data confirmed that chytrid infection was dependent on water temperature, with infections predominantly occurring between 19°C and 23°C. Additionally, water turbulence can significantly reduce the infectivity of chytrids, as infections were mostly found in stagnant mesocosms. Further, decreasing the water circulation promoted the growth of the cyanobacterial population, while increasing water agitation promoted the growth of green algae (Chlorophyta). This study starts to explore the environmental factors that affect chytrid pathogenesis which can provide valuable insights into controlling measures to reduce the prevalence of harmful algal blooms and improve water quality in GLSM and similarly affected waterbodies.


Subacute recanalization and reocclusion in patients with acute ischemic stroke following endovascular treatment.
To determine the rate of subacute recanalization and reocclusion and its effect on clinical outcomes among patients with ischemic stroke treated with endovascular treatment. Subacute recanalization and reocclusion occurring hours after completion of the intravenous or intra-arterial thrombolysis for acute ischemic stroke has been reported in anecdotal cases. We performed cerebral angiography at 24 h to determine the status of occlusion after endovascular treatment (compared with immediate post-procedure angiogram) in a series of patients with ischemic stroke treated with endovascular treatment. Clinical and radiological evaluations were performed before and 24 h, and prior to discharge or 1-3 months after treatment. We performed multivariate analysis to evaluate the effect of subacute recanalization on clinical outcome graded using modified Rankin scale (mRS). Favorable outcome was defined by mRS of 0-2. A total of 56 patients (mean age 66 +/- 14 years; 22 were men) were analyzed. Subacute recanalization was observed in 16 (29%) patients and consisted of additional recanalization in 8 patients with early recanalization. Subacute recanalization was associated with a trend toward a higher rate of favorable outcome (Wald chi-square 3.3, P = 0.19) after adjusting for other covariates. Subacute recanalization was not associated with either neurological deterioration or symptomatic intracranial hemorrhage. Subacute reocclusion was observed in 5 (9%) patients. Subacute reocclusion was associated with a trend toward higher rate of neurological deterioration within 24 h (Wald chi-square 2.1, P = 0.15) after adjusting for other covariates. We found that new or additional recanalization occurs in one-fourth of the patients within 24 h of endovascular treatment and is not associated with any adverse consequences. Subacute reocclusion occurs infrequently after endovascular treatment.


[Remnant like particles as a risk factor for coronary artery disease].
Plasma triglyceride(TG) has now emerged as an independent risk factor for coronary artery disease(CAD). In contrast to LDL, TG-rich lipoproteins are heterogenous in size and apolipoprotein composition. Remnant is proatherogenic TG-rich lipoproteins, thereby drawing much research interest of how to isolate and quantify remnants. Remnant like particles(RLP) was developed by using immunoaffinity gels coupled to anti-apoA-I and anti-apoB-100 antibodies. RLP has been shown to be positively correlated with coronary vasocontraction to acetylcholine in CAD patients, suggesting that RLP causes endothelial dysfunction. Further study revealed that CAD patient with relatively high RLP-C levels had a significantly poor prognosis as compared to low RLP-C counterpart. Both Framingham heart study and VA-HIT also found RLP-C as a significant risk factor for CAD. In conclusions, RLP-C is a reasonable indicator for proatherogenic remnants, thus considered as a new risk factor for CAD.


[New blood pressure lowering drugs in childhood].
The treatment by antihypertensive agents has recently been improved by the introduction of angiotensin converting-enzyme inhibitors, and of calcium antagonists, which have been applied successfully in children with acute and chronic hypertension. The converting enzyme inhibitor captopril is used increasingly for the treatment of severe forms of persistent hypertension in children. Side effects from this drug can largely be avoided by using low daily doses. The calcium-antagonist nifedipine can now be regarded as the drug of choice in the treatment of acute elevation of blood pressure in infants and children. For this indication it appears to be superior to other drugs because of its prompt and safe efficacy after sublingual administration.


Estimation in signal-dependent film-grain noise.
Optimal estimators are derived for a signal-dependent film-grain noise model, and the effect of signal-dependence on the estimators's structures is investigated. Due to the mathematical complexity of these optimal estimators, various suboptimal estimators are proposed. Computer simulations are then presented which compare the optimal and suboptimal estimators with regard to mean square estimation error, sensitivity to signal-dependence, and robustness with respect to the a priori signal probability density function.


