Promoter Sequence of Rat Thimet Oligopeptidase

Biochemical Society Transactions. Feb, 1998  |  Pubmed ID: 10909773

SPECT Imaging of Feet Using Uniplanar Fad-beam Collimators

Nuclear Medicine Review. Central & Eastern Europe. 1998  |  Pubmed ID: 14601002

This study was performed to assess the utility of bone SPECT in the feet using a new commercially available uniplanar fan-beam collimator originally designed for cardiac imaging.

Supramolecular Complexation of Polynuclear Aqua Ions: A Crown Ether Adduct of a µ-Oxo-Bridged Iron(III) Aqua Dimer

Angewandte Chemie (International Ed. in English). Aug, 1999  |  Pubmed ID: 10425490

Hydrolysis and polymerization of [Fe(OH(2))(6)](3+) in aqueous solution leads, in the early stages, to the oxo-bridged binuclear aqua ion [(H(2)O)(5)Fe(µ-O)Fe(OH(2))(5)](4+), which could be obtained in crystalline form through the use of [18]crown-6. The complex exhibits an almost linear Fe-O-Fe moiety and antiferromagnetic coupling that is consistent with current descriptions of exchange coupling in mono oxo-bridged binuclear Fe(III) complexes.

B- and T-cell Immune Responses to Pneumococcal Conjugate Vaccines: Divergence Between Carrier- and Polysaccharide-specific Immunogenicity

Infection and Immunity. Sep, 1999  |  Pubmed ID: 10456942

Conjugation of various serotypes of pneumococcal polysaccharide (PnPS) to carrier protein enhances the magnitude of the polysaccharide-specific antibody response, presumably by eliciting T-cell help. However, variability in PnPS serotype-specific immunogenicity has been observed. CBA/J mice immunized with either 6B or 19F PnPS conjugated to the protein carrier Cross Reactive Material(197) (CRM(197)) produce a strong anti-PnPS antibody response; however, when mice are immunized with 23F PnPS conjugated to CRM(197), they fail to produce a significant anti-PnPS response. In order to determine whether this difference was related to alterations in antigen processing of the carrier protein and the subsequent T-cell responses, we studied proliferation of lymphocytes from CBA/J mice immunized with CRM(197) alone or conjugated to 6B, 19F, or 23F PnPS. T-cell proliferative responses to synthetic peptides demonstrated that lymph node cells elicited by the poorly immunogenic conjugate 23F-CRM(197) recognized many, but not all, of the epitopes recognized by lymph node cells elicited by 6B- and 19F-CRM(197) as well as additional epitopes. Despite marked differences in PnPS-specific immunogenicity, all mice made high titers of CRM(197) antibodies of the immunoglobulin G(1) isotype. Cells from mice immunized with any of the conjugates yielded vigorous T-cell responses to whole antigen. We conclude that the serotype of PnPS can alter the peptide specificities of T-cell responses, but even a poorly immunogenic PnPS conjugate can elicit a significant T-cell response. Thus, conjugation of PnPS to a carrier protein that elicits carrier-specific T- and B-cell responses does not necessarily enhance PnPS immunogenicity.

Distribution of Thimet Oligopeptidase (E.C. 3.4.24.15) in Human and Rat Testes

Journal of Cell Science. Oct, 1999  |  Pubmed ID: 10504294

Thimet oligopeptidase (TOP:E.C. 3.4.24.15) is a thiol sensitive metalloendopeptidase which is widely distributed and active in most tissues including testis, brain and pituitary. In the median eminence it is postulated to play a role in the degradation of GnRH released from the hypothalamus and thus to modulate LH levels. In the rat and human, the testis is the richest source of TOP activity with levels 3- to 5-fold higher than that of the brain. In order to define the exact localisation of this enzyme within the rat and human testis, the distribution of TOP in the developing and adult gonad was examined in situ and in isolated cells by immunohistochemistry, western blotting and northern blotting analysis. Ontogeny studies have demonstrated that TOP is detectable by western blotting from 9 days with levels of expression increasing with the age of the animal. Immunolocalisation of the protein in the interstitium was positive from 9 days onwards but was negative within the seminiferous tubules before 35 days of age, whereas TOP mRNA was not detected within the testis until 35 days of age with subsequent stable expression levels up to 90 days. In the adult rat testis, a strong TOP immunoreactivity was observed within seminiferous tubules, in elongating and elongated spermatids and residual bodies. In the interstitial compartment, immunoreactivity was also observed in Leydig cells and throughout the interstitial space. Western blot analyses confirmed the distribution of expression observed using immunochemistry, however Leydig cells display a lower signal than expected from the immunohistochemical data. Northern hybridization showed that the transcript is present in pachytene spermatocytes, early spermatids, and residual bodies, whereas its presence was not observed in Leydig cells probably due to very low levels of expression of the message. Analyses of various human tissue extracts showed that the testis displays the highest levels of TOP mRNA, with immunohistochemical experiments revealing that, as in the rat, the protein is principally expressed in elongated spermatids/residual bodies, and in Leydig cells. It is concluded that in the human and rat testes, TOP is highly expressed, in particular in post-meiotic germ cells and Leydig cells. The possible involvement of TOP in proteolytic events associated with the process of spermiogenesis and Leydig cell function is currently under investigation.

Size Effect in Resin/glass Composite Flexure Strengths

Journal of Oral Rehabilitation. Oct, 1999  |  Pubmed ID: 10564432

The objective of this study was to test the hypothesis that composite restorative materials possess an elastic-brittle nature and therefore will exhibit a size effect for flexure strength data. The experimental material consisted of 20 wt% 60:40 BISGMA:TEGDMA, 10 wt% colloidal silica, and 70 wt% Sr glass and was cured by light irradiation. Two sizes of flexure specimens were fabricated: 3.2x1.6x35 mm, and 6.25x3.1x35 mm. Half of the specimens made were soaked to equilibrium weight gain in 50:50 ethanol:water. The fracture strengths were measured in four-point bending tests. The beams under load were modelled by the finite element package ABAQUS. A statistical fracture mechanics methodology embodied in a public domain computer program called CARES/LIFE, developed by NASA, utilized the ABAQUS input and the fracture strengths of the smaller specimens to predict the fracture strengths of the larger specimens. In making the computation it used an approach that combines a Weibull distribution of flaw size with Batdorf's fracture mechanical model for failure at a material flaw. Both the soaked and unsoaked specimens exhibited Weibull behaviour, with shape parameters ranging from 4.04 to 8.15. Soaking had a clearly detrimental effect on the strengths of specimens of both sizes, and produced a comparable percentage reduction in the estimated scale parameter of the fracture strength distribution. Both the soaked and unsoaked specimens also exhibited a clear and comparable size effect, i.e. the larger specimens had a fracture strength that was lower than that of the smaller specimens by roughly the same percentage. Moreover, the magnitude of the size effect was well predicted by the CARES/LIFE methodology for both the soaked and the dry specimens. The elastic-brittle character of both soaked and unsoaked composite specimens was validated by load-deflection data, the magnitude of the Weibull shape parameters of the observed fracture strength data (<10), and the observed effect of specimen size. The accuracy of CARES/LIFE in predicting the magnitude of the observed size effect in beams of two different sizes strongly suggests that CARES/LIFE will be useful for computation of failure probabilities for clinically relevant structures.

Focus of Doctor-patient Communication in Follow-up Consultations for Patients Treated Surgically for Colorectal Cancer

Journal of Management in Medicine. 1999  |  Pubmed ID: 10747448

A series of consultations between patients treated surgically for colorectal cancer and their hospital consultants were examined to establish the main focus of the consultation at various stages in the post-surgical period. The results showed that follow-up consultations were predominantly doctor driven. Patients interviewed less than 12 months since the time of surgery (short-term group) were more likely to receive a longer consultation with a significantly higher number of verbal interactions (questions, responses) than patients more than 12 months since surgery at the time of interview (long-term group). Furthermore, patients in the short-term group played a greater participatory role within consultations than patients in the long-term group. The predominant focus throughout all consultations was biomedical, with little attention afforded to patients' expressions of post-operative anxiety. At present, it appears that out-patient consultations play a minimal role in either detecting or addressing psychosocial morbidity amongst colorectal cancer patients in the post-surgical period.

A Comparison of Phonemic, Semantic, and Alternating Word Fluency in Parkinson's Disease

Archives of Clinical Neuropsychology : the Official Journal of the National Academy of Neuropsychologists. Apr, 1999  |  Pubmed ID: 14590594

Word fluency in 45 medicated non-demented Parkinson's disease (PD) patients and 45 normal control subjects was studied with a Phonemic Word Fluency (PWF) task using the letters F, A, and S, a Semantic Word Fluency (SWF) task using the categories animals, boys' names, and states, and an Alternating Word Fluency (AWF) task requiring the person to alternate between colors and occupations, animals and states, and words beginning with C and P. The number of words generated did not differ for trials with F, A, S, or states, but PD patients generated significantly fewer animal names and boys' names. PD patients also generated significantly fewer words on each of the three AWF trials. The PD patients scored 21% lower than the normal control group on the total AWF score, but only 10% lower for the PWF and SWF scores. The greater impairment on the AWF task which requires the use of internal attentional control to rapidly shift mental set can be considered a type of executive functioning deficit. This is consistent with the growing literature suggesting frontal systems dysfunction in PD and with the view that dopaminergic treatment only incompletely restores functioning in the frontostriatal system.

The Cationic C-terminus of Rat Muc2 Facilitates Dimer Formation Post Translationally and is Subsequently Removed by Furin

European Journal of Biochemistry / FEBS. May, 2000  |  Pubmed ID: 10806399

Earlier immunolocalization experiments showed that the extreme cationic C-terminus of the rat intestinal mucin Muc2 (RMC) was present at the base of intestinal goblet cells in the vicinity of ER and golgi compartments, but was not found with the rest of the mucin in apical storage granules. This prompted us to investigate the possibility that an early proteolytic cleavage reaction occurs post-translationally. A plasmid pRMC, encoding the C-terminal 534 amino acids of the mucin, was expressed in COS-7 cells and was shown to undergo cleavage at an R-T-R-R sequence located within the C-terminal 14 amino acids. Cleavage did not occur with the construct RMCfH, a furin site-mutated (A-T-A-A) counterpart of pRMCH (poly His6 tagged RMC). Addition of a furin inhibitor to COS-7 cell incubations also prevented cleavage of RMC and RMCH products. 35S pulse-chase kinetic experiments revealed that a truncated mutant lacking the C-terminal 14 amino acids (pRMCDeltaCT) forms faulty (doublet) dimers in the ER. These were not secreted as efficiently as the normal dimer of wild-type (pRMC) constructs. Thus the cationic C-terminus of rMuc2 apppears to facilitate the correct formation of normal Muc2 domain dimers.

CpG Oligodeoxynucleotides Act As Adjuvants for Pneumococcal Polysaccharide-protein Conjugate Vaccines and Enhance Antipolysaccharide Immunoglobulin G2a (IgG2a) and IgG3 Antibodies

Infection and Immunity. Mar, 2000  |  Pubmed ID: 10678959

Pneumococcal polysaccharide-protein conjugate vaccines elicit antipolysaccharide antibodies, but multiple doses are required to achieve protective antibody levels in children. In addition, the immunogenicity of experimental multivalent pneumococcal conjugate vaccines varies with different polysaccharide serotypes. One strategy to improve these vaccines is to incorporate an adjuvant to enhance their immunogenicity. Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are adjuvants that promote T-cell and T-dependent antibody responses to protein antigens, but it has been unclear whether CpG ODN can enhance polysaccharide-specific antibody responses. The present studies demonstrate significant adjuvant activity of CpG ODN for antibody responses against Streptococcus pneumoniae polysaccharide types 19F and 6B induced by conjugates of 19F and 6B with the protein carrier CRM(197). BALB/c ByJ mice were injected with 19F-CRM(197) or 6B-CRM(197) with or without CpG ODN, and sera were tested for anti-19F or anti-6B antibodies by enzyme-linked immunosorbent assay. The polysaccharide-specific antibody response to 19F-CRM(197) alone was predominantly of the immunoglobulin G1 (IgG1) and IgM isotypes, but addition of CpG ODN markedly increased geometric mean titers of total anti-19F antibody (23-fold), anti-19F IgG2a (26-fold), and anti-19F IgG3 (>246-fold). The polysaccharide-specific antibody response to 6B-CRM(197) alone consisted only of IgM, but addition of CpG ODN induced high titers of anti-6B IgG1 (>78-fold increase), anti-6B IgG2a (>54-fold increase), and anti-6B IgG3 (>3,162-fold increase). CpG ODN also increased anti-CRM(197) IgG2a and IgG3. Adjuvant effects were not observed with control non-CpG ODN. Thus, CpG ODN significantly enhance antipolysaccharide IgG responses (especially IgG2a and IgG3) induced by these glycoconjugate vaccines.

