Identifying the characteristics of nurse opinion leaders to aid the integration of genetics in nursing practice.
To identify the characteristics of nurses opinion leaders in the context of genetics in health care and consider the findings for the integration of genetics in nursing practice. Nurses need a basic understanding of the role genetics plays in their practice and about how best to support patients using genetic knowledge. Opinion leaders have been used previously to incorporate change initiatives and increase educational application. Identifying the characteristics of nurse opinion leaders may aid the engagement and continued integration of genetics into nursing practice. A primarily quantitative approach over two phases, using online surveys conducted during 2011. This article focuses on Phase 2 of a wider study. Oncology and primary care nurses were surveyed to identify the characteristics and demographic indicators of nurse opinion leaders. Tests for data normality followed by the suitable test for group comparison was applied with significance level set at <0·05. Nineteen respondents (n = 19/88; 21·6%) were categorized as opinion leaders and two subgroups were identified: Genetic Opinion Leaders and Opinion Leaders with an Interest in Genetics. Seven characteristics were deemed statistically significant (Mann-Whitney, Chi-Square, t-test) in identifying nurse opinion leaders, including being open to experience and having a perceived level of influence over others. The identified characteristics could be used to enhance the integration of genetics into nursing practice through the use of opinion leaders. Further thought needs to be given to the refinement of the identified characteristics and to the use of such a unique group of nurses.


Structural determination of the novel fragmentation routes of zwitteronic morphine opiate antagonists naloxonazine and naloxone hydrochlorides using electrospray ionization tandem mass spectrometry.
Electrospray ionization quadrupole time-of-flight (ESI-QqToF) mass spectra of the zwitteronic salts naloxonazine dihydrochloride 1 and naloxone hydrochloride 2, a common series of morphine opiate receptor antagonists, were recorded using different declustering potentials. The singly charged ion [M+H-2HCl](+) at m/z 651.3170 and the doubly charged ion [M+2H-2HCl](2+) at m/z 326.1700 were noted for naloxonazine dihydrochloride 1; and the singly charged ion [M+H-HCl](+) at m/z 328.1541 was observed for naloxone hydrochloride 2. Low-energy collision-induced dissociation tandem mass spectrometry (CID-MS/MS) experiments established the fragmentation routes of these compounds. In addition to the characteristic diagnostic product ions obtained, we noticed the formation of a series of radical product ions for the zwitteronic compounds 1 and 2, and also the formation of a distonic ion product formed from the singly charged ion [M+H-HCl](+) of naloxone hydrochloride 2. Confirmation of the various established fragmentation routes was effected by conducting a series of ESI-CID-QqTof-MS/MS product ion scans, which were initiated by CID in the atmospheric pressure/vacuum interface using a higher declustering potential. Deuterium labeling was also performed on the zwitteronic salts 1 and 2, in which the hydrogen atoms of the OH and NH groups were exchanged with deuterium atoms. Low-energy CID-QqTof-MS/MS product ion scans of the singly charged and doubly charged deuteriated molecules confirmed the initial fragmentation patterns proposed for the protonated molecules. Precursor ion scan analyses were also performed with a conventional quadrupole-hexapole-quadrupole tandem mass spectrometer and allowed the confirmation of the genesis of some diagnostic ions.


Personality modulates the efficacy of treatment in patients with major depressive disorder.
Effects of depression treatment are obscured by heterogeneity among patients. Personality types could be one source of heterogeneity that explains variability in treatment response. Clinically meaningful variations in personality patterns could be captured with data-driven subgroups. The aim of this study was to identify such personality types and to explore their predictive value for treatment efficacy. Participants (N = 146) in the current exploratory study came from a randomized controlled trial in primary care depressed patients, conducted between January 1998 and June 2003, comparing different treatments. All participants were diagnosed with a major depressive disorder (MDD) according to the DSM-IV. Primary (care as usual [CAU] or CAU plus a psychoeducational prevention program [PEP]) and specialized (CAU + PEP + psychiatric consultation or cognitive-behavioral therapy) treatment were compared. Personality was assessed with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI). Personality classes were identified with latent profile analysis (LPA). During 1 year, weekly depression ratings were obtained by trimonthly assessment with the Composite International Diagnostic Interview. Mixed models were used to analyze the effects of personality on treatment efficacy. A 2-class LPA solution fit best to the NEO-FFI data: Class 1 (vulnerable, n = 94) was characterized by high neuroticism, low extraversion, and low conscientiousness, and Class 2 (resilient, n = 52) by medium neuroticism and extraversion and higher agreeableness and conscientiousness. Recovery was quicker in the resilient class (class × time: P < .001). Importantly, specialized treatment had added value only in the vulnerable class, in which it was associated with quicker recovery than primary treatment (class × time × treatment: P < .001). Personality profile may predict whether specialized clinical efforts have added value, showing potential implications for planning of treatments.


Virulence plasmid instability in Shigella flexneri 2a is induced by virulence gene expression.
Expression of the predominantly plasmid-encoded virulence regulon of Shigella flexneri 2a is induced by growth at 37 degrees C and repressed by growth at 30 degrees C. During growth at 37 degrees C, spontaneous S. flexneri mutants arise which have undergone virulence plasmid curing or rearrangement and no longer display the virulent phenotype. In the laboratory, the unstable nature of the virulence plasmid causes complete loss of virulence in a growing population. We have undertaken an analysis of virulence plasmid instability, classifying events which produced individual avirulent derivatives within a virulent population and identifying the factor(s) which controlled conversion. Multiplex PCR analysis of DNA obtained from spontaneous avirulent derivatives indicated that virF and virB were deleted or otherwise inactivated in over 97% of the isolates. The virF and virB loci encode regulatory proteins required for transcriptional activation of the virulence regulon. Inactivation of these key regulatory loci in the vast majority of avirulent derivatives which arose during growth at 37 degrees C suggested that virulence gene expression induced virulence plasmid instability. Consistent with this hypothesis, we observed stable virulence plasmid maintenance during growth of a wild-type strain at 30 degrees C where virulence gene expression was repressed. The virulence plasmid was also stably maintained in virF and virB mutants grown at 37 degrees C. Conversely, virulence plasmid destabilization was induced at 30 degrees C and accelerated at 37 degrees C through expression of VirF or VirB from multicopy plasmids. These results indicate that exposure of S. flexneri to conditions favoring induction of the virulent phenotype also favor its loss. The significance of this paradox of Shigella pathogenicity is discussed.


Hypertrophic scars and keloids: Overview of the evidence and practical guide for differentiating between these abnormal scars.
Although hypertrophic scars and keloids both generate excessive scar tissue, keloids are characterized by their extensive growth beyond the borders of the original wound, which is not observed in hypertrophic scars. Whether or not hypertrophic scars and keloids are two sides of the same coin or in fact distinct entities remains a topic of much debate. However, proper comparison between the two ideally occurs within the same study, but this is the exception rather than the rule. For this reason, the goal of this review was to summarize and evaluate all publications in which both hypertrophic scars and keloids were studied and compared to one another within the same study. The presence of horizontal growth is the mainstay of the keloid diagnosis and remains the strongest argument in support of keloids and hypertrophic scars being distinct entities, and the histopathological distinction is less straightforward. Keloidal collagen remains the strongest keloid parameter, but dermal nodules and α-SMA immunoreactivity are not limited to hypertrophic scars alone. Ultimately, the current hypertrophic scars-keloid differences are mostly quantitative in nature rather than qualitative, and many similar abnormalities exist in both lesions. Nonetheless, the presence of similarities does not equate the absence of fundamental differences, some of which may not yet have been uncovered given how much we still have to learn about the processes involved in normal wound healing. It therefore seems pertinent to continue treating hypertrophic scars and keloids as separate entities, until such a time as new findings more decisively convinces us otherwise.


[Development and application of a genome specific marker for Secale africanum].
Genome in situ hybridization (GISH) analysis of wheat-Secale africanum amphiploid revealed that the S. africanum genome displayed significant divergence to the Secale cereale genome. It is thus valuable to deploy genes from S. africanum. We performed the PCR analysis on S. africanum, wheat-S. afticanum amphiploid, T. eastivum cv. Anyuepaideng and other genetic stocks by 100 ISSR primers. A specific segment of 561 bp, named pSaUBC815561, was obtained from S. africanum using primer UBC815. This segment was not amplified from the control wheat lines. Primer UBC815 also am-plified fragments from wild species of genus Secale, including S. vavilovii, S. sylvestre, and other cultivated ryes. Based on the sequence of pSaUBC815561, a pair of special primers U815-F and U815-R was designed and was used to amplify the DNA of wheat related species in Triticeae aimed at validating the specificity of pSaUBC815561. PCR analysis indicated that this specific DNA fragment was amplified not only from a set of Chinese Spring wheat-Imperial rye chromosome addition lines but also from certain wheat-rye introgression lines. Therefore, pSaUBC815561 can be used as a specific marker for detection of chromosomes of Secale genome in wheat.


Tuning DO:DM Ratios Modulates MHC Class II Immunopeptidomes.
Major histocompatibility complex class II (MHC-II) antigen presentation underlies a wide range of immune responses in health and disease. However, how MHC-II antigen presentation is regulated by the peptide-loading catalyst HLA-DM (DM), its associated modulator, HLA-DO (DO), is incompletely understood. This is due largely to technical limitations: model antigen-presenting cell (APC) systems that express these MHC-II peptidome regulators at physiologically variable levels have not been described. Likewise, computational prediction tools that account for DO and DM activities are not presently available. To address these gaps, we created a panel of single MHC-II allele, HLA-DR4-expressing APC lines that cover a wide range of DO:DM ratio states. Using a combined immunopeptidomic and proteomic discovery strategy, we measured the effects DO:DM ratios have on peptide presentation by surveying over 10,000 unique DR4-presented peptides. The resulting data provide insight into peptide characteristics that influence their presentation with increasing DO:DM ratios. These include DM sensitivity, peptide abundance, binding affinity and motif, peptide length, and choice of binding register along the source protein. These findings have implications for designing improved HLA-II prediction algorithms and research strategies for dissecting the variety of functions that different APCs serve in the body.