Genomic instability in cancer.
One of the fundamental challenges facing the cell is to accurately copy its genetic material to daughter cells. When this process goes awry, genomic instability ensues in which genetic alterations ranging from nucleotide changes to chromosomal translocations and aneuploidy occur. Organisms have developed multiple mechanisms that can be classified into two major classes to ensure the fidelity of DNA replication. The first class includes mechanisms that prevent premature initiation of DNA replication and ensure that the genome is fully replicated once and only once during each division cycle. These include cyclin-dependent kinase (CDK)-dependent mechanisms and CDK-independent mechanisms. Although CDK-dependent mechanisms are largely conserved in eukaryotes, higher eukaryotes have evolved additional mechanisms that seem to play a larger role in preventing aberrant DNA replication and genome instability. The second class ensures that cells are able to respond to various cues that continuously threaten the integrity of the genome by initiating DNA-damage-dependent "checkpoints" and coordinating DNA damage repair mechanisms. Defects in the ability to safeguard against aberrant DNA replication and to respond to DNA damage contribute to genomic instability and the development of human malignancy. In this article, we summarize our current knowledge of how genomic instability arises, with a particular emphasis on how the DNA replication process can give rise to such instability.


Defensins: antimicrobial peptides for therapeutic development.
A novel class of endogenous antimicrobial peptides called defensins has shown great versatility in their activity against a diverse range of microorganisms including bacteria, viruses and fungi. Their mode of action of bacterial cell lysis seems largely nonspecific and so promises to avert the development of resistance. These two features have made them an area of intense research activity and growing commercial interest. A successful multidisciplinary effort to investigate and develop novel defensins analogues has been established in Singapore that involves computer modeling, biochemistry, proteomics, chemical synthesis, molecular biology and clinical sciences.


Feasible and successful: genome-wide interaction analysis involving all 1.9 x 10(11) pair-wise interaction tests.
The Genome-Wide Association Study (GWAS) is the study design of choice for detecting common genetic risk factors for multifactorial diseases. The performance of full Genome-Wide Interaction Analyses (GWIA) has always been considered computationally challenging. Two-stage strategies to reduce the amount of numerical analysis require the detection of single marker effects or prior pathophysiological hypotheses before the analysis of interaction. This prevents the detection of pure epistatic effects. Our case-control study in idiopathic generalized epilepsy demonstrates that a full GWIA is feasible through use of data compression, specific data representation, interleaved data organization, and parallelization of the analysis on a multi-processor system. Following extensive quality control of the genotypes, our final list of top interaction hits contains only pairs of interacting SNPs with negligible marginal effects. The TOP HIT interaction was between a SNP-pair intragenic to gene DNER (chr 2) and gene CTNNA3 (chr 10). Both of these genes are functionally involved in neuronal migration, synaptogenesis, and the formation of neuronal circuits. Our results therefore indicate a possible interaction between these two genes in epileptogenesis. Results from GWAS are beginning to reveal a 'missing heritability' in complex traits and diseases. Systematic, hypothesis-free analysis of epistatic interaction (GWIA) may help to close this increasingly recognized gap in heritability.


[Experimental infection of Galba pervia, Radix swinhoei and Physa acuta with Fasciola hepatica in Dali, Yunnan].
To determine the intermediate host of Fasciola hepatica in Dali of Yunnan Province, and investigate its development and characteristics. F. hepatica eggs from cattle were collected from July 2012 to July 2013, and placed in 28 degrees C water bath for incubation. Galba pervia, Radix swinhoei, and Physa acuta were collected from Dali, and used to be infected with F. hepatica in the laboratory. Trematode infections were excluded from the snails before experiment. All the snails were infected with F. hepatica miracidia, reared in mud pots. Dead snails were dissected for observing the development of F. hepatica. The metacercariae were collected and identified by PCR amplification of partial sequence of mitochondrial cytochrome oxidase subunit I (COX1) gene. A total of 1 146 R. swinhoei, 996 P. acuta, and 3 307 G. pervia snails were infected with F. hepatica, respectively. Mother rediae were found in two R. swinhoei snails, but no child rediae were observed in the snails. No larval forms were found in P. acuta. G. pervia was infected by F. hepatica with an infection rate of 27.2% (900/3307). The miracidium escaped from the egg and penetrated into G. pervia at temperature 22 degrees C, developed into a sporocyst after 7-15 days, which transformed into mother redia at the 11 st-20th day post-infection. The mother redia developed into daughter redia at the 30th-37th day, and produced cercaria with longtail, and became metacercaria at the 42nd-55th day. PCR confirmed that the metacercariae were that of F. hepatica, with an obvious band (approximately 500 bp). Among the three potential intermediate hosts in Dali, G. pervia is experimentally infected with F. hepatica.


