Engineering new synaptic connections in the C. elegans connectome.
Most of what we currently know about how neural circuits work we owe to methods based on the electrical or optical recording of neural activity. This is changing dramatically. First, the advent of optogenetic techinques has enabled precise manipulation of the activity of specific neurons. Second, the development of super-resolution methods for obtaining detailed maps of synaptic connectivity has paved the way for uncovering the connectomes of entire brains or brain regions. We describe a third and complementary new strategy for investigating and manipulating neural circuits: the artificial insertion of new synapses into existing neural circuits using genetic engineering tools. We have successfully accomplished this in C. elegans. Thus, In addition to being the first animal with an entirely mapped connectome, C. elegans is now also the first animal to have an editable connectome. Variations on this approach may be applicable in more complex nervous systems.


Evidence of ultrashort electron bunches in laser-plasma interactions at relativistic intensities.
The second harmonic of the laser light (2omega(0)) is observed on the rear side of thick solid targets irradiated by a laser beam at relativistic intensities. This emission is explained by the acceleration by the laser pulse in front of the target of short bunches of electrons separated by the period (or half the period) of the laser light. When reaching the rear side of the target, these electron bunches emit coherent transition radiation at 2omega(0). The observations indicate that, in our conditions, the minimum fraction of the laser energy transferred to these electron bunches is of the order of 1%.


Identification of a complete dibenzothiophene biodesulfurization operon and its regulator by functional metagenomics.
Functional screening for aromatic ring oxygenases of an oil contaminated soil metagenome identified 25 different clones bearing monooxygenases coding genes. One fosmid bore an operon containing four tightly linked genes coding for a complete dibenzothiophene biodesulfurization pathway, which included the predicted monooxygenases DszC and DszA, the desulfinase DszB, and an FMN-oxidoreductase designated DszE. The dszEABC operon provided Escherichia coli with the ability to use dibenzothiophene as the only sulfur source. Transcription of the operon is driven from a σN -dependent promoter and regulated by an activator that was designated dszR. DszR has been purified and characterized in vitro and shown to be a constitutively active σN -dependent activator of the group IV, which binds to two contiguous sequences located upstream of the promoter. The dsz promoter and dszE and dszR genes have apparently been recruited from an aliphatic sulfonate biodegradation pathway. If transcribed from a heterologous upstream promoter, the σN -dependent promoter region functions as an 'insulator' that prevents translation of dszE, by binding with its ribosome binding site. Translational coupling, in turn, prevents translation of the downstream dszABC genes. The silencer combined with translational coupling thus represents an effective way of preventing expression of operons when spuriously transcribed from upstream promoters.


Sulfoxide Reduction/C(sp3)-S Metathesis Cascade in Ionic Liquid.
A sulfoxide reduction/C-S bond metathesis cascade between sulfoxides and alkyl bromides has been developed to access high-value sulfides without the use of any catalysts or bases. In this cascade, classical Kornblum oxidation is employed to reduce sulfoxides with alkyl bromides in ionic liquid. This protocol features high functional tolerance, mild conditions, promising scalability, and sustainable solvents.


Posterior arch C-1 screw technique: a cadaveric comparison study.
OBJECTIVE Posterior atlantoaxial stabilization and fusion using C-1 lateral mass screw fixation has become commonly used in the treatment of instability and for reconstructive indications since its introduction by Goel and Laheri in 1994 and modification by Harms in 2001. Placement of such lateral mass screws can be challenging because of the proximity to the spinal cord, vertebral artery, an extensive venous plexus, and the C-2 nerve root, which overlies the designated starting point on the posterior center of the lateral mass. An alternative posterior access point starting on the posterior arch of C-1 could provide a C-2 nerve root-sparing starting point for screw placement, with the potential benefit of greater directional control and simpler trajectory. The authors present a cadaveric study comparing an alternative strategy (i.e., a C-1 screw with a posterior arch starting point) to the conventional strategy (i.e., using the lower lateral mass entry site), specifically assessing the safety of screw placement to preserve the C-2 nerve root. METHODS Five US-trained spine fellows instrumented 17 fresh human cadaveric heads using the Goel/Harms C-1 lateral mass (GHLM) technique on the left and the posterior arch lateral mass (PALM) technique on the right, under fluoroscopic guidance. After screw placement, a CT scan was obtained on each specimen to assess for radiographic screw placement accuracy. Four faculty spine surgeons, blinded to the surgeon who instrumented the cadaver, independently graded the quality of screw placement using a modified Upendra classification. RESULTS Of the 17 specimens, the C-2 nerve root was anatomically impinged in 13 (76.5%) of the specimens. The GHLM technique was graded Type 1 or 2, which is considered "acceptable," in 12 specimens (70.6%), and graded Type 3 or 4 ("unacceptable") in 5 specimens (29.4%). In contrast, the PALM technique had 17 (100%) of 17 graded Type 1 or 2 (p = 0.015). There were no vertebral artery injuries found in either technique. All screw violations occurred in the medial direction. CONCLUSIONS The PALM technique showed statistically fewer medial penetrations than the GHLM technique in this study. The reason for this is not clear, but may stem from a more angulated "up-and-in" screw direction necessary with a lower starting point.


[Treatment of recurrent herpes simplex with thymopoietin-pentapeptide].
Treatment resistant recurrent herpes simplex persisting for years in 7 patients was treated with thymopoietin pentapeptide for 6 weeks, 50 mg subcutaneously three times per week. During treatment and follow-up of 6 weeks a pronounced reduction of frequency and duration of recurrences were observed. There was some tendency for normalisation of deranged lymphocyte and granulocyte function. The mode of action of thymopoietin pentapeptide in recurrent herpes simplex remains uncertain. An indirect effect via stimulation of production of interferon may be assumed.


Patterns of cross-contamination in a multispecies population genomic project: detection, quantification, impact, and solutions.
Contamination is a well-known but often neglected problem in molecular biology. Here, we investigated the prevalence of cross-contamination among 446 samples from 116 distinct species of animals, which were processed in the same laboratory and subjected to subcontracted transcriptome sequencing. Using cytochrome oxidase 1 as a barcode, we identified a minimum of 782 events of between-species contamination, with approximately 80% of our samples being affected. An analysis of laboratory metadata revealed a strong effect of the sequencing center: nearly all the detected events of between-species contamination involved species that were sent the same day to the same company. We introduce new methods to address the amount of within-species, between-individual contamination, and to correct for this problem when calling genotypes from base read counts. We report evidence for pervasive within-species contamination in this data set, and show that classical population genomic statistics, such as synonymous diversity, the ratio of non-synonymous to synonymous diversity, inbreeding coefficient FIT, and Tajima's D, are sensitive to this problem to various extents. Control analyses suggest that our published results are probably robust to the problem of contamination. Recommendations on how to prevent or avoid contamination in large-scale population genomics/molecular ecology are provided based on this analysis.


[Adenovirus mediated double suicide gene under controlling by KDR promoter selectively kills vascular endothelial cells and colorectal tumor cells].
To investigate the selectively killing effect of adenovirus (Ad) mediated double suicide gene under the regulation of KDR promoter on vascular endothelial cells and colorectal tumor cells. 293 packaging cells were transfected with the plasmids of pAdEasy- KDR- CDglyTK and pAdEasy- CMV- CDglyTK and the infectious viruses were generated. The KDR expressive cells of ECV304,SW620 and the KDR inexpressive cells of LS174T were infected by two Ads. The infection rate was observed and the expression of CDglyTK was detected by RT- PCR. After treatment with different concentrations of 5- FC and GCV,the killing effect and bystander effect on ECV304,SW620 and LS174T were examined. The titers of these two purified Ads were 2.0 x 10(12 ) pfu/ml. There was no significant difference in infection rate between two recombinant Ads infecting various cells,and the infection rate increased in accordance with the enhancing titers of Ads. RT- PCR demonstrated that there existed the product of CDglyTK gene in all the cells infected by Ad- CMV- CDglyTK and the cells infected by Ad- KDR- CDglyTK except in the SL174T. The curative effect in this system on various cells was shown as follows: (1) All cells infected with Ad- CMV- CDglyTK and some cells of ECV304 and SW620 infected with Ad- KDR- CDglyTK were highly sensitive to the prodrugs,but there was no significant differences among them (P > 0.05); compared with ECV304 and SW620 cells,LS174T cells were not sensitive to the two prodrugs (P< 0.001). (2) The efficacy of double suicide gene was better than that of single suicide gene (P< 0.001). (3) The system had considerable bystander effect. The double suicide gene under the regulation of KDR promoter has specific killing effect on the KDR- expressing endothelial cells and colorectal tumor cells.


Monitoring Reactions on Solid Phases with Raman Spectroscopy.
The benefits of Raman spectroscopy were shown for the on-bead monitoring of diverse reactions. Raman spectroscopy was used for the development of new procedures on established linker systems, the real-time observation of several reactions on solid phases and the estimation of the reaction time for a new cleavage strategy. Selected conversions on solid phases, such as the on-bead conversion of functional groups and the attachment of novel building blocks, were demonstrated. Raman spectra were obtained after isolation and purification of the solid supports, but they were also measured directly in the reaction vessels. Even the detection of Raman-active functional groups in swollen polymer resins and in reaction mixtures was demonstrated, and allows real-time observation of the progress of diverse reactions on solid supports.


Application of Ultrasound in Detecting and Removing Migrating Grass Awns in Dogs and Cats: A Systematic Review.
Migrating grass awns are an important cause of disease in dogs and cats. Plant awns can migrate into several body tissues and cavities because of their fusiform shape and backward-pointing barbs. Their migration causes inflammatory tissue reaction and clinical signs depend upon their localization. Ultrasound has been described as a useful, noninvasive, and readily available tool to identify and guide vegetal foreign bodies removal in animals. The aim of this systematic review was to summarize current knowledge on the application of ultrasonography in the identification and removal of grass awns from various anatomic locations in dogs and cats. We selected and analyzed 46 papers on the application of ultrasonography in dogs and cats affected by migrating grass awns. The ultrasonographic appearance of grass awns is characteristic, although their size and location can influence the visualization and the attempt of removal. In some cases, migrating grass awns are not directly visualized by ultrasonography, but the lesions caused by their migration can be easily seen. Ultrasonography can be considered a useful diagnostic tool to localize and remove migrating grass awns; however, when the migration occurs in less accessible locations or discrete foreign bodies are present, this diagnostic tool should be considered as a part of a multidisciplinary approach with advanced diagnostic imaging modalities.