Grasping the weight cut-off for anorexia nervosa in children and adolescents.
The Diagnostic and Statistical Manual of Mental Disorders 5 suggests the 5th age-adjusted body mass index (BMI) percentile as the numeric cut-off for anorexia nervosa (AN) in children and adolescents. We aimed to investigate the degree to which the 5th age-adjusted percentile as the numeric cut-off for AN in youths reflects the clinical population of patients accepted for treatment. From a specialized eating disorder clinic, 305 patients with AN below 18 years of age were grouped according to age-adjusted BMI percentiles [below the 5th (low), above the 10th (high), and between the 5th and the 10th (medium)]. The distribution of eating disorder diagnoses and severity measured by the Eating Disorder Examination was compared. Full-syndrome anorexia nervosa (F.50.0) was found in 182 (59.5%) patients and atypical anorexia nervosa (F.50.1) in 123 patients (40.5%). The number of patients in the low, medium, and high BMI percentile groups was 189 (62.0%), 34 (11.1%), and 82 (26.9%), respectively. Patients in the low BMI group differed from patients in the medium BMI group by a lower frequency of vomiting. The high BMI group presented with more weight and shape concern than the lower BMI group. Age was not a confounder of these associations. We question the applicability of the 5th BMI percentile as a substantiated cut-off for the weight criterion in anorexia nervosa in youths and argue that the cut-off should not be ascribed great clinical importance as this may hinder early detection of illness and initiation of treatment.


Transcatheter aortic valve replacement in patients with bicuspid aortic valve stenosis: national trends and in-hospital outcomes.
Bicuspid aortic valve (BAV) disease is considered the most common congenital heart disease and the main etiology of aortic valve stenosis (AS) in young adults. Although transcatheter aortic valve replacement (TAVR) is routinely used in high- and intermediate-risk patients with AS, BAV patients with AS were excluded from all pivotal trials that led to TAVR approval. We sought, therefore, to examine in-hospital outcomes of patients with BAV who underwent TAVR in comparison with surgical aortic valve replacement (SAVR). Using the National Inpatient Sample from 2011 to 2014, we identified patients with BAV with International Classification of Diseases-Ninth Revision-CM code 746.4. Patients who underwent TAVR were identified using ICD-9 codes 35.05 and 35.06 and those who underwent SAVR were identified using codes 35.21 and 35.22 during the same period. A total of 37,052 patients were found to have BAV stenosis. Among them, 36,629 patients (98.8%) underwent SAVR, whereas 423 patients (1.14%) underwent TAVR. One-third of enrolled patients were female, and the majority of the patients were White with a mean age of 65.9 ± 15.1 years. TAVR use for BAV stenosis significantly increased from 0.39% in 2011 to 4.16% in 2014 (P < 0.001), which represents a 3.77% overall growth in procedure rate. The median length of stay decreased significantly throughout the study period (mean 12.2 ± 8.2 days to 7.1 ± 5.9 days, P < 0.001). There was no statistically significant difference between SAVR and TAVR groups in the in-hospital mortality (0% vs. 5.9%; adjusted P = 0.119). There is a steady increase in TAVR use for BAV stenosis patients along with a significant decrease in length of stay.


Challenge and hindrance appraisals of job demands: one man's meat, another man's poison?
Background and objectives: Many job stress models assume that all workers experience a particular job demand in the same way - an assumption that may or may not be warranted and that has rarely been tested. Building on appraisal theory, we explore (a) how individuals appraise particular job demands (i.e., as a challenge or as a hindrance) and (b) how these appraisals affect the relationship between job demands and engagement/burnout.Design and Methods: A multi-occupation cross-sectional study was conducted among 527 Chinese workers (321 females, 60.9%; Mage = 32.74, SD = 6.70). The data were analyzed using hierarchical multiple regression analysis.Results: We found that the appraisal of job demands (time urgency, role conflict, and emotional demands) as a challenge moderated the associations between these demands and burnout/engagement. Generally, the results indicate that the presence of high job demands was associated with negative outcomes. However, these detrimental effects were weaker if workers appraised these characteristics as being high-challenge.Conclusions: This study extends research on job demands within the challenge-hindrance framework by focusing on the moderating effects of appraisals. Given the important role of appraisal, we conclude that researchers should include appraisal more systematically in their theorizing and research on the effects of job demands on well-being.


Frequency dependent viscoelastic properties of porcine brain tissue.
Brain tissue is vulnerable and sensitive, predisposed to potential damage under complicated loading conditions. Its material properties have been investigated, but the characterization of its viscoelastic properties is currently limited. The aim of this study was to investigate the viscoelastic properties of brain tissue. Porcine brain samples, dissected ex vivo in the coronal plane, were tested under compression using dynamic mechanical analysis over a range of frequencies between 0.1 and 35 Hz. Indenters with varying diameters of 8, 12 and 16 mm were used to study the effect on viscoelastic properties under a sinusoidally varying displacement with varying mean displacements (10%, 15% and 20% of a specimen height). As the indenter size increased, the storage and loss stiffness significantly increased (p < 0.05). The storage stiffness decreased significantly as the mean displacement decreased (p < 0.05). The average storage modulus was found to be 8.09 kPa and the average loss modulus was found being 4.85 kPa. Frequency dependent viscoelastic properties of brain are important to improve the accuracy in the computational modelling of the head to develop the prediction of brain injuries.


Coping and quality of life in patients awaiting lung transplantation.
Patients with end-stage lung disease (ESLD) experience significant decrements in quality of life (QOL). Although coping strategies are related to QOL in patients with ESLD, the extent to which specific native lung disease moderates this relationship is unknown. We investigated the relationship between coping, native lung disease, and QOL among 187 patients awaiting lung transplantation, including 139 patients with chronic obstructive pulmonary disease (COPD) and 48 with cystic fibrosis (CF). Participants completed a psychosocial battery assessing psychological QOL, physical QOL, and coping strategies. For both COPD and CF patients, higher levels of Active Coping (P< .0001) and lower levels of Disengagement (P< .0001) were associated with better psychological QOL. For physical QOL, we observed a Native Disease x Coping interaction (P=.01) such that Active Coping was associated with better physical QOL in patients with COPD but not in patients with CF. The relationship between coping and QOL may vary as a function of native lung disease. Patients' native disease may need to be considered in order to develop effective interventions to help patients cope successfully with ESLD.


Cell-of-Origin Subtyping of Diffuse Large B-Cell Lymphoma by Using a qPCR-based Gene Expression Assay on Formalin-Fixed Paraffin-Embedded Tissues.
The well-established cell-of-origin (COO) algorithm categorizes diffuse large B-cell lymphoma (DLBCL) into activated B-cell-like (ABC) and germinal center B-cell-like (GCB) subgroups through gene expression profiling. We aimed to develop and validate a qPCR-based gene expression assay to determine the COO subgroups of DLBCL with formalin-fixed paraffin-embedded (FFPE) tissue. We first established a DLBCL transcriptome database of 1,016 samples retrieved from three published datasets (GSE10846, GSE22470, and GSE31312). With this database, we identified a qPCR-based 32-gene expression signature (DLBCL-COO assay) that is significantly associated with the COO subgroups. The DLBCL-COO assay was further validated in a cohort of 160 Chinese DLBCL patients. Biopsy samples from DLBCL patients with paired FFPE and fresh frozen tissue were collected to assign COO subtypes based on the immunohistochemistry (IHC) algorithm (Han's algorithm), DLBCL-COO assay, and global gene expression profiling with RNA-seq. For 111 paired FFPE and fresh DLBCL samples, the concordance between the IHC, qPCR, and RNA-seq methods was 77.5% and 91.9%, respectively. The DLBCL-COO assay demonstrated a significantly superior concordance of COO determination with the "gold standard" RNA-seq compared with the IHC assignment with Han's algorithm (P = 0.005). Furthermore, the overall survival of GCB patients defined by the DLBCL-COO assay was significantly superior to that of ABC patients (P = 0.023). This effect was not seen when the tumors were classified by the IHC algorithm. The DLBCL-COO assay provides flexibility and accuracy in DLBCL subtype characterization. These findings demonstrated that the DLBCL-COO assay might serve as a useful tool for guiding prognostic and therapeutic options for DLBCL patients.


Cytoplasmic particles and aminoacyl transferase I activity.
It has been possible to show by electron microscopy of samples selected from sucrose gradients that particles of specific size and shape are present in supernatant fluids derived from nucleated animal and plant cells, but not in extracts from Escherichia coli. Aminoacyl transferase I activity in these same gradients sediments in two peaks representing material of approximately 5-7S and 18-20S. A rectangular particle, 100 x 145 A in size, sediments at 19S and coincides with the second peak of transferase I activity. The possibility that the rectangular particle may be a "carrier" particle associated with transferase I is discussed.


Supercritical fluid assisted impregnation of indomethacin into chitosan thermosets for controlled release applications.
Supercritical carbon dioxide (sc-CO(2)) was used to impregnate indomethacin (a non-steroidal anti-inflammatory drug) into chitosan thermosets for the preparation of controlled release formulations. The products were analyzed by a range of methods including powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The effects of the experimental temperature and pressure of the sc-CO(2) on the thermal behavior of chitosan-indomethacin drug composites (DCs) was investigated via differential scanning calorimeter (DSC). The interaction of chitosan and indomethacin after impregnation was then studied by Fourier transform infrared (FTIR) and Raman spectroscopy, respectively. Our results suggest that the supercritical fluid impregnation process results in indomethacin being amorphously dispersed within the chitosan matrix. FTIR data suggest that the aliphatic carbonyl group of indomethacin interacts with the NH(2) group of the chitosan backbone. In vitro dissolution studies (via UV-vis spectroscopy) reveal that the dissolution rate of indomethacin substantially increases after processing in sc-CO(2), particularly, under the experimental conditions 20.7 MPa and 70 degrees C.


Effects of DAGO on the rodent hippocampal evoked potentials using different perfusion solutions.
Opioid receptor agonists exert excitatory effects in the hippocampus by inhibiting GABA release. We report that the mu-opioid agonist, DAGO, increases the amplitude of the population spikes (PS) measured in the stratum pyramidale of the CA1 cell layer in mouse and rat hippocampal slices perfused with an artificial cerebrospinal fluid (ACSF), but not when perfused in Krebs solution. The GABAA agonist, 3-APS, induces inhibitory responses when perfused in either ACSF or Krebs. Also, the field excitatory postsynaptic potentials (EPSP) measured on stratum radiatum do not differ when the slice is perfused with either ACSF or Krebs. The increase in the amplitude of the PS induced by DAGO is not obtained when perfused in a modified. ACSF whose concentration of MgSO4 was lowered to its concentration in the Krebs solution (from 2.4 mM to 1.2 mM). Thus, changes in the concentration of MgSO4 seem to be responsible for the different responses induced by DAGO.