Characterization of Strychnine-sensitive Glycine Receptors in Acutely Isolated Adult Rat Basolateral Amygdala Neurons

Brain Research. Mar, 2000  |  Pubmed ID: 10719083

Large concentrations of the beta-amino acid, taurine, can be found in many forebrain areas such as the basolateral amygdala, a portion of the limbic forebrain intimately associated with the regulation of fear/anxiety-like behaviors. In addition to its cytoprotective and osmoregulatory roles, taurine may also serve as an agonist at GABA(A)- and strychnine-sensitive glycine receptors. In this latter context, the present study demonstrates that application of taurine to acutely isolated neurons from the basolateral amygdala of adult rats causes significant alterations in resting membrane current, as measured by whole-cell patch clamp electrophysiology. Using standard pharmacological approaches, we find that currents gated by concentrations of taurine

Exercise-induced Asthma

Medicine and Health, Rhode Island. Feb, 2000  |  Pubmed ID: 10730054

Diaphragm Recruitment During Nonrespiratory Activities

American Journal of Respiratory and Critical Care Medicine. Aug, 2000  |  Pubmed ID: 10934070

We previously found that weight lifters could generate greater inspiratory pressures and had more diaphragm mass than control subjects. We postulated that the weight-lifting activity itself provided a strength-training stimulus to the diaphragm. To evaluate the extent to which the diaphragm is recruited during strenuous nonrespiratory activities, we measured transdiaphragmatic pressure (Pdi) in six healthy subjects during biceps curls, bench press, power lift, and sit-ups. Each maneuver was performed with and without added weight (control), and with and without an abdominal binder. The weighted maneuvers were performed either during inspiration or expiration. Maximal static transdiaphragmatic pressure (Pdi(max)) was measured during a combined inspiratory and expulsive maneuver. Group mean values of Pdi increased during all activities when compared with control (57 +/- 24 versus 18 +/- 10 cm H(2)O [mean +/- SD] [p < 0.001]), as task intensity increased (98 +/- 14 versus 35 +/- 13 cm H(2)O for high- and low-intensity activities, respectively) (p < 0.001), and with abdominal binding (75 +/- 25 versus 59 +/- 25 cm H(2)O) (p < 0.05). Peak levels of Pdi attained during the activities were 126 +/- 11 cm H(2)O or 0.65 +/- 0.09 of Pdi(max). Changes in gastric pressure accounted for 85 +/- 4% of the increase in Pdi during the activities whereas it accounted for only 58 +/- 9% of the rise in Pdi during the control activities (p < 0.001). We conclude that during a range of weight-lifting activities, the diaphragm is recruited and Pdi is raised to a level that may provide a significant strength-training stimulus to the diaphragm.

Effects of the Supine and Prone Position on Diaphragm Thickness in Healthy Term Infants

Archives of Disease in Childhood. Sep, 2000  |  Pubmed ID: 10952643

The physiological basis underlying the decline in the incidence of sudden infant death syndrome (SIDS) associated with changing the sleep position from prone to supine remains unknown.

Improved Method for the Production of Gold Colloid Monolayers for Use in the Phagokinetic Track Assay for Cell Motility

Analytical Biochemistry. Dec, 2000  |  Pubmed ID: 11112285

Expression of the Thimet Oligopeptidase Gene is Regulated by Positively and Negatively Acting Elements

DNA and Cell Biology. Dec, 2000  |  Pubmed ID: 11177571

Thimet oligopeptidase (TOP) is a thiol-dependent metallopeptidase, which can cleave and thereby modulate the activity of many neuropeptides. The enzyme is active in many endocrine tissues, including testis, brain, and pituitary. In rat, the richest source of TOP is the testes, with a specific activity fivefold that of brain. The mechanism whereby rat TOP expression is regulated at the transcriptional level has been examined by reporter gene assay and electromobility shift assays after isolation of 1020 bp of upstream sequence. Computer analysis predicts a number of potential transcription factor-binding sites, which were examined by deletion analysis and DNA-binding studies. The promoter or its deletion fragments were fused to luciferase reporter gene vectors and introduced into GH3 pituitary, COS-1 kidney, MAT-Lu prostate, and GC-2spd(ts) spermatid cells. Two regions of the promoter have been identified: a positively acting region (-901/-219) and a strong negatively acting region (-219/-102). Concomitantly, potential transcription factors interacting with the cis-acting elements of the promoter were studied by gel electromobility shift assays. This work has identified a number of transcription factor-binding sites. However, no differences in the binding behavior in the various cell lines was observed.

A1 Adenosine Receptors Inhibit Multiple Voltage-gated Ca2+ Channel Subtypes in Acutely Isolated Rat Basolateral Amygdala Neurons

British Journal of Pharmacology. Feb, 2001  |  Pubmed ID: 11181429

1. The anticonvulsant properties of 2-chloroadenosine (CADO) in the basolateral amygdala rely on the activation of adenosine-specific heptahelical receptors. We have utilized whole-cell voltage-clamp electrophysiology to examine the modulatory effects of CADO and other adenosine receptor agonists on voltage-gated calcium channels in dissociated basolateral amygdala neurons. 2. CADO, adenosine, and the A1 subtype-selective agonists N6-(L-2-Phenylisopropyl)adenosine (R-PIA) and 2-chloro-N6-cyclopentyladenosine (CCPA) reversibly modulated whole cell Ba2+ currents in a concentration-dependent fashion. CADO inhibition of barium currents was also sensitive to the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). 3. The A2A-selective agonist 4-[2-[[6-Amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid (CGS21680) was without effect. 4. CADO inhibition was predominantly voltage-dependent and sensitive to the sulphydryl-modifying reagent N:-ethylmaleimide, implicating a membrane-delimited, G(i/o)-coupled signal transduction pathway in the channel regulation. 5. Using Ca2+ channel subtype-selective antagonists, CADO inhibition appeared to target multiple channel subtypes, with the inhibition of omega-conotoxin GVIA-sensitive calcium channels being more prominent. 6. Our results indicate that the anti-convulsant effects CADO in the basolateral amygdala may be mediated, in part, by the A1 receptor-dependent inhibition of voltage gated calcium channels.

Adolescent Perceptions of Smoking Imagery in Film

Social Science & Medicine (1982). May, 2001  |  Pubmed ID: 11314853

Smoking amongst adolescents in New Zealand continues to be a problem, with more than a one-third increase in smoking prevalence between 1992 and 1997. Favourable portrayals of smoking in the media have been cited as potential motivators of the initiation of smoking among adolescents. To date, however, its role in influencing smoking perceptions and behaviours has not received systematic analysis. A qualitative study was conducted to explore how adolescents interpret and decode smoking imagery in movies. Data was collected through focus groups. Same-gender groups of 12- and 13-year-old students were interviewed at their schools. Participants discussed their recollections of and responses to portrayals of smoking in recently viewed films, as well as their perceptions of smoking in general. Students perceived that smoking in film is both highly prevalent and recognisable, and they regarded on-screen-smoking imagery as an accurate reflection of reality. Adolescents in this study were predominantly nonchalant towards the inclusion of smoking images in film, and they perceived an unrealistically high prevalence of smoking amongst peers and adults. Their noncholant response is linked with the perception that smoking is normal and prevalent and with the broad understanding of the constructed nature of media imagery. Smoking imagery in film may play a critical role in reinforcing cultural interpretations of tobacco use, such as its role as a means of stress relief, development of self-image and as a marker of adult independence.

Lifetime Predictions for Resin-based Composites Using Cyclic and Dynamic Fatigue

Journal of Biomedical Materials Research. May, 2001  |  Pubmed ID: 11319737

Because dental restorative materials undergo fatigue in use, testing is often performed in the laboratory to evaluate material responses to cyclic loading. The purpose of this study was to compare the lifetime predictions resulting from two methods of fatigue testing: dynamic and cyclic fatigue. Model composites were made in which one variable was the presence of a silanizing agent, and specimens tested in 4-point flexure. Cyclic fatigue was carried out at a frequency of 5 Hz, while dynamic fatigue testing spanned seven decades of stress rate application. Data were reduced and the crack propagation parameters for each material were calculated from both sets of fatigue data. These parameters were then used to calculate an equivalent static tensile stress for a 5-year survival time. The 5-year survival stresses predicted by dynamic fatigue data were approximately twice those predicted by cyclic fatigue data. In the absence of filler particle silanization, the survival stress was reduced by half. Aging in a water-ethanol solution reduced the survival stresses by a factor of four to five. Cyclic fatigue is a more conservative means of predicting lifetimes of resin-based composites.

Leak Compensation in Positive Pressure Ventilators: a Lung Model Study

The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. Feb, 2001  |  Pubmed ID: 11334129

Leak compensating abilities of six different positive pressure ventilators commonly used to deliver noninvasive positive pressure ventilation, including the bilevel positive airway pressure (BiPAP) S/T-D and Quantum (Respironics Inc, Murrysville, PA, USA), 335 and O'NYX (Mallinckrodt Inc, St Louis, MO, USA), PLV 102 (Respironics), and Siemens Servo 900C (Siemens Inc, Danvers, MA, USA). Using a test lung model, compensatory capabilities of the ventilators were tested for smaller and larger leaks using the assist/control or timed modes. Back-up rate was 20 min(-1), inspiratory pressure was 18 cmH2O, and expiratory pressure was 5 cmH2O. It was found that even in the absence of air leaking, delivered tidal volume differed substantially between the ventilators during use of pressure-targeted modes, depending on inspiratory flows, inaccuracies in set versus delivered pressures, and inspiratory duration. Also during pressure-targeted ventilation, increasing the tI/ttot up to, but not beyond, 0.5 improved compensation by lengthening inspiratory duration, whereas use of a sensitive flow trigger setting tended to cause autocycling during leaking, interfering with compensation. Leaking interfered with cycling of the BiPAP S/T, inverting the I:E ratio, shortening expiratory time, and reducing delivered tidal volume. Volume-targeted modes achieved limited compensation for small air leaks, but compensated poorly for large leaks. To conclude, leak-compensating capabilities differ markedly between ventilators but pressure-targeted ventilators are preferred for noninvasive positive pressure ventilation in patients with substantial air leaking. Adequate inspiratory flows and durations should be used, triggering sensitivity should be adjusted to prevent autocycling, and a mechanism should be available to limit inspiratory time and avoid I:E ratio inversion.

Assessment of Progressive Changes in Exercise Performance in Patients with a Systemic Right Ventricle Following the Atrial Switch Repair

Pediatric Cardiology. May-Jun, 2001  |  Pubmed ID: 11343144

There is a high prevalence of right ventricular dysfunction and reduced exercise performance in survivors of atrial switch repair for transposition of the great arteries. However, it is not known whether the impairment in exercise performance is progressive. We performed paired comparison of exercise performance in 28 patients who underwent two serial incremental exercise tests at an interval of 5.0 +/- 1.4 years between the two tests (age 11.5 +/- 3.7 years at first test, 16.4 +/- 3.6 years at second test). There was no change in the chronotropic response between the two tests. However, there was a reduction in both the peak VO2 (32.5 +/- 8.3 vs 29.6 +/- 5.7 ml/kg/min, p = 0.05) and anerobic threshold (22.1 +/- 5.1 vs 18.3 +/- 4.2 ml/kg/min, p < 0.01) with time. Furthermore, there was a decline in the O2 pulse (oxygen uptake/beat) at anaerobic threshold (% predicted value 95 +/- 23% vs 82 +/- 23%, p =.02), O2 pulse at a heart rate of 140 (% predicted value 100 +/- 30% vs 85 +/- 19%, p = 0.02), and the maximum O2 pulse (z value -0.27 +/- 1.31 vs -1.27 +/- 1.16, p < 0.01) when compared to growth-related normal values. We conclude that there is a progressive reduction in aerobic response to exercise in patients with a systemic right ventricle. The maintenance of chronotropic response suggests that the stroke volume response of the systemic right ventricle during exercise does not increase commensurate with somatic growth.

PhaC and PhaR Are Required for Polyhydroxyalkanoic Acid Synthase Activity in Bacillus Megaterium

Journal of Bacteriology. Jul, 2001  |  Pubmed ID: 11418564

Polyhydroxyalkanoic acids (PHAs) are a class of polyesters stored in inclusion bodies and found in many bacteria and in some archaea. The terminal step in the synthesis of PHA is catalyzed by PHA synthase. Genes encoding this enzyme have been cloned, and the primary sequence of the protein, PhaC, is deduced from the nucleotide sequences of more than 30 organisms. PHA synthases are grouped into three classes based on substrate range, molecular mass, and whether or not there is a requirement for phaE in addition to the phaC gene product. Here we report the results of an analysis of a PHA synthase that does not fit any of the described classes. This novel PHA synthase from Bacillus megaterium required PhaC (PhaC(Bm)) and PhaR (PhaR(Bm)) for activity in vivo and in vitro. PhaC(Bm) showed greatest similarity to the PhaCs of class III in both size and sequence. Unlike those in class III, the 40-kDa PhaE was not required, and furthermore, the 22-kDa PhaR(Bm) had no obvious homology to PhaE. Previously we showed that PhaC(Bm), and here we show that PhaR(Bm), is localized to inclusion bodies in living cells. We show that two forms of PHA synthase exist, an active form in PHA-accumulating cells and an inactive form in nonaccumulating cells. PhaC was constitutively produced in both cell types but was more susceptible to protease degradation in the latter type. Our data show that the role of PhaR is posttranscriptional and that it functions directly or indirectly with PhaC(Bm) to produce an active PHA synthase.

