Staufen 1 is expressed by neural precursor cells in the developing murine cortex but is dispensable for NPC self-renewal and neuronal differentiation in vitro.

BACKGROUND: Proper development of the cerebral cortex relies on asymmetric divisions of neural precursor cells (NPCs) to produce a recurring NPC and a differentiated neuron. Asymmetric divisions are promoted by the differential localization of cell-fate determinants, such as mRNA, between daughter cells. Staufen 1 (Stau1) is an RNA-binding protein known to localize mRNA in mature hippocampal neurons. Its expression pattern and role in the developing mammalian cortex remains unknown. RESULTS: Both stau1 mRNA and Stau1 protein were found to be expressed in all cells of the developing murine cortex. Stau1 protein expression was characterized spatially and temporally throughout cortical development and found to be present in all stages investigated. We observed expression in the nucleus, cytoplasm and distal processes of both NPCs and newly born neurons and found it to shuttle between the nucleus and the cytoplasm. Upon shRNA-mediated knock-down of Stau1 in primary cultures of the developing cortex, we did not observe any phenotype in NPCs. They were able to both self-renew and generate neurons in the absence of Stau1 expression. CONCLUSIONS: We propose that Stau1 is either dispensable for the development of the cerebral cortex or that its paralogue, Stau2, is able to compensate for its loss.

The incidence and outcomes of nurse bullying in the Russian Federation.

AIM: The aim of this study was to describe bullying experienced by professional nurses working in the Russian Federation. The frequency and type of bullying behaviours experienced, the personal and professional consequences of bullying and the actions taken to address bullying were all examined. BACKGROUND/INTRODUCTION: Workplace bullying negatively affects nurses, patients and healthcare organizations. To date, no research has been conducted on workplace bullying among nurses in the Russian Federation. METHODS: This was a descriptive study using survey methodology. Members of the Russian Nurses Association were invited to participate via email and social media. Participants completed the 26-item, web-based Bullying in the Workplace Survey. Data were analysed using descriptive statistics. RESULTS: Of the 438 participants, 63% reported being bullied at some point during their career. The majority were female and worked fulltime for an average of 20 years. Over half the nurses were working in staff positions when bullying occurred, and administrators were most commonly identified as the bully. Bullying caused moderate to severe distress in 73.5%. Half of the nurses reported that bullying affected their work, and 83.3% reported that it affected their health. Just over 70% took action to address the bullying situation; 59% of those who did were dissatisfied with the outcome. CONCLUSION: Bullying is prevalent in the nursing workplace in the Russian Federation. The perpetrators were most frequently the nurse administrator or physician administrator. Workplace bullying negatively affects nurses' ability to function and subsequently impacts nursing teamwork and patient care. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Identifying bullying, its antecedents and consequences in the Russian Federation are a requisite for developing meaningful interventions and contributing to shaping local and international policy.

Stimulation of nodulation in Medicago truncatula by low concentrations of ammonium: quantitative reverse transcription PCR analysis of selected genes.

Although mineral nitrogen generally has negative effects on nodulation in legume-rhizobia symbioses, low concentrations of ammonium stimulate nodulation in some legumes. In this study, the effects of ammonium and nitrate on growth, nodulation and expression of 2 nitrogen transport and 12 putative nodulation-related genes of the model symbiosis of Medicago truncatula - Sinorhizobium meliloti are investigated. After 3 weeks of hydroponic growth, whole-plant nodulation was enhanced in all the ammonium treatments and up to three-fold in the 0.5 mM treatment compared with the zero-nitrogen control. Specific nodulation (nodules g(-1) root dry weight) was greatly stimulated in the 0.1 and 0.5 mM NH4+ treatments, to a lower extent in the 0.1 mM NO3- treatment, and inhibited in all other treatments. Expression of the 14 selected genes was observed at 0, 6, 12 and 24 h after exposure to rhizobia and nitrogen. Expression of nitrogen transporter genes increased significantly, but responses of the three genes putatively associated with symbiosis signaling/nodule initiation were mixed. There were infrequent responses of genes coding for an ABA-activated protein kinase or a gibberellin-regulated protein, but an ethylene-responsive element-binding factor showed increased expression in various treatments and sampling times. Three auxin-responsive genes and three cytokinin-responsive genes showed varied responses to ammonium and nitrate. This study indicates that low concentrations of ammonium stimulate nodulation in M. truncatula, but the data were inconclusive in verifying the hypothesis that a relatively high ratio of cytokinin to auxin in roots may be an underlying mechanism in this stimulation of nodulation.