High levels of physical activity and obesity co-exist amongst Inuit adults in Arctic Canada.
Existing evidence indicates that Inuit in Arctic Canada are undergoing a lifestyle transition leading to decreased physical activity (PA) and increased body mass index (BMI). Data specific to PA and BMI amongst Inuit in Nunavut, Canada, are currently limited. The present study aimed to characterise current PA and BMI levels in a sample of Inuit adults. Inuit adults randomly selected from a cross-sectional survey of three communities in Nunavut, Canada, completed an adapted International Physical Activity Questionnaire (IPAQ) and an anthropometric survey. Data were analysed by gender and age group using standardised IPAQ protocol. Response rates ranged from 69-93%. Two hundred and eighteen Inuit adults [180 women, 38 men; mean (standard deviation (SD)) ages 42.3 (13.0) and 42.4 (14.8) years respectively; age range 19-89 years] completed the IPAQ. All men and 97% of women allowed height and weight measurements; the remainder were self-reported. Mean (SD) BMI was 27.7 (6.3) kg/m(2) for males and 30.3 (8.0) kg/m(2) for females. The largest proportion of women and participants in both age groups had a BMI in the obese category; males were evenly split between the normal and obese categories. Self-reported PA was high, with most men, women and participants ≤50 years in the high category of PA. Participants >50 years were evenly split across the medium and high categories. Most participants (72%) were classified as being overweight or obese, yet reported medium or high levels of PA (89%). The findings obtained in the present study indicate the co-existence of high BMI and high self-reported PA amongst Inuit adults.


Genetic transformation of cotton with a harpin-encoding gene hpaXoo confers an enhanced defense response against different pathogens through a priming mechanism.
The soil-borne fungal pathogen Verticillium dahliae Kleb causes Verticillium wilt in a wide range of crops including cotton (Gossypium hirsutum). To date, most upland cotton varieties are susceptible to V. dahliae and the breeding for cotton varieties with the resistance to Verticillium wilt has not been successful. Hpa1Xoo is a harpin protein from Xanthomonas oryzae pv. oryzae which induces the hypersensitive cell death in plants. When hpa1Xoo was transformed into the susceptible cotton line Z35 through Agrobacterium-mediated transformation, the transgenic cotton line (T-34) with an improved resistance to Verticillium dahliae was obtained. Cells of the transgenic T-34, when mixed with the conidia suspension of V. dahliae, had a higher tolerance to V. dahliae compared to cells of untransformed Z35. Cells of T-34 were more viable 12 h after mixing with V. dahliae conidia suspension. Immunocytological analysis showed that Hpa1Xoo, expressed in T-34, accumulated as clustered particles along the cell walls of T-34. In response to the infection caused by V. dahliae, the microscopic cell death and the generation of reactive oxygen intermediates were observed in leaves of T-34 and these responses were absent in leaves of Z35 inoculated with V. dahliae. Quantitative RT-PCR analysis indicated that five defense-related genes, ghAOX1, hin1, npr1, ghdhg-OMT, and hsr203J, were up-regulated in T-34 inoculated with V. dahliae. The up-regulations of these defense-relate genes were not observed or in a less extent in leaves of Z-35 after the inoculation. Hpa1Xoo accumulates along the cell walls of the transgenic T-34, where it triggers the generation of H2O2 as an endogenous elicitor. T-34 is thus in a primed state, ready to protect the host from the pathogen. The results of this study suggest that the transformation of cotton with hpa1Xoo could be an effective approach for the development of cotton varieties with the improved resistance against soil-borne pathogens.


sim1000G: a user-friendly genetic variant simulator in R for unrelated individuals and family-based designs.
Simulation of genetic variants data is frequently required for the evaluation of statistical methods in the fields of human and animal genetics. Although a number of high-quality genetic simulators have been developed, many of them require advanced knowledge in population genetics or in computation to be used effectively. In addition, generating simulated data in the context of family-based studies demands sophisticated methods and advanced computer programming. To address these issues, we propose a new user-friendly and integrated R package, sim1000G, which simulates variants in genomic regions among unrelated individuals or among families. The only input needed is a raw phased Variant Call Format (VCF) file. Haplotypes are extracted to compute linkage disequilibrium (LD) in the simulated genomic regions and for the generation of new genotype data among unrelated individuals. The covariance across variants is used to preserve the LD structure of the original population. Pedigrees of arbitrary sizes are generated by modeling recombination events with sim1000G. To illustrate the application of sim1000G, various scenarios are presented assuming unrelated individuals from a single population or two distinct populations, or alternatively for three-generation pedigree data. Sim1000G can capture allele frequency diversity, short and long-range linkage disequilibrium (LD) patterns and subtle population differences in LD structure without the need of any tuning parameters. Sim1000G fills a gap in the vast area of genetic variants simulators by its simplicity and independence from external tools. Currently, it is one of the few simulation packages completely integrated into R and able to simulate multiple genetic variants among unrelated individuals and within families. Its implementation will facilitate the application and development of computational methods for association studies with both rare and common variants.


Vibrio cholerae accessory colonisation factor AcfC: a chemotactic protein with a role in hyperinfectivity.
Vibrio cholerae O1 El Tor is an aquatic Gram-negative bacterium responsible for the current seventh pandemic of the diarrheal disease, cholera. A previous whole-genome analysis on V. cholerae O1 El Tor strains from the 2010 epidemic in Pakistan showed that all strains contained the V. cholerae pathogenicity island-1 and the accessory colonisation gene acfC (VC_0841). Here we show that acfC possess an open reading frame of 770 bp encoding a protein with a predicted size of 28 kDa, which shares high amino acid similarity with two adhesion proteins found in other enteropathogens, including Paa in serotype O45 porcine enteropathogenic Escherichia coli and PEB3 in Campylobacter jejuni. Using a defined acfC deletion mutant, we studied the specific role of AcfC in V. cholerae O1 El Tor environmental survival, colonisation and virulence in two infection model systems (Galleria mellonella and infant rabbits). Our results indicate that AcfC might be a periplasmic sulfate-binding protein that affects chemotaxis towards mucin and bacterial infectivity in the infant rabbit model of cholera. Overall, our findings suggest that AcfC contributes to the chemotactic response of WT V. cholerae and plays an important role in defining the overall distribution of the organism within the intestine.


Long-term aboveground and belowground consequences of red wood ant exclusion in boreal forest.
Despite their ubiquity, the role of ants in driving ecosystem processes both aboveground and belowground has been seldom explored, except within the nest. During 1995 we established 16 ant exclusion plots of approximately 1.1 x 1.1 m, together with paired control plots, in the understory layer of a boreal forest ecosystem in northern Sweden that supports high densities of the mound-forming ant Formica aquilonia, a red wood ant species of the Formica rufa group. Aboveground and belowground measurements were then made on destructively sampled subplots in 2001 and 2008, i.e., 6 and 13 years after set-up. While ant exclusion had no effect on total understory plant biomass, it did greatly increase the relative contribution of herbaceous species, most likely through preventing ants from removing their seeds. This in turn led to higher quality resources entering the belowground subsystem, which in turn stimulated soil microbial biomass and activity and the rates of loss of mass and carbon (C) and nitrogen (N) from litter in litterbags placed in the plots. This was accompanied by losses of approximately 15% of N and C stored in the humus on a per area basis. Ant exclusion also had some effects on foliar stable isotope ratios for both C and N, most probably as a consequence of greater soil fertility. Further, exclusion of ants had multitrophic effects on a microbe-nematode soil food web with three consumer trophic levels and after six years promoted the bacterial-based relative to the fungal-based energy channel in this food web. Our results point to a major role of red wood ants in determining forest floor vegetation and thereby exerting wide-ranging effects on belowground properties and processes. Given that the boreal forest occupies 11% of the Earth's terrestrial surface and stores more C than any other forest biome, our results suggest that this role of ants could potentially be of widespread significance for biogeochemical nutrient cycling, soil nutrient capital, and sequestration of belowground carbon.


Action-Centered Exposure Therapy (ACET): A New Approach to the Use of Virtual Reality to the Care of People with Post-Traumatic Stress Disorder.
Post-Traumatic Stress Disorder (PTSD) can be seen as the result of dysfunctional beliefs that associate stimuli with a danger or a threat leading to anxious reactions. Exposure therapy is so far considered to be the most effective treatment, and research suggests that it is mainly based on a habituation process. Based on learning theories, it appears that a passive systemic exposure to traumatic stimuli should not be the best option for the treatment of PTSD. We hypothesis that an active learning of safer and healthier coping strategies combined with systematic exposure should be more effective in reducing the psychological distress associated with PTSD. In this paper, we describe the theoretical foundations of this approach that focuses on the action and activity of the patient in his or her exposure environment. In this approach, we take advantage of Virtual Reality technologies and learning mechanics of serious games to allow the patient to learn new safe associations while promoting the empowerment. We named this action-centered exposure therapy (ACET). This approach exploits behaviorism, cognitivism, and constructivism learning theories. With the different benefits of virtual reality technologies, this approach would easily integrate with in-virtuo exposure therapy and would allow us to exploit as much as possible the enormous potential of these technologies. As a first step toward validation, we present a case study that supports the ACET approach.


Information on quantum states pervades the visible spectrum of the ubiquitous Au144(SR)60 gold nanocluster.
Absorption spectra of very small metal clusters exhibit individual peaks that reflect the discreteness of their localized electronic states. With increasing size, these states develop into bands and the discrete absorption peaks give way to smooth spectra with, at most, a broad localized surface-plasmon resonance band. The widely accepted view over the last decades has been that clusters of more than a few dozen atoms are large enough to have necessarily smooth spectra. Here we show through theory and experiment that for the ubiquitous thiolate cluster compound Au144(SR)60 this view has to be revised: clearly visible individual peaks pervade the full near-IR, VIS and near-UV ranges of low-temperature spectra, conveying information on quantum states in the cluster. The peaks develop well reproducibly with decreasing temperature, thereby highlighting the importance of temperature effects. Calculations using time-dependent density-functional theory indicate the contributions of different parts of the cluster-ligand compound to the spectra.