Effects of Mutations Involving Cell Division, Recombination, and Chromosome Dimer Resolution on a PriA2::kan Mutant

Proceedings of the National Academy of Sciences of the United States of America. Jul, 2001  |  Pubmed ID: 11459954

Recombinational repair of replication forks can occur either to a crossover (XO) or noncrossover (non-XO) depending on Holliday junction resolution. Once the fork is repaired by recombination, PriA is important for restarting these forks in Escherichia coli. PriA mutants are Rec(-) and UV sensitive and have poor viability and 10-fold elevated basal levels of SOS expression. PriA sulB mutant cells and their nucleoids were studied by differential interference contrast and fluorescence microscopy of 4',6-diamidino-2-phenylindole-stained log phase cells. Two populations of cells were seen. Eighty four percent appeared like wild type, and 16% of the cells were filamented and had poorly partitioned chromosomes (Par(-)). To probe potential mechanisms leading to the two populations of cells, mutations were added to the priA sulB mutant. Mutating sulA or introducing lexA3 decreased, but did not eliminate filamentation or defects in partitioning. Mutating either recA or recB virtually eliminated the Par(-) phenotype. Filamentation in the recB mutant decreased to 3%, but increased to 28% in the recA mutant. The ability to resolve and/or branch migrate Holliday junctions also appeared crucial in the priA mutant because removing either recG or ruvC was lethal. Lastly, it was tested whether the ability to resolve chromosome dimers caused by XOs was important in a priA mutant by mutating dif and the C-terminal portion of ftsK. Mutation of dif showed no change in phenotype whereas ftsK1cat was lethal with priA2kan. A model is proposed where the PriA-independent pathway of replication restart functions at forks that have been repaired to non-XOs.

The Enhanced Anticaries Efficacy of a Sodium Fluoride and Dicalcium Phosphate Dihydrate Dentifrice in a Dual-chambered Tube. A 2-year Caries Clinical Study on Children in the United States of America

American Journal of Dentistry. May, 2001  |  Pubmed ID: 11481926

To clinically evaluate and compare a dentifrice system in a dual-chambered tube, wherein one chamber contained sodium fluoride in a silica base and the other chamber contained dicalcium phosphate dihydrate (Test Dentifrice delivering 0.243% sodium fluoride), to a dentifrice containing 0.243% sodium fluoride in a silica base (Positive Control Dentifrice).

The Enhanced Anticaries Efficacy of a Sodium Fluoride and Dicalcium Phosphate Dihydrate Dentifrice in a Dual-chambered Tube. A 2-year Caries Clinical Study on Children in Brazil

American Journal of Dentistry. May, 2001  |  Pubmed ID: 11481927

To clinically evaluate and compare a dentifrice system in a dual-chambered tube, wherein one chamber contained sodium fluoride in a silica base and the other chamber contained dicalcium phosphate dihydrate (Test Dentifrice delivering 0.243% sodium fluoride), to a dentifrice containing 0.243% sodium fluoride in a silica base (Positive Control Dentifrice).

The Comparative Anticaries Efficacy of a Dentifrice Containing 0.3% Triclosan and 2.0% Copolymer in a 0.243% Sodium Fluoride/silica Base and a Dentifrice Containing 0.243% Sodium Fluoride/silica Base: a Two-year Coronal Caries Clinical Trial on Adults in Israel

The Journal of Clinical Dentistry. 2001  |  Pubmed ID: 11505964

The purpose of this two-year clinical study was to provide a comparison of the anticaries efficacy associated with two commercially available, American Dental Association-accepted dentifrices: Colgate Total Toothpaste, which contains 0.3% triclosan and 2% copolymer in a 0.243% sodium fluoride/silica base; and Crest Cavity Fighting Toothpaste with Fluoristat, which contains 0.243% sodium fluoride in a silica base. The study was conducted in harmony with the published 1988 American Dental Association guidelines for studies geared toward the comparison of fluoride dentifrices. The study employed a double-blind parallel-group design, and involved adults living in communities throughout Israel. Qualifying subjects were randomly assigned to the two treatment groups, with multiple subjects in the same household all assigned to the dentifrice randomly allocated to the first among them. Caries examinations were conducted in accordance with U.S. Food and Drug Administration guidelines for the clinical evaluation of drugs to prevent dental caries. Two calibrated examiners performed all of the measurements. After treatment assignment, study participants were instructed to brush their teeth at home with their assigned dentifrice at least twice daily. Brushing instructions were reinforced by indoctrination in proper oral hygiene techniques by dental professionals, supplemented by pamphlets supplied by the sponsor and yearly mailings to participants, emphasizing good oral hygiene and the need to ensure compliance with the study. Post-baseline examinations were performed after one year of product use, and again after two years of product use. Three-thousand, three-hundred and ninety-two (3,392) subjects completed this two-year study. For these subjects, the mean caries scores (DFS, decayed or filled surfaces) at baseline were 21.96 for the Colgate Total Toothpaste group, and 21.49 for the Crest Cavity Fighting Toothpaste with Fluoristat group. For caries increment after one year, the respective means were 1.37 for the Colgate Total Toothpaste group, and 1.56 for the Crest Cavity Fighting Toothpaste with Fluoristat group. After two years, the mean caries increments were 1.46 for the Colgate Total Toothpaste group, and 1.75 for the Crest Cavity Fighting Toothpaste with Fluoristat group. No statically significant difference was indicated between the treatment groups at baseline. However, for both the one-year and two-year increments, there was a statistically significant difference between treatment groups. Relative to the Crest Cavity Fighting Toothpaste with Fluoristat group, the Colgate Total Toothpaste group presented a 12.2% reduction in caries increment scores at one year, and a 16.6% reduction in caries increment scores at two years. In accordance with the procedures and standards provided by the published guidelines of the American Dental Association for the comparison of the anticaries efficacy of fluoride dentifrices, the results of this study support the conclusion that Colgate Total Toothpaste provides a superior level of coronal anticaries efficacy compared to Crest Cavity Fighting Toothpaste with Fluoristat.

PriA Mutations That Affect PriA-PriC Function During Replication Restart

Molecular Microbiology. Aug, 2001  |  Pubmed ID: 11532137

In Escherichia coli, repair and restart of collapsed replication forks is thought to be essential for cell growth. The replication restart proteins, PriA, PriB, PriC, DnaB, DnaC, DnaG, DnaT and Rep, form redundant pathways that recognize repaired replication forks and restart them. Recognition, modulation of specific DNA structures and loading of the replicative helicase by the replication restart proteins, is likely to be important for replication restart. It has been hypothesized that PriB and PriC function with PriA in genetically separate and redundant PriA-PriB and PriA-PriC pathways. In this study, the del(priB)302 or priC303:kan mutations were used to isolate the PriA-PriB and PriA-PriC pathways genetically so that the effects of three priA missense mutations, priA300 (K230R), priA301 (C479Y) and priA306 (L557P), on these pathways could be assessed. In a wild-type background, the three priA mutations had little, if any, effect on the phenotypes of UV resistance, basal levels of SOS expression and cell viability. In the priB mutant, priA300 and priA301 caused dramatic negative changes in the three phenotypes listed above (and others), whereas the third priA mutant allele, priA306, showed very little negative effect. In the priC mutant, all three priA mutations behaved similarly, producing little, if any, changes in phenotypes. We conclude that priA300 and priA301 mostly affect the PriA-PriC pathway and do so more than priA306. We suggest that PriA's helicase activity is important for the PriA-PriC pathway of replication restart.

Complete Urethral Disruption Without Pelvic Fracture

The Journal of Urology. Oct, 2001  |  Pubmed ID: 11547103

Fatigue of Restorative Materials

Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 2001  |  Pubmed ID: 11603506

Failure due to fatigue manifests itself in dental prostheses and restorations as wear, fractured margins, delaminated coatings, and bulk fracture. Mechanisms responsible for fatigue-induced failure depend on material ductility: Brittle materials are susceptible to catastrophic failure, while ductile materials utilize their plasticity to reduce stress concentrations at the crack tip. Because of the expense associated with the replacement of failed restorations, there is a strong desire on the part of basic scientists and clinicians to evaluate the resistance of materials to fatigue in laboratory tests. Test variables include fatigue-loading mode and test environment, such as soaking in water. The outcome variable is typically fracture strength, and these data typically fit the Weibull distribution. Analysis of fatigue data permits predictive inferences to be made concerning the survival of structures fabricated from restorative materials under specified loading conditions. Although many dental-restorative materials are routinely evaluated, only limited use has been made of fatigue data collected in vitro: Wear of materials and the survival of porcelain restorations has been modeled by both fracture mechanics and probabilistic approaches. A need still exists for a clinical failure database and for the development of valid test methods for the evaluation of composite materials.

Subunit Composition of Strychnine-sensitive Glycine Receptors Expressed by Adult Rat Basolateral Amygdala Neurons

The European Journal of Neuroscience. Oct, 2001  |  Pubmed ID: 11683900

In neonatal rats, strychnine-sensitive glycine receptors are widely expressed in the spinal cord, brainstem and forebrain. During development, these 'neonatal' receptors are replaced by an adult isoform, the expression of which becomes restricted primarily to brain stem and spinal cord. Unlike most forebrain regions, functional strychnine-sensitive glycine receptors appear to persist within adult rat amygdala. However, the subunit composition of glycine receptors expressed by amygdala neurons and its relationship to the adult isoform in brain stem/spinal cord has not been defined precisely. In this report, we have utilized RT-PCR and single-cell RT-PCR to demonstrate that the 'neonatal' alpha2-subunit mRNA persists in adult rat amygdala neurons and is the predominant alpha-subunit. We further demonstrate that native amygdala glycine receptors are relatively insensitive to the receptor antagonist picrotoxin, suggesting that alpha2- and beta-subunits may be present together in the same multisubunit complex. We further demonstrate that alpha2- and beta-subunits cloned from adult rat amygdala can form functional channels when expressed in a heterologous system. Together, these studies highlight both the unique characteristics of strychnine-sensitive glycine receptors in the adult rat amygdala as well as the possibility that alpha2/beta channels may represent the adult forebrain isoform of the strychnine-sensitive glycine receptor.

Diaphragm Dimensions of the Healthy Preterm Infant

Pediatrics. Nov, 2001  |  Pubmed ID: 11694675

The diaphragm is the major inspiratory muscle in the neonate; however, human neonatal diaphragm development has not been extensively studied. We hypothesized that diaphragm thickness (t(di)) would be positively related to postmenstrual age (PMA), body weight, body length, head circumference, and nutritional intake.

Effects of Continuous Positive Airway Pressure on Diaphragm Dimensions in Preterm Infants

Journal of Perinatology : Official Journal of the California Perinatal Association. Dec, 2001  |  Pubmed ID: 11774012

The use of continuous positive airway pressure (CPAP) in the treatment of a variety of neonatal respiratory conditions is associated with improvement in arterial oxygen saturation, decreased long-term morbidity, and an overall improvement in infant survival. We reasoned that CPAP might change diaphragm length by increasing end-expiratory lung volume (EEV), but the extent to which this occurs has not been assessed. This study was designed to evaluate (1) the extent to which CPAP shortens the diaphragm and (2) the relationship of diaphragm thickness and excursion with arterial oxygen saturation in spontaneously breathing preterm infants.

The Scottish Centre for Autism Preschool Treatment Programme. I: A Developmental Approach to Early Intervention

Autism : the International Journal of Research and Practice. Dec, 2001  |  Pubmed ID: 11777254

Early intervention is an area of intense current interest for parents and professionals. This article describes a mainstream National Health Service (NHS) approach to early intervention, developed at the Scottish Centre for Autism. The aims of treatment are to improve the child's early social communication and social interaction skills, leading to the potential development of play and flexibility of behaviour. This is achieved by 1:1 intensive treatment by trained therapists, and a schedule of parent training. The treatment protocol incorporates a child led approach; the use of imitation as a therapeutic strategy; using language contingent on activities; and the introduction of flexibility into play and social exchanges.

Challenges in Research with Incarcerated Parents and Importance in Violence Prevention

American Journal of Preventive Medicine. Jan, 2001  |  Pubmed ID: 11146261

Incarcerated parents present several risk factors for later violence by their children. This study uses comparison groups and repeated measures to evaluate an inmate parenting program. Subjects are inmates at a county detention center, their children, and primary caregivers. Challenges to program implementation and longitudinal research with inmates were identified, along with recommendations to assist future research and programming. Training material should use illustrated, basic language format. Acceptance and participation by inmates and staff require ongoing outreach and communication. Severed relationships are common and future research on inmates with stable family relationships is recommended. Because of inmate transience, integrating parent training into post-release programming is suggested.

Respiratory System Mechanics in a Patient with Massive Subcutaneous Emphysema

Medicine and Health, Rhode Island. Nov, 2001  |  Pubmed ID: 12355665

Strength and Fatigue of Polyacid-modified Restorative Materials (compomers)

Journal of Materials Science. Materials in Medicine. Jun, 2002  |  Pubmed ID: 15348593

The purpose of this study was to compare the fatigue behavior of a hybrid composite, four compomers, and two viscous glass ionomers after short- and long-term soaking in distilled water. Bars with dimensions of 30 mm x 2 mm x 2 mm were formed in stainless steel molds, finished with 600 grit SiC, then soaked for either 24 h or one year, and tested in 3-point flexure at stressing rates between 0.001 and 2500 MPa s(-1). Data were plotted as fracture stress vs. stressing rate, and the exponent N in the power law for crack growth rate was computed from the slope of these plots. All compomer and resin composite materials tested exhibited subcritical crack growth (i.e. a reduction in strength with a decrease in stressing rate). Soaking lowered the slope for all materials, that is, increased the crack propagation rate. F2000 exhibited an increase in fracture strength while Hytac and Compoglass exhibited a decrease following long-term soaking in distilled water. Crack-growth exponents obtained from these fatigue data were used to estimate the stresses which would result in a five-year lifetime for these materials.