The use of Targeted MicroCurrent Therapy in postoperative pain management.
Effective postoperative analgesia is a prerequisite to enhance the recovery process and reduce morbidity. The use of local anesthetic techniques is well documented to be effective, but single-dose techniques (infiltration, peripheral blocks, neuraxial blocks) have been of limited value in major operations because of their short duration of analgesia. Recent advances in technology have led to the development of a noninvasive device, targeted MicroCurrent Therapy, which enhances postsurgical recovery by stimulating the body's natural healing process. This therapy transmits gentle, short bursts of electrical current targeted to the tissue cells at the surgical site. This article reviews recent clinical experience and evidence of this device in plastic and reconstructive surgery.


Mixed valency in hydrogen bonded 'dimers of dimers'.
Dimolybdenum quadruply bonded compounds containing a pendant lactam functional group form self-complementary hydrogen bonded 'dimers of dimers' in the solid-state and CH(2)Cl(2) solutions. Electrochemical studies in CH(2)Cl(2) show two consecutive one-electron redox processes corresponding to oxidation of the Mo(2)(4+) cores. Spectroelectrochemical studies on the 'dimers of dimers' show no evidence of intervalence charge transfer bands in the mixed valence radical cations formed by one-electron oxidation, indicating that they are examples of proton-coupled mixed valency.


Widow spider envenomation (latrodectism): a worldwide problem.
The objective of this study was to review widow spider envenomation on a worldwide basis, with an emphasis on regional variability in management, particularly between the United States and Australia. Data sources were the Medline database (1966-1997) for English language references using as key words widow spider, latrodectism, and red back spider, and Mesh headings. Textbooks of toxinology were also used. Studies involving clinical reports and series were selected. The data indicated that envenomation by widow spiders (latrodectism) is common worldwide. Local pain and sweating predominate, in about 25% of cases becoming generalized or developing in remote sites. The mortality in published series varies from 5% to 10%, although these may be overestimates. Australia may have the highest rate of latrodectism in the world. The literature reveals regional disparities in the treatment and outcome of latrodectism. In Australia, intramuscular antivenin has been used liberally for more than 40 years with a very low rate (0.5% to 0.8%) of allergic reactions and no deaths recorded since its introduction. Antivenin is routinely successful in relieving the effects of latrodectism. In the United States, the antivenin is given intravenously, is usually reserved for very severe cases, and the rate of allergic reaction is high (from 9% up to 80% in those skin testing positive). Deaths have been recorded after antivenin. The literature suggests that antivenin to one species of Latrodectus is likely to be effective against other species. The conclusion drawn was that latrodectism is a common envenomation worldwide. There is a strong case for a comparative trial of Australian vs US antivenin in treating latrodectism due to the black widow spider in the United States.


Interplay between structural changes, surface states and quantum confinement effects in semiconducting Mg2Si and Ca2Si thin films.
Ab initio techniques have been used to investigate structural changes in semiconducting Mg2Si and Ca2Si thin films (from 17 nm down to 0.2 nm corresponding to the 2D structure) along with band-gap variations due to quantum confinement. Cubic Mg2Si(111) thin films being dynamically stable at thicknesses (d) larger than 0.3 nm displayed an indirect band gap, the reduction of which with increasing d could be reasonably well described by the simple effective mass approximation. Only 2D Mg2Si has a unique structure because of the orthorhombic distortion and the direct band gap. Since the surface energy of cubic Ca2Si(111) films was lower with respect to any surface of the orthorhombic phase, which is the ground state for the Ca2Si bulk, the metastable in-bulk cubic phase in the form of thin films turned out to be preferable in total energy than any orthorhombic Ca2Si thin film for d < 3 nm. Sizable structural distortion and the appearance of surface states in the gap region of Ca2Si thin films with d < 3 nm could be the reason for an odd dependence of the band-gap variation on d.


Short-term (48 hours) intravenous serelaxin infusion has no effect on myogenic tone or vascular remodeling in rat mesenteric arteries.
Short-term IV sRLX (recombinant human relaxin-2) infusion enhances endothelium-dependent relaxation in mesenteric arteries. This is initially underpinned by increased NO followed by a transition to prostacyclin. The effects of short-term IV sRLX treatment on pressure-induced myogenic tone and vascular remodeling in these arteries are unknown. Therefore, we investigated the effects of sRLX infusion on pressure-induced myogenic tone and passive mechanical wall properties in mesenteric arteries. Mesenteric artery myogenic tone and passive mechanics were examined after 48-hours and 10-days infusion of sRLX. Potential mechanisms of action were assessed by pressure myography, qPCR, and Western blot analysis. Neither 48-hours nor 10-days sRLX treatment had significant effects on myogenic tone, passive arterial wall stiffness, volume compliance, or axial lengthening. However, in 48-hours sRLX -treated rats, incubation with the NO synthase blocker L-NAME significantly increased myogenic tone (P<.05 vs placebo), demonstrating an increased contribution of NO to the regulation of myogenic tone. eNOS dimerization, but not phosphorylation, was significantly upregulated in the arteries of sRLX -treated rats. In mesenteric arteries, 48-hours sRLX treatment upregulates the role of NO in the regulation of myogenic tone by enhancing eNOS dimerization, without altering overall myogenic tone or vascular remodeling.


[The functional pathology of hypophyseal adenomas].
This review summarizes some aspects of pituitary adenoma pathology. A new embracing pituitary adenoma classification has been developed which correlates morphologic findings with endocrine activity. It is based on hormone content, histologic, immunohistochemical and ultrastructural features, cellular composition and cytogenesis, and separates pituitary adenomas into 7 distinct entities.


Antifungal and Antibacterial Activities of Apple Vinegar of Different Cultivars.
This study was designed to assess the antimicrobial potencies of apple vinegar against pathogenic microbes. The acidity and total phenolic content were carried out by titration with NaOH 0.1 N and the Folin-Ciocalteu method, respectively, while the spread plate method, agar well diffusion, and MIC assays were used to determine the antimicrobial activities of different vinegar samples. Acidity and phenolic content were dependent on the variety, where the highest values were observed in S2 with 4.02 ± 0.04% and 1.98 ± 0.05 mg GAE/mL for acidity and total phenolic content, respectively. The spread plate method revealed that samples S1 and S2 obtained from the Red delicious variety and Golden delicious variety, respectively, inhibit the growth of all tested strains, while S3 obtained from different varieties and S4 obtained from the Gala royal variety inhibit only two microbes (Escherichia coli and Vibrio cholerae). Sample S1 presented moderate antimicrobial effect against all examined strains with a diameter of inhibition ranging from 11 ± 0.7 to 19 ± 0.5 mm and with MIC values ranging between 1/2 and 1/100. The findings of the current study confirm the usefulness of apple vinegar as a natural sanitizer that inhibits the growth of pathogenic microbes.


An unusual bone loss around implants.
Pre-implant disease is an inflammatory process that affects the surrounding tissues of a functional osseointegrated implant. It is usually the result of a disequilibrium between the micro-flora and the defense system. This case reports a 57-year-old man with unusual bone loss around dental implants. This was an unusual case of peri-implantitis that occurred only in the implants on one side of the mouth although they were all unloaded implants.


Duchenne muscular dystrophy: genome editing gives new hope for treatment.
Duchenne muscular dystrophy (DMD) is a progressive wasting disease of skeletal and cardiac muscles, representing one of the most common recessive fatal inherited genetic diseases with 1:3500-1:5000 in yearly incidence. It is caused by mutations in the DMD gene that encodes the membrane-associated dystrophin protein. Over the years, many have been the approaches to management of DMD, but despite all efforts, no effective treatment has yet been discovered. Hope for the development of potential therapeutics has followed the recent advances in genome editing and gene therapy. This review gives an overview to DMD and summarises current lines of evidence with regard to treatment and disease management alongside the appropriate considerations.


Chemotherapeutic profiles of human tumors implanted in SCID mice showing appreciable inconsistencies with those in nude mice.
Sensitivities to antitumor drugs of human tumor xenografts (HTXs) implanted in C.B-17-scid and in BALB/cA-nu were compared to examine whether genetic backgrounds of immune deficiency of the host mice influenced the chemotherapeutic profiles of implanted tumors. In a total of 25 pairs of corresponding experiments with each host mouse strain (5 HTXs x 5 drug treatment groups), we obtained consistent results in 23 (92.0%) experiments consisting of 10 which were both significantly effective and 13 which were both ineffective, although the remaining two (8.0%) experiments showed inconsistent results. A human T-cell lymphoma cell line, LM-2-JCK, implanted in nude mice, was resistant to treatment with 65 mg/kg of cyclophosphamide, but this tumor showed sensitivity to the same treatment when implanted in either SCID mice or mice with a recombination activating gene 2 defect [BALB/cA-TgH (Rag2)], suggesting that the genetic immune background of the host mouse should not be overlooked as a factor affecting tumors.


[Congenital uterine anomalies: diagnosis, prognosis and management in 2008].
The müllerian anomalies or congenital uterine anomalies are relatively frequent if we keep in mind that 3-4% of our female patients present with a müllerian anomaly, although many among them are asymptomatic. It is important to evoke this diagnosis for all patients with a history of recurrent miscarriage, late abortion and premature delivery, for the adolescent consulting for primary amenorrhea, dysmenorrhea or dyspareunia as well as for the woman consulting for infertility. We will review pathogenesis, diagnostic methods, standard classification with a description of the different types of congenital uterine anomalies and the recommended management.


Neurobiology of chronicization.
In the past few years, research on chronicization of headache has focussed primarily on migraine, even though there are other types of primary headache that over time can turn into chronic forms. Only a minority of migraine sufferers will develop a chronic condition, with attacks that are likely to vary in their clinical features. As a result, in chronic migraine the specific diagnostic criteria for this headache type do not always exhibit the typical features of migraine. Among the factors that play a major role in favouring chronicization are a high frequency of migraine attacks since the beginning, overuse of symptomatic medication and onset of depression or arterial hypertension. Several neurophysiology, biochemistry and functional neuroimaging studies suggest that chronic migraine may be associated with structural, functional and metabolic changes in the brain, especially involving the brainstem.