Prospective, randomized study of ropivacaine wound infusion versus intrathecal morphine with intravenous fentanyl for analgesia in living donors for liver transplantation.
Postoperative analgesia and care for living liver donors have become particular interests for clinicians as the use of living donor liver transplantation has increased. Local anesthetic-based analgesia has been known to provide effective pain control. In this prospective, randomized study, we compared the postoperative analgesic efficacy of local anesthetic-based analgesia (PainBuster) with the efficacy of opioid-based analgesia [intrathecal morphine (ITM) with intravenous (IV) fentanyl] in liver donors. Forty adult donors were randomly allocated to 1 of 2 groups: an ITM/IV fentanyl group (n = 21) and a PainBuster group (n = 19). Donors in the PainBuster group received 0.5% ropivacaine via a multi-orifice catheter (ON-Q PainBuster) placed at the wound. Donors in the ITM/IV fentanyl group received ITM sulfate (400 μg) preoperatively and a continuous IV fentanyl infusion postoperatively. A visual analogue scale (VAS) at rest and with coughing and rescue IV fentanyl and meperidine consumption were assessed for 72 hours after the operation. Side effects, including sedation, dizziness, nausea, vomiting, pruritus, respiratory depression, wound seroma or hematoma, and the first time to flatus, were recorded. The VAS score at rest during the first 12 postoperative hours was significantly lower for the ITM/IV fentanyl group. At other times, the VAS scores were comparable between the groups. In the PainBuster group, rescue IV fentanyl and meperidine use was significantly reduced 24 to 48 hours and 48 to 72 hours after surgery in comparison with the first 24 postoperative hours. The time to first flatus was significantly reduced in the PainBuster group. There were no differences in side effects. In conclusion, analgesia was more satisfactory with ITM/IV fentanyl versus PainBuster during the first 12 hours after surgery, but they became comparable thereafter, with a shortened bowel recovery time in the PainBuster group. The concurrent use of ITM with PainBuster may be considered in a future investigation.


Physiological significance of behavioral hypothermia in hypoxic toads (Bufo marinus).
We tested the hypotheses that hypoxic toads (Bufo marinus) in a thermal gradient would select a lower than normal temperature and that this behavioral response would be beneficial. Under normoxic conditions, selected body temperature was 24.2 +/- 3.6 degrees C. When inspired O2 was 10% or less, mean selected temperature decreased to 15.3 +/- 2.4 degrees C. The theoretical advantages of hypoxia-induced hypothermia we tested include (1) a reduction of oxygen uptake (VO2) by a Q10 effect; (2) increased arterial saturation (SaO2), (3) a decreased ventilatory response, and (4) a decreased stress response. Gas exchange, hematocrit, hemoglobin, SaO2, PaO2 and pH were measured at 25 degrees C (normal preferred temperature) and 15 degrees C (hypoxia preferred temperature) in toads breathing normoxic or hypoxic gas mixtures. During graded hypoxia at 15 degrees C, SaO2 was significantly increased and VO2 was significantly reduced compared with 25 degrees C. Graded hypoxia did not significantly affect VO2 at 25 degrees C, despite evidence for increased ventilation at that temperature (increased pH and respiratory exchange ratio, RE). At 15 degrees C, graded hypoxia had a significant effect on VO2 only at an inspired O2 of 4%. Increased RE with hypoxia was significant at 25 degrees C but not at 15 degrees C. Hematocrit and [hemoglobin] rose significantly during graded hypoxia at 25 degrees C but did not change at 15 degrees C. Toads exposed to 10% O2 (the value that elicits behavioral hypothermia) showed a significant respiratory alkalosis at 25 degrees C but not at 15 degrees C. Likewise, hypoxia caused a significant drop in SaO2 and PO2 at 25 degrees C. Cooling to 15 degrees C during hypoxia caused a significant rise in SaO2 but no change in PaO2. In conclusion, behavioral hypothermia is a beneficial response to hypoxia in Bufo marinus.


Is fetal brain monoamine oxidase inhibition the missing link between maternal smoking and conduct disorders?
Smoking is the leading cause of preventable illness in the world today. Prenatal cigarette smoke exposure (PCSE) is a particularly insidious form because so many of its associated health effects befall the unborn child and produce behavioural outcomes that manifest themselves only years later. Among these are the associations between PCSE and conduct disorders, which have been mostly ascribed to the deleterious effects of nicotine on the fetal brain. Here we hypothesize that inhibition of brain monoamine oxidase (MAO) during fetal brain development, secondary to maternal cigarette smoking and in addition to nicotine, is a likely contributor to this association. MAOs play a central role in monoaminergic balance in the brain, and their inhibition during fetal development - but not during adult life - is known to result in an aggressive phenotype in laboratory animals. This paper provides theoretical and experimental support for the notion that cigarette smoke-induced inhibition of MAO in the fetal brain, particularly when it occurs in combination with polymorphisms in the MAOA gene that lead to lower enzyme concentration in the brain, may result in brain morphologic and functional changes that enhance the risk of irritability, poor self-control and aggression in the offspring. It also encourages research to evaluate whether the interaction of smoking exposure during fetal development and MAOA genotype increases the risk for conduct disorder over that incurred by mere fetal exposure to tobacco smoke.


Characterization of HcaA, a novel autotransporter protein in Helicobacter cinaedi, and its role in host cell adhesion.
Helicobacter species are classified as gastric or enterohepatic according to their habitat. Among enterohepatic Helicobacter species, which inhabit the intestine, colon, and liver, Helicobacter cinaedi has been most frequently isolated from humans. H. cinaedi often causes bacteremia and cellulitis in immunocompromised hosts. Here, we focused on the H. cinaedi autotransporter protein A (HcaA), a novel virulence factor in H. cinaedi. We discovered that HcaA contributes to cell adhesion via its Arg-Gly-Asp motif. Furthermore, in animal experiments, bacterial colonization was reduced in mice infected with HcaA-knockout strains, supporting the hypothesis that HcaA contributes to H. cinaedi adhesion to host cells. Our study provides a novel mechanism for the establishment of H. cinaedi infections and provides new insights into the role of autotransporter proteins in the establishment of Helicobacter infection.


Shared decision making by United Kingdom osteopathic students: an observational study using the OPTION-12 instrument.
At the crux of patient centred care is Shared Decision Making (SDM), which benefits patient and practitioner. Despite external pressures, studies indicate that SDM remains poorly practised across a variety of healthcare professions. The degree of SDM engagement within United Kingdom osteopathic undergraduate teaching clinics is currently unknown. In 2014 we used the reliable and validated OPTION-12 (O12) instrument to calculate a score that reflected the degree of SDM utility in one United Kingdom Osteopathic Educational Institute's teaching clinic. We also aimed to compare these scores with those previously obtained for physiotherapists working within the United Kingdom's National Health Service. Student-patient initial and follow-up encounters were audio recorded, transcribed and scored using the O12. Comparisons between the following O12 scores were performed: the Osteopathic Educational Institute's 4th and 3rd year students; the Osteopathic Educational Institute's student's initial and follow-up patient encounters; the Osteopathic Educational Institute's students and National Health Service physiotherapists. We analysed 35.5 h of transcribed data from 30 student-patient encounters (7 initial: 23 follow-up). An O12 score of 0.6% (range 0-10.4%) was calculated. No significant differences were found between year groups or encounter types. Significant differences were found compared to National Health Service physiotherapist (score = 24.4%): (U = 144, z = 4.25, p < 0.0005); although both scores are below the 60% threshold for competent SDM behaviour. Undergraduate osteopaths did not appear to engage in competent SDM behaviours, implying traditional and paternalistic styles of decision making that align with results from other manual therapy professions. Students in this study did not practise competent SDM behaviours. Effective educational strategies are required to ensure SDM behaviours reach competent levels.


The promise of the CCD: challenges and opportunity for quality improvement and population health.
Interoperability is a requirement of recent electronic health record (EHR) adoption incentive programs in the United States. One approved structure for clinical data exchange is the continuity of care document (CCD). While primarily designed to promote communication between providers during care transitions, coded data in the CCD can be re-used to aggregate data from different EHRs. This provides an opportunity for provider networks to measure quality and improve population health from a consolidated database. To evaluate such potential, this research collected CCDs from 14 organizations and developed a computer program to parse and aggregate them. In total, 139 CCDs were parsed yielding 680 data in the core content modules of problems, medications, allergies and results. Challenges to interoperability were catalogued and potential quality metrics evaluated based on available content. This research highlights the promise of CCDs for population health and recommends changes for future interoperability standards.


Comparison of numbers of interneurons in three thalamic nuclei of normal and epileptic rats.
The inhibitory sources in the thalamic nuclei are local interneurons and neurons of the thalamic reticular nucleus. Studies of models of absence epilepsy have shown that the seizures are associated with an excess of inhibitory neurotransmission in the thalamus. In the present study, we used light-microscopic gamma-aminobutyric acid (GABA) immunocytochemistry to quantify the interneurons in the lateral geniculate (LGN), ventral posteromedial (VPM), and ventral posterolateral (VPL) thalamic nuclei, and compared the values from normal Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS). We found that in both Wistar rats and GAERS, the proportion of interneurons was significantly higher in the LGN than in the VPM and VPL. In the LGN of Wistar rats, 16.4% of the neurons were interneurons and in the GAERS, the value was 15.1%. In the VPM, the proportion of interneurons was 4.2% in Wistar and 14.9% in GAERS; in the VPL the values were 3.7% for Wistar and 11.1% for the GAERS. There was no significant difference between Wistar rats and the GAERS regarding the counts of interneurons in the LGN, whereas the VPM and VPL showed significantly higher counts in GAERS. Comparison of the mean areas of both relay cells and interneuronal profiles showed no significant differences between Wistar rats and GAERS. These findings show that in the VPL and the VPM there are relatively more GABAergic interneurons in GAERS than in Wistar rats. This may represent a compensatory response of the thalamocortical circuitry to the absence seizures or may be related to the production of absence seizures.


EUV-induced carbon growth at contaminant pressures between 10-10 mbar and 10-6 mbar: Experiment and model.
Carbon contamination induced by ultraviolet (UV) radiation affects precision optics in applications as diverse as semiconductor lithography and satellite observations of the Sun. Our previous experiments have shown that low-intensity UV-induced surface contamination depends quasi-logarithmically on the partial pressure of the organic contaminant due to the poly-dispersive nature of the surface-adsorbate system. This complex dependence presents difficulties because, without a physically motivated model, it cannot be extrapolated to low pressures. We present measurements and a model of carbon growth induced by UV exposure in the presence of tetradecane vapor. The model, which includes a coverage-dependent adsorption energy, describes the measurements over four orders of magnitude in pressure, and we expect that it can be extrapolated to the lower pressures of interest to the extreme ultraviolet (EUV) lithography and solar astronomy communities. Our experience with other contaminants leads us to expect that other organic contaminants will behave similar to tetradecane. The results also provide insights into the kinetics governing coverage isotherms at extremely low partial pressures.