Respiratory Muscle Evaluation of the Patient with Neuromuscular Disease

Seminars in Respiratory and Critical Care Medicine. Jun, 2002  |  Pubmed ID: 16088612

This review presents clinically relevant issues regarding the assessment of respiratory muscles in individuals with neuromuscular disorders, and discusses the advantages and disadvantages of methods generally available to the clinician. Vital capacity (VC) and total lung capacity (TLC) are routinely measured in pulmonary function laboratories and are typically reduced in the context of severe respiratory muscle weakness, but the sensitivity and specificity of these measures are limited. Better measures of respiratory muscle weakness are maximal static inspiratory and expiratory pressures (PI max and PE max). PI max is reduced even with mild or moderate degrees of inspiratory muscle weakness, but low values also may be related to submaximal effort. To circumvent this problem, pressures can be measured using simpler maneuvers such as a maximal sniff. Specific tests of diaphragm function such as measurements of maximal transdiaphragmatic pressure are invasive and not routinely available to the clinician. Recently, noninvasive methods that specifically assess diaphragm function, such as diaphragm ultrasound of the zone of apposition and magnetic or electrophrenic nerve stimulation, have shown promise as new techniques for clinical use.

Patients' Views on Smoking Cessation and Tobacco Harm Reduction During Drug Treatment

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2002  |  Pubmed ID: 12573178

Efforts to help smokers in drug treatment quit smoking have met with little success. To explore barriers to quitting and interest in tobacco harm reduction we conducted focus groups and interviews among 78 patients from five Methadone Maintenance Treatment (MMT) sites. Measures included a written survey and open-ended questions on (a) motivation for quitting, (b) what quit methods worked and what didn't work, and (c) interest in smoking reduction and nicotine maintenance as an alternative to complete cessation. Discussions were audiotaped, transcribed, and coded using computer-based qualitative software; our interobserver reliability was 83%. Successful quitters used in general a combination of quit methods such as prayer, nicotine gum, keeping busy, quitting 'one day at a time,' nicotine patches, deep breathing, and avoidance of triggers. Nicotine craving, rather than withdrawal, was cited as the biggest challenge to staying quit. Some current smokers feared quitting smoking would divert them from their goal of quitting illicit drug use or tapering off MMT. Current smokers were interested in smoking reduction as an alternative to quitting; however, those who had tried but failed to reduce smoking preferred complete cessation. Nicotine maintenance was favored by only a few participants with major health problems who didn't hold out hope for quitting. Findings suggest combination pharmacotherapy could help patients control withdrawal and acute episodes of craving. Patients have a number of skills from coping with illicit drug dependence that are useful in combating nicotine dependence. Behavioral methods and short-term pharmacotherapy to help patients reduce tobacco exposure should be explored.

Birth in the United States: an Overview of Trends Past and Present

The Nursing Clinics of North America. Dec, 2002  |  Pubmed ID: 12587371

The picture of birth in the United States today is complex and, as the data above indicates, difficult to describe in simplistic terms. Though many women today have come to believe that there are choices surrounding pregnancy and birth, the beliefs and practices of providers, insurers, and hospital administrators play a major role in either influencing those choices or dictating how they will be manifested. On one hand, technological advances have given women greater options with regard to the outcomes of pregnancy and birth. On the other hand, these very same technological advances place limits on the choices available to the individual. For example, increased efficiency in the placement and use of epidural anesthesia has made this a pain-control option for most of the childbearing women in the United States. The use of an epidural, however, puts limits on the choice of an institution at which to give birth and on the movements/activities of the woman during labor. Twentieth-century developments led to the almost complete demise of midwifery practice in the United States, thus taking birth away from the control of the individual woman and her close, matriarchal support system, and placing it in the hands of the patriarchal world of medicine and the institutions (i.e., hospitals) at which this approach to health care is practiced. Most births went from being normal, home-based events to becoming illness-oriented, hospital-based procedures. Just as some steps were being taken in the latter part of the twentieth century to return some of the control of birth back to pregnant women (e.g., childbirth education classes, the modern home-birth movement, increases in the number of midwifery-tended births), technological advances contributed to continued control by physicians and the hospitals of their practice (e.g., fetal monitoring, epidural anesthesia). Advances in technology have made birth possible for many individuals who otherwise would not have had the opportunity for this experience or a chance for a positive outcome (e.g., sufferers of infertility or the woman whose fetus has congenital yet repairable problems). But the widespread application of many of these advances to almost all pregnant and laboring women has raised questions as to just what is necessary for a healthy pregnancy, and are there limits to the role that technology should play in the course of what is viewed by many as a normal, nonmedical event. Just as the characters in 2001: A Space Odyssey recognized the incredible power of change that occurred in their lives as a result of the monolith being "born" into their world, so too do many women acknowledge the prodigious nature of giving birth in terms of the experience itself and the resulting effect on their lives [14]. But, as with the acknowledgment of Dr. Dave Bowman in 2001: A Space Odyssey that the technology of the fictitious future still could be wrong, thoughts of U.S. women giving birth today tend to be "in-between" a belief in the integrity of nature and a trust in the power of technology [14]. One can certainly conjecture that birth in the United States today, more than any other time in history, is at a crossroads, one in which the mostly natural, matriarchal community system of the sixteenth through nineteenth centuries is intersecting with the mostly technological, patriarchal system of the twentieth century. Will birth return to the home under the guidance of midwives, as was the case for most of America's past and as remains the case throughout much of the world? [32] Or will technology take birth to the other extreme, making it possible to eventually gestate outside the womb and rendering "delivery" a term not referring to passage through the birth canal, but to the dropping off a healthy term baby at the respective mother's doorstep? Certainly no one can predict what is to occur, but whatever that may be, hindsight will likely point to the start of the twenty-first century as the beginning of a new paradigm for birth in the United States. It should make for an interesting future.

The Immune Response to Pneumococcal Proteins During Experimental Human Carriage

The Journal of Experimental Medicine. Feb, 2002  |  Pubmed ID: 11828011

Colonization of the nasopharynx is the initial step in all infections caused by Streptococcus pneumoniae. The antibody response to carriage was examined in an experimental model of human colonization in healthy adults. Asymptomatic colonization was detected in 6/14 subjects and continued for up to 122 d. Susceptibility to carriage did not correlate with total serum immunoglobulin (Ig)G to the homotypic capsular polysaccharide. All of the colonized subjects, in contrast, developed a serum IgG and secretory IgA response to a 22 kD protein, whereas 7 of 8 subjects who did not become colonized had preexisting antibody to this protein. Analysis of the 22 kD protein identified it as the NH(2)-terminal region of pneumococcal surface protein A (PspA). Our findings provide evidence for the role of antibody to this protein fragment in preventing pneumococcal carriage by humans.

Single-cell RT-PCR Detects Shifts in MRNA Expression Profiles of Basal Forebrain Neurons During Aging

Brain Research. Molecular Brain Research. Jan, 2002  |  Pubmed ID: 11834297

The medial septum and nucleus of the diagonal band (MS/nDB) contain cholinergic and GABAergic neuronal populations that have been identified based on immunohistochemical staining and/or electrophysiological properties. We explored the molecular diversity of MS/nDB neurons using single-cell reverse transcription-polymerase chain reaction (scRT-PCR) to assess gene expression profiles during aging in individual neurons acutely isolated from young (2-4 months) and aged (26-27 months) F344 rats. Neuronal gene expression profiles were characterized by detection of mRNAs for choline acetyltransferase (ChAT, cholinergic) and glutamate decarboxylase (GAD67, GABAergic), as well as mRNAs for calcium binding proteins (CaBPs) calbindin-D28k, calretinin and parvalbumin. Four major neuronal populations were identified: ChAT-positive (ChAT+) cells, GAD-positive (GAD+) cells, ChAT+/GAD+ cells and ChAT negative/GAD negative (ChAT-/GAD-) cells. With age, the percentage of cells expressing ChAT mRNA decreased from 53% in young to 40%, and the expression of GAD67 mRNA was reduced from 56 to 35% of the cells tested. The percentage of cells with detectable levels of both ChAT and GAD67 mRNA was reduced from 24% in young to 9% in aged. Concomitantly, the percentage of ChAT-/GAD- cells increased from 15 to 34% with age. Of the CaBPs, calretinin expression was observed most frequently in this study, and its detection decreased from 33 to 22% of the cells with age. Observations concerning the CaBPs were confirmed using in situ hybridization. These results suggest a shift in the mRNA expression profiles of MS/nDB neuronal populations during aging and exemplify the molecular diversity of cholinergic and GABAergic cells.

The Elderly Nutrition Program: an Effective National Framework for Preventive Nutrition Interventions

Journal of the American Dietetic Association. Feb, 2002  |  Pubmed ID: 11846117

To guide national policy, Congress mandated the 1992 research evaluation of the Elderly Nutrition Program (ENP), the nation's oldest framework for providing community- and home-based preventive nutrition and health-related services to older persons. This article summarizes key findings on the program's influence on nutritional health, the targeting and costs of its nutrition services, and the study's policy implications.

Cadmium- and Mercury-induced Intercellular Adhesion Molecule-1 Expression in Immortalized Proximal Tubule Cells: Evidence for a Role of Decreased Transforming Growth Factor-beta1

Toxicology and Applied Pharmacology. Feb, 2002  |  Pubmed ID: 11884233

A definitive association between the aberrant expression of cytokines and adhesion molecules in renal failure has been established. In this regard a relationship between cytokine and adhesion molecule expression is suggested but has not been shown in models of proximal tubular cell injury. To investigate the impact of acute injury on the relationship between transforming growth factor-beta 1 (TGF-beta1) and intercellular adhesion molecule-1 (ICAM-1) expression, two immortalized mouse proximal tubular epithelial cell lines were exposed to cadmium chloride or mercuric chloride (0-50 microM) for 0-8 h. ELISA and Western blot measured expression of secreted and intercellular TGF-beta1, respectively. Direct cellular ELISA or Western blot was used to assess ICAM-1 expression. Challenge with cadmium caused a greater loss of cell viability than did mercury. Interestingly, cadmium significantly decreased the amount of TGF-beta1 in the conditioned media. Although a similar trend was seen in mercury-challenged cells, no significant differences were observed. The decrease in TGF-beta1 in the culture media was not due to decreased expression of this cytokine, as intercellular levels were not affected by metal-induced injury. Significant increases in ICAM-1 protein expression were observed following cadmium and mercury challenge. The increase in ICAM-1 appears to be due to increased mRNA, as Northern blot analysis demonstrated increased message expression following a 4-h cadmium or mercury challenge. Supplementation of the culture media with exogenous TGF-beta1 decreased basal ICAM-1 expression and attenuated the cadmium-induced increase. These data suggest that metal-induced injury is associated with increased ICAM-1 expression. The mechanism of this induction may involve the decreased TGF-beta1 in the conditioned media following metal challenge. Taken together, these studies suggest a link between cytokine and adhesion molecule expression in renal injury.

The Scottish Centre for Autism Preschool Treatment Programme. II: The Results of a Controlled Treatment Outcome Study

Autism : the International Journal of Research and Practice. Mar, 2002  |  Pubmed ID: 11918108

This article evaluates the effectiveness of a developmentally based early intervention programme. Two groups of children were compared, a treatment group and a no-treatment control group. Standardized assessments were administered before and after the intervention period by an independent clinician. Pre-treatment comparisons revealed that the control group had a significantly higher pre-treatment IQ; but the two groups were comparable for age, mental age, socioeconomic status and number of hours of non-experimental therapy. Results demonstrated that children in the treatment group improved significantly more than those in the control group on measures of joint attention, social interaction, imitation, daily living skills, motor skills and an adaptive behaviour composite. A measure of requesting behaviour fell short of statistical significance. The total stress index reduced for treatment group parents and increased for the control group parents (but not significantly). The results of the study are considered to support the efficacy of this treatment approach.

Pulmonary Function Characteristics in Patients with Different Patterns of Methacholine Airway Hyperresponsiveness

Chest. Jun, 2002  |  Pubmed ID: 12065344

The American Thoracic Society guidelines for methacholine-induced airway hyperresponsiveness include a > or = 20% reduction in FEV(1) or a > or = 40% reduction in specific airway conductance (sGaw). The objectives of the current study are to assess the concordance between these two criteria and to characterize the pulmonary function and respiratory symptoms of patients with different patterns of methacholine hyperresponsiveness.

Short-sequence Tandem and Nontandem DNA Repeats and Endogenous Hydrogen Peroxide Production Contribute to Genetic Instability of Streptococcus Pneumoniae

Journal of Bacteriology. Aug, 2002  |  Pubmed ID: 12142409

Loss-of-function mutations in the following seven pneumococcal genes were detected and analyzed: pspA, spxB, xba, licD2, lytA, nanA, and atpC. Factors associated with these mutations included (i) frameshifts caused by reversible gain and loss of single bases within homopolymeric repeats as short as 6 bases, (ii) deletions caused by recombinational events between nontandem direct repeats as short as 8 bases, and (iii) substitutions of guanine residues caused at an increased frequency by the high levels of hydrogen peroxide (>2 mM) typically generated by this species under aerobic growth conditions. The latter accounted for a frequency as high as 2.8 x 10(-6) for spontaneous mutation to resistance to optochin and was 10- to 200-fold lower in the absence of detectable levels of H2O2. Some of these mutations appear to have been selected for in vivo during pneumococcal infection, perhaps as a consequence of immune pressure or oxidative stress.