Provocative diskography: safety and predictive value in the outcome of spinal fusion or pain intervention for chronic low-back pain.
There is still no clear definition of diskogenic low-back pain and no consensus on a generally agreed test, such as provocative diskography (PD), to diagnose painful disk degeneration, and probably more importantly, to predict the outcome of therapy intended to reduce pain that is presumed to be diskogenic in nature. Nevertheless, PD is the most specific procedure to diagnose diskogenic low-back pain. Its accuracy, however, is rather low or at best unknown. Although rare, the most prevalent complication, postdiskography diskitis, can be devastating for the individual patient, so all measures, like strict sterile conditions and antibiotic prophylaxis, should be taken to avoid this complication. It is advised to perform the procedure in a pressure-controlled way with a constant low flow, and optionally computed tomography imaging. PD should not be performed in morphologically normal disks. A standardized execution of the test should be established in order to perform high-quality studies to determine its accuracy to lead to meaningful interventions, and find best practices for diagnosis and treatment of diskogenic back pain. Possibly, PD may have detrimental effects on the disk, causing early degeneration, although it is unknown whether this will be related to clinical symptoms. Especially with these possible adverse side effects in mind, the risk-benefit ratio with the lack of clear benefits from treatments provided, and possible complications of disk puncture, the rationale for PD is questionable, which should be stressed to patients in the process of shared decision making. Diskography as a stand-alone test is not recommended in clinical decision making for patients with chronic low-back pain.


Dietary Nitrate for Methane Mitigation Leads to Nitrous Oxide Emissions from Dairy Cows.
Nitrate supplements to cattle diets can reduce enteric CH emissions. However, if NO metabolism stimulates NO emissions, the effectiveness of dietary NO for CH mitigation will be reduced. We quantified NO emissions as part of a dairy cow feeding experiment in which urea was substituted in nearly iso-N diets with 0, 5, 14 or 21 g NO kg dry matter (DM). The feeding experiment was a Latin square with repetition of Period 1. Each period lasted 4 wk, with CH emission measurements in Week 4 using respiration chambers. During Period 3, NO concentrations in chamber outlet air were monitored semicontinuously during 48 h. High, but fluctuating, NO concentrations were seen at the two highest NO levels (up to between 2 and 5 μL L), and dynamics were linked with recent feed intake. In Periods 4 and 5, NO concentrations and feed intake were determined from all four respiration chambers during two 7-h periods. Emissions of NO coincided with feed intake, again with NO concentrations in the microliter per liter range at the two highest NO intake levels. Neither feed nor excretion of NO via urine were significant sources of NO, indicating that emissions came from the animals. Leakages due to rumen fistulation could also not account for NO emissions. The possibility that NO is produced in the oral cavity is discussed. Nitrous oxide emission factors ranged between 0.7 and 1.0% except in one case at 21 g NO kg DM, where it was 3.4%. When accounting for NO emissions at the highest NO intake level, the overall GHG mitigation effect in two different animal-diet combinations changed from -47 to -40%, and from -19 to -17%, respectively, due to NO emissions.


Correlation between angiographic features and pathologic changes in breast carcinoma.
The correlation between angiographic tumor blushing and underlying pathologic factors was studied. Twenty female patients with breast cancer were divided into three groups according to the degree of tumor blushing. Primary tumors were divided into three areas: marginal, central and intermediate areas. In each area, the number of blood vessels per 10(4) mu 2 was randomly counted in 10 fields and a mean value of vessels was compared among the three groups. It was found that the following pathologic findings were significantly related to strong angiographic staining: (i) well-circumscribed border; (ii) large tumor nest; (iii) severe inflammatory cell infiltration; (iv) mild stromal fibrosis; and (v) absence of lymph node metastasis. The mean value of blood vessels in the strongly positive group was significantly increased in the overall and the intermediate areas. The density of the vessels in the intermediate area was thus thought to be responsible for the tumor blushing.