Effects of the overexpression of a soybean cytosolic glutamine synthetase gene (GS15) linked to organ-specific promoters on growth and nitrogen accumulation of pea plants supplied with ammonium.

A soybean cytosolic glutamine synthetase gene (GS15) fused to a constitutive promoter (CaMV 35S), a putative nodule-specific promoter (LBC(3)), or a putative root-specific promoter (rolD) was transformed into Pisum sativum L. cv. Greenfeast. Four lines with single copies (Lines 1, 7, 8 and 9) and four lines with two copies each of GS15 (Lines 2, 4, 6 and 11) were compared to the wild-type (WT) parental line for levels of cytosolic glutamine synthetase (GS1), glutamine synthetase (GS) activity, N accumulation, N derived form the atmosphere (NDFA), and biomass of plants grown on 0.0, 0.1, 1.0 or 10.0 mM NH(4)(+). Enhanced levels of GS1 were detected in leaves of one of the two lines transformed with the 35S-GS15 construct, and all three lines containing the rolD-GS15 construct. All three lines containing the LBC(3)-GS15 construct had increased levels of GS1 in nodules. Despite the increased levels of GS1 in many transformants, only the roots of lines containing the rolD-GS15 construct consistently demonstrated enhanced levels of GS activity (up to 12-fold). Positive responses in plant N content, NDFA, and biomass were rare, but increases in plant biomass and N content of up to 17% and 54%, respectively, occurred in some of the rolD-GS15 lines at certain levels of ammonium. In general, GS15 copy number did not seem to differentially affect phenotype of the transformants, and transformants respond to ammonium concentrations in similar patterns to that previously observed with nitrate. Despite the fact that the rolD-GS15 transformants consistently resulted in increased GS activity in roots and resulted in some occurrences of increases in biomass and plant N content, the lack of consistent positive growth effect across all transformants indicates that the generalized overexpression of GS1 in tissues holds little potential for positive growth responses in pea.

Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line.

BACKGROUND: Reduction of T to DHT by 5alphaR in the prostate enhances androgenic activity for most targets. Inhibition of 5alphaR activity with finasteride attenuates androgen action in men and animal models. The objective of this study was to compare and contrast the effects of a potent new 5alphaR inhibitor, dutasteride, with finasteride in the LNCaP prostate cancer cell line. METHODS: LNCaP cells were incubated for varying times with T or DHT in steroid-free medium in the absence or presence of increasing doses of dutasteride or finasteride and the effects on 5alphaR activity, PSA accumulation in the medium, and on cell proliferation were determined. Drug effects on apoptosis were investigated using Annexin V staining and a cell death ELISA assay. Effects of the drugs on AR ligand-binding activity and on AR protein levels were determined. RESULTS: Dutasteride inhibited (3)H-T conversion to (3)H-DHT and, as anticipated, inhibited T-induced secretion of PSA and proliferation. However the drug also inhibited DHT-induced PSA secretion and cell proliferation (IC(50) approximately 1 microM). Finasteride also inhibited DHT action but was less potent than dutasteride. Dutasteride competed for binding the LNCaP cell AR with an IC(50) approximately 1.5 microM. High concentrations of dutasteride (10-50 microM), but not finasteride, in steroid-free medium, resulted in enhanced cell death, possibly by apoptosis. This was accompanied by loss of AR protein and decreased AR ligand-binding activity. Occupation of AR by R1881 partly protected against cell death and loss of AR protein. PC-3 prostate cancer cells, which do not contain AR, also were killed by high concentrations of dutasteride, as well as by 50 microM finasteride. CONCLUSIONS: Dutasteride exhibited some inhibitory actions in LNCaP cells possibly related to 5alphaR inhibition but also had antiandrogenic effects at relatively low concentrations and cell death-promoting effects at higher concentrations. Finasteride also was antiandrogenic, but less than dutasteride. The antiandrogenic effects may be mediated by the mutant LNCaP cell AR. Promotion of cell death by dutasteride can be blocked, but only in part, by androgens.