Tidal Volume and Respiratory Timing Derived from a Portable Ventilation Monitor

Chest. Aug, 2002  |  Pubmed ID: 12171851

To determine the accuracy of a portable magnetometer designed to measure tidal volume (VT), inspiratory time (TI), and expiratory time (TE).

Ciliary Neurotrophic Factor Induces Glial Fibrillary Acidic Protein in Retinal Müller Cells Through the JAK/STAT Signal Transduction Pathway

Current Eye Research. Apr, 2002  |  Pubmed ID: 12324870

Intravitreal injection of ciliary neurotrophic factor (CNTF) is known to induce glial intermediate filament protein (GFAP) expression in retinal Müller cells. Because CNTF binding can activate multiple signaling kinases, we have examined the involvement of JAK/STAT pathway in GFAP induction in Müller cells.

Effects of Early Postnatal Ethanol Intubation on GABAergic Synaptic Proteins

Brain Research. Developmental Brain Research. Oct, 2002  |  Pubmed ID: 12354645

Fetal alcohol syndrome includes brain damage from aberrant synaptogenesis, altered cell-cell signaling and blunted plasticity in surviving neurons. Distortion of neurotrophic GABA signals by ethanol-mediated allosteric modulation of GABA(A) receptor (GABA(A)R) activity during brain maturation may play a role. In this regard, early postnatal binge-like ethanol treatment on postnatal days (PDs) 4-9 acutely inhibits whole cell GABA(A)R Cl(-) current and subsequently blunts GABA(A)R function in medial septum/diagonal band (MS/DB) neurons and cerebellar Purkinje cells [Dev. Brain Res. 130 (2001) 25-40; Brain Res. 810 (1998) 100-113; Brain Res. 832 (1999) 124-135]. In light of these functional changes, we hypothesized that ethanol treatment also would decrease levels of proteins important for assembly of GABAergic synapses in maturing brain. To test this relationship, binge-like ethanol intubation was administered to rat pups on PDs 4-9 producing peak blood ethanol concentrations in the range of 302.5+/-6.3 mg/dl. GABAergic synaptic proteins were measured in brain tissue on PDs 13-14 when GABA(A)R currents in individual MS/DB neurons are reduced, but those of cerebellar Purkinje neurons are not yet altered [Dev. Brain Res. 130 (2001) 25-40; Brain Res. 810 (1998) 100-113; Brain Res. 832 (1999) 124-135]. Surprisingly, ethanol did not decrease protein levels of GABA(A)R alpha1/beta2 subunits, GAD(67) or gephyrin in MS/DB at this time when whole cell recordings indicate GABA(A)R function is impaired in acutely dissociated individual neurons. However, in cerebellum where ethanol treated Purkinje cell GABA(A)R function remains normal on PDs 13-14 [Brain Res. 832 (1999) 124-135], reduced levels of several GABAergic synaptic proteins including: GAD(67), GABA(A)R alpha1 subunit, ClC-2 a voltage-gated Cl(-) channel, synaptotagmin a synaptic vesicle protein, and N-cadherin, a synapse associated cell adhesion molecule, were found. These results indicate that binge-like ethanol exposure differentially decreases GABAergic synaptic proteins in some brain areas in a pattern that does not parallel reductions in GABA(A)R function of individual neurons that survive this ethanol insult.

Interpretations of Smoking in Film by Older Teenagers

Social Science & Medicine (1982). Mar, 2003  |  Pubmed ID: 12593875

Research testifies that images of tobacco use in popular films are highly pervasive and typically glamorised. There are concerns that these images may promote motivations to smoke in adolescents, but little is known about how these images are interpreted by members of this age group. A qualitative study was conducted to explore how older teenagers interpret and decode smoking imagery in film. This study builds on earlier work with a younger age group (12 and 13 years) to explore how various interpretations of smoking imagery shape and support common understandings about smoking among older teenagers. Data were collected through focus groups. Eighty-eight 16 and 17 year old students were interviewed at school. Participants discussed their recollections of and responses to recently viewed films. Older teens were receptive to smoking imagery when it was used in a credible manner to portray an emotional state, sub-culture affiliation, and lifestyle. Experience as a smoker appeared to inflate the credibility of realistic smoking images, particularly those presented in gritty realism/drama film. Older teens perceived realistic images, as opposed to stereotypical images, as a salient reference to their own lives. Stereotypical images were also readily recalled and appeared to perform an important role in supporting misconceptions about smoking and contributing to popular ideologies about tobacco use. Stereotypical images presented in comedy and action genre also serve to present paradoxical and contradictory messages about tobacco use. In particular, participants recalled tobacco use in film as associated with stress and anxiety, drug use, and seduction. Film images of tobacco use in specific contexts appear to hold specific and significant meanings for older teens. Realistic images offered salient representations of the perceived reality of smoking for this group. Pervasive and credible smoking scenes in film may offer support and reassurance to older teens who currently smoke or hold ambivalent views about smoking. Consistent with younger adolescents, older teens presented a predominantly nonchalant response to smoking imagery in film, which is a powerful indicator of the pervasiveness and acceptability of smoking in general. In contrast with younger adolescent, older teens tend to draw upon their own experience with tobacco use when interpreting smoking images in film.

A Novel Form of Manually Assisted Ventilation

Chest. Mar, 2003  |  Pubmed ID: 12628900

We report an individual with limb-girdle muscular dystrophy who has devised a way to assist her respiration by using her hands braced against the tray of her wheelchair. Utilizing this method, she was able to increase her tidal volume (VT) and lower her respiratory rate compared to unassisted spontaneous breathing, thereby maintaining a stable minute volume. The manually assisted VT measurements were comparable to those achieved using an intermittent abdominal pressure respirator (pneumatic belt). We believe that others with neuromuscular syndromes could use this technique, possibly decreasing their dependence on mechanical ventilatory assist devices.

Effects of Chronic Alcohol Ingestion on Rat Lateral/basolateral Amygdala Ligand-gated Chloride Channels

Annals of the New York Academy of Sciences. Apr, 2003  |  Pubmed ID: 12724181

Silane Treatment Effects on Glass/resin Interfacial Shear Strengths

Dental Materials : Official Publication of the Academy of Dental Materials. Jul, 2003  |  Pubmed ID: 12742441

Methacrylic resin-based dental composites normally use a bifunctional silane coupling agent with an intermediary carbon connecting segment to provide the interfacial phase that holds together the organic polymer matrix with the reinforcing inorganic phase. In this study, fiber pull-out tests were used to measure the interfacial bond strength at the fiber-matrix interface.

Mechanical Evaluation of a Porous Bone Graft Substitute Based on Poly(propylene Glycol-co-fumaric Acid)

Journal of Biomedical Materials Research. Part B, Applied Biomaterials. Jul, 2003  |  Pubmed ID: 12808589

A porous, resorbable polymer composite based on poly(propylene glycol-co-fumaric acid) (PPF) was mechanically evaluated in vitro for use as a bone graft substitute and fracture fixative. The test material created a dynamic system capable of initially providing mechanical integrity to bony voids and a degradative mechanism for ingrowth by native bone. The unsaturated polymer, PPF, was crosslinked in the presence of effervescent agents to yield a porous microstructure upon curing. An in vitro degradation study first assessed the temporal mechanical properties of the test material. This research was followed by an ex vivo study using a long-bone osteotomy model to characterize the mechanics of fixation. Results showed the initial compressive strength of the cross-linked PPF system was comparable to cancellous bone. The rate of strength loss was commensurate with the predicted mechanical recovery of healing bone with analogous results in a composite that comprised also 25% (by weight) autograft. Mechanical testing in the long-bone model demonstrated that PPF-based bone-graft substitute increased the flexural strength of K-wire stabilized osteotomies. These results suggest that this type of bone graft substitute may have clinical utility in the stabilization of complex tubular bone fractures.

Smoking Behaviour and Expectations Among Auckland Adolescents

The New Zealand Medical Journal. Jun, 2003  |  Pubmed ID: 12835806

To compare the relationships of age level, gender, smoking status and ethnicity with Form Two and Form Six students' beliefs about smoking and their familial smoking behaviour.

Ratio Between Forced Expiratory Flow Between 25% and 75% of Vital Capacity and FVC is a Determinant of Airway Reactivity and Sensitivity to Methacholine

Chest. Jul, 2003  |  Pubmed ID: 12853503

The ratio between forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) and FVC is thought to reflect dysanapsis between airway size and lung size. A low FEF(25-75)/FVC ratio is associated with airway responsiveness to methacholine in middle-aged and older men. The current study was designed to assess this relationship in both male and female subjects over a broader range of ages.

American Headache Society Members' Assessment of Headache Diagnostic Criteria

Headache. Jan, 2003  |  Pubmed ID: 12864752

We assessed the views of physicians interested in headache as to the diagnosis of the most commonly occurring and currently controversial headaches.

Genetic Variation Influences the B-cell Response to Immunization with a Pneumococcal Polysaccharide Conjugate Vaccine

Infection and Immunity. Sep, 2003  |  Pubmed ID: 12933893

CBA/J mice immunized with pneumococcal 23F-CRM(197) vaccine produce significantly lower titers of 23F-specific antibodies and fewer 23F-specific antibody-secreting cells (ASC) than did BALB/c or (CBA/J x BALB/c)F(1) (CCBAF(1)) mice. The reduced 23F-specific titers of CBA/J versus BALB/c or CCBAF(1) mice are presumably related to lower frequencies of 23F-specific ASC influenced by genetic variation.

Serum Immunoglobulin G Response to Candidate Vaccine Antigens During Experimental Human Pneumococcal Colonization

Infection and Immunity. Oct, 2003  |  Pubmed ID: 14500493

The immune response to pneumococcal surface structures during colonization was examined in a model of experimental human pneumococcal carriage. Healthy uncolonized adults were given a type 23F or 6B pneumococcus, and a portion of these subjects became colonized (6 of 14 with type 23F and 6 of 8 with type 6B). Sera from colonized and uncolonized subjects were used to determine the titer of antibody specific to pneumococcal surface components under consideration in development of noncapsular polysaccharide-based vaccines. These vaccine candidates included pneumococcal surface protein A (PspA), choline binding protein A (CbpA), lipoteichoic acid, immunoglobulin A1 (IgA1) protease, pneumolysin, proteinase maturation protein A, and pneumococcal surface adhesin A. Only the two related choline binding proteins, PspA and CbpA, were immunogenic in colonized subjects as determined by a statistically significant rise in the serum IgG titer. The serum IgG response to PspA was shown previously to correlate inversely with susceptibility to carriage and was localized to a region within the N-terminal portion of PspA. This region is highly variable in amino acid sequence between pneumococcal strains. Despite the sequence diversity in the immunodominant regions of both PspA and CbpA, a significant strain-to-strain cross-reactivity in the serum IgG response following experimental human carriage was observed. These findings support the need for further investigation of the human antibody response to PspA and CbpA and the potential use of one or both of these proteins as novel vaccine antigens for the prevention of pneumococcal colonization.

Nonhuman Primate Parthenogenetic Stem Cells

Proceedings of the National Academy of Sciences of the United States of America. Sep, 2003  |  Pubmed ID: 14504386

Parthenogenesis is the biological phenomenon by which embryonic development is initiated without male contribution. Whereas parthenogenesis is a common mode of reproduction in lower organisms, the mammalian parthenote fails to produce a successful pregnancy. We herein describe in vitro parthenogenetic development of monkey (Macaca fascicularis) eggs to the blastocyst stage, and their use to create a pluripotent line of stem cells. These monkey stem cells (Cyno-1 cells) are positive for telomerase activity and are immunoreactive for alkaline phosphatase, octamer-binding transcription factor 4 (Oct-4), stage-specific embryonic antigen 4 (SSEA-4), tumor rejection antigen 1-60 (TRA 1-60), and tumor rejection antigen 1-81 (TRA 1-81) (traditional markers of human embryonic stem cells). They have a normal chromosome karyotype (40 + 2) and can be maintained in vitro in an undifferentiated state for extended periods of time. Cyno-1 cells can be differentiated in vitro into dopaminergic and serotonergic neurons, contractile cardiomyocyte-like cells, smooth muscle, ciliated epithelia, and adipocytes. When Cyno-1 cells were injected into severe combined immunodeficient mice, teratomas with derivatives from all three embryonic germ layers were obtained. When grown on fibronectin/laminin-coated plates and in neural progenitor medium, Cyno-1 cells assume a neural precursor phenotype (immunoreactive for nestin). However, these cells remain proliferative and express no functional ion channels. When transferred to differentiation conditions, the nestin-positive precursors assume neuronal and epithelial morphologies. Over time, these cells acquire electrophysiological characteristics of functional neurons (appearance of tetrodotoxin-sensitive, voltage-dependent sodium channels). These results suggest that stem cells derived from the parthenogenetically activated nonhuman primate egg provide a potential source for autologous cell therapy in the female and bypass the need for creating a competent embryo.

Why Do So Many Drug Users Smoke?

Journal of Substance Abuse Treatment. Jul, 2003  |  Pubmed ID: 14512107

To better understand why most persons in drug treatment smoke, we explored patients' views of the relationship between their smoking, methadone, and drug use. Recruiting from four methadone clinics, we held seven focus groups with 68 current smokers, and 10 individual interviews with former smokers. Sessions were audio-taped, transcribed, and coded. Participants were > or =18 years old, smoked > or =5 cigarettes per day, and had used prescription methadone for > or =2 years. Most patients linked smoking, methadone, and drug use in three ways. First, patients said smoking and drug use were complementary. Examples included smoking to reduce methadone after taste and using drugs to reduce smoking-related throat pain. Second, smoking and drug use were similar because they shared cues and withdrawal symptoms. Third, smoking differed from drug use because it had fewer acute consequences. Because smoking, methadone, and drug use are closely interrelated, future addictions research and treatment protocols should address them in combination.