Fluoroquinolone use and fluoroquinolone resistance: is there an association?
In an assessment of potential risk factors for nosocomial infections caused by fluoroquinolone-resistant gram-negative organisms, 68 patients who developed a nosocomial infection caused by a fluoroquinolone-resistant gram-negative bacillus were compared with 191 patients who developed a nosocomial infection caused by a fluoroquinolone-susceptible gram-negative bacillus. A history of previous infection, immunosuppression, prior receipt of fluoroquinolones, and hospitalization on the burn unit were independent risk factors. Except for immunosuppression, the same risk factors were identified when the 50 patients whose isolates were resistant to fluoroquinolones, aminoglycosides, and beta-lactam antibiotics were compared with the 95 patients whose isolates were susceptible to all of these classes of antimicrobial agents. The identification of hospitalization on the burn unit as a risk factor was attributable to an outbreak of infections caused by a resistant strain of Pseudomonas aeruginosa during the study period. The occurrence of nosocomial outbreaks and the selective pressure of fluoroquinolone use were the main exogenous risk factors involved in the emergence of resistance to fluoroquinolones.


The Role of Oxidative Stress, Adhesion Molecules and Antioxidants in Preeclampsia.
Oxidative stress is a consequence of reduction in the antioxidant capacity and excessive production of reactive oxygen and nitrogen species (ROS). Oxidative agents, which are overproduced due to ischemic-reperfusion injury in the placenta, may overwhelm the normal antioxidant activity. This imbalance is a key feature in the pathogenesis of preeclampsia. A decrease in glutathione peroxidase (GPX) activity is associated with the synthesis of vasoconstrictive eicosanoids such as F2-isoprostanes and thromboxane, which are known to be upregulated in preeclampsia. Biochemical markers of lipid peroxidation, such as malondialdehyde and F2-isoprostane in the placenta, are also increased. Adhesion molecules participate in the pathophysiology of preeclampsia by contributing to a reduced invasion by the trophoblast and increased vascular endothelial damage. Superoxide dismutase (SOD), catalase (CAT) and GPX play important roles counteracting oxidative stress. Other antioxidant factors participate in the etiology of preeclampsia. Levels of antioxidants such as Lycopene, Coenzyme 10, as well as some vitamins, are reduced in preeclamptic gestations.


Systematic Bias Introduced by Genomic DNA Template Dilution in 16S rRNA Gene-Targeted Microbiota Profiling in Human Stool Homogenates.
Variability in representation of microbial communities can be caused by differences in microbial composition or artifacts introduced at sample collection or processing. Alterations in community representation introduced by variations in starting DNA concentrations have not been systematically investigated in stool samples. The goal of this study was to evaluate the effect of the genomic DNA (gDNA) concentration in the resulting 16S rRNA gene library composition and compare its effect to other sample processing variables in homogenized human fecal material. Compared to a gDNA input of 1 ng/μl, inputs of ≤1.6 × 10-3 ng/μl resulted in a marked decrease in the concentration of the 16S rRNA gene amplicon (P < 0.001). Low gDNA concentrations (≤1.6 × 10-3 ng/μl) were also associated with a decrease (P < 0.001) in the number of operational taxonomic units and significant divergence in β-diversity profiles (unweighted UniFrac distance, P < 0.001), as characterized by an overestimation of Proteobacteria and underestimation of Firmicutes. Even a gDNA concentration of 4 × 10-2 ng/μl showed a significant impact on the β-diversity profile (unweighted UniFrac distance, P = 0.03). Overall, the gDNA concentration explained 22.4% to 38.1% of the microbiota variation based on various β-diversity measures (P < 0.001). By comparison, the DNA extraction methods and PCR volumes tested did not significantly affect the microbial composition profile, and the PCR cycling method explained less than 3.7% of the microbiota variation (weighted UniFrac distance, P = 0.03). The 16S rRNA gene yield and the microbial community representation of human homogenized stool samples are significantly altered by gDNA template concentrations of ≤1.6 × 10-3 ng/μl. In addition, data from studies with a gDNA input of ≤4 × 10-2 ng/μl should be interpreted with caution. IMPORTANCE The genomic DNA input for stool samples utilized for microbiome composition has not been determined. In this study, we determined the reliable threshold level under which conclusions drawn from the data may be compromised. We also determined the type of microbial bias introduced by less-than-ideal genomic input.


Patient waiting time in the outpatient clinic at a central surgical hospital of Vietnam: Implications for resource allocation.
Background: Patient waiting time is considered as a crucial parameter in the assessment of healthcare quality and patients' satisfaction towards healthcare services. Data concerning this has remained limited in Vietnam. Thus, this study aims to assess patient waiting time in the outpatient clinic in Viet Duc Hospital (Hanoi, Vietnam) in order to enable stakeholders to inform evidence-based interventions to improve the quality of healthcare services. Methods: A cross-sectional study was conducted from June 2014 to June 2015 in the outpatient clinic at Viet Duc Hospital. Waiting time stratified by years (2014 and 2015), months of the year, weekdays, and hours of the day were extracted from Hospital Management software and carefully calculated. Stata 12.0 was employed to analyze data, including the average time (M± SD), frequencies and percentage (%). Results: There was a total of 137,881 patients involved in the study. The average waiting time from registration to preliminary diagnosis in 2014 was 50.41 minutes, and in 2015 was 42.05 minutes. A longer waiting time was recorded in the morning and in those having health insurance. Conclusions: Our study highlights the essential need for human resource promotion to reduce patient waiting time. Also, attention should be paid to the simplification of administrative procedures in order to reduce waiting time among insured patients.


Metabolic syndrome and C-reactive protein in bank employees.
The ultrasensitive C-reactive protein (us-CRP) is used for the diagnosis of cardiovascular disease, but it is not well described as a marker for the diagnosis of metabolic syndrome (MS). An observational and transversal study of bank employees evaluated anthropometric, hemodynamic, and biochemical data. CRP values were determined using commercial kits from Roche Diagnostics Ltd, and MS criteria were analyzed according to National Cholesterol Education Program's - Adult Treatment Panel III (NCEP/ATP III). A total of 88 individuals had MS, and 77.3% (n=68) of these showed alterations of us-CRP (P=0.0001, confidence interval [CI] 0.11-0.34). Individuals with MS had higher mean values of us-CRP in global measures (P=0.0001) and stratified by sex (P=0.004) than individuals without the syndrome. This marker exhibited significant differences with varying criteria for MS, such as waist circumference (P=0.0001), triglycerides (P=0.002), and diastolic blood pressure (P=0.007), and the highest levels of us-CRP were found in individuals with more MS criteria. us-CRP was strongly associated with the presence of MS and MS criteria in this group of workers. us-CRP is a useful and effective marker for identifying the development of MS and may be used as a reference in routine care.


Dye Decolorization by a Miniaturized Peroxidase Fe-MimochromeVI*a.
Oxidases and peroxidases have found application in the field of chlorine-free organic dye degradation in the paper, toothpaste, and detergent industries. Nevertheless, their widespread use is somehow hindered because of their cost, availability, and batch-to-batch reproducibility. Here, we report the catalytic proficiency of a miniaturized synthetic peroxidase, Fe-Mimochrome VI*a, in the decolorization of four organic dyes, as representatives of either the heterocyclic or triarylmethane class of dyes. Fe-Mimochrome VI*a performed over 130 turnovers in less than five minutes in an aqueous buffer at a neutral pH under mild conditions.


Molecular cloning and characterization of a cDNA encoding poplar UDP-glucose dehydrogenase, a key gene of hemicellulose/pectin formation.
Plant UDP-glucose dehydrogenase (UGDH) is an important enzyme in the formation of hemicellulose and pectin, the components of newly formed cell walls. A cDNA clone (Ugdh) corresponding to UGDH was isolated from a cDNA library prepared from cambial zone of poplar (Populus tremula x tremuloides). Within the 1824-nucleotide (nt)-long clone, an open reading frame encoded a protein of 481 amino acids (aa), with a calculated molecular weight of 53.1 kDa. The derived aa sequence showed 90% and 63% identity with UGDHs from soybean and bovine liver, respectively, and had highly conserved aa motifs believed to be of importance for nt binding and catalytic efficiency. In poplar, the Ugdh corresponds to one or two genes, as found by genomic Southern analysis. The gene was expressed predominantly in differentiating xylem and young leaves, with little expression in the phloem zone of the stem. The expression pattern matched that of UGDH protein, as found by immunoblotting. In leaves, the Ugdh expression was upregulated by a short-term feeding with sucrose, sorbitol and polyethylene glycol, and this effect was to some extent mimicked by light exposure. The data suggest that Ugdh is regulated via an osmoticum-dependent pathway, possibly related to the availability of osmotically active carbohydrate precursors to UDP-glucose, a substrate of UGDH.


Establishment of a specific cell death induction system in Bombyx mori by a transgene with the conserved apoptotic regulator, mouse Bcl-2-associated X protein (mouse Bax).
The induction of apoptosis in vivo is a useful tool for investigating the functions and importance of particular tissues. B-cell leukaemia/lymphoma 2-associated X protein (Bax) functions as a pro-apoptotic factor and induces apoptosis in several organisms. The Bax-mediated apoptotic system is widely conserved from Caenorhabditis elegans to humans. In order to establish a tissue-specific cell death system in the domestic silkworm, Bombyx mori, we constructed a transgenic silkworm that overexpressed mouse Bax (mBax) in particular tissues by the Gal4-upstream activation sequence system. We found that the expression of mBax induced specific cell death in the silk gland, fat body and sensory cells. Fragmentation of genomic DNA was observed in the fat body, which expressed mBax, thereby supporting apoptotic cell death in this tissue. Using this system, we also demonstrated that specific cell death in sensory cells attenuated the response to the sex pheromone bombykol. These results show that we successfully established a tissue-specific cell death system in vivo that enabled specific deficiencies in particular tissues. The inducible cell death system may provide useful means for industrial applications of the silkworm and possible utilization for other species.