5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium.

PURPOSE: In the prostate testosterone is converted to the more potent androgen dihydrotestosterone by the enzymes 5alpha-reductase (5alphaR) types 1 (5alphaR1) and 2 (5alphaR2). Since 5alphaR2 is the dominant prostatic enzyme, the 5alphaR2 selective inhibitor finasteride has been widely used to treat benign prostatic hyperplasia (BPH). However, inhibition of both 5alphaR enzymes provides a greater decrease in serum dihydrotestosterone. We developed a specific antibody to 5alphaR1 and assessed expression in BPH and prostate cancer (pCa) tissue. The presence of this isoenzyme in localized prostate cancer would provide a rationale for assessing the efficacy of dual inhibition for prostate cancer prevention. MATERIALS AND METHODS: A polyclonal antibody to 5alphaR1 was developed and validated using 5alphaR1 and 5alphaR2 transfected COS-1 cells. A total of 26 BPH and 53 pCa specimens were assessed for 5alphaR1 protein expression using immunocytochemical methods. Also, 29 BPH and 37 pCa specimens were assayed for 5alphaR1 and 5alphaR2 enzyme activity. RESULTS: Specificity of the 5alphaR1 antibody was confirmed using transfected COS-1 cells. Cells transfected with 5alphaR1 showed specific staining in immunocytochemistry experiments and on Western blotting of cell lysates the expected 24 kDa band was observed. High intensity immunoreactivity for 5alphaR1 was observed in the tumor epithelium of 28% of pCa specimens. No high intensity epithelial staining was observed in BPH specimens. In 19% of pCa and 7% of BPH specimens 5alphaR1 enzyme activity was detected. CONCLUSIONS: The presence of increased 5alphaR1 in some prostatic malignancies suggests that it is worthwhile to investigate the use of a dual 5alphaR inhibitor to prevent or treat early stage prostate cancer.

Overexpression of a soybean cytosolic glutamine synthetase gene linked to organ-specific promoters in pea plants grown in different concentrations of nitrate.

A glutamine synthetase gene ( GS15) coding for soybean cytosolic glutamine synthetase (GS1) fused to a constitutive promoter (CaMV 35S), a putative nodule-specific promoter (LBC(3)) and a putative root-specific promoter (rolD) was transformed into Pisum sativum L. cv. Greenfeast. Four lines with single copies of GS15 (one 35S-GS15 line, one LBC (3) -GS15 line, and two rolD-GS15 lines) were tested for the expression of GS15, levels of GS1, GS activity, N accumulation, N(2) fixation, and plant growth at different levels of nitrate. Enhanced levels of GS1 were detected in leaves of three transformed lines (the 35S-GS15 and rolD-GS15 transformants), in nodules of three lines (the LBC (3) -GS15 and rolD-GS15 transformants), and in roots of all four transformants. Despite increased levels of GS1 in leaves and nodules, there were no differences in GS activity in these tissues or in whole-plant N content, N(2) fixation, or biomass accumulation among all the transgenic lines and the wild-type control. However, the rolD-GS15 transformants, which displayed the highest levels of GS1 in the roots of all the transformants, had significantly higher GS activity in roots than the wild type. In one of the rolD-GS15 transformed lines (Line 8), increased root GS activity resulted in a lower N content and biomass accumulation, supporting the findings of earlier studies with Lotus japonicus (Limami et al. 1999 ). However, N content and biomass accumulation was not negatively affected in the other rolD-GS15 transformant (Line 9) and, in fact, these parameters were positively affected in the 0.1 mM treatment. These findings indicate that overexpression of GS15 in various tissues of pea does not consistently result in increases in GS activity. The current study also indicates that the increase in root GS activity is not always consistent with decreases in plant N and biomass accumulation and that further investigation of the relationship between root GS activity and growth responses is warranted.