Increased Auditory Startle Response and Reduced Prepulse Inhibition of Startle in Transgenic Mice Expressing a Double Mutant Form of Amyloid Precursor Protein

Brain Research. Dec, 2003  |  Pubmed ID: 14642453

Prepulse inhibition (PPI), a form of sensorimotor gating, occurs when an auditory startle response is markedly inhibited by a preceding sub-threshold stimulus (prepulse). Deficits in PPI have been demonstrated in patients with certain psychiatric disorders, such as schizophrenia, and in laboratory animals following specific pharmacological manipulations. Patients with Alzheimer's disease (AD) have not been tested in PPI, but have been shown to have abnormal sensory gating in another paradigm. Transgenic (Tg) CRND8 mice, which model Alzheimer's disease, carry the Swedish and Indiana familial Alzheimer's disease mutations of the human amyloid precursor protein gene and show age-related increases in beta-amyloid (Abeta) production, as well as plaque deposition. The present experiment investigated auditory startle threshold and PPI in TgCRND8 mice at various ages. In two longitudinal studies, PPI was examined in male TgCRND8 mice and non-transgenic (non-Tg) controls at 6-8 weeks of age (pre-plaque), and every 2 weeks thereafter until all mice were at least 16 weeks old (post-plaque). In a cross-sectional study, three different age sets of nai;ve TgCRND8 and non-Tg mice were tested: 10-12, 12-14, and 15-17 weeks old. In all three studies, TgCRND8 mice consistently and robustly demonstrated an enhanced response to a range of auditory startle stimuli compared to non-Tg mice. In addition, the TgCRND8 mice exhibited modest reductions in PPI, compared to non-Tg controls. These PPI deficits were present at pre- and post-plaque time points and did not appear to intensify with age; thus, they do not seem to correlate with the known neuropathology of TgCRND8 mice.

Dietary Intake and Nutritional Status of Older Adult Homeless Women: a Pilot Study

Journal of Nutrition for the Elderly. 2003  |  Pubmed ID: 14650550

A pilot study was conducted to identify eating patterns, food sources, and nutritional problems among a limited population of older homeless women located in a large urban area. Most of these women's food came from shelter meals, and their food intake was inadequate for most nutrients. The availability of fruits, vegetables, dairy products, and whole grains was very limited. Foods high in saturated fats and simple carbohydrates provided most of their caloric intake. Although some women were obese, most were found to have low BMI and mid-arm muscle mass area measurements indicating low body fat stores and potential muscle wasting.

Influenza Vaccine and FDG-PET

Lancet. Dec, 2003  |  Pubmed ID: 14683672

Effects of Chronic Ethanol Consumption on Rat GABA(A) and Strychnine-sensitive Glycine Receptors Expressed by Lateral/basolateral Amygdala Neurons

Brain Research. Feb, 2003  |  Pubmed ID: 12560122

It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABA(A) and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABA(A) receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor's response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABA(A) receptors composed of unique alpha subunits were differentially sensitive to acute ethanol. Likewise, the presence of the beta subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the alpha(2) subunit. Our results suggest that the facilitation of GABA(A) receptors during chronic ethanol exposure may help explain the maintenance of ethanol's anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABA(A) and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure.

Diaphragm Dimensions of the Healthy Term Infant

Acta Paediatrica (Oslo, Norway : 1992). Sep, 2003  |  Pubmed ID: 14599071

Human neonatal diaphragm development has not been extensively studied. Previous work in children and adults suggests that diaphragm thickness (t(di)) is in scale with body size such that maximal transdiaphragmatic pressure (P(dimax)) remains relatively constant. Such assessments have not been made in healthy term infants. This study was designed to evaluate the relationships among t(di), body dimensions and P(dimax) in healthy term infants.

Chronic Ethanol Ingestion Facilitates N-methyl-D-aspartate Receptor Function and Expression in Rat Lateral/basolateral Amygdala Neurons

The Journal of Pharmacology and Experimental Therapeutics. Dec, 2003  |  Pubmed ID: 14534353

Withdrawal anxiety after chronic alcohol is likely to contribute to drug seeking and relapse in alcoholics. The brain regions regulating fear/anxiety behaviors, especially neurotransmitter systems with acute ethanol sensitivity, are potential targets for chronic ethanol-induced adaptations. We have therefore examined N-methyl-d-aspartate (NMDA) receptors after chronic ethanol ingestion in rat lateral/basolateral amygdala. Whole cell patch-clamp measurements indicate that chronic ethanol ingestion significantly increased NMDA receptor current density. This enhanced NMDA receptor function was also associated with an increase in ifenprodil inhibition and a decrease in apparent calcium-dependent current inactivation. These findings suggest that NR2B-containing receptors may be specifically enhanced and suggest that processes dependent upon calcium influx through amygdala NMDA receptors may potentially be enhanced by chronic ethanol ingestion. We measured subunit mRNA expression to investigate possible molecular mechanisms that control functional receptor adaptations to chronic ethanol. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that NR1 subunit mRNA expression, but not NR2 or NR3 expression, was enhanced in samples from chronic ethanol-exposed animals. Single-cell RT-PCR was then used to confirm that NR2 mRNA expression was unaltered by chronic ethanol. Most GAD-, presumed projection neurons expressed both NR2A and NR2B mRNAs, and this profile did not change during chronic ethanol exposure. Our results suggest that both transcriptional and nontranscriptional adaptations to chronic ethanol ultimately contribute to alterations in NMDA receptor function. Because amygdala NMDA receptors play a significant role in many learned fear behaviors, chronic ethanol-induced adaptations in these receptors may influence the expression of withdrawal anxiety.

Limited Role of Antibody in Clearance of Streptococcus Pneumoniae in a Murine Model of Colonization

Infection and Immunity. Oct, 2004  |  Pubmed ID: 15385481

Colonization is the first step in the interaction between Streptococcus pneumoniae and its human host. To better understand the mechanisms contributing to natural carriage, a mouse model of pneumococcal colonization was developed with a clinical isolate of S. pneumoniae previously characterized in experimental colonization of humans. Similar to carriage events in humans, colonization of mice was self-limited and there was no evidence of lower respiratory tract or invasive disease. Carriage induced a serum antibody response to whole pneumococci that was associated temporally with clearance of colonization in three inbred strains of mice. Individual mice, however, did not demonstrate a correlation between the density of colonization and amounts of serum or of mucosal antibodies, including antibodies of different isotypes and antigenic specificities. The role of antibody in the clearance of carriage was then examined in mice with genetic defects in humoral immunity. xid mice, which have deficient responses to polysaccharide antigens, cleared colonization at the same rate as the parent strain. Finally, we showed that microMT mice, which lack mature B cells and fail to produce antibody, were unaffected in the density or duration of colonization. These results demonstrate that antibody is not required for clearance of pneumococcal colonization in mice.

Measurement of SOS Expression in Individual Escherichia Coli K-12 Cells Using Fluorescence Microscopy

Molecular Microbiology. Sep, 2004  |  Pubmed ID: 15387814

Many recombination, DNA repair and DNA replication mutants have high basal levels of SOS expression as determined by a sulAp-lacZ reporter gene system on a population of cells. Two opposing models to explain how the SOS expression is distributed in these cells are: (i) the 'Uniform Expression Model (UEM)' where expression is evenly distributed in all cells or (ii) the 'Two Population Model (TPM)' where some cells are highly induced while others are not at all. To distinguish between these two models, a method to quantify SOS expression in individual bacterial cells was developed by fusing an SOS promoter (sulAp) to the green fluorescent protein (gfp) reporter gene and inserting it at attlambda on the Escherichia coli chromosome. It is shown that the fluorescence in sulAp-gfp cells is regulated by RecA and LexA. This system was then used to distinguish between the two models for several mutants. The patterns displayed by priA, dnaT, recG, uvrD, dam, ftsK, rnhA, polA and xerC mutants were explained best by the TPM while only lexA (def), lexA3 (ind-) and recA defective mutants were explained best by the UEM. These results are discussed in a context of how the processes of DNA replication and recombination may affect cells in a population differentially.

Lihouidine, a Novel Spiro Polycyclic Aromatic Alkaloid from the Marine Sponge Suberea N. Sp. (Aplysinellidae, Verongida)

The Journal of Organic Chemistry. Nov, 2004  |  Pubmed ID: 15527252

An investigation of a new species of sponge from the genus Suberea collected at Lihou Reef in the Coral Sea afforded lihouidine, an unprecedented cytotoxic spiro nonacyclic polyaromatic alkaloid. The structure of the alkaloid, which was racemic, was determined by a combination of 1D and 2D NMR techniques and single-crystal X-ray structural analysis.

Smoking Cessation Services in U.S. Methadone Maintenance Facilities

Psychiatric Services (Washington, D.C.). Nov, 2004  |  Pubmed ID: 15534014

Most patients in drug treatment smoke cigarettes. This study established the prevalence and types of nicotine dependence services offered in methadone and other opioid treatment clinics in the United States.

The Definition and Assessment of Pain

Journal of Midwifery & Women's Health. Nov-Dec, 2004  |  Pubmed ID: 15544975

Pain in Women's Health: a Multi-faceted Approach Toward Understanding

Journal of Midwifery & Women's Health. Nov-Dec, 2004  |  Pubmed ID: 15544976

Pain has always been a part of women's health experiences, inherent to such physiologic processes as menstrual cramping, labor contractions, and uniquely female illnesses, such as cervical or ovarian cancer. However, the understanding of pain-its nature, its purpose, and its sometimes debatable need for removal-remains elusive. Pain's origins are in the physical realm, but it is manifested through an array of psychological, social, and cultural factors. The concept of pain is explored using an evolutionary approach to understanding the mechanisms associated with the physiologic, psychological, developmental, and sociocultural aspects of this phenomenon. The relevance of this exploratory look at pain as it relates to offering health care to women is discussed. The manner in which pain affects individuals and the methods with which it can be treated are critical elements in the provision of quality health care.

Obstetric Anesthesia: Changes and Choices

Journal of Midwifery & Women's Health. Nov-Dec, 2004  |  Pubmed ID: 15544979

This article is a review of analgesics and anesthetics offered to laboring women, including intravenous drugs, epidural and spinal agents, and inhalational anesthetics. An overview of the uses, risks, and benefits is provided for each anesthetic alternative. To provide the most effective care to women in labor, clinicians have a responsibility to have current knowledge of the best evidence for safety and efficacy of these pharmacologic agents and techniques and be able to effectively communicate this information to clients.

When the Search Consultant Calls. A Nationally Recognized Authority Shares Tips for Working with Search Consultants

Healthcare Executive. Jan-Feb, 2004  |  Pubmed ID: 14716932

A Randomized Crossover Trial of PAPNET for Primary Cervical Screening

Journal of Clinical Epidemiology. Jan, 2004  |  Pubmed ID: 15019013

To develop and demonstrate efficient methods to estimate the relative true positive and false positive rates of two cervical screening tests (conventional cytology and PAPNET).

Indicators of Sustainability: Challenges and Opportunities at the Interface of Science and Policy

Environmental Management. Mar, 2004  |  Pubmed ID: 15031759

Rising global interest in sustainability has triggered attention in indicators as a means of achieving a more sustainable world. Although the search for indicators has led to the development of criteria for good indicators, it has also been dominated by scientific elites. The consequences of such dominance leads to significant social and policy implications, particularly with regard to how the search for sustainability has become defined primarily as a technical/scientific exploration when it is actually a moral and ethical issue. Our discussion about sustainability and appropriate indicators centers on what constitutes the public interest, a question that requires inclusiveness and centers on the interface of science and policy. The paper reviews the rationale for selecting indicators, the functions they serve, and the implications and consequences involved when one sector-science-dominates the debate. The paper concludes with suggestions about appropriate roles of science, policy and the public in the indicator selection process.

Activation of CAMP-guanine Exchange Factor Confers PKA-independent Protection from Hepatocyte Apoptosis

American Journal of Physiology. Gastrointestinal and Liver Physiology. Aug, 2004  |  Pubmed ID: 15044179

cAMP has previously been shown to promote cell survival in a variety of cell types, but the downstream signaling pathway(s) of this antiapoptotic effect is unclear. Thus the role of cAMP signaling through PKA and cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs) in cAMP's antiapoptotic action was investigated in the present study. cAMP's protective effect against bile acid-, Fas ligand-, and TNF-alpha-induced apoptosis in rat hepatocytes was largely unaffected by the selective PKA inhibitor, Rp-8-(4-chlorophenylthio)-cAMP (Rp-cAMP). In contrast, a novel cAMP analog, 8-(4-chlorophenylthio)-2'-O-methyl (CPT-2-Me)-cAMP, which activated cAMP-GEFs in hepatocytes without activating PKA, protected hepatocytes against apoptosis induced by bile acids, Fas ligand, and TNF-alpha. The role of cAMP-GEF and PKA on activation of Akt, a kinase implicated in cAMP survival signaling, was investigated. Inhibition of PKA with RP-cAMP had no effect on cAMP-mediated Akt phosphorylation, whereas CPT-2-Me-cAMP, which did not activate PKA, induced phosphatidylinositol 3-kinase (PI3-kinase)-dependent activation of Akt. Pretreatment of hepatocytes with the PI3-kinase inhibitor, Ly-294002, prevented CPT-2-Me-cAMP's protective effect against bile acid and Fas ligand, but not TNF-alpha-mediated apoptosis. Glucagon, CPT-cAMP, and CPT-2-Me-cAMP all activated Rap 1, a downstream effector of cAMP-GEF. These results suggest that a PKA-independent cAMP/cAMP-GEF/Rap pathway exists in hepatocytes and that activation of cAMP-GEFs promotes Akt phosphorylation and hepatocyte survival. Thus a cAMP/cAMP-GEF/Rap/PI3-kinase/Akt signaling pathway may confer protection against bile acid- and Fas-induced apoptosis in hepatocytes.