Stages in the incorporation of fatty acids into red blood cells.
Mature human erythrocytes were incubated with (14)C-labeled palmitic acid bound to crystalline human albumin. Energy-dependent incorporation of the labeled palmitic acid into cell membrane phospholipids occurred, and various stages in this incorporation were defined. Initially the palmitic acid was rapidy transferred from the albumin to a "superficial" membrane pool of free fatty acid (F-1), which was removable when the cells were washed with defatted albumin. This process was independent of red cell metabolism. The labeled fatty acid then passed into a second "deeper" membrane pool of free fatty acids (F-2), which was not extractable with albumin. This process was energy-dependent and proceeded at a slower rate than the initial transfer from albumin to F-1. Ultimately the labeled fatty acid was incorporated into phosphatides (PL). This process also was dependent upon cellular metabolism. The kinetics of pulse label studies suggest that the processes observed were sequential and that precursor-product relationships exist between the F-1 and F-2 pools and the F-2 and PL pools. [Formula: see text] From the size and specific activities of these pools, calculations of the extent of phospholipid turnover were made. An approximate figure of 2% /hr or 30 nmoles/ml of packed red blood cells per hr was obtained. The figure was further calculated to represent an energy cost to the red blood cell of approximately 5% of the energy available from glycolysis.


Optimizing the long-term operating plan of railway marshalling station for capacity utilization analysis.
Not only is the operating plan the basis of organizing marshalling station's operation, but it is also used to analyze in detail the capacity utilization of each facility in marshalling station. In this paper, a long-term operating plan is optimized mainly for capacity utilization analysis. Firstly, a model is developed to minimize railcars' average staying time with the constraints of minimum time intervals, marshalling track capacity, and so forth. Secondly, an algorithm is designed to solve this model based on genetic algorithm (GA) and simulation method. It divides the plan of whole planning horizon into many subplans, and optimizes them with GA one by one in order to obtain a satisfactory plan with less computing time. Finally, some numeric examples are constructed to analyze (1) the convergence of the algorithm, (2) the effect of some algorithm parameters, and (3) the influence of arrival train flow on the algorithm.


How the environment shapes cancer genomes.
The mutational patterns of cancer genomes allow conclusions or generation of hypotheses as to what mechanisms or environmental, dietary or occupational exposures might have created the mutations and therefore will have contributed to the formation of the cancer. The arguments for cancer causation are particularly convincing when epidemiological evidence can support the theory that a particular exposure is linked to the cancer and when the mutational process can be recapitulated in experimental systems. In this review, I will summarize recent evidence from cancer genome sequencing studies to exemplify how the environment can modulate tumor genomes. Mutation data from cancer genomes clearly implicate the ultraviolet B component of sunlight in melanoma skin cancers, tobacco carcinogen-induced DNA damage in lung cancers and aristolochic acid, a chemical compound found in certain herbal medicines, in urothelial carcinomas of exposed populations. However, large-scale sequencing is beginning to unveil other unique mutational spectra in particular cancers, such as A-to-C mutations at 5'AA dinucleotides in esophageal adenocarcinomas and complex mutational patterns in liver cancer. These datasets can form the basis for future studies aimed at identifying the carcinogens at work. The findings have substantial implications for our understanding of cancer causation and cancer prevention.


Cost-sensitive Active Learning for Phenotyping of Electronic Health Records.
Developing high-throughput and high-performance phenotyping algorithms is critical to the secondary use of electronic health records for clinical research. Supervised machine learning-based methods have shown good performance, but often require large annotated datasets that are costly to build. Simulation studies have shown that active learning (AL) could reduce the number of annotated samples while improving the model performance when assuming that the time of labeling each sample is the same (i.e., cost-insensitive). In this study, we proposed a cost- sensitive AL (CostAL) algorithm for clinical phenotyping, using the identification of breast cancer patients as a use case. CostAL implements a linear regression model to estimate the actual time required for annotating each individual sample. We recruited two annotators to manual review medical records of 766 potential breast cancer patients and recorded the actual time of annotating each sample. We then compared CostAL, AL, and passive learning (PL, aka random sampling) using this annotated dataset and generated learning curves for each method. Our experimental results showed that CostAL achieved the highest area under the curve (AUC) score among the three algorithms (PL, AL, and CostAL are 0.784, 0.8501, and 0.8673 for user 1 and 0.8006, 0.8806 and 0.9006 for user 2). To achieve an accuracy of 0.94, AL and CostAL could save 36% and 60% annotation time for user 1 and 53% and 70% annotation time for user 2, when they were compared with PL, indicating the value of cost-sensitive AL approaches.


The Periodic-Table-A Universal Icon: Its Birth 150 Years Ago, and Its Popularization Through Literature Art and Music.
This Essay projects the spark of genius of Mendeleev, whose efforts led to the effective formulation of the periodic table, which has placed the entire world of chemical matter on a palm. The periodic table gave rise to a central paradigm, which did for chemistry what Newton had done for physics and Darwin for biology. Subsequently the Essay recounts the popularization of the Periodic Table through literature by Primo Levi, Oliver Sacks and others, and through music and art by composers and artists, such as Jerry Feldman, the King Crimson band, Tom Lehrer, and George Brecht, Blair Bradshaw, Eugènia Balcells, etc.


Pharmacotherapy for personality disorders.
Although there are many methodological uncertainties in the treatment of personality disorders, which make it difficult to be confident about efficacy, there is growing evidence that at least in some personality disorders, drug treatment may be of value. Borderline personality disorder is a condition in which treatment evidence is the most promising, but it is also one of the most difficult disorders to disentangle the mental state from personality components. In summary, there is reasonable evidence that antidepressants, particularly serotonin re-uptake inhibitors and monoamine oxidase inhibitors, have beneficial effects independent of their antidepressive ones and albeit, less favourable, evidence that antipsychotic drugs and mood stabilisers may also be of value. None of this evidence is yet sufficient to point to any specific drug treatment indications.


Characterization of rough surfaces with vibrated drops.
Wetting transitions were studied with vertically-vibrated drops on various artificial and natural rough substrates. Alternative pathways of wetting transitions were observed. The model of wetting transition is presented. Multiple minima of the Gibbs free energy of a drop deposited on a rough surface explain alternative pathways of wetting transitions. We demonstrate that a wetting transition occurs when the constant force resulting from vibrations, Laplace and hydrostatic pressure acts on the triple line. It is shown that the final wetting states are mainly the Cassie impregnating wetting state with water penetrating the pores in the outer vicinity of the droplet or the Wenzel state with water inside the pores under the droplet whereas the substrate ahead the drop is dry.


Visualization of chemokine binding sites on human brain microvessels.
The chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) aid in directing leukocytes to specific locales within the brain and spinal cord during central nervous system inflammation. However, it remains unclear how these chemokines exert their actions across a vascular barrier, raising speculation that interaction with endothelial cells might be required. Therefore, experiments were performed to determine whether binding domains for these chemokines exist along the outer surface of brain microvessels, a feature that could potentially relay chemokine signals from brain to blood. Using a biotinylated chemokine binding assay with confocal microscopy and three-dimensional image reconstruction, spatially resolved binding sites for MCP-1 and MIP-alpha around human brain microvessels were revealed for the first time. Binding of labeled MCP-1 and MIP-1alpha could be inhibited by unlabeled homologous but not heterologous chemokine, and was independent of the presence of heparan sulfate, laminin, or collagen in the subendothelial matrix. This is the first evidence of specific and separate binding domains for MCP-1 and MIP-1alpha on the parenchymal surface of microvessels, and highlights the prospect that specific interactions of chemokines with microvascular elements influence the extent and course of central nervous system inflammation.


[An investigation on the incidence and risk factors of injuries in middle school students of Hunan province].
To study the incidence of injuries in middle school students of Hunan province and to explore its influencing factors. Both stratified and cluster sampling were used to obtain the samples in Hunan province, and students from 96 classes in 16 middle schools together with their parents were selected to participate in this investigation. Recognized criteria for injuries, self-rating depression scale, self-rating anxiety scale, interpersonal sensitivity of symptom checklist, family assessment device, parenting locus of the control scale, and self-developed questionnaire were used together to collect data. Chi-square test and logistic regression were employed for data analysis. The overall incidence rate of injuries among middle school students in Hunan province was 48.74% with 95% CI as (47.43%, 50.05%). Data from the comparisons of injury incidences between males and females, single child and non-single child in the family or among different regions and grades, showed significant differences (P < 0.05). However, no statistical difference was found between students from key or ordinary middle schools (P > 0.05). The results of logistic regression showed that region, grade, gender, having single child or not in the family, tired of staying at school, depression, anxiety, and with peers who often hunt the recreational places were the influencing factors to injury with ORs seen as 1.13, 0.94, 0.72, 0.84, 1.14, 1.47, 1.16, and 2.20, respectively. In addition, compared to the students whose fathers were being unemployed or retirees had a lower chance to experience an injuries, OR = 0.53. The overall prevalence of injuries among middle school students in Hunan province was 48.74%. The influencing factors for injuries in middle school students would include: region of resicence, grade, gender, being single child or not, tired of staying at school, under depression, anxiety, with peers who often hunt the recreational places, and father' s job situation.


Functional result and visual outcome in early versus conventional treatment of retinopathy of prematurity.
Retinopathy of prematurity (ROP) is a significant cause of blindness in childhood worldwide. The objective of the present study is to assess long-term structural and functional results of early (received first treatment at pre-threshold stage) versus conventional treatment (treated at threshold stage) of ROP MATERIAL AND METHOD: Survivors of ROP patients who underwent early or conventional treatment between 1997 and 2001 were reassessed in 2006. Functional outcome [refractive state, best corrected visual acuity (BCVA)] and anatomical outcome (retina status, ocular alignment) were compared between the two treatments using Chi-square test at p < 0.05. Of 68 patients, 39 (57.4%) returned for reassessment: 11 patients (22 eyes) were in the early treatment group and 28 patients (56 eyes) were in the conventional group. At 5 years or more, a favorable outcome (BCVA > 20/200) was achieved in 72.7% of the early group vs. 53.6% in the conventional group (p > 0.05). Normal to near normal vision (20/12-20/60 or log MAR 0.1-0.5) was significantly found in the early group (54.5% vs. 23.2%, p = 0.008) and none in the early group lost vision to no light perception. Prevalence of high myopia > 5 diopters and astigmatism were significantly higher in the conventional group (p = 0.001 and p = 0.002 respectively). Smaller degree of ET developed significantly in the early treated group (p = 0.018) whereas ET 15 prisms or more developed exclusively in the conventional group (p = 0.04). Retinal detachment occurred in 18.1% of the early treated compared to 28.5% of the conventional groups (p = 0.402). Early treatment of ROP at pre-threshold stage offered a better structural and functional outcome than at threshold. ROP patients should undergo periodic fundus examination between 6 months and 1 year of age and yearly thereafter for early detection and repair as well as yearly refraction and ocular alignment assessment to identify high refractive errors, astigmatism and strabismus for early recognition and correction.