Effects of Pterional and Osteoplastic Craniotomy on Temporalis Muscle and Calvarial Bone Graft Atrophy.
This study aims to compare the effects of osteoplastic craniotomy on temporalis muscle and bone graft atrophy in patients operated on with a pterional approach to the standard technique. Patients operated on for an intracranial aneurysm with a pterional approach between 2014 and 2018 were studied. Following the exclusion criteria, 36 patients were included in this retrospective study. Temporalis muscle volume and bone graft volume were calculated. The volumes were compared from preoperative and postoperative computed tomography images for temporalis muscle and from early and late postoperative computed tomography images for the bone graft. The osteoplastic craniotomy group (group I) had 17 patients, and the standard craniotomy group had 19 patients (group II). Temporalis muscle volume and bone graft volume decreased statistically significantly in group II after surgery. However, no significant volume difference was found in group I measurements. When compared with the standard technique, osteoplastic craniotomy reduces the likelihood of postoperative temporalis muscle and bone graft atrophy in patients undergoing pterional craniotomy. As a result, the patients' cosmetic and functional well-being is improved.


Co-expressed type of ER and HER2 protein as a predictive factor in determining resistance to antiestrogen therapy in patients with ER-positive and HER2-positive breast cancer.
The purpose of this study was to analyze whether inter-site variation types on estrogen receptor (ER) and HER2 expression may be a predictive factor for evaluating the effectiveness of endocrine therapy in patients with ER-positive and HER2-positive breast cancer. A total of 366 consecutive women with invasive breast cancer who had undergone curative surgical treatment between 1996 and 2001 were included in this study. ER status was evaluated using the Allred score and HER-2 status was evaluated according to the HercepTest. In ER-positive and HER2-positive tumors, the expression of ER and HER2 was described as the co-expressed type or the differently expressed type using double staining with ER and HER2. Of the 366 patients, 249 (68.1%) were positive for ER and 74 (20.2%) were positive for HER2. ER-positive and HER2-negative tumors were found in 221 patients (60.4%), ER-negative and HER2-negative in 71 (19.4%), ER-negative and HER-2-positive in 46 (12.6%), and ER-positive and HER2-positive in 28 (7.7%). HER2 status was inversely correlated (p<0.01) with ER status. In ER-positive tumors, an inverse correlation between ER and HER2 was also observed. The co-expressed type was found in 10 patients, and the differently expressed type was found in 18. There was no difference in tumor size and nodal involvement between the two types. There was no significant difference in disease-free survival between patients with the co-expressed type tumor and the differently expressed type tumor. In patients with the differently expressed type tumor, those who received antiestrogen therapy showed a significantly better disease-free survival rate than those who did not receive antiestrogen therapy. As for patients with the co-expressed type of tumor, no significant difference in disease-free survival was observed between patients with and without antiestrogen treatment. The present study suggests that the co-expressed type of tumour might be a resistant factor to antiestrogen therapy in ER-positive and HER2-positive breast cancer.


Photocurrent response of MoS₂ field-effect transistor by deep ultraviolet light in atmospheric and N₂ gas environments.
Molybdenum disulfide (MoS2), which is one of the representative transition metal dichalcogenides, can be made as an atomically thin layer while preserving its semiconducting characteristics. We fabricated single-, bi-, and multilayer MoS2 field-effect transistor (FET) by the mechanical exfoliation method and studied the effect of deep ultraviolet (DUV) light illumination. The thickness of the MoS2 layers was determined using an optical microscope and further confirmed by Raman spectroscopy and atomic force microscopy. The MoS2 FETs with different number of layers were assessed for DUV-sensitive performances in various environments. The photocurrent response to DUV light becomes larger with increasing numbers of MoS2 layers and is significantly enhanced in N2 gas environment compared with that in atmospheric environment.


A near miss: the importance of context in a public health informatics project in a New Zealand case study.
This article describes the near failure of an information technology (IT) system designed to support a government-funded, primary care-based hepatitis B screening program in New Zealand. Qualitative methods were used to collect data and construct an explanatory model. Multiple incorrect assumptions were made about participants, primary care workflows and IT capacity, software vendor user knowledge, and the health IT infrastructure. Political factors delayed system development and it was implemented untested, almost failing. An intensive rescue strategy included system modifications, relaxation of data validity rules, close engagement with software vendors, and provision of intensive on-site user support. This case study demonstrates that consideration of the social, political, technological, and health care contexts is important for successful implementation of public health informatics projects.