Task decomposition and module combination based on class relations: a modular neural network for pattern classification.
In this paper, we propose a new method for decomposing pattern classification problems based on the class relations among training data. By using this method, we can divide a K-class classification problem into a series of ((2)(K)) two-class problems. These two-class problems are to discriminate class Ci from class Cj for i=1, ..., K and j = i+1, while the existence of the training data belonging to the other K-2 classes is ignored. If the two-class problem of discriminating class Ci from class Cj is still hard to be learned, we can further break down it into a set of two-class subproblems as small as we expect. Since each of the two-class problems can be treated as a completely separate classification problem with the proposed learning framework, all of the two-class problems can be learned in parallel. We also propose two module combination principles which give practical guidelines in integrating individual trained network modules. After learning of each of the two-class problems with a network module, we can easily integrate all of the trained modules into a min-max modular (M3) network according to the module combination principles and obtain a solution to the original problem. Consequently, a large-scale and complex K-class classification problem can be solved effortlessly and efficiently by learning a series of smaller and simpler two-class problems in parallel.


[Pharmacokinetics of lincomycin in experimental animals].
When administered parentally, lincomycin satisfactorily penetrated into the organs and tissues of experimental animals. Pronounced tropism of the antibiotic in the bone tissue was observed which provided its recommendation for the treatment of osteomyelitis. The antibiotic was excreted with urine and bile.


Relationship between disease and psychological adaptation in children in the Childhood Asthma Management Program and their families. CAMP Research Group.
To test the hypotheses that the burden of childhood asthma compromises psychological adaptation and that the degree of compromise increases with disease severity. The Childhood Asthma Management Program (CAMP) is a multicenter randomized clinical trial initiated and funded by the National Heart, Lung, and Blood Institute. Study sites were located in Albuquerque, NM, Baltimore, Md, Boston, Mass, Denver, Colo, St Louis, Mo, San Diego, Calif, Seattle, Wash, and Toronto, Ontario. A total of 1,041 children aged 5 to 12 years were randomized to the trial after confirming their mild to moderate asthma. Psychological questionnaires administered at baseline to parents and participants assessed anxiety, depression, behavioral competence, social support, and family functioning. Psychological difficulty was not increased in this group of asthmatic children and their families. Psychological adaptation in the children was associated with the psychological adaptation of the family but not with disease-related variables. Scores from the Impact on Family Scale, a measure of family quality of life related to the child's illness, were associated more strongly with the overall psychological characteristics of the family and child and very little with disease characteristics or severity. Mild to moderate asthma has imposed modest effects on the daily life but not the psychological health of this group of children. Variation in the psychological characteristics of these children was, as is the case for most children, traceable to the overall psychological adaptation of their families.


Spectrum-to-spectrum searching using a proteome-wide spectral library.
The unambiguous assignment of tandem mass spectra (MS/MS) to peptide sequences remains a key unsolved problem in proteomics. Spectral library search strategies have emerged as a promising alternative for peptide identification, in which MS/MS spectra are directly compared against a reference library of confidently assigned spectra. Two problems relate to library size. First, reference spectral libraries are limited to rediscovery of previously identified peptides and are not applicable to new peptides, because of their incomplete coverage of the human proteome. Second, problems arise when searching a spectral library the size of the entire human proteome. We observed that traditional dot product scoring methods do not scale well with spectral library size, showing reduction in sensitivity when library size is increased. We show that this problem can be addressed by optimizing scoring metrics for spectrum-to-spectrum searches with large spectral libraries. MS/MS spectra for the 1.3 million predicted tryptic peptides in the human proteome are simulated using a kinetic fragmentation model (MassAnalyzer version2.1) to create a proteome-wide simulated spectral library. Searches of the simulated library increase MS/MS assignments by 24% compared with Mascot, when using probabilistic and rank based scoring methods. The proteome-wide coverage of the simulated library leads to 11% increase in unique peptide assignments, compared with parallel searches of a reference spectral library. Further improvement is attained when reference spectra and simulated spectra are combined into a hybrid spectral library, yielding 52% increased MS/MS assignments compared with Mascot searches. Our study demonstrates the advantages of using probabilistic and rank based scores to improve performance of spectrum-to-spectrum search strategies.


Aquaporins constitute a large and highly divergent protein family in maize.
Aquaporins (AQPs) are an ancient family of channel proteins that transport water and neutral solutes through a pore and are found in all eukaryotes and most prokaryotes. A comparison of the amino acid sequences and phylogenetic analysis of 31 full-length cDNAs of maize (Zea mays) AQPs shows that they comprise four different groups of highly divergent proteins. We have classified them as plasma membrane intinsic proteins (PIPs), tonoplast intrinsic proteins, Nod26-like intrinsic proteins, and small and basic intrinsic proteins. Amino acid sequence identities vary from 16% to 100%, but all sequences share structural motifs and conserved amino acids necessary to stabilize the two loops that form the aqueous pore. Most divergent are the small and basic integral proteins in which the first of the two highly conserved Asn-Pro-Ala motifs of the pore is not conserved, but is represented by alanine-proline-threonine or alanine-proline-serine. We present a model of ZmPIP1-2 based on the three-dimensional structure of mammalian AQP1. Tabulation of the number of times that the AQP sequences are found in a collection of databases that comprises about 470,000 maize cDNAs indicates that a few of the maize AQPs are very highly expressed and many are not abundantly expressed. The phylogenetic analysis supports the interpretation that the divergence of PIPs through gene duplication occurred more recently than the divergence of the members of the other three subfamilies. This study opens the way to analyze the function of the proteins in Xenopus laevis oocytes, determine the tissue specific expression of the genes, recover insertion mutants, and determine the in planta function.


In-the-spectacle-lens telescopic device.
Spectacle-mounted telescopic systems are prescribed for individuals with visual impairments. Bioptic telescopes are typically mounted toward the top of the spectacle lens (or above the frame) with the telescope eyepiece positioned above the wearer's pupil. This allows the wearer to use up and down head tilt movements to quickly alternate between the unmagnified wide view (through the carrier lens) and the magnified narrow field of view (available through the eyepiece). Rejection of this visual aid has been attributed mainly to its appearance and to the limited field of view through the smaller Galilean designs. We designed a wide-field Keplerian telescope that is built completely within the spectacle lens. The design uses embedded mirrors inside the carrier lens for optical pathway folding, and conventional lenses or curved mirrors for magnification power. The short height of the ocular, its position, and a small tilt of the ocular mirror enable the wearer to simultaneously view the magnified field above the unmagnified view of the uninterrupted horizontal field. These features improve the cosmetics and utility of the device. The in-the-lens design allows the telescope to be mass produced as a commodity ophthalmic lens blank that can be surfaced to include the wearer's spectacle prescription.


Assessment of the condition of Iowa augers, auger-related injuries, and farmers' perceptions about auger-related injuries.
This study provides an insight into auger-related injuries, Iowa farmers' perceptions of auger-related injuries and the condition of augers used in Iowa agriculture. Specific auger-related injury data (437 records) from the Iowa Department of Public Health (IDPH) was examined and interpreted. The most likely body part injured was the finger and 11:00 A.M., 3:00 P.M., and 5:00 P.M. were the times of the day with the highest number of injuries reported. In addition, a survey was administered to 400 farmers to ascertain their awareness of auger-related injuries and to determine the condition of their augers. Farmers' perceptions of what body part is most likely to be injured by an auger and the level of severity expected from those injuries coincided with injury records from 1993 to 1997. A total 34% of the primary and secondary augers reported were unshielded or without guarding. This assessment provides insight for development of intervention countermeasures to reduce auger-related injuries.


Designed fluorescent probes reveal interactions between amyloid-beta(1-40) peptides and GM1 gangliosides in micelles and lipid vesicles.
A hallmark of the common Alzheimer's disease (AD) is the pathological conversion of its amphiphatic amyloid-beta (Abeta) peptide into neurotoxic aggregates. In AD patients, these aggregates are often found to be tightly associated with neuronal G(M1) ganglioside lipids, suggesting an involvement of G(M1) not only in aggregate formation but also in neurotoxic events. Significant interactions were found between micelles made of newly synthesized fluorescent G(M1) gangliosides labeled in the polar headgroup or the hydrophobic chain and Abeta(1-40) peptide labeled with a BODIPY-FL-C1 fluorophore at positions 12 and 26, respectively. From an analysis of energy transfer between the different fluorescence labels and their location in the molecules, we were able to place the Abeta peptide inside G(M1) micelles, close to the hydrophobic-hydrophilic interface. Large unilamellar vesicles composed of a raftlike G(M1)/bSM/cholesterol lipid composition doped with labeled G(M1) at various positions also interact with labeled Abeta peptide tagged to amino acids 2 or 26. A faster energy transfer was observed from the Abeta peptide to bilayers doped with 581/591-BODIPY-C(11)-G(M1) in the nonpolar part of the lipid compared with 581/591-BODIPY-C(5)-G(M1) residing in the polar headgroup. These data are compatible with a clustering process of G(M1) molecules, an effect that not only increases the Abeta peptide affinity, but also causes a pronounced Abeta peptide penetration deeper into the lipid membrane; all these factors are potentially involved in Abeta peptide aggregate formation due to an altered ganglioside metabolism found in AD patients.


Micronodules and emphysema in coal mine dust or silica exposure: relation with lung function.
The aim of this study was to investigate the respective effects of micronodules and pulmonary emphysema, detected by computed tomography (CT), on lung function in workers exposed to silica and coal mine dust. Eighty-three subjects exposed to silica (n=35) or to coal mine dust (n=48), without progressive massive fibrosis, were investigated by high-resolution and conventional CT scans to detect micronodules and to quantify pulmonary emphysema by measuring the relative area of the lung with attenuation values lower than -950 Hounsfield units. Sixty-six (54.5%) subjects had evidence of micronodules on CT scans. Smokers had micronodules more rarely than nonsmokers. Significant correlations were found between the forced expiratory volume in one second (FEV(1); % predicted) (r=-0.41, p<0.001), FEV1/vital capacity (VC) (r=-0.61, p<0.001), diffusing capacity of the lung for carbon monoxide (DL,CO) (r=-0.36, p<0.001) and the extent of emphysema. No difference was demonstrated in the linear relationships between the extent of emphysema and the pulmonary function according to the type of exposure or the presence of micronodules on CT scans. This study suggests that micronodules detected by computed tomography have no influence, by themselves, on pulmonary function and that they should only be considered as a marker of exposure.