Indoleamine 2,3-dioxygenase Expression is Restricted to Fetal Trophoblast Giant Cells During Murine Gestation and is Maternal Genome Specific

Journal of Reproductive Immunology. Apr, 2004  |  Pubmed ID: 15063630

Pharmacologic inhibition of indoleamine 2,3 dioxygenase (IDO) activity during murine pregnancy results in rejection of allogeneic fetuses by the maternal immune system. Here, we show that IDO expression is restricted to perinuclear regions of primary trophoblast giant cells (TGCs) of fetal origin at mid-gestation (E10.5). After placentation (E14), no IDO expression was detected at the maternal-fetal interface. Matings involving IDO-deficient females revealed that paternally inherited IDO alleles were inactive in primary TGCs, presumably due to paternal genome-specific gene inactivation. Allogeneic matings in which both parents were genetically IDO-deficient produced litters of normal sizes at normal rates compared to IDO-sufficient parental mice, implying that compensatory or redundant immunosuppressive mechanisms protected allogeneic fetuses during gestation in IDO-deficient mice. Consistent with this notion, treatment with IDO inhibitor did not affect allogeneic pregnancy rates when both parents were IDO-deficient, confirming that IDO was the relevant pharmacologic target of the IDO inhibitor in matings involving IDO-sufficient mice. Hence, IDO is a key immunosuppressive mechanism in normal murine pregnancies, and it is regulated entirely through maternally inherited fetal genes.

On Competition and Collaboration: Nursing, Midwifery, and U.S. News & World Report

Journal of Professional Nursing : Official Journal of the American Association of Colleges of Nursing. May-Jun, 2004  |  Pubmed ID: 15211421

The Interleukin 1beta Gene Promoter Polymorphism (-511) Acts As a Risk Factor for Psychosis in Alzheimer's Dementia

Annals of Neurology. Jul, 2004  |  Pubmed ID: 15236409

The explanation for why some patients develop psychotic change in Alzheimer's disease (AD) is unclear. "Psychosis-modifier genes" may act in the setting of neurodegeneration to produce AD plus psychosis in a similar way to how genetic modulation during neurodevelopment leads to schizophrenia. Because there is increasing interest in the common disruption of cytokine pathways seen in both AD and schizophrenia, we tested the association between the functional interleukin-1beta -511 promoter polymorphism with delusions and hallucinations in AD. Significant associations between psychotic symptoms and the CC genotype (p = 0.001 - p = 0.043) and C allele (p = 0.014 vs p = 0.048) were found, thus confirming the previously noted increased risk in schizophrenia.

Publication of Science, Terror, and the First Amendment

Journal of Midwifery & Women's Health. Jul-Aug, 2004  |  Pubmed ID: 15236706

Interface Effects on Mechanical Properties of Particle-reinforced Composites

Dental Materials : Official Publication of the Academy of Dental Materials. Sep, 2004  |  Pubmed ID: 15236943

Effective bonding between the filler and matrix components typically improves the mechanical properties of polymer composites containing inorganic fillers. The aim of this study was to test the hypothesis that composite flexural modulus, flexure strength, and toughness are directly proportional to filler-matrix interfacial shear strength.

A DnaT Mutant with Phenotypes Similar to Those of a PriA2::kan Mutant in Escherichia Coli K-12

Genetics. Jun, 2004  |  Pubmed ID: 15238512

The ability to repair damaged replication forks and restart them is important for cell survival. DnaT is essential for replication restart in vitro and yet no definite genetic analysis has been done in Escherichia coli K-12. To begin, dnaT822, an in-frame six-codon (87-92) deletion was constructed. DnaT822 mutants show colony size, cell morphology, inability to properly partition nucleoids, UV sensitivity, and basal SOS expression similar to priA2::kan mutants. DnaT822 priA2::kan double mutants had phenotypes similar to those of the single mutants. DnaT822 and dnaT822 priA2::kan mutant phenotypes were fully suppressed by dnaC809. Previously, a dominant temperature-sensitive lethal mutation, dnaT1, had been isolated in E. coli 15T(-). DnaT1 was found to have a base-pair change relative to the E. coli 15T(-) and E. coli K-12 dnaT genes that led to a single amino acid change: R152C. A plasmid-encoded E. coli K-12 mutant dnaT gene with the R152C amino acid substitution did not display a dominant temperature-sensitive lethal phenotype in a dnaT(+) strain of E. coli K-12. Instead, this mutant dnaT gene was found to complement the E. coli K-12 dnaT822 mutant phenotypes. The significance of these results is discussed in terms of models for replication restart.

Long-term Ethanol Self-administration by Cynomolgus Macaques Alters the Pharmacology and Expression of GABAA Receptors in Basolateral Amygdala

The Journal of Pharmacology and Experimental Therapeutics. Dec, 2004  |  Pubmed ID: 15280440

We have recently demonstrated that chronic ethanol ingestion alters the functional and pharmacological properties of GABAA receptors measured in acutely isolated rat lateral/basolateral amygdala neurons, a limbic forebrain region involved with fear-learning and innate anxiety. To understand relevance of these results in the context of primates, we have examined the effects of long-term ethanol self-administration on basolateral amygdala GABAA receptor pharmacology and expression in cynomolgus macaques (Macaca fascicularis). The impact of this 18-month-long exposure on GABAA receptor function was assessed in acutely isolated neurons from basolateral amygdala with whole-cell patch-clamp electrophysiology. Neurons from control animals expressed maximal current densities that were not significantly different from the maximal current densities of neurons from ethanol-treated animals. However, the GABA concentration-response relationships from ethanol-exposed neurons were significantly right-shifted compared with control neurons. These adaptations were associated with significant alterations in some characteristics of macroscopic current desensitization. To understand the mechanism governing these adaptations, we quantified GABAA alpha subunit mRNAs in basolateral amygdala from the same animals. mRNA levels of the alpha2 and alpha3 subunits were significantly decreased, whereas decreases in alpha1 expression only approached statistical significance. There were no changes in alpha4 mRNA levels. These findings indicate that ethanol-induced alterations in GABAA function may be regulated in part by selective changes in the expression of particular alpha subunits. We conclude that adaptations of basolateral amygdala GABAA receptors after long-term ethanol self-administration by the cynomolgus macaque are similar, but not identical, to those described in rodents after a brief forced ethanol exposure.

Extrinsic Factors Regulate Partial Agonist Efficacy of Strychnine-sensitive Glycine Receptors

BMC Pharmacology. Aug, 2004  |  Pubmed ID: 15301692

Strychnine-sensitive glycine receptors in many adult forebrain regions consist of alpha2 + beta heteromeric channels. This subunit composition is distinct from the alpha1 + beta channels found throughout the adult spinal cord. Unfortunately, the pharmacology of forebrain alpha2beta receptors are poorly defined compared to 'neonatal' alpha2 homomeric channels or 'spinal' alpha1beta heteromers. In addition, the pharmacologic properties of native alpha2beta glycine receptors have been generally distinct from receptors produced by heterologous expression. To identify subtype-specific pharmacologic tools for the forebrain alpha2beta receptors, it is important to identify a heterologous expression system that closely resembles these native glycine-gated chloride channels.

Apolipoprotein E E4 Allele Influences Aggressive Behaviour in Alzheimer's Disease

Journal of Neurology, Neurosurgery, and Psychiatry. Sep, 2004  |  Pubmed ID: 15314125

The rising number of people with cognitive impairment is placing health care budgets under significant strain. Dementia related behavioural change is a major independent risk factor for admission to expensive institutional care, and aggressive symptoms in particular are poorly tolerated by carers and frequently precipitate the collapse of home coping strategies. Aggressive change may result from known genetic risk factors for Alzheimer's disease (AD) and therefore accompany conventional markers such as apolipoprotein E (ApoE). We tested this hypothesis in 400 moderately to severely affected AD patients who were phenotyped for the presence of aggressive or agitated behaviour during the month prior to interview using the Neuropsychiatric Inventory with Caregiver Distress. The proportion of subjects with aggression/agitation in the month prior to interview was 51.8%. A significantly higher frequency of the e4 allele was found in individuals recording aggression/agitation in the month prior to interview (chi2 = 6.69, df = 2, p = 0.03). The additional risk for aggression/agitation conferred by e4 was also noted when e4 genotypes were compared against non-e4 genotypes (chi2 = 5.45, df = 1, p = 0.02, OR = 1.60, confidence interval (CI) 1.06 to 2.43). These results indicate that advanced Alzheimer's disease patients are at greater risk of aggressive symptoms because of a genetic weakness in apolipoprotein E.

Stereotyping the Smoker: Adolescents' Appraisals of Smokers in Film

Tobacco Control. Sep, 2004  |  Pubmed ID: 15333889

To assess the relation between demographic factors and film smoking stereotypes in adolescents and the potential influence of smoker stereotypes on smoking susceptibility.

Cross-reactivity of Human Immunoglobulin G2 Recognizing Phosphorylcholine and Evidence for Protection Against Major Bacterial Pathogens of the Human Respiratory Tract

The Journal of Infectious Diseases. Oct, 2004  |  Pubmed ID: 15346335

Phosphorylcholine (ChoP) is an antigenic component on the cell surface of many commensal and pathogenic bacteria that reside in the upper airway. In the present study, human ChoP-specific antibody was affinity-purified from pooled serum gamma globulin. This naturally acquired antibody, which is primarily of the immunoglobulin (Ig) G2 subtype, recognized ChoP on the lipoteichoic acid of Streptococcus pneumoniae and on the lipopolysaccharide of Haemophilus influenzae, 2 of the leading etiologic agents of infection involving the human respiratory tract. In in vitro killing assays, anti-ChoP IgG2 was effective against some clinical isolates of nontypeable H. influenzae and against isolates of several common serotypes of S. pneumoniae. Moreover, passively administered human anti-ChoP antibody protected mice against lethal challenge with a transparent isolate of S. pneumoniae type 6A. The effectiveness of human antibody to this conserved bacterial structure suggests that, if it can be manipulated to broaden its activity, it could function as a single vaccine antigen that targets multiple pathogens.

Respiratory Muscle Strength Training with Nonrespiratory Maneuvers

Journal of Applied Physiology (Bethesda, Md. : 1985). Feb, 2004  |  Pubmed ID: 14514702

The diaphragm and abdominal muscles can be recruited during nonrespiratory maneuvers. With these maneuvers, transdiaphragmatic pressures are elevated to levels that could potentially provide a strength-training stimulus. To determine whether repeated forceful nonrespiratory maneuvers strengthen the diaphragm, four healthy subjects performed sit-ups and biceps curls 3-4 days/wk for 16 wk and four subjects served as controls. The maximal transdiaphragmatic pressure was measured at baseline and after 16 wk of training. Maximum static inspiratory and expiratory mouth pressures and diaphragm thickness derived from ultrasound were measured at baseline and 8 and 16 wk. After training, there were significant increases in diaphragm thickness [2.5 +/- 0.1 to 3.2 +/- 0.1 mm (mean +/- SD) (P < 0.001)], maximal transdiaphragmatic pressure [198 +/- 21 to 256 +/- 23 cmH2O (P < 0.02)], maximum static inspiratory pressure [134 +/- 22 to 171 +/- 16 cmH2O (P < 0.002)], maximum static expiratory pressure [195 +/- 20 to 267 +/- 40 cmH2O (P < 0.002)], and maximum gastric pressure [161 +/- 5 to 212 +/- 40 cmH2O (P < 0.03)]. These parameters were unchanged in the control group. We conclude that nonrespiratory maneuvers can strengthen the inspiratory and expiratory muscles in healthy individuals. Because diaphragm thickness increased with training, the increase in maximal pressures is unlikely due to a learning effect.

The Inflammatory Responses to Silk Films in Vitro and in Vivo

Biomaterials. Jan, 2005  |  Pubmed ID: 15207461

Silks have a long history of biomedical use as sutures. Silk can be purified, chemically modified to attach RGD sequences and processed into highly porous scaffolds for tissue engineering. We report biocompatibility studies of silk films (with or without covalently bound RGD) that were seeded with bone-marrow derived mesenchymal stem cells (MSC) and (a) cultured in vitro with human MSC or (b) seeded with autologous rat MSC and implanted in vivo. Controls for in vitro studies included tissue culture plastic (TCP; negative control), TCP with lipopolysaccharide (LPS) in the cell culture medium (positive control), and collagen films; controls for in vivo studies included collagen, PLA and TCP. After 9 h of culture, the expression of the pro-inflammatory Interleukin 1 beta (IL-1beta) and inflammatory cyclooxygenase 2 (COX-2) in human MSC were comparable for silk, collagen and TCP. After 30 and 96 h, gene expression of IL-1beta and COX-2 in MSC returned to the baseline (pre-seeding) levels. These data were corroborated by measuring IL-1beta and prostaglandin E2 levels in culture medium. The rate of cell proliferation was higher on silk films than either on collagen or TCP. In vivo, films made of silk, collagen or PLA were seeded with rat MSCs, implanted intramuscularly in rats and harvested after 6 weeks. Histological and immunohistochemical evaluation of silk explants revealed the presence of circumferentially oriented fibroblasts, few blood vessels, macrophages at the implant-host interface, and the absence of giant cells. Inflammatory tissue reaction was more conspicuous around collagen films and even more around PLA films when compared to silk. These data suggest that (a) purified degradable silk is biocompatible and (b) the in vitro cell culture model (hMSC seeded and cultured on biomaterial films) gave inflammatory responses that were comparable to those observed in vivo.