Evidence for protection of nitrogenase from O(2) by colony structure in the aerobic diazotroph Gluconacetobacter diazotrophicus.

Gluconacetobacter diazotrophicus is an endophytic diazotroph of sugarcane which exhibits nitrogenase activity when growing in colonies on solid media. Nitrogenase activity of G. diazotrophicus colonies can adapt to changes in atmospheric partial pressure of oxygen (pO(2)). This paper investigates whether colony structure and the position of G. diazotrophicus cells in the colonies are components of the bacterium's ability to maintain nitrogenase activity at a variety of atmospheric pO(2) values. Colonies of G. diazotrophicus were grown on solid medium at atmospheric pO(2) of 2 and 20 kPa. Imaging of live, intact colonies by confocal laser scanning microscopy and of fixed, sectioned colonies by light microscopy revealed that at 2 kPa O(2) the uppermost bacteria in the colony were very near the upper surface of the colony, while the uppermost bacteria of colonies cultured at 20 kPa O(2) were positioned deeper in the mucilaginous matrix of the colony. Disruption of colony structure by physical manipulation or due to 'slumping' associated with colony development resulted in significant declines in nitrogenase activity. These results support the hypothesis that G. diazotrophicus utilizes the path-length of colony mucilage between the atmosphere and the bacteria to achieve a flux of O(2) that maintains aerobic respiration while not inhibiting nitrogenase activity.

Nurses' attitudes concerning the delivery of brief cessation advice to hospitalized smokers.

BACKGROUND: Nurses have a unique opportunity to assist hospitalized smokers with cessation. However, relatively little is known about nurses' attitudes and beliefs toward their role in assisting patients with cessation. METHODS: A cross-sectional survey of staff nurses at four hospitals was conducted. Four scales based on constructs from the Theory of Planned Behavior were developed for this survey: attitudes toward offering cessation advice, beliefs about the outcome of offering advice, perceived normative beliefs, and perceived ability to offer advice. Other survey items included sociodemographics, employment characteristics (shift, unit worked), and personal smoking status. RESULTS: Of the nurses surveyed, 397 (68%) returned completed questionnaires. Nurses had a relatively positive attitude toward helping patients to quit smoking, 63% believed that hospitalization was an ideal time for patients to try to quit smoking, and 59% believed a nurse had an obligation to advise patients to quit smoking. In the final multiple linear regression model, self-reported delivery of cessation advice was related to attitudes toward offering cessation advice, perceived ability to offer advice, and unit worked. CONCLUSIONS: Efforts should be made to educate staff nurses about the efficacy of brief cessation advice and current smoking cessation methods and practices.

Response of the endophytic diazotroph Gluconacetobacter diazotrophicus on solid media to changes in atmospheric partial O(2) pressure.

Gluconacetobacter diazotrophicus is an N(2)-fixing endophyte isolated from sugarcane. G. diazotrophicus was grown on solid medium at atmospheric partial O(2) pressures (pO(2)) of 10, 20, and 30 kPa for 5 to 6 days. Using a flowthrough gas exchange system, nitrogenase activity and respiration rate were then measured at a range of atmospheric pO(2) (5 to 60 kPa). Nitrogenase activity was measured by H(2) evolution in N(2)-O(2) and in Ar-O(2), and respiration rate was measured by CO(2) evolution in N(2)-O(2). To validate the use of H(2) production as an assay for nitrogenase activity, a non-N(2)-fixing (Nif(-)) mutant of G. diazotrophicus was tested and found to have a low rate of uptake hydrogenase (Hup(+)) activity (0.016 +/- 0.009 micromol of H(2) 10(10) cells(-1) h(-1)) when incubated in an atmosphere enriched in H(2). However, Hup(+) activity was not detectable under the normal assay conditions used in our experiments. G. diazotrophicus fixed nitrogen at all atmospheric pO(2) tested. However, when the assay atmospheric pO(2) was below the level at which the colonies had been grown, nitrogenase activity was decreased. Optimal atmospheric pO(2) for nitrogenase activity was 0 to 20 kPa above the pO(2) at which the bacteria had been grown. As atmospheric pO(2) was increased in 10-kPa steps to the highest levels (40 to 60 kPa), nitrogenase activity decreased in a stepwise manner. Despite the decrease in nitrogenase activity as atmospheric pO(2) was increased, respiration rate increased marginally. A large single-step increase in atmospheric pO(2) from 20 to 60 kPa caused a rapid 84% decrease in nitrogenase activity. However, upon returning to 20 kPa of O(2), 80% of nitrogenase activity was recovered within 10 min, indicating a "switch-off/switch-on" O(2) protection mechanism of nitrogenase activity. Our study demonstrates that colonies of G. diazotrophicus can fix N(2) at a wide range of atmospheric pO(2) and can adapt to maintain nitrogenase activity in response to both long-term and short-term changes in atmospheric pO(2).