Driving in search of analyses.
Although transportation safety has greatly improved over the past 2 decades, motor vehicle crash injuries remain a leading cause of morbidity and mortality, particularly among young drivers. Driver errors and behaviors such as speeding and distraction contribute disproportionately to crashes among inexperienced novices, who develop safe driving judgment only with substantial driving experience, commonly described as the "young driver problem." Research on young drivers has applied a range of research methods, including analyses of national archival data (mainly from police reports), crash analyses, observation of driver behavior, surveys of driver behavior and dispositions, and experimental research on driver behavior and vehicle crash worthiness. Prominent research questions regarding young driver safety include what and how do novices learn to drive safely, what are the predictors of young driver crashes, what is the variability and overtime trajectories of young driver performance and outcomes, and to what extent is the young driver problem due mainly to average population risk or high-risk groups? Current research on young drivers is complicated by small sample sizes, relatively rare events, high within and between group variability, missing data, the need to estimate exposure, and the lack of longitudinal and experimental designs, problems that require complex analytic methods. In this paper, we provide an overview of driving research methods, examples of research addressing the young driver problem, and examples of statistical collaboration on young driver research, focusing particularly on estimating prediction of crash risk and estimating variability in young driver performance and outcomes.


[Ulinastatin attenuates hyper-permeability of vascular endothelialium cells induced by serum from patients with sepsis].
Objective To study the effect of ulinastatin (UTI) on the hyper-permeability of human umbilical vein endothelial cell induced by the serum from patients with severe sepsis. Methods The serum level of tumor necrosis factor α (TNF-α) was examined by ELISA in 5 healthy volunteers and 5 patients with septic shock. EA.hy926 human umbilical vein endothelial cells were cultured in vitro and treated with different concentrations of UTI (10, 100, 1000 U/mL), 300 μL serum of septic shock patients and 22 ng/mL TNF-α. The permeability and the electrical resistance (TER) of EA.hy926 cells were detected by a TranswellTM chamber system and epithelial volt-ohm meter (EVOM) method, respectively. The morphological characteristics and distribution of F-actin were measured by immunofluorescence technique. Results The serum level of TNF-α in sepsis patients was significantly higher than that in healthy volunteers. After EA.hy926 cells were treated with the serum of septic shock patients, the TER significantly decreased; the cell permeability significantly increased; F-actin cytoskeleton was significantly redistributed; and intracellular stress fibers increased. But UTI could attenuate the above changes. Conclusion UTI attenuates the hyper-permeability of EA.hy926 cells induced by the serum of septic shock patients in a dose-dependent manner.


COllaborative Neonatal Network for the first European CPAM Trial (CONNECT): a study protocol for a randomised controlled trial.
Consensus is lacking on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM). For future studies, the CONNECT consortium (the COllaborative Neonatal Network for the first European CPAM Trial)-an international collaboration of specialised caregivers-has established consensus on a core outcome set of outcome parameters concerning respiratory insufficiency, surgical complications, mass effect and multifocal disease. These outcome parameters have been incorporated in the CONNECT trial, a randomised controlled trial which, in order to develop evidence-based practice, aims to compare conservative and surgical management of patients with an asymptomatic CPAM. Children are eligible for inclusion after the CPAM diagnosis has been confirmed on postnatal chest CT scan and they remain asymptomatic. On inclusion, children are randomised to receive either conservative or surgical management. Subsequently, children in both groups are enrolled into a standardised, 5-year follow-up programme with three visits, including a repeat chest CT scan at 2.5 years and a standardised exercise tolerance test at 5 years.The primary outcome is exercise tolerance at age 5 years, measured according to the Bruce treadmill protocol. Secondary outcome measures are molecular genetic diagnostics, validated questionnaires-on parental anxiety, quality of life and healthcare consumption-, repeated imaging and pulmonary morbidity during follow-up, as well as surgical complications and histopathology. This trial aims to end the continuous debate surrounding the optimal management of asymptomatic CPAM. This study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Centre Rotterdam, The Netherlands, has approved this protocol (MEC-2022-0441). Results will be disseminated through peer-reviewed scientific journals and conference presentations. NCT05701514.