Long-term retention of the habituation of lick suppression and startle response produced by a single auditory stimulus.
Response decrement produced by a single, 2-sec, 98 dB, auditory stimulus in rats was retained without detectable loss for intervals ranging from approximately 30 sec to 30 days. Response decrements produced by stimulation over these intervals reached an apparent asymptote after 2 or 3 stimulus presentations. These response decrements were unambiguously associated with stimulus presentation for the lick suppression measure, but nonspecific decremental effects may have contributed to the startle response decrements. After these long-term decrements had reached asymptote, 300 stimulus presentations with 1-sec interstimulus intervals produced further response decrements, but these decrements recovered completely within 24 hr., responsiveness returning to the previously established long-term asymptote. The data show that unreinforced stimulus presentations can produce both relatively permanent response decrements and apparently independent short-term decrements. The data also suggest that long-term retention may be more generally characteristic of habituation than is usually assumed.


Prognostic Factors Associated with Recovery of Ambulation and Urinary Continence in Dogs with Acute Lumbosacral Spinal Cord Injury.
Limited information is available about prognostic factors for recovery after spinal cord injury (SCI) to the L4-S3 segments. Previous research suggests that L4-S3 SCI does not have a worse prognosis than T3-L3 SCI. To elucidate prognostic factors for regaining urinary continence and ambulation in dogs with L4-S3 SCI and compare prognosis to T3-L3 SCI. A retrospective study on 61 nonambulatory dogs with L4-S3 SCI, matched to dogs with T3-L3 SCI, compared 3 weeks after onset. Prognostic factors explored using logistic regression and used for matching: nonchondrodystrophic dogs >15 kg versus dogs that were chondrodystrophic or <15 kg; compressive versus noncompressive lesions; presence versus absence of conscious pain perception (CPP); and lower vs upper motor neuron (LMN/UMN) incontinence. Fewer L4-S3 dogs regained continence compared to T3-L3 dogs (64 vs 85%, P = .0033), but no difference existed for regaining ambulation (66 vs 75%, P = .1306). In L4-S3 SCI dogs, fewer dogs regained continence with loss of CPP (P < .001), LMN incontinence (P = .004), and noncompressive lesions (P = .006). Negative prognostic factors for regaining ambulation included absent CPP (P < .001) and large nonchondrodystrophic breed (P = .022). Dogs with L4-S3 SCI have a poorer short-term prognosis than do dogs with T3-L3 SCI. Dogs with L4-S3 SCI had a poor prognosis with loss of CPP, or noncompressive lesions combined with LMN incontinence. Small-breed or chondrodystrophic dogs with retained CPP, compressive lesions, and UMN incontinence had an excellent prognosis. These findings may help guide decision-making in L4-S3 SCI.


Effective one-step saccharification of lignocellulosic biomass using magnetite-biocatalysts containing saccharifying enzymes.
Lignocellulosic biomass, packed with sugars, is one of the most available renewable resources for biofuels and bioproducts production. To release the sugars for the production, enzymatic hydrolysis (saccharification) of pretreated lignocellulosic biomass are required. However, the saccharification process is costly, inefficient, and requires multi-step operations. This is in part due to the high cost and the limited selection of commercial enzymes which commonly have different optimal pH and temperatures. Here we reported a one-step saccharification of pretreated lignocellulosic biomass using immobilized biocatalysts containing five different saccharifying enzymes (SEs) with a similar optimum pH and temperature. The five SEs - endo-1,4-β-d-glucanase (an endoglucanase, eglS), cellobiohydrolase (an exoglucanase, cbhA), and β-glucosidase (bglH), endo-1,4-β-xylanase (an endoxylanase, xynC) and β-xylosidase (bxlB) - were successfully expressed and produced by E. coli BL21. Better saccharification of pretreated corn husks was observed when using the five crude SE enzymes than those using two commonly used SEs, endo-1,4-β-d-glucanase and β-glucosidase. The five SEs were cross-linked in the absence or the presence of magnetic nanoparticles (hereafter referred as SE-CLEAs and M-SE-CLEAs, respectively). By using SE-CLEAs, the highest amount of reduced sugar (250 mg/g biomass) was measured. The activity of immobilized SEs is better than free crude SEs. The M-SE-CLEAs can be reused at least 3 times for effective saccharification of pretreated lignocellulosic biomass.


LOCAL ADAPTATION IN TWO SUBSPECIES OF AN ANNUAL PLANT: IMPLICATIONS FOR MIGRATION AND GENE FLOW.
Plant populations often adapt to local environmental conditions. Here we demonstrate local adaptation in two subspecies of the California native annual Gilia capitata using standard reciprocal transplant techniques in two sites (coastal and inland) over three consecutive years. Subspecies performance in each site was measured in four ways: probability of seedling emergence, early vegetative size (length of longest leaf), probability of flowering, and total number of inflorescences produced per plant. Analysis of three of the four variables demonstrated local adaptation through site-by-subspecies interactions in which natives outperformed immigrants. The disparity between natives and immigrants in their probability of emergence and probability of flowering was greater at the coastal site than at the inland site. Treated in isolation, these two fitness components suggest that migration from the coast to the inland site may be less restricted by selection than migration in the opposite direction. Two measurements of individual size (leaf length and number of inflorescences), suggest (though not strongly) that immigrants may be subject to weaker selection at the coastal site than at the inland site. A standard cohort life table is used to compare replacement rates (R0 ) for each subspecies at each site. Comparisons of R0 s suggest that immigrants are under a severe demographic disadvantage at the coastal site, but only a small disadvantage at the inland site. The results point out the importance of integrating over several fitness components when documenting the magnitude of local adaptation.


[Usefulness of serology in the diagnosis of Candida tropicalis septicemia].
In this study, we have evaluated the usefulness of eight serologic tests in the diagnosis of a Candida tropicalis septicaemia in a patient with acute myeloid leukaemia. Among the tests used, detection of mannose and candida antigen in serum allowed a high degree of suspicion of infection, earlier than the isolation of this species on mycological cultures from blood or oesophagic samples. Detection of anti-C. albicans antibodies was useless but low titres of anti-C. tropicalis antibodies were observed. In spite of early diagnosis and antifungal treatment, the complication of the disseminated candidiasis with a Pseudomonas aeruginosa septicaemia, concluded with the patient's exitus.


Polarization dependent enhanced optical transmission through a sub-wavelength polygonal aperture surrounded by polygonal grooves.
Enhanced optical transmission (EOT) and its polarization extinction ratio (PER) of a sub-wavelength polygonal aperture surrounded by polygonal grooves are investigated numerically by finite difference time domain (FDTD) method. Effects of light polarization on EOT were analyzed and compared for four types of geometrical structures: triangle aperture surrounded by triangle grooves, square aperture surrounded by square grooves, rhombus aperture surrounded by rhombus grooves, and pentagon aperture surrounded by pentagon grooves. The effects of relative angles between the symmetry axes of polygons and the light polarization were thoroughly analyzed. Among these plasmonic polygonal bull's eye structures, the rhombus showed a maximum EOT several times larger than others. In contrast to the prior normal incident condition, we further analyzed the impacts of the incident angle and we found a wideband tunability of EOT wavelengths.


[Periodontal disease in children with diabetes mellitus type 1].
The aim of the article was to study the occurrence of periodontal diseases in children with type I diabetes mellitus. The examination of 78 children revealed periodontal diseases in 40 children with type I diabetes. OHI-S, CPITN, PMA indices were determined. Pathological changes in periodontal tissues were revealed in 100% of cases. The following were identified: gingival hemorrhage (100%), over - and under-gingival dental tartar (100%), inflammation of gingival papilla (87,5%) marginal (80%) and alveolar gingiva (55%). Spread of periodontal disease among children with I type diabetes is characterized as high and is equal to 100%. Degree of periodontal sickness is evaluated as average and is M=2,28; SD=0,47 according to CPITN index. Treatment and preventive measures should be carried out taking into account major somatic disease.


Bringing home the bacon? The next step in cardiac sodium channelopathies.
Mutations in SCN5A, which encodes the α subunit of the major cardiac sodium channel Na(V)1.5, are associated with multiple cardiac arrhythmias, including Brugada syndrome. It is not clear why mutations in SCN5A result in such a variety of cardiac phenotypes, and introduction of analogous Scn5a mutations into small-animal models has not recapitulated alterations in cardiac physiology associated with human disease. In this issue of the JCI, Park and colleagues present a pig model of cardiac sodium channelopathy that was generated by introducing a human Brugada syndrome-associated SCN5A allele. This large-animal model exhibits many phenotypes seen in patients with SCN5A loss-of-function mutations and has the potential to provide important insight into sodium channelopathies.


Cellular and molecular mechanisms of single and collective cell migrations in Drosophila: themes and variations.
The process of cell migration is essential throughout life, driving embryonic morphogenesis and ensuring homeostasis in adults. Defects in cell migration are a major cause of human disease, with excessive migration causing autoimmune diseases and cancer metastasis, whereas reduced capacity for migration leads to birth defects and immunodeficiencies. Myriad studies in vitro have established a consensus view that cell migrations require cell polarization, Rho GTPase-mediated cytoskeletal rearrangements, and myosin-mediated contractility. However, in vivo studies later revealed a more complex picture, including the discovery that cells migrate not only as single units but also as clusters, strands, and sheets. In particular, the role of E-Cadherin in cell motility appears to be more complex than previously appreciated. Here, we discuss recent advances achieved by combining the plethora of genetic tools available to the Drosophila geneticist with live imaging and biophysical techniques. Finally, we discuss the emerging themes such studies have revealed and ponder the puzzles that remain to be solved.


Sequential combination chemotherapy of advanced head and neck carcinoma: re-evaluation of a highly effective regimen.
Twenty-seven evaluable patients with advanced head and neck squamous carcinoma were treated with a polychemotherapeutic regimen described in 1975 by Price et al. Chemotherapy consisted of vincristine, adriamycin, bleomycin, methotrexate, 5-fluorouracil, hydroxyurea, 6-mercaptopurine and citrovorum factor administered sequentially. One complete remission, 4 partial remissions, 7 minor responses were obtained for a total of 12/77 (44%) objective responses. Toxicity was acceptable. The results obtained were not better than those observed with less complicated regimens administrable on an outpatient basis.