Factors associated with the risk of liver enzyme elevation in patients with type 2 diabetes treated with a thiazolidinedione.

STUDY OBJECTIVE: To characterize frequency of liver enzyme elevation in patients with type 2 diabetes mellitus receiving troglitazone. DESIGN: Retrospective study. SETTING: Hospital-affiliated medical center. PATIENTS: Two hundred ninety-one patients with type 2 diabetes mellitus. INTERVENTION: Data from patients with an average troglitazone exposure of 412.7 +/- 255.6 days were studied. MEASUREMENTS AND MAIN RESULTS: Enzyme elevations more than 1.5 times the upper limit of normal (ULN) occurred in 17 patients (5.8%) and more than 3-fold elevations in 6 (2.1%). The relationship among enzyme elevation events, demographic factors, duration of troglitazone exposure, frequency of monitoring, and concurrent drugs (limited to glucose and lipid-lowering agents) was assessed by multiple logistic regression. Age was an independent predictor of risk (p=0.009), and concurrent insulin therapy approached statistical significance (p=0.051) for 1.5-fold ULN elevation in liver enzymes. Age and concurrent therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were the only significant predictors of 3-fold ULN elevations (p=0.03 and p=0.04, respectively). CONCLUSION: Several factors appear to increase the risk of enzyme elevation events in patients treated with troglitazone.

Natural approaches to children's health: herbals and complementary and alternative medicine.

Complementary and alternative medicine (CAM) practices are widely used with pediatric populations. An overview of herbal medicines, use of common therapies with children, and advisory information is discussed.

Evaluating the value of screening for hypertension: an evidence-based approach.

No recommendations regarding in-school blood pressure (BP) screening currently exist. The purpose of this project was to use an evidence-based approach to determine whether BP screening should be initiated as part of one school district's standard screening protocols. Pediatric BP measurement, risk factors for hypertension, issues for determining youth at risk for hypertension, and eligibility criteria for determining conditions appropriate for screening are discussed. BPs of 1st, 6th, and 11th graders were evaluated according to standardized criteria. The evidence indicated that BP screening in school appears warranted, although a formalized study is needed before a definitive decision can be made regarding the incorporation of BP screening into school health services.

Self-medication with common household medicines by young adolescents.

Our study examines the self-medication practices of children ages 10-14. We developed a questionnaire that addressed several aspects of such behavior. A convenience sample of subjects (n = 86) completed the questionnaires in school settings in a northeastern metropolitan area. The data showed that a vast majority of the adolescents (89%) have access to the medicine in their households: 36% of them medicated themselves the last time they had any medicine. Most of their medication choices were appropriate, except in the area of gastrointestinal problems. There is a need for further investigation of this issue and incorporating the findings into the practice of pediatric nurses.

Patient recall versus physician documentation in report of smoking cessation counselling performed in the inpatient setting.