Estimates of conditional survival in gastric cancer reveal a reduction of racial disparities with long-term follow-up.
In prior analyses, conditional survival (CS) estimates for gastric cancer have weighed clinical and pathologic factors to predict prognosis at time intervals after surgery. Since racial disparities in gastric cancer outcomes were not considered, our objective was to determine whether race influences CS estimates. Data from the Surveillance, Epidemiology, and End Results cancer registry were used to identify gastric adenocarcinoma patients who underwent curative surgical intervention between 1988 and 2005. Five-year relative conditional survival (RCS) was computed for patients who survived at least 1 to 5 years after surgery. RCS was calculated by assessing observed and expected survival in an age- and race-matched standard population. Results were compared across time and racial groups (white, black, and Asian) using z test statistics. Of 14,067 patients, 63.8 % were white, 15.5 % black, and 20.7 % Asian. Racial disparities among groups were observed with improved survival of Asians at time point zero and improved RCS at 1 year. At 5 years following curative surgery, each racial group had increased RCS and the greatest magnitude of relative increase was observed in white and black patients (121 and 118 %, respectively). Comparison of RCS at the 5-year time point revealed a reduction of racial disparities in survival among the three groups. Our investigation shows that racial disparities in gastric cancer outcomes are pronounced at the time of curative surgery but diminish after years of survival, thus suggesting race has less influence over outcomes the longer patients survive. The reasons for reduction of racial disparities remain unclear and warrant future study.


Different lipid A types in lipopolysaccharides of phototrophic and related non-phototrophic bacteria.
Lipid A analyses confirm not only the present taxa of the purple nonsulfur bacteria (formerly Rhodospirillaceae), but also phylogenetical relatedness of distinct phototrophic to distinct non-phototrophic bacteria, as was suggested by cataloguing 16S rRNA. For example, lipid A with ester-bound 3-OH-10:0 and the rare amide-linked 3-oxo-14:0 is common to the phototrophic Rhodobacter capsulatus and Rhodobacter sphaeroides and also to Paracoccus denitrificans and Thiobacillus versutus. 'Lipid ADAG' (lipid A with 2,3-diamino-D-glucose (DAG)) occurs in the phototrophic Rhodopseudomonas viridis and Rhodopseudomonas palustris and also in the related non-phototrophic species, e.g., Nitrobacter winogradskyi, Pseudomonas diminuta, or Thiobacillus ferrooxidans. The phylogenetically more coherent purple sulfur bacteria (Chromatiaceae) uniformly contain D-mannose in their phosphate-free lipid A. Among the green bacteria, only the Chlorobiaceae but not the likewise chlorosome-containing Chloroflexaceae contain lipopolysaccharide. Lipid ADAG from R. viridis is a structural analogue of a biosynthetic precursor (lipid X) of enterobacterial lipid A. Lipid A synthase from Salmonella accepts not only lipid X but also the synthetic di-N-acyl-2,3-diamino-D-glucose analogue as substrate (Raetz, C.R.H., unpublished results). More and more naturally occurring lipid A's with both, 2,3-diaminoglucose and glucosamine ('mixed' lipid A, with 2,3-diaminoglucose or glucosamine dominating) are being found. Newly recognized lipid A and lipid ADAG types might offer the possibility of differentially stimulating desired biological activities in animals without also having the undesired endotoxic activities. The non-toxic lipid A from Rhodopseudomonas viridis for example is able to stimulate prostaglandin secretion in peritoneal macrophages and can be used as an antagonist to the endotoxic shock caused by Salmonella lipopolysaccharide.


Olmesartan-Induced Enteropathy.
Olmesartan-induced enteropathy mimics celiac disease clinically and pathologically. As in celiac disease, the pathologic findings are villous atrophy and increased intraepithelial lymphocytes. Clinical presentation of olmesartan-induced enteropathy includes diarrhea, weight loss, and nausea. In contrast to celiac disease, tissue transglutaminase is not elevated and there is no response to a gluten-free diet. Including this entity in the differential diagnosis of sprue-like enteropathy is critical for its early diagnosis since replacing olmesartan with an alternative antihypertensive drug can simplify the diagnostic workup and provide both clinical and histologic improvement.