Clinical application of double-capsule fecal catheter device in ICU patients with fecal incontinence.
To explore and analyze the clinical effect and potential value of a double-capsule fecal catheter device in patients with fecal incontinence in the intensive care unit (ICU). A total of 107 patients with fecal incontinence who were admitted to the ICU of the First Affiliated Hospital of Gannan Medical University from May 2017 to April 2023 were selected and randomly divided into the observation group and the control group, with 68 cases in the observation group and 39 cases in the control group. The observation group was given a double-capsule fecal catheter device, and the control group was given an ordinary fecal catheter device for drainage. The clinical baseline data, adverse events, skin conditions, changes of patients' quality of life (QoL), indicators from laboratory test, working pressure and burden of nursing, average length of stay (ALOS) and prognosis of patients were compared between the two groups. There was no significant difference in age, gender, body mass index (BMI), hypertension history, diabetes mellitus history and smoking history between the observation group and the control group (all P>0.05). The occurrence probability of the number of catheter obstructions, perianal leakage, catheter prolapse and the incidence of discomfort reactions in the observation group were significantly lower than those in the control group, and the difference was statistically significant (P<0.01). After the use of the double-capsule fecal catheter device, the skin condition of the patient's perineum and perianal area was significantly improved and remained dry and comfortable for a long time, and the recovery of the primary disease in patients with fecal incontinence was also more optimistic. After application of the double-capsule fecal catheter device, the scores of QoL significantly increased in patients from the observation group (P<0.05). After using the double-capsule fecal catheter device, the levels of WBC, neutrophils count, PCT and IL-6 in the observation group were significantly lower than those in the control group after nursing (P<0.05). However, there was no significant difference in levels of CRP, TNF-α, albumin and prealbumin between the two groups (P>0.05). The responsible nurses of the patients in the control group expressed significantly higher nursing work burden than the observation group (P<0.05). Patients in the observation group had shorter ALOS and lower mortality than those in the control group (P<0.01). The application of the novel double-capsule fecal catheter device can reduce the adverse events and working pressure and burden of nursing, it also improved skin condition and patients' QoL. Correspondingly, it improved relevant prognostic indicators during the patient's hospitalization. It has beneficial clinical practicability and popularity for fecal incontinence in patients, and it is worthy of use and promotion.


Comparison of a full sternotomy with a minimally invasive approach for concomitant mitral and tricuspid valve surgery.
The need for concomitant tricuspid surgery in patients who need mitral valve surgery casts doubt on its feasibility via a minimally invasive approach. Our goal was to evaluate the short-term outcomes of patients undergoing concomitant mitral and tricuspid valve surgery either with a standard full sternotomy (full-MTS) or a minimally invasive approach (mini-MTS). The outcomes of patients who had combined mitral and tricuspid valve surgery in 11 centres were retrospectively evaluated. The primary outcome was the incidence of 30-day mortality. A propensity score matched cohort was selected to create 2 comparable groups stratified by surgery (valve replacement or repair). During the study period, 1048 consecutive patients had combined mitral and tricuspid valve surgery (730 full-MTS, 318 mini-MTS). The matching procedure paired 192 full-MTS to 192 mini-MTS procedures. After matching, mini-MTS was associated with longer cardiopulmonary bypass [123 min, standard deviation (SD) 46, vs 102 min, SD 36, P = 0.001] and cross-clamping times (89 min, SD 34, vs 78 min, SD 29, P = 0.003). Although the hospital length of stay was shorter (8 days, interquartile range 7-12 vs 9 days, interquartile range 7-14, P = 0.034) with mini-MTS before matching, this difference disappeared after matching. No differences in other major complications or in 30-day mortality were observed: 48 deaths (4.6%), 36 of which (4.9%) occurred in patients who had a full-MTS and 12 (3.8%), in patients who had a mini-MTS (4.7% in both approaches paired by propensity). The mini-MTS approach proved to be safe and effective in patients requiring concomitant mitral and tricuspid surgery. We could not demonstrate any difference in short-term outcomes between the 2 surgical approaches, indicating that there is not a preferred surgical approach.


The impact of agriculture production and renewable energy consumption on CO2 emissions in developing countries: the role of governance.
Environmental pollution has aggravated the climate change issues posing unusual challenges to the survival and growth of humanity, including extreme weather, loss of species, and sustainability of the ecosystem in developing countries. Unlike previous studies, this paper adds new dimension to the literature by incorporating corruption into agriculture production-environment nexus. This study adds new dimension to the literature by examining corruption, agriculture, and renewable energy on CO2 emissions. The study therefore examines the effects of governance (corruption) and agriculture production on CO2 emissions in 20 countries in Africa from 1990 to 2019. The study employed recent panel econometric approach which accounts for cross-sectional dependence in the variables. The findings of the fixed effect model and panel dynamic ordinary least squares (PDOLS) show that forest and renewable energy consumption decrease CO2 emissions. However, corruption, agriculture production, export, and urbanization escalate CO2 emissions in African countries covered in the paper. Moreover, the Dumitrescu-Hurlin Granger causality indicates a bidirectional causality between agriculture production and CO2 emissions, renewable energy use, agricultural output, and forest. Also, unidirectional Granger causality runs from corruption to forest and agriculture production. On these premises, consented efforts by governments should be made to support good institutions in order to promote good governance to avert pervasive consequences of corruption on the environment.


Client-therapist agreement in the termination process and its association with therapeutic relationship.
There is no consensus among different therapeutic approaches on the process of termination when therapy does not have a prefixed duration. Moreover, both clinicians and researchers are still exploring decision making in the termination of treatment. The present study assessed former client's perspective of therapy termination in a nonprobabilistic sample from Buenos Aires, Argentina. Seventy-three semistructured interviews, lasting ∼60 min each, were conducted with participants that had finished a therapeutic treatment or dropped out. They were asked about several aspects of therapy, including their experience of termination, specifically who decided to terminate, if there was agreement on termination or not, and their thoughts on the termination process. All interviews were transcribed and analyzed using an adaptation of Consensual Qualitative Research (CQR). Quantitative analyses were also conducted to examine associations between variables. Two main factors emerged from the analysis: client/therapist initiative on termination; and level of agreement between client and therapist regarding termination. Whereas nearly all (95%) of therapist-initiated termination cases agreed on termination, client-initiated termination cases could be sorted in agreed (49%) and disagreed (51%) terminations. Both therapist-initiated terminations and agreed upon terminations presented more categories of positive termination motives, better therapeutic bond, and higher overall satisfaction with treatment. Implications for research and clinical practice are discussed. (PsycINFO Database Record


A new photon scattering method for bone mineral density measurements.
A new technique for the determination of bone mineral density, based on the detection of both coherently and Compton scattered photons in a narrow beam geometry, is described. Initial results show that this method delivers an accuracy of less than 2% when varying quantities of materials surround the measuring site.


Blood pressure in adult Lapps and Skolts.
Casual blood pressures were recorded in 331 Lapps and 221 Skolts over the age of 20. The systolic pressure was found to rise more with age in women than in men. In neither sex did age affect the diastolic pressure. A general tendency towards higher blood pressure in Lapps than in Skolts was noted up to the age of 50-60 years. Comparison with a Finnish population and one from the Aland Islands revealed similar systolic blood pressures in females, but definitely lower values in male Lapps and Skolts. The Lapps and Skolts did not have the clear age dependence of the diastolic blood pressure as occurs in Finns. These findings, together with other population studies, support the hypothesis that the setting of the resting blood pressure level is influenced by different kinds of stress associated with technological development and with an urbanized way of life.


Resistance-based, reciprocal upper and lower limb locomotor training in chronic stroke: a randomized, controlled crossover study.
To determine efficacy of a bilateral reciprocal training regimen on affected leg impairment and dynamic balance. Randomized, controlled, single-blinded crossover study. Outpatient rehabilitation hospital. Seven patients who experienced stroke >1 year prior to study entry exhibiting affected leg weakness. Subjects were randomly assigned to receive both of the following in a randomized, sequential order: (a) a resistance-based, reciprocal, affected leg locomotor training protocol using the NuStep apparatus (n = 4) and (b) a home exercise programme (HEP) consisting of self-supervised practice with fractionated joint movements of the lower limb. Each phase of the intervention was performed for 30 minutes each session, three days a week, and conducted over an eight-week period. Outcomes were evaluated by a blinded rater using the lower extremity scale of the Fugl-Meyer and the Berg Balance Scale. After HEP participation, subjects showed nominal or no changes on any of the outcome measures. After NuStep participation, patients in both treatment groups showed impairment reductions as shown by the Fugl-Meyer (+4.3; +2.2), and increased balance as shown by the Berg Balance Scale (+4.0; +4.0). These trends were exhibited regardless of group assignment. Impairment reductions and balance gains may be achieved using a resistance-based, reciprocal upper and lower limb locomotor training protocol.


Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity.
The vav proto-oncogene product (Vav), which is specifically expressed in hematopoietic cells, contains multiple structural motifs commonly used by intracellular signaling molecules. Although a variety of stimuli including erythropoietin (Epo) have been shown to tyrosine phosphorylate Vav, little is known about the Vav signal transduction pathway. Here, we have investigated the role of Vav in the Epo signaling pathway by characterizing its interaction with other proteins, using the human Epo-responsive cell line, F-36P. Immunoprecipitation and immunoblot analyses have demonstrated that Vav was associated with the Epo receptor (EpoR) in an Epo-independent manner and was tyrosine-phosphorylated after Epo stimulation. Furthermore, two phosphotyrosine proteins (pp70 and pp100) co-immunoprecipitated with the regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) (p85) were identified as EpoR and Vav, respectively. The interaction between Vav and p85 was shown to be mediated through the SH2 domains of p85 by an in vitro binding assay and confirmed by the presence of in vitro PI3-kinase activity associated with Vav. Treatment of the cells with antisense-vav and -p85 abrogated Epo-induced cell proliferation and PI3-kinase activity. Finally, we found that JAK2 was associated with Vav in vivo and that Vav could be tyrosine-phosphorylated by activated JAK2 in vitro. These results suggest the possible role of JAK2 for tyrosine phosphorylation of Vav and involvement of Vav and PI3-kinase in Epo-induced proliferative signals.