The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance.
Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The non-malignant form of the disease is termed chondroma. Correctly distinguishing between the two forms is essential for making therapeutic decisions. However, due to their similar histological appearances and the lack of a reliable diagnostic marker, it is often difficult to distinguish benign tumors from low-grade chondrosarcoma. Therefore, it is necessary to search for a potential marker that has diagnostic and prognostic values in chondrosarcoma. In this study, we demonstrated by immunohistochemistry that elevated leukemia/lymphoma-related factor (LRF) expression was associated with increased malignancy in human chondrosarcoma tissue microarrays. Moreover, siRNA depletion of LRF drastically reduced proliferation of chondrosarcoma cell lines and effectively induced senescence in these cells. This could be attributed to the observation that LRF-depleted cells were arrested at the G(1) phase, and had increased p53 and p21 expression. Moreover, LRF depletion not only drastically reduces the cellular migration and invasion potentials of chondrosarcoma cells but also sensitized these cells to the apoptosis-inducing chemotherapeutic agent doxorubicin. We conclude that LRF is a survival factor in chondrosarcomas and its expression correlates with tumor malignancy and chemoresistance. Our data implicate the potential role of LRF as both a diagnostic marker and therapeutic target for chondrosarcomas.


An ultra-sensitive platinized nanocavity electrode for analysis of cytosolic catecholamines in one living cell.
The catecholamines, mainly dopamine (DA), are present in the cellular cytosol with low abundance, while, play key roles in various neurodegenerative disorders. Here, platinized nanocavity carbon electrodes are employed to analyze cytosolic catecholamines in a single living PC12 cell, which is not easily quantified using the classic electrodes. The confined structure and excellent conductivity in the platinized nanocavity accelerate the electron transfer of the DA, resulting in a low detection limit down to 50 nM. The sensitivity of DA detection is improved to be 10.73 pA mM-1 nm-1 in the response range of 50 nM-100 μM, which guarantees quantitative analysis of cytosolic catecholamines with low abundance. Eventually, the platinized nanocavity electrode is employed to detect cytosolic catecholamines in a single PC12 cell without an obvious interruption of cellular catecholamine level. The cytosolic catecholamines in a single PC12 cell is measured in situ to be 0.1 μM, which is achieved for the first time at the single cell level using the electrochemical method. The results demonstrate that the nanocavity electrode with a high sensitivity could offer a promising means to dynamically track catecholamines in a single cell.


Triggering efficient reconstructions of Co/Fe dual-metal incorporated Ni hydroxide by phosphate additives for electrochemical hydrogen and oxygen evolutions.
Alkaline electrochemical water splitting has been considered as an efficient way for the green hydrogen production in industry, where the electrocatalysts play the critical role for the electricity-to-fuel conversion efficiency. Phosphate salts are widely used as additives in the fabrication of electrocatalysts with improved activity, but their roles on the electrocatalytic performance have not been fully understood. Herein, we fabricate Co, Fe dual-metal incorporated Ni hydroxide on Ni foam using NaH2PO4 ((Co, Fe)NiOxHy-pi) and NaH2PO2 ((Co, Fe)NiOxHy-hp) as additive, respectively. We find that (Co, Fe)NiOxHy-hp with NaH2PO2 in the fabrication shows high activity and stability for both HER and OER (a overpotential of -0.629 V and 0.65 V at 400 mA cm-2 for HER and OER, respectively). Further experiment reveals that the reconstructed structures of electrocatalyst by using NaH2PO2 (hp) endow high electrocatalytic performances: (1) in-situ generated active metal improves the accumulation, transportation and activity of hydrogen species in the HER process; and (2) in-situ generated poor-crystalline hydroxide endows superior charge/mass transportation and kinetics improvements in the OER process. Our study may provide an insightful understanding on the catalytic performance of non-precious metal electrocatalysts by controlling additives and guidance for the design and synthesis of novel electrocatalysts.


Virus-host coexistence in phytoplankton through the genomic lens.
Virus-microbe interactions in the ocean are commonly described by "boom and bust" dynamics, whereby a numerically dominant microorganism is lysed and replaced by a virus-resistant one. Here, we isolated a microalga strain and its infective dsDNA virus whose dynamics are characterized instead by parallel growth of both the microalga and the virus. Experimental evolution of clonal lines revealed that this viral production originates from the lysis of a minority of virus-susceptible cells, which are regenerated from resistant cells. Whole-genome sequencing demonstrated that this resistant-susceptible switch involved a large deletion on one chromosome. Mathematical modeling explained how the switch maintains stable microalga-virus population dynamics consistent with their observed growth pattern. Comparative genomics confirmed an ancient origin of this "accordion" chromosome despite a lack of sequence conservation. Together, our results show how dynamic genomic rearrangements may account for a previously overlooked coexistence mechanism in microalgae-virus interactions.


A PKS/NRPS/FAS hybrid gene cluster from Serratia plymuthica RVH1 encoding the biosynthesis of three broad spectrum, zeamine-related antibiotics.
Serratia plymuthica strain RVH1, initially isolated from an industrial food processing environment, displays potent antimicrobial activity towards a broad spectrum of Gram-positive and Gram-negative bacterial pathogens. Isolation and subsequent structure determination of bioactive molecules led to the identification of two polyamino antibiotics with the same molecular structure as zeamine and zeamine II as well as a third, closely related analogue, designated zeamine I. The gene cluster encoding the biosynthesis of the zeamine antibiotics was cloned and sequenced and shown to encode FAS, PKS as well as NRPS related enzymes in addition to putative tailoring and export enzymes. Interestingly, several genes show strong homology to the pfa cluster of genes involved in the biosynthesis of long chain polyunsaturated fatty acids in marine bacteria. We postulate that a mixed FAS/PKS and a hybrid NRPS/PKS assembly line each synthesize parts of the backbone that are linked together post-assembly in the case of zeamine and zeamine I. This interaction reflects a unique interplay between secondary lipid and secondary metabolite biosynthesis. Most likely, the zeamine antibiotics are produced as prodrugs that undergo activation in which a nonribosomal peptide sequence is cleaved off.


Electrochemistry of carbon nanotubes: reactive processes, dual sensing-actuating properties and devices.
Single-walled carbon nanotubes (SWCNT) embedded in a non-electroactive polymer are electrochemically characterized. The increasing voltammetric maximums obtained with rising temperature or electrolyte concentration point to a chemical nature of the processes. The chemical kinetic control of the processes is corroborated by its empirical chemical kinetics: the initial reaction rates are obtained from the chronoamperometric responses to potential steps. The activation energy of the reaction includes information about the structural state of the SWCNT before the potential step. Under constant current the potential evolution (chronopotentiometric response) and consumed electrical energy at any time change as a function of (are sensors of) the experimental temperature or the electrolyte concentration. The reactive material, or any device based on this material, senses these working variables, and shows dual and simultaneous actuating-sensing properties.


Does ErbiumiYttrium-Aluminum-Garnet Laser to Enamel improve the Performance of Etch-and-rinse and Universal Adhesives?
This study aims to evaluate the effect of erbium: Yttrium-aluminum-garnet (Er:YAG) laser irradiation on the enamel microshear bond strength (μSBS), followed by the utilization of etch-and-rinse and universal adhesive systems. A total of 32 molars were sectioned in the mesiodistal direction producing 64 samples that were randomized into two groups (n = 32): single bond 2 (SB2) (etch-and-rinse system; 3M), SB universal (SBU) (universal etching system; The SB2 and SBU groups were then divided into two subgroups (n = 16): (i) enamel was irradiated with an Er:YAG laser (λ = 2.94 μm, 60 mJ, 10 Hz), and (ii) enamel served as a control. The samples were restored with TPH3 (Dentsply), stored in artificial saliva for 24 hours, and subjected to a micro-shear test. Kruskal-Wallis (p < 0.05) and Mann-Whitney U tests indicated no significant differences in uSBS between the groups, and the fractures were predominately at the resin-enamel interface. The previous irradiation of enamel with Er:YAG laser does not interfere with the performance of simplified two-step etch-and-rinse and universal adhesive systems. The increasing use of Er:YAG laser is important to evaluate the influence of this irradiation on the adhesion of restorative materials. Thus, to obtain the longevity of the restorative procedures, it is necessary to know the result of the association of the present adhesive systems to the irradiated substrate.


Maternal Th17/Treg Cytokines and Small Extracellular Vesicles in Plasma as Potential Biomarkers for Preeclampsia.
Preeclampsia is one of the most serious pregnancy complications. It may be caused by immunological changes in the early placental microenvironment. The contents of small EVs may serve as biomarkers of pregnancy complications. Evidence suggests that the balance between T helper 17 (Th17) and regulatory T (Treg) cells are critical for preventing preeclampsia. The study recruited 39 pregnant women with preeclampsia and 127 healthy pregnant women. We assessed the levels of both Th17 and Treg cytokines (IL-10, IL-17, IL-21, IL-22, and TGF-β) in their plasma and small EVs. We found significant differences in the levels of all cytokines in the plasma between the two groups during the second trimester. We also observed significant differences between the two groups in the levels of EV-encapsulated cytokines IL-21, IL-22, and TGF-β, as well as in total small EVs, during the second trimester. The ROC analysis showed that the classification efficiency (AUC) of TGF-β in small EVs was 0.81. TGF-β had the best discriminant ability of all the single EV biomarkers tested, the cross-validation of the accuracy was 0.89. Th17 and Treg cytokines in plasma and small EVs may contribute to maternal immune activation and clarify the potential mechanisms of small EVs and cytokines in preeclampsia.