OBJECTIVES: To determine rates of patient reported and physician documented counselling; to identify predictors of each report; and to identify the impact of each report on smoking cessation attempts after discharge from the hospital. DESIGN: Stickers on subjects' charts prompted physicians to give brief smoking cessation counselling to patients in the hospital. Patients reported counselling received and quit attempts in a phone interview conducted 7-18 days after discharge. Rates of counselling and correlations were calculated, and multivariate analysis identified predictors of patient report, physician documentation, and quit attempts. SETTING: Four hospitals in the Minneapolis/St Paul metropolitan area. SUBJECTS: 682 hospital patients who had smoked more than 100 cigarettes in their lifetime and had smoked in the last three months. RESULTS: 71.0% of patients reported counselling, and physicians documented counselling in the charts of 46.2% of patients (correlation = 0.15, kappa = 0.13). Patient report was predicted by specific hospital, belief that their hospitalisation was smoking related, diagnosis of a smoking related disease, and physician documentation of counselling. Physician documentation was predicted by female patient, specific hospital, longer hospital stay, and marginally predicted by smoking related disease. Quit attempts were predicted by patient report of counselling, but not physician documentation. CONCLUSIONS: Physicians document counselling in the hospital at a lower rate than patients report it, and the correlation between reports is very low, making an accurate assessment of true rates of counselling difficult. While it is important to increase physician documentation, it is even more important to increase patient recall, as this is the only report that predicts a quit attempt.

A study of children's concepts of their internal bodies: a comparison of children with and without congenital heart disease.

This study examined the following: (1) the knowledge children with and without congenital heart disease have about their internal bodies, (2) the relationship of this knowledge with age, disease severity, and previous health care experiences, and (3) how the differences between beliefs about the interior body and the value assigned to specific body parts differed between children with congenital heart disease and their unaffected peers. One hundred participants, 50 with cardiac disease and 50 comparisons, between 5 and 15 years of age, completed the inside the Body Test; the severity of the conditions of the children with cardiac problems was evaluated with the Permanent Impairment Evaluation Guide. Results indicated that there were no differences between the 2 groups on knowledge of body parts, body-part function, nor the values that were assigned. Implications for practice are discussed.

Using distraction to reduce reported pain, fear, and behavioral distress in children and adolescents: a multisite study.

ISSUES AND PURPOSE: Distraction during painful procedures has been shown to be effective in previous studies, yet this simple intervention is not used routinely. This study examined the effectiveness and feasibility of distraction in reducing behavioral distress, pain, and fear during venipuncture or intravenous insertion. DESIGN AND METHODS: A two-group randomized design with 384 children in 13 children's hospitals. RESULTS: Age was a significant factor in observed behavioral distress, reports of fear, and self-reported pain. The use of a kaleidoscope, however, did not significantly reduce pain or distress during venipuncture or i.v. insertion. PRACTICE IMPLICATIONS: Failure of the distraction intervention to reach statistical significance in this study is puzzling, given anecdotal reports of clinical efficacy. Methodological issues may have obscured actual differences between experimental and control groups.

Diabetes disease stage predicts weight loss outcomes with long-term appetite suppressants.

OBJECTIVES: Characterize degree of weight loss with stage of diabetes and describe its effect on cardiovascular disease risk factors in obese patients with and without diabetes. RESEARCH METHODS AND PROCEDURES: Retrospective cohort analysis from patients participating in a long-term weight management protocol using diet, exercise, behavioral modification, and appetite-suppressant therapy. Patient groups, with (n = 19) and without diabetes (n = 19) were matched for age, gender, and weight before weight loss therapy. The effect of 12 months of therapy on weight, blood pressure, glycemic control, lipid profile, and medication requirements were tested. Additionally, patients were grouped or staged based upon therapy required for control of diabetes at the beginning of weight loss intervention. Analysis of covariance described relationships between diabetes disease stage and weight loss at 12 months. RESULTS: Nondiabetic patients had greater mean reduction in BMI than the diabetic group (7.98 kg/m2 vs. 4.77 kg/m2, p<0.01). A significant linear trend (p<0.001) for decreasing weight loss with stage of diabetes was observed. Blood pressure, lipid profile, and glycemia improved significantly. The average daily glyburide-equivalent dose decreased from 9.4 to 3.0 mg (p<0.01). DISCUSSION: Patients with diabetes lost less weight than similarly obese patients without diabetes. Regardless of differential weight loss between groups, cardiovascular disease risk factors improved. Hypoglycemic medication requirements decreased with weight loss therapy. A predictive relationship may exist between diabetes disease stage before weight loss therapy and future weight loss potential.