PEG-coated gold nanoparticles attenuate β-adrenergic receptor-mediated cardiac hypertrophy.
Gold nanoparticles (AuNPs) are widely used as a drug delivery vehicle, which can accumulate in the heart through blood circulation. Therefore, it is very important to understand the effect of AuNPs on the heart, especially under pathological conditions. In this study, we found that PEG-coated AuNPs attenuate β-adrenergic receptor (β-AR)-mediated acute cardiac hypertrophy and inflammation. However, both isoproterenol, a non-selective β-AR agonist, and AuNPs did not induce cardiac function change or cardiac fibrosis. AuNPs exerted an anti-cardiac hypertrophy effect by decreasing β1-AR expression and its downstream ERK1/2 hypertrophic pathway. Our results indicated that AuNPs might be safe and have the potential to be used as multi-functional materials (drug carrier systems and anti-cardiac hypertrophy agents).


Long-lasting effect of infant rats endotoxemia on heat shock protein 60 in the pancreatic acinar cells: involvement of toll-like receptor 4.
Introduction. Lipopolysaccharide endotoxin (LPS) is responsible for septic shock and multiorgan failure, but pretreatment of rats with low doses of LPS reduced pancreatic acute damage. Aim. We investigated the effects of the endotoxemia induced in the early period of life on Toll-like receptor 4 (TLR4), heat shock protein 60 (HSP60) and proapoptotic Bax, caspase-9 and -3 or antiapoptotic Bcl-2 protein expression in the pancreatic acinar cells of adult animals. Material and Methods. Newborn rats (25 g) were injected with endotoxin (Escherichia coli) for 5 consecutive days. Two months later, pancreatic acinar cells were isolated from all groups of animals and subjected to caerulein stimulation (10(-8) M). Protein expression was assessed employing Western blot. For detection of apoptosis we have employed DNA fragmentation ladder assay. Results. Preconditioning of newborn rats with LPS increased TLR4, Caspase-9 and -3 levels, but failed to affect basal expression of HSP60, Bax, and Bcl-2. Subsequent caerulein stimulation increased TLR4, Bcl-2, and caspases, but diminished HSP60 and Bax proteins in pancreatic acinar cells. Endotoxemia dose-dependently increased TLR4, Bax, HSP60, and both caspases protein signals in the pancreatic acini, further inhibiting antiapoptotic Bcl-2. Conclusions. Endotoxemia promoted the induction of HSP60 via TLR4 in the infant rats and participated in the LPS-dependent pancreatic tissue protection against acute damage.


Multiple neoplasms: a case report.
Patients diagnosed with Chronic Lymphocytic Leukemia (CLL) have an increased risk of developing second primary cancers. However, as far as we know, more than one type of subsequent malignancy in one patient has not been described. We report a case of two different skin cancers following CLL. A 68-year-old female patient, in whom CLL was diagnosed 5 years earlier, presented with a pigmentation in the left lower eyelid. Biopsy showed a melanoma. The tumor was excised and histopathological examination revealed a superficial spreading melanoma. Half a year later, a new pigmented tumor was seen in the transplant of the left lower eyelid. Biopsy was performed and histopathological examination showed an intraepithelial squamous cell carcinoma. This was treated with 5 fluorouracil 1% eyedrops.


Development of the community nurse in learning disability: 2.
In order to carry out core skills practitioners should not only obtain a postbasic qualification to practise competently but also take up other specialised courses for effective intervention. This article, the second in a two-part series, analyses the difference between qualified and unqualified community nurses in learning disability.


Camellia sinensis: historical perspectives and future prospects.
As the source of brewed tea preparations, Camellia sinensis has operated for centuries at the interface of agriculture, politics, and biology. The purpose of this review is to present an inter-disciplinary survey of issues surrounding cultivation, processing, and consumption of the tea plant. Particular attention is given to the biologic effects of tea: first, assessing at the level of human physiology its value as a chemopreventive and chemotherapeutic agent; second, examining effects of production upon local ecosystems, due to resource demands and industrial farming practices. In sum, C. sinensis emerges as a potentially powerful contributor to both public health and economic growth if its role is managed from a prospective, sustainable, and evidence-based vantage.


Zinc-induced differential oxidative stress and antioxidant responses in Chlorella sorokiniana and Scenedesmus acuminatus.
Algae are frequently exposed to toxic metals, and zinc (Zn) is one of the major toxicants present. We exposed two green microalgae, Chlorella sorokiniana and Scenedesmus acuminatus, to sub-lethal concentrations (1.0 and 0.6mM) of Zn for seven days. Algal responses were analysed at the level of growth, oxidative stress, and antioxidants. Growth parameters such as cell culture yield and pigment content were less affected by Zn in C. sorokiniana, despite the fact that this alga accumulated more zinc than S. acuminatus. Also, C. sorokiniana, but not S. acuminatus, was able to acclimatize during long-term exposure to toxic concentrations of the test metals (specific growth rate (µ) was 0.041/day and total chlorophyll was 14.6mg/mL). Although, Zn induced oxidative stress in both species, C. sorokiniana experienced less stress than S. acuminatus. This could be explained by a higher accumulation of antioxidants in C. sorokiniana, where flavonoids, polyphenols, tocopherols, glutathione (GSH) and ascorbate (ASC) content increased. Moreover, antioxidant enzymes glutathione S transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), peroxidase (POX) and ascorbate peroxidase (APX), showed increased activities in C. sorokiniana. In addition to, and probably also underlying, the higher Zn tolerance in C. sorokiniana, this alga also showed higher Zn biosorption capacity. Use of C. sorokiniana as a bio-remediator, could be considered.


Testicular Adrenal Rest Tumor in Two Brothers with a Novel Mutation in the 3-Beta-Hydroxysteroid Dehydrogenase-2 Gene.
Testicular adrenal rest tumors (TART) occur frequently in adolescents and adults with 21-hydroxylase deficiency. There have been no reports of TART in children with 3β-hydroxysteroid dehydrogenase deficiency (HSD3β). Biopsy proven TART was diagnosed in a 31/12-year-old male patient and also in his 22-month-old sibling. Hormonal and anthropometric measurements were performed during glucocorticoid and fludrocortisone treatment. The mutational analysis was performed by direct DNA sequencing of the complete coding region of the HSD3β2 gene. Initially, both siblings were treated with high doses of hydrocortisone and fludrocortisone. TART regressed with dexamethasone treatment in both patients. However, growth velocity decreased and weight gain increased in both patients. Dexamethasone was changed to high-dose hydrocortisone (>20 mg/m2/d). Sequencing analyses revealed a novel homozygous p.W355R (c.763 T>C) mutation at exon 4 of the HSD3β2 gene in both siblings. These two patients are, to our knowledge, the first known cases of TARTs with a novel mutation in the HSD3β2 gene detected during childhood. High-dose hydrocortisone treatment is more reliable for TART in children.


Prevalence of photoprotection and its associated factors in risk group for skin cancer in Teresina, Piauí.
The incidence of skin cancer has increased worldwide, particularly melanoma rates, which had a mean development of 2.6 % a year in the last 10 years. The agreement on the relation between long-term or chronic exposure to the sun and the emergence of these neoplasias has made several workers who perform activities exposed to solar radiation to form a risk group for the development of skin cancer, community health agents included. To analyze the prevalence of sunscreen-use-related factors to skin cancer in a labor risk group. Cross-sectional study with community health agents selected through simple random sampling. After collecting data using semi-structured interviews, a descriptive analysis was performed for the qualitative variables, bivariate analysis was employed for checking the association between sunscreen use and sociodemographic, occupational and knowledge about skin variables, and multivariate analysis was conducted to check independent variables associated to sunscreen use. A 5% significance level was used. Of 261 health gents selected, 243 were able to participate in the study. The prevalence rate of sunscreen use was 34.2% (95% CI: 28.2-40.2). Factors associated with sunscreen use were female sex, advanced age, use of sunscreen in situations when the skin got burnt, knowledge of the negative effects of the sun on the skin and skin cancer history. The prevalence found reveals that there is a need for implementing educational strategies in health services regarding photoprotection.


Comparison of Urinary Tract Infection Rates Associated with Transurethral Catheterization, Suprapubic Tube and Clean Intermittent Catheterization in the Postoperative Setting: A Network Meta-Analysis.
We performed a network meta-analysis of available randomized, controlled trials to elucidate the risks of urinary tract infection associated with transurethral catheterization, suprapubic tubes and intermittent catheterization in the postoperative setting. PubMed®, EMBASE® and Google Scholar™ searches were performed for eligible randomized, controlled trials from January 1980 to July 2015 that included patients who underwent transurethral catheterization, suprapubic tube placement or intermittent catheterization at the time of surgery and catheterization lasting up to postoperative day 30. The primary outcome of comparison was the urinary tract infection rate via a network meta-analysis with random effects model using the netmeta package in R 3.2 (www.r-project.org/). Included in analysis were 14 randomized, controlled trials in a total of 1,391 patients. Intermittent catheterization and suprapubic tubes showed no evidence of decreased urinary tract infection rates compared to transurethral catheterization. Suprapubic tubes and intermittent catheterization had comparable urinary tract infection rates (OR 0.903, 95% CI 0.479-2.555). On subgroup analysis of 10 randomized, controlled trials with available mean catheterization duration data in a total of 928 patients intermittent catheterization and suprapubic tube were associated with significantly decreased risk of urinary tract infection compared to transurethral catheterization when catheterization duration was greater than 5 days (OR 0.173, 95% CI 0.073-0.412 and OR 0.142, 95% CI 0.073-0.276, respectively). Transurethral catheterization is not associated with an increased urinary tract infection risk compared to suprapubic tubes and intermittent catheterization if catheterization duration is 5 days or less. However, a suprapubic tube or intermittent catheterization is associated with a lower rate of urinary tract infection if longer term catheterization is expected in the postoperative period.


Chemotherapy alone in laryngeal squamous cell carcinoma.
To evaluate the results of chemotherapy alone in patients with invasive squamous cell carcinoma of the larynx who have achieved a complete clinical response after an induction chemotherapy protocol. A comparison of results in a group of complete responders managed with a chemotherapy alone protocol, matched with those of an incomplete responder group managed with conventional modalities. The survival rate of the complete responder group was significantly higher than that of the incomplete responder group. No statistically significant difference was noted between the two groups in terms of local failure and nodal recurrence. Our results confirm the fact that chemotherapy alone is a viable option in selected patients with carcinoma of the larynx who have achieved a complete clinical response after an induction chemotherapy protocol. This therapeutic approach allows surgery and/or radiation therapy to be reserved for the management of metachronous second primary tumours.