Detection of genetic variants of transthyretin by liquid chromatography-dual electrospray ionization fourier-transform ion-cyclotron-resonance mass spectrometry.
One of the numerous proteins causing amyloidosis is transthyretin (TTR), a protein usually responsible for the transport of thyroxine and retinol-binding protein. Variants within TTR cause it to aggregate and form insoluble fibers that accumulate in tissue, leading to organ dysfunction. TTR was immunoprecipitated from serum by use of a polyclonal antibody and subsequently reduced with tris(2-carboxyethyl)phosphine. The purified TTR was then analyzed by fast-gradient liquid chromatography-dual-electrospray ionization Fourier-transform ion-cyclotron-resonance (FT-ICR) mass spectrometry. DNA sequencing was performed on all samples used in this study. Because of the inherent limitations in achieving high mass measurement accuracy based on the most abundant isotopic mass, we applied a fitting procedure that allowed determination of monoisotopic mass. Wild-type TTR (mean molecular mass, 13,761 Da) and its associated variant forms could be distinguished because of the high molecular mass accuracy afforded by FT-ICR (< or = 3 ppm) except for instances involving isobaric species or when isotopic distributions overlapped significantly. The [M + 11 H+]11+ charge state for all samples was used to determine the mass accuracies for both wild-type and variant forms of the protein. We correctly assigned seven of seven TTR variants. Moreover, using a combination of proteomic and genomic technologies, we discovered and characterized a previously unreported cis double mutation with a mass only 2 Da different from wild-type TTR. Furthermore, DNA sequencing of the TTR gene for all individuals in this study completely agreed with the intact protein measurements. FT-ICR mass spectrometry has sufficient mass accuracy to identify genetic variants of immunoaffinity-purified TTR. We believe that 91% of known TTR variants could be detected by this technique.


Lacto-N-fucopentaose III activity in the serum of patients with ovarian carcinoma.
The expression of the lacto-N-fucopentaose III (LNF III) epitope by tumor cells of the gastrointestinal tract and ovary has been observed in tissue sections with the use of the murine monoclonal antibody GA 29-1. The presence of the LNF III epitope in the circulation of patients with colorectal cancer has also been reported. In this preliminary study, we describe the presence of LNF III activity in the serum of patients with adenocarcinoma of the ovary. Twelve of 18 (66%) patients with stage I-IV disease demonstrated high reactivity to the GA 29-1 monoclonal antibody. This serum reactivity was independent of disease stage and histologic cell type. In contrast, only 1 of 6 control patients demonstrated a false-positive level of reactivity to GA 29-1. These preliminary results suggest that LNF III warrants further study of its potential application as a serum tumor marker test in patients with adenocarcinoma of the ovary.


Homeostasis of intracellular Ca2+ in equine chondrocytes: response to hypotonic shock.
Ca2+ homeostasis in articular chondrocytes affects synthesis and degradation of the cartilage matrix, as well as other cellular functions, thereby contributing to joint integrity. Although it will be affected by mechanical loading, the sensitivity of intracellular Ca2+ concentration ([Ca2+]i) in equine articular chondrocytes to many stimuli remains unknown. An improved understanding of Ca2+ homeostasis in equine articular chondrocytes, and how it is altered during joint loading and pathology, will be important in understanding how joints respond to mechanical loads. [Ca2+]i was determined using the fluorophore fura-2. We examined the effects of hypotonic shock, a perturbation experienced in vivo during mechanical loading cycles. We used inhibitors of Ca2+ transporters to ascertain the important factors in Ca2+ homeostasis. Under isotonic conditions, [Ca2+]i was 148 +/- 23 nmol/l, increasing by 216 +/- 66 nmol/l in response to reduction in extracellular osmolality of 50%. Resting [Ca2+]i, and the increase following hypotonic shock, were decreased by Ca2+ removal; they were both elevated when extracellular [Ca2+] ([Ca2+]o) was raised or following Na+ removal. The hypotonicity-induced rise in [Ca2+]i was inhibited by exposure of cells to gadolinium (Gd3+; 10 micromol/l), an inhibitor of mechanosensitive channels. [Ca2+]i was also elevated following treatment of cells with thapsigargin (10 micromol/l), an inhibitor of the Ca2+ pump of intracellular stores. A model is presented which interprets these findings in relation to Ca2+ homeostasis in equine articular chondrocytes, including the presence of mechanosensitive channels allowing Ca2+ entry, a Na+/Ca2+ exchanger for removal of intracellular Ca2+ and intracellular stores sensitive to thapsigargin. A more complete understanding of Ca2+ homeostasis in equine chondrocytes may allow development of future therapeutic regimes to ameliorate joint disease.


Jointly modeling of sleep variables that are objectively measured by wrist actigraphy.
Recently developed actigraphy devices have made it possible for continuous and objective monitoring of sleep over multiple nights. Sleep variables captured by wrist actigraphy devices include sleep onset, sleep end, total sleep time, wake time after sleep onset, number of awakenings, etc. Currently available statistical methods to analyze such actigraphy data have limitations. First, averages over multiple nights are used to summarize sleep activities, ignoring variability over multiple nights from the same subject. Second, sleep variables are often analyzed independently. However, sleep variables tend to be correlated with each other. For example, how long a subject sleeps at night can be correlated with how long and how frequent he/she wakes up during that night. It is important to understand these inter-relationships. We therefore propose a joint mixed effect model on total sleep time, number of awakenings, and wake time. We develop an estimating procedure based upon a sequence of generalized linear mixed effects models, which can be implemented using existing software. The use of these models not only avoids computational intensity and instability that may occur by directly applying a numerical algorithm on a complicated joint likelihood function, but also provides additional insights on sleep activities. We demonstrated in simulation studies that the proposed estimating procedure performed well in estimating both fixed and random effects' parameters. We applied the proposed model to data from the Women's Interagency HIV Sleep Study to examine the association of employment status and age with overall sleep quality assessed by several actigraphy measured sleep variables.


Coastal ocean and shelf-sea biogeochemical cycling of trace elements and isotopes: lessons learned from GEOTRACES.
Continental shelves and shelf seas play a central role in the global carbon cycle. However, their importance with respect to trace element and isotope (TEI) inputs to ocean basins is less well understood. Here, we present major findings on shelf TEI biogeochemistry from the GEOTRACES programme as well as a proof of concept for a new method to estimate shelf TEI fluxes. The case studies focus on advances in our understanding of TEI cycling in the Arctic, transformations within a major river estuary (Amazon), shelf sediment micronutrient fluxes and basin-scale estimates of submarine groundwater discharge. The proposed shelf flux tracer is 228-radium (T1/2 = 5.75 yr), which is continuously supplied to the shelf from coastal aquifers, sediment porewater exchange and rivers. Model-derived shelf 228Ra fluxes are combined with TEI/ 228Ra ratios to quantify ocean TEI fluxes from the western North Atlantic margin. The results from this new approach agree well with previous estimates for shelf Co, Fe, Mn and Zn inputs and exceed published estimates of atmospheric deposition by factors of approximately 3-23. Lastly, recommendations are made for additional GEOTRACES process studies and coastal margin-focused section cruises that will help refine the model and provide better insight on the mechanisms driving shelf-derived TEI fluxes to the ocean.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.


The tolerance of the field slug Deroceras reticulatum to freezing temperatures.
Cold hardiness of ectotherms has been widely studied in arthropods, but there is a more limited literature on the survival of molluscs at low temperatures. A number of intertidal species have been examined in detail, but terrestrial molluscs have largely been overlooked until recently. This paper reports results of laboratory experiments to evaluate the cold hardiness of the terrestrial slug, Deroceras reticulatum. The mean supercooling point (SCP) rose from -4.2 degree C in summer to -3.6 degree C in winter. The SCP that caused 50 percent mortality (LSCP50) remained constant at -4.7 to -4.8 degree C in both seasons, but slugs were able to survive the frozen state for longer in winter (LD50 of 31.8 minutes compared with 17.0 minutes in summer). Slug survival at freezing temperatures was prolonged to at least five hours when placed on a moist, absorbent substrate. D. reticulatum exhibits partial freeze tolerance, with an increased survival in winter. The results are discussed in relation to the natural environment of slugs.


The Meal Pattern Questionnaire: A psychometric evaluation using the Eating Disorder Examination.
Meal pattern is an important variable in both obesity treatment and treatment for eating disorders. Momentary assessment and eating diaries are highly valid measurement methods but often cumbersome and not always feasible to use in clinical practice. The aim of this study was to design and evaluate a self-report instrument for measuring meal patterns. The Pattern of eating item from the Eating Disorder Examination (EDE) interview was adapted to self-report format to follow the same overall structure as the Eating Disorder Examination Questionnaire. The new instrument was named the Meal Patterns Questionnaire (MPQ) and was compared with the EDE in a student sample (n=105) and an obese sample (n=111). The individual items of the MPQ and the EDE showed moderate to high correlations (rho=.63-89) in the two samples. Significant differences between the MPQ and EDE were only found for two items in the obese sample. The total scores correlated to a high degree (rho=.87/.74) in both samples and no significant differences were found in this variable. The MPQ can provide an overall picture of a person's eating patterns and is a valid way to collect data regarding meal patterns. The MPQ may be a useable tool in clinical practice and research studies when more extensive instruments cannot be used. Future studies should evaluate the MPQ in diverse cultural populations and with more ecological assessment methods.


Gallstone Classification in Western Countries.
In order to compare gallstone disease data from India and Asian countries with Western countries, it is fundamental to follow a common gallstone classification. Gallstone disease has afflicted humans since the time of Egyptian kings, and gallstones have been found during autopsies on mummies. Gallstone prevalence in adult population ranges from 10 to 15 %. Gallstones in Western countries are distinguished into the following classes: cholesterol gallstones that contain more than 50 % of cholesterol (nearly 75 % of gallstones) and pigment gallstones that contain less than 30 % of cholesterol by weight, which can be subdivided into black pigment gallstones and brown pigment gallstones. It has been shown that ultrastructural analysis with scanning electron microscopy is useful in the classification and study of pigment gallstones. Moreover, x-ray diffractometry analysis and infrared spectroscopy of gallstones are of fundamental importance for an accurate stone analysis. An accurate study of gallstones is useful to understand gallstone pathogenesis. In fact, bacteria are not important in cholesterol gallstone nucleation and growth, but they are important in brown pigment gallstone formation. On the contrary, calcium bilirubinate is fundamental in black pigment gallstone formation and probably also plays an important role in cholesterol gallstone nucleation and growth.