Integrative Bioinformatics Analysis of The Cell Division Cycle and Ribosomal Pathways in The Rat Varicocele: Implications for Drug Discovery.
Varicocele is a common cause of male infertility, affecting a substantial proportion of infertile men. Recent studies have employed transcriptomic analysis to identify candidate genes that may be implicated in the pathogenesis of this condition. Accordingly, this study sought to leverage rat gene expression profiling, along with protein-protein interaction networks, to identify key regulatory genes, related pathways, and potentially effective drugs for the treatment of varicocele. In this in-silico study, differentially expressed genes (DEGs) from the testicular tissue of 3 rats were screened using the edgeR package in R software and the results were compared to 3 rats in the control group. Data was obtained from GSE139447. Setting a -1<LogFC>1 and P<0.05 as cutoff points for statistical significance, up and down-regulated genes were identified. Based on Cytoscape plugins, protein-protein interaction (PPI) networks were drawn, and hub genes were highlighted. ShinyGO was used for pathway enrichment. Finally, effective drugs were identified from the drug database. Among the 1277 DEGs in this study, 677 genes were up-regulated while 600 genes were down-regulated in rats with varicocele compared to the control group. Using protein-protein interaction networks, we identified the top five up-regulated genes and the top five down-regulated genes. Enrichment analysis showed that the up-regulated genes were associated with the cell division cycle pathway, while the down-regulated genes were linked to the ribosome pathway. Notably, our findings suggested that dexamethasone may be a promising therapeutic option for individuals with varicocele. The current investigation indicates that in varicocele the cell division cycle pathway is up-regulated while the ribosome pathway is down-regulated compared to controls. Based on these findings, dexamethasone could be considered a future candidate drug for the treatment of individuals with varicocele.


Human Papillomavirus (HPV) 16 and 18/45 Genotyping-Directed Follow-up of Women With Messenger RNA HPV-Positive, Cytology-Negative Cervical Screening Test Results.
In this study, we sought to correlate genotype test results for human papillomavirus (HPV) types 16, 18, and 45 with histopathologic follow-up diagnoses in patients with messenger RNA (mRNA) high-risk HPV-positive, cytology-negative results. We identified 1,157 patients with mRNA HPV-positive, cytology-negative cervical screening test results between June 2015 and June 2018. Reflex HPV 16/18/45 genotype results were documented in 1,018 women aged 30 years or older, 318 of whom had follow-up within 18 months. Histopathologic findings of cervical intraepithelial neoplasia 2 or worse (CIN2+) were diagnosed in 14 of 122 (11.5%) patients positive for HPV 16/18/45 vs in seven of 196 (3.6%) HPV 16/18/45-negative patients. Three patients with high-risk HPV-positive, cytology-negative cervical screening test results were diagnosed with stage I cervical adenocarcinomas following early colposcopic referral and biopsy after HPV 16/18/45-positive genotype results. Immediate reflex HPV 16/18/45 genotyping of mRNA HPV-positive, cytology-negative patients led to early colposcopic referral and histopathologic diagnoses of three difficult-to-detect, low-stage, cervical adenocarcinomas and significantly increased overall early detection of CIN2+ lesions.


Identification of bifurcation transitions in biological regulatory networks using Answer-Set Programming.
Numerous cellular differentiation processes can be captured using discrete qualitative models of biological regulatory networks. These models describe the temporal evolution of the state of the network subject to different competing transitions, potentially leading the system to different attractors. This paper focusses on the formal identification of states and transitions that are crucial for preserving or pre-empting the reachability of a given behaviour. In the context of non-deterministic automata networks, we propose a static identification of so-called bifurcations, i.e., transitions after which a given goal is no longer reachable. Such transitions are naturally good candidates for controlling the occurrence of the goal, notably by modulating their propensity. Our method combines Answer-Set Programming with static analysis of reachability properties to provide an under-approximation of all the existing bifurcations. We illustrate our discrete bifurcation analysis on several models of biological systems, for which we identify transitions which impact the reachability of given long-term behaviour. In particular, we apply our implementation on a regulatory network among hundreds of biological species, supporting the scalability of our approach. Our method allows a formal and scalable identification of transitions which are responsible for the lost of capability to reach a given state. It can be applied to any asynchronous automata networks, which encompass Boolean and multi-valued models. An implementation is provided as part of the Pint software, available at http://loicpauleve.name/pint.


NMR for structural proteomics of Thermotoga maritima: screening and structure determination.
This paper describes the NMR screening of 141 small (<15 kDa) recombinant Thermotoga maritima proteins for globular folding. The experimental data shows that approximately 25% of the screened proteins are folded under our screening conditions, which makes this procedure an important step for selecting those proteins that are suitable for structure determination. A comparison of screening based either on 1D 1H NMR with unlabeled proteins or on 2D [1H,15N]-COSY with uniformly 15N-labeled proteins is presented, and a comprehensive analysis of the 1D 1H NMR screening data is described. As an illustration of the utility of these methods to structural proteomics, the NMR structure determination of TM1492 (ribosomal protein L29) is presented. This 66-residue protein consists of a N-terminal 3(10)-helix and two long alpha-helices connected by a tight turn centered about glycine 35, where conserved leucine and isoleucine residues in the two alpha-helices form a small hydrophobic core.


Techniques for performing multidetector-row computed tomographic angiography.
The introduction of multidetector-row computed tomography (CT) scanners has substantially improved the quality and ease of performing CT angiography. CT angiography is a robust method of volumetric vascular imaging that offers benefits over conventional angiography. As CT angiography has become a mainstream examination in many radiology departments, a discussion of techniques toward optimizing CT angiography performed with multidetector-row CT scanners is important. Key principles for optimizing spiral CT acquisition are discussed, and an explanation of multidetector-row CT principles germane to peripheral vascular imaging is presented. A discussion of contrast medium administration strategies ensues, with attention toward injection protocol and bolus timing. An overview of 3-dimensional visualization techniques is subsequently presented, followed by some general rules for CT angiographic interpretation. The article concludes with anatomically directed protocol considerations for the carotid and intracranial circulation, thoracic aorta, pulmonary arteries, abdominal aortoiliac system, renal arteries, and lower extremity arterial inflow and run-off.


Key role of CD36 in Toll-like receptor 2 signaling in cerebral ischemia.
Toll-like receptors (TLRs) and the scavenger receptor CD36 are key molecular sensors for the innate immune response to invading pathogens. However, these receptors may also recognize endogenous "danger signals" generated during brain injury, such as cerebral ischemia, and trigger a maladaptive inflammatory reaction. Indeed, CD36 and TLR2 and 4 are involved in the inflammation and related tissue damage caused by brain ischemia. Because CD36 may act as a coreceptor for TLR2 heterodimers (TLR2/1 or TLR2/6), we tested whether such interaction plays a role in ischemic brain injury. The TLR activators FSL-1 (TLR2/6), Pam3 (TLR2/1), or lipopolysaccharide (TLR4) were injected intracerebroventricularly into wild-type or CD36-null mice, and inflammatory gene expression was assessed in the brain. The effect of TLR activators on the infarct produced by transient middle cerebral artery occlusion was also studied. The inflammatory response induced by TLR2/1 activation, but not TLR2/6 or TLR4 activation, was suppressed in CD36-null mice. Similarly, TLR2/1 activation failed to increase infarct volume in CD36-null mice, whereas TLR2/6 or TLR4 activation exacerbated postischemic inflammation and increased infarct volume. In contrast, the systemic inflammatory response evoked by TLR2/6 activation, but not by TLR2/1 activation, was suppressed in CD36-null mice. In the brain, TLR2/1 signaling requires CD36. The cooperative signaling of TLR2/1 and CD36 is a critical factor in the inflammatory response and tissue damage evoked by cerebral ischemia. Thus, suppression of CD36-TLR2/1 signaling could be a valuable approach to minimize postischemic inflammation and the attendant brain injury.


Translation of Credentialing Examination for Providers with English as a Second Language: An Exploratory Study.
Racial and ethnic minorities disproportionately suffer the burden of adverse health outcomes in the United States. Increasing the diversity of healthcare providers may help decrease disparities in outcomes. Unfortunately, language barriers may affect performance in nursing school and credentialing examinations. The purpose of this exploratory study was to identify current practices and trends affecting the translation of credentialing examinations. Commissioned by the National Board of Certification and Recertification for Nurse Anesthetists, a survey was sent to the credentialing organizations soliciting information about their exam translation practices and considerations. Among the 27 credentialing organizations (two licensure and 25 certification organizations) that completed the survey, 63% were from healthcare. All the organizations offered their credentialing examinations in English. Some offered their examination in Chinese/Mandarin (15%), Spanish (11%), French (7%), and Arabic (7%). The majority (78%) do not translate their examinations into another language. Among the six credentialing organizations translating their examinations, 67% translate one, and 17% translate two examinations. Most use the forward and back-translation techniques. For organizations embarking on a multilingual credentialing program, it is imperative to ensure psychometric equivalence of their examinations. Translation can help ensure that candidates are tested on their intended competencies, not their language proficiency.


Isolation and characterization of a thermally extracted yeast cell wall fraction potentially useful for improving the foaming properties of sparkling wines.
Two different yeast cell wall extracts were obtained using enzymatic digestion and thermal treatment. The effects of the extracts obtained on the foaming properties of a model wine and two sparkling wines were studied. The model wine and sparkling wines, supplemented with the thermal extract, presented better foaming properties than did the samples supplemented with the enzymatic extract. The fractioning (Con A chromatography) and characterization (SDS-PAGE, SEC, GC, and RP-HPLC) of both extracts showed that the fraction responsible for the foaming properties is constituted by mannoproteins with a relative molecular weight between 10 and 30 kDa, presenting an equilibrated composition of the hydrophobic and hydrophilic protein domains. This thermal extract did not modify the protein stability in both the model wine and the sparkling wines. These results demonstrate that the enrichment of a sparkling wine with mannoproteins extracted by mild heat procedures will contribute to improving its foaming properties.