Human leptospirosis in Detroit and the role of rats as chronic carriers.
Human leptospirosis was diagnosed in three patients from Detroit General Hospital. Epidemiological studies of these cases revealed heavy rat infestations in the residences of two of the patients. Leptospires serotype icterohaemorrhagiae were isolated from the rats and one of the patients. Cultural isolation was attempted from numerous blood and urine samples from each patient. Media containing different selective contaminant inhibitor substances was also utilized. Only two samples were culturally positive. It appears that very few viable cells are shed by human patients intermittently. Clinical reports and leptospirosis diagnosis are reported for each of the cases. The agglutinin-absortion test proved to be helpful in elucidating the true etiologic agent in the absence of cultural isolation. A serological survey for leptospirosis was conducted among swine slaughterhouse workers in Detroit. Significant titres to Leptospira pomona were observed.


Active T-rosette-forming cells in the peripheral blood of cancer patients.
We studied a subpopulation of the thymus-dependent rosette-forming lymphocytes from the peripheral blood of normal individuals and of untreated patients with solid tumors or hematological cancers. This subpopulation of the thymus-dependent rosette-forming cells (T-RFC), termed the "active T-RFC," may be relatively more immunocompetent than the total thymus-dependent population. The mean percentages and absolute numbers of active T-RFC of 40 healthy adult controls were 25.8 +/- 4.3 and 626 +/- 213, respectively. There was no difference in the percentage of active T-RFC between the controls (smokers and nonsmokers) and the 102 untreated patients with solid (localized or metastasized) tumors, 4 patients with Hodgkin's disease, or the 10 patients with non-Hodgkin's lymphomas. However, the absolute number of active T-RFC was significantly less in the cancer patients than in the controls. Eight patients with chronic lymphocytic leukemia had lower percentages but higher absolute numbers of active T-RFC, whereas 6 patients with multiple myeloma had higher percentage and lower absolute numbers than the controls. Following radiation therapy, 61 patients with solid tumors showed no difference in the percentage of active T-RFC, but the corresponding absolute numbers declined significantly. A good correlation was seen with patients having positive microbial skin test responses and normal percentage of active T-RFC. The significance of both the percentages and absolute numbers of active T-RFC and their relationship to patient status are discussed.


A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia.
Histamine has important functions as regulator of several other key neurotransmitters. Patients with schizophrenia have lower histamine H1 receptor levels. Since a case report in 1990 of an effect of the H2 antagonist famotidine on negative symptoms in schizophrenia, some open-label trials have been performed, but no randomized controlled trial. Recently, it was shown that clozapine is a full inverse agonist at the H2 receptor. We performed a researcher-initiated, academically financed, double-blind, placebo-controlled, parallel-group, randomized trial with the histamine H2 antagonist famotidine in treatment-resistant schizophrenia. Thirty subjects with schizophrenia were randomized to have either famotidine (100 mg twice daily, n = 16) or placebo (n = 14) orally, added to their normal treatment regimen for 4 weeks. They were followed up weekly with the Scale for the Assessment of Negative Symptoms (SANS), the PANSS (Positive and Negative Syndrome Scale), and Clinical Global Impression (CGI) Scale. In the famotidine group, the SANS score was reduced by 5.3 (SD, 13.1) points, whereas in the placebo group the SANS score was virtually unchanged (mean change, +0.2 [SD, 9.5]). The difference did not reach statistical significance (P = 0.134) in Mann-Whitney U analysis. However, the PANSS Total score and the General subscore as well as the CGI showed significantly (P < 0.05) greater change in the famotidine group than in the placebo group. No significant adverse effects were observed. This is the first placebo-controlled, randomized clinical trial showing a beneficial effect of histamine H2 antagonism in schizophrenia. H2 receptor antagonism may provide a new alternative for the treatment of schizophrenia.


Aging after spinal cord injury: an exploratory study.
To identify the relationship between two aspects of aging (age at injury onset and years since injury onset) with the post-injury prevalence of six classes of secondary conditions among a sample of participants with spinal cord injury (SCI). A cross-sectional study to identify the relationship between the two aging variables and secondary conditions after spinal cord injury. A large southeastern rehabilitation hospital, with the collaboration of two midwestern hospitals. Three hundred and forty-seven participants, all of whom had traumatic SCI of an average duration of 18.2 years. The Secondary Conditions Questionnaire (SCQ), a 50-item self-report screening measure for secondary conditions after SCI, was used to measure the post-injury prevalence of six classes of secondary conditions. There was a significantly greater odds of kidney stones, non-urinary related infections, and three types of musculoskeletal conditions (ie, curvature of the spine, contractures, and fractures) among participant cohorts who were 20-29 years post-injury and 30 or more years post-injury. The odds of heart problems and bowel obstructions were higher with a greater age at injury onset, whereas the odds of seven other conditions decreased among older cohorts at injury. Among these seven conditions, the most dramatic findings were for kidney stones, where individuals who were less than 18 at injury had over 30 times the odds of having had the condition since injury than those who were injured at 40 or older. Although the study was cross-sectional in nature, the results point to secondary conditions which may be problematic with increasing years since injury, as well as those conditions which are more or less likely to occur among individuals injured at different points in their lives.


Durable improvements in efficiency, safety, and satisfaction in the operating room.
Enhanced productivity and efficiency in the operating room must be balanced with patient safety and staff satisfaction. In December 2004, transition to an expanded replacement hospital resulted in mandatory overtime, unpredictable work hours, and poor morale among operating room (OR) staff. A staff-retention crisis resulted, which threatened the viability of the OR and the institution. We report the changes implemented to efficiently deliver safe patient care in a supportive environment for surgeons and OR staff. University of Alabama at Birmingham University Hospital OR data were evaluated for fiscal year 2004 and compared with fiscal years 2005 and 2006. Case volumes, number of operational ORs, and on-time case starts were evaluated. OR adverse events were tabulated. Percentage of registered nurse hires and staff departures served as a proxy for staff satisfaction. Short, intermediate, and longterm strategies were implemented by an engaged OR management committee with the guidance of surgical, anesthesia, and hospital leadership. These included new block time release policies; use of traveling nurses until new staff could be hired and trained; and incentive-based, voluntary, employee-scheduled overtime. Mandatory nursing education time was blocked weekly. Enforcement of the National Patient Safety Goals were implemented and adjudicated with a "surgeon-of-the-day" system providing backup for nurse management. We demonstrated an increase in operations per year, on-time starts, and registered nurse hires in fiscal years 2005 and 2006. During this same time, we were able to markedly decrease the number of adverse events, admitting delays, and staff departures. Change is difficult to accept but essential when vital clinical activities are impaired and at risk. To maintain important clinical environments like the OR in an academic center, we developed and implemented effective, data-driven changes. This allowed us to retain critical human resources and restore a supportive environment for the patients, the doctors, and the staff.


Sites of phosphorylation by protein kinase A in CDC25Mm/GRF1, a guanine nucleotide exchange factor for Ras.
Activation of the neuronal Ras GDP/GTP exchange factor (GEF) CDC25Mm/GRF1 is known to be associated with phosphorylation of serine/threonine. To increase our knowledge of the mechanism involved, we have analyzed the ability of several serine/threonine kinases to phosphorylate CDC25Mm in vivo and in vitro. We could demonstrate the involvement of cAMP-dependent protein kinase (PKA) in the phosphorylation of CDC25Mm in fibroblasts overexpressing this RasGEF as well as in mouse brain synaptosomal membranes. In vitro, PKA was found to phosphorylate multiple sites on purified CDC25Mm, in contrast to protein kinase C, calmodulin kinase II, and casein kinase II, which were virtually inactive. Eight phosphorylated serines and one threonine were identified by mass spectrometry and Edman degradation. Most of them were clustered around the Ras exchanger motif/PEST motifs situated in the C-terminal moiety (residues 631-978) preceding the catalytic domain. Ser745 and Ser822 were the most heavily phosphorylated residues and the only ones coinciding with PKA consensus sequences. Substitutions S745D and S822D showed that the latter mutation strongly inhibited the exchange activity of CDC25Mm on Ha-Ras. The multiple PKA-dependent phosphorylation sites on CDC25Mm suggest a complex regulatory picture of this RasGEF. The results are discussed in the light of structural and/or functional similarities with other members of this RasGEF family.


A thraustochytrid diacylglycerol acyltransferase 2 with broad substrate specificity strongly increases oleic acid content in engineered Arabidopsis thaliana seeds.
Diacylglycerol acyltransferase (DGAT) catalyses the last step in acyl-CoA-dependent triacylglycerol (TAG) biosynthesis and is an important determinant of cellular oil content and quality. In this study, a gene, designated TaDGAT2, encoding a type 2 DGAT (DGAT2)-related enzyme was identified from the oleaginous marine protist Thraustochytrium aureum. The deduced TaDGAT2 sequence contains a ~460 amino acid domain most closely related to DGAT2s from Dictyostelium sp. (45-50% identity). Recombinant TaDGAT2 restored TAG biosynthesis to the Saccharomyces cerevisiae H1246 TAG-deficient mutant, and microsomes from the complemented mutant displayed DGAT activity with C16 and C18 saturated and unsaturated fatty acyl-CoA and diacylglycerol substrates. To examine its biotechnological potential, TaDGAT2 was expressed under control of a strong seed-specific promoter in wild-type Arabidopsis thaliana and the high linoleic acid fad3fae1 mutant. In both backgrounds, little change was detected in seed oil content, but a striking increase in oleic acid content of seeds was observed. This increase was greatest in fad3fae1 seeds, where relative amounts of oleic acid increased nearly 2-fold to >50% of total fatty acids. In addition, >2-fold increase in oleic acid levels was detected in the triacylglycerol sn-2 position and in the major seed phospholipid phosphatidylcholine. These results suggest that increased seed oleic acid content mediated by TaDGAT2 is influenced in part by the fatty acid composition of host cells and occurs not by enhancing oleic acid content at the TAG sn-3 position directly but by increasing total oleic acid levels in seeds, presumably by limiting flux through phosphatidylcholine-based desaturation reactions.


Altered taste and stroke: a case report and literature review.
Patients with altered taste perception following stroke are at risk for malnutrition and associated complications that may impede recovery and adversely affect quality of life. Such deficits often induce and exacerbate depressive symptomatology, which can further hamper recovery. It is important for clinicians and rehabilitation specialists to monitor stroke patients for altered taste perception so that this issue can be addressed. The authors present the case of a patient who experienced an isolated ischemic infarct affecting a primary cortical taste area. This case is unusual in that the isolated injury allowed the patient to remain relatively intact cognitively and functionally, and thus able to accurately describe her taste-related deficits. The case is further used to describe the relevant neurological taste pathways and review potential taste-related therapies.