Expiratory Effort Enhancement and Peak Expiratory Flow in Humans

European Journal of Applied Physiology. May, 2005  |  Pubmed ID: 15627207

Peak expiratory flow (PEF) has previously been considered an effort-dependent, non flow-limited parameter that is constrained by the force-velocity relationship of the respiratory muscles. It has also been assumed that, if the muscles were able to augment the expiratory pressure, the PEF would increase. We tested the validity of this notion in normal volunteers who were able to enhance their expiratory pressure with maneuvers utilizing the stretch-shortening cycle (greater force when contractions were immediately preceded by eccentric contractions). Five healthy volunteers [35 (2) years] performed two successive maximal expiratory flow-volume maneuvers (MEFV) in rapid sequence. MEFV1 was a standard maneuver, whereas MEFV2 included a forceful inspiration to total lung capacity; a strategy designed to augment expiratory pressure via the stretch-shortening cycle. Neither maneuver included a post-inspiratory pause. We measured PEF, esophageal pressure (P(es)), and the electromyographic activity of the abdominal muscles. Compared to MEFV1, MEFV2 produced greater activation of the abdominal muscles during inspiration (eccentric contraction), greater peak expiratory P(es), greater rate of rise of P(es), shorter time to PEF, but similar PEF. Our findings directly demonstrate the inability of the augmented expiratory effort to increase PEF and thus support the notion that PEF is determined by a flow-limiting mechanism and not by the velocity of muscle shortening.

Attention: Reaction Time and Accuracy Reveal Different Mechanisms

Journal of Experimental Psychology. General. Feb, 2005  |  Pubmed ID: 15702964

The authors propose that there are 2 different mechanisms whereby spatial cues capture attention. The voluntary mechanism is the strategic allocation of perceptual resources to the location most likely to contain the target. The involuntary mechanism is a reflexive orienting response that occurs even when the spatial cue does not indicate the probable target location. Voluntary attention enhances the perceptual representation of the stimulus in the cued location relative to other locations. Hence, voluntary attention affects performance in experiments designed around both accuracy and reaction time. Involuntary attention affects a decision as to which location should be responded to. Because involuntary attention does not change the perceptual representation, it affects performance in reaction time experiments but not accuracy experiments. The authors obtained this pattern of results in 4 different versions of the spatial cuing paradigm.

Transgenic Overexpression of Neuromedin U Promotes Leanness and Hypophagia in Mice

The Journal of Endocrinology. Apr, 2005  |  Pubmed ID: 15817836

Recent work has shown that neuromedin U (NmU), a peptide initially identified as a smooth muscle contractor, may play a role in regulating food intake and energy homeostasis. To further evaluate this putative function, we measured food intake, body weight, energy expenditure and glucose homeostasis in transgenic mice that ubiquitously overexpress murine proNmU. NmU transgenic mice were lighter and had less somatic and liver fat, were hypophagic, and had improved insulin sensitivity as judged by an intraperitoneal insulin tolerance test. Transgenic mice had higher levels of hypothalamic NPY, POMC and MCH mRNA. There was no difference in O2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding. There were no behavioral disturbances in the NmU transgenic mice that could account for the results (e.g. changes in locomotor activity). When placed on a high-fat diet, transgenic mice remained lighter than wild-type mice and ate less, but gained weight at a rate similar to wild-type mice. Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide.

Age-progressing Cognitive Impairments and Neuropathology in Transgenic CRND8 Mice

Behavioural Brain Research. May, 2005  |  Pubmed ID: 15863231

Patients with Alzheimer's disease suffer from progressive cognitive impairments and show distinct post-mortem neuropathology, including beta-amyloid plaques. Transgenic (Tg) CRND8 mice carry a mutated human amyloid precursor protein gene and show age-related increases in beta-amyloid production and plaque deposition. It was previously reported that during the early stages of plaque deposition, Tg CRND8 mice demonstrated Morris maze impairments. However, it is unknown if Tg mice would be impaired at an earlier age prior to plaque deposition or more impaired at a later age with more extensive plaque deposition. In the current study, we describe Tg CRND8 age-progressing beta-amyloid neuropathology and cognitive abilities in greater detail. At all ages, Tg mice showed normal short-term memory in the Y-maze. Pre-plaque Tg and age-matched Non-Tg mice did not differ in learning the spatial Morris water maze. However, both early and late plaque Tg mice showed impairments during acquisition. In addition, although early plaque Tg mice performed well in the probe trial, late plaque Tg mice demonstrated impaired probe trial performance. Therefore compared to their Non-Tg littermates, Tg CRND8 mice demonstrate cognitive impairments that progressed with age and seemed to coincide with the onset of beta-amyloid plaque deposition.

The Influence of Smoking Imagery on the Smoking Intentions of Young People: Testing a Media Interpretation Model

The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine. Jun, 2005  |  Pubmed ID: 15901512

To assess a theoretical model of adolescents' exposure to films, perceptions of smoking imagery in film, and smoking intentions.

Benefits of and Barriers to Providing Smoking Treatment in Methadone Clinics: Findings from a National Study

The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. Jul-Sep, 2005  |  Pubmed ID: 16188716

Although smoking increases morbidity and mortality among patients in addictions clinics, few clinics provide routine smoking treatment. To understand staff attitudes toward treatment, we surveyed leaders of outpatient methadone treatment clinics nationwide. Our response rate was 59% (408/697). Most clinic leaders thought they should provide smoking treatment (76%) or refer patients for care (91%); however, fewer than half of these had provided treatment in the month prior to the survey. Leaders said smoking treatment would benefit their clinics, patients and communities, but said barriers-primarily insufficient staff training-prevented routine care. Addressing these barriers could increase smoking treatment in addictions clinics and save lives.

Integrated Recombinant Protein Expression and Purification Platform Based on Ralstonia Eutropha

Applied and Environmental Microbiology. Oct, 2005  |  Pubmed ID: 16204482

Protein purification of recombinant proteins constitutes a significant cost of biomanufacturing and various efforts have been directed at developing more efficient purification methods. We describe a protein purification scheme wherein Ralstonia eutropha is used to produce its own "affinity matrix," thereby eliminating the need for external chromatographic purification steps. This approach is based on the specific interaction of phasin proteins with granules of the intracellular polymer polyhydroxybutyrate (PHB). By creating in-frame fusions of phasins and green fluorescent protein (GFP) as a model protein, we demonstrated that GFP can be efficiently sequestered to the surface of PHB granules. In a second step, we generated a phasin-intein-GFP fusion, wherein the self-cleaving intein can be activated by the addition of thiols. This construct allowed for the controlled binding and release of essentially pure GFP in a single separation step. Finally, pure, active beta-galactosidase was obtained in a single step using the above described method.

Dual Pharmacotherapy and Motivational Interviewing for Tobacco Dependence Among Drug Treatment Patients

Journal of Addictive Diseases. 2005  |  Pubmed ID: 16368658

This pilot study is the first to examine the feasibility and outcomes of dual pharmacotherapy for smoking cessation among drug treatment patients. The intervention consisted of 7 weeks of bupropion (300 mg), 12 weeks of nicotine gum, and 6 sessions of motivational interviewing. The trial was conducted among 28 patients recruited from 5 methadone clinics and employed a pretest-posttest design. At 6 months post quit date, 14% of participants met criteria for biochemically-verified abstinence. Among those still smoking, number of cigarettes smoked decreased significantly and most (88%) had made at least 1 serious quit attempt. Participation rates were excellent and no adverse effects on alcohol or illicit drug use were found. Although not a definitive test of the intervention, findings suggest that a multi-component approach to tobacco dependence is feasible and potentially effective in helping drug treatment patients achieve smoking cessation well beyond the end of treatment and that a large-scale randomized trial is warranted.

Chronic Ethanol Ingestion Modulates Proanxiety Factors Expressed in Rat Central Amygdala

Alcohol (Fayetteville, N.Y.). Jun, 2005  |  Pubmed ID: 16396741

Withdrawal anxiety following chronic ethanol exposure is often associated with relapse in recovering alcoholics. It is likely that brain regions regulating anxiety-like behaviors adapt during chronic ethanol exposure to ultimately regulate such behaviors. The central amygdala contains numerous neurotransmitter systems that have been implicated in the regulation of anxiety-like behavior, including corticotropin releasing factor (CRF) and NMDA-type glutamate receptors. Chronic ethanol exposure causes functional adaptations in both CRF and NMDA receptors that are likely to regulate anxiety-like behaviors expressed during withdrawal. However, the molecular mechanisms governing these adaptations remain unexplored. We therefore evaluated these neurotransmitter systems in Sprague-Dawley rats during chronic ingestion of an ethanol-containing liquid diet. Quantitative real-time reverse transcription-PCR demonstrated that preproCRF mRNA was significantly upregulated by chronic ethanol exposure, whereas mRNA expression of CRF binding protein did not change. There were also no significant changes observed in any of the NMDA subunit mRNAs, although there was a trend toward greater NR2A mRNA expression during chronic ethanol exposure. Using Western blotting analysis we measured NMDA receptor subunit protein expression. Chronic ethanol exposure did not affect protein levels of the NR1 and NR2B subunits. Like the mRNA measures, chronic ethanol exposure did influence NR2A protein levels but the effects were modest. Our results demonstrate that NMDA receptor subunit mRNA and protein expressions are not strongly influenced by exposure to chronic ethanol. This suggests that the functional NMDA receptor adaptations identified in previous studies [Roberto, M., Schweitzer, P., Madamba, S. G., Stouffer, D. G., Parsons, L. H., & Siggins, G. R. (2004). Acute and chronic ethanol exposure alter glutamatergic transmission in rat central amygdala: an in vitro and in vivo analysis. J Neurosci 24, 1594-1603] are likely to be mediated by post-translational events. In contrast, enhanced levels of CRF during/after chronic ethanol exposure are likely to be mediated by increased levels of prepro CRF mRNA. Together, our findings suggest that adaptations to chronic ethanol exposure by proanxiety factors expressed in the central nucleus appear to be mediated by distinct cellular and molecular mechanisms.

Inaccessible Hydroxyl Groups on Silica Are Accessible in Supercritical CO2

The Journal of Physical Chemistry. B. May, 2005  |  Pubmed ID: 16852060

The three main types of hydroxyl groups on a silica surface are classified as isolated, hydrogen bonded, and inaccessible. The isolated and hydrogen bonded groups are the most important as these readily exchange with D(2)O and thus are exposed to reactant molecules. However, it has generally been accepted that the inaccessible groups do not participate in surface reactions as only a small fraction of these groups exchange with D(2)O. It is shown that the inaccessible hydroxyl groups on nonporous fumed silica and mesoporous MCM-48 silica powders and films fully exchange with D(2)O and are reactive with octadecylydimethylchlorosilane when supercritical CO(2) is used as the solvent. Furthermore, it is found that the CO(2) penetrating the regions containing the inaccessible groups is not removed by simple evacuation but rather slowly diffuses from the silica over periods of months.

Characterization of the Nociceptin Receptor (ORL-1) Agonist, Ro64-6198, in Tests of Anxiety Across Multiple Species

Psychopharmacology. Oct, 2005  |  Pubmed ID: 16025321

Previous studies have demonstrated behaviors indicative of anxiolysis in rats pretreated with the nociceptin receptor (opioid receptor like-1, ORL-1) agonist, Ro64-6198.

Community-acquired Pneumonia Guidelines and Resident Behavior

The American Journal of Medicine. Aug, 2005  |  Pubmed ID: 16084192

A Simple FTIR Technique for Estimating the Surface Area of Silica Powders and Films

Journal of Colloid and Interface Science. Mar, 2006  |  Pubmed ID: 16125717

A simple technique using FTIR spectroscopy to estimate the surface area of porous and non-porous silica powders is presented. The surface area is estimated by comparing the integrated area of the band due to isolated silanol groups on different silicas. We have found that by using a fumed silica as a calibrant, an accuracy of about 7% in the surface area of several silica materials is obtained when compared to the surface area computed by BET nitrogen adsorption techniques. The FTIR technique for computing surface area is simple and takes very little time to complete the analysis. The principle advantage of this method is that it enables surface area measurements of silica films on porous supports. To the best of our knowledge, there are no other methods that provide this information.

Training of Staff for the Delivery of PET/CT Services in the UK

Nuclear Medicine Communications. Dec, 2006  |  Pubmed ID: 17088687

Evidence for the cost effectiveness of PET/CT imaging is now driving the widespread introduction of PET/CT services throughout the UK. The provision of PET/CT facilities will require a workforce of medical, scientific, technical and engineering staff who are adequately trained and fit for purpose. Suitably trained staff in this speciality are scarce. The development and accreditation of training courses and other educational resources for training programmes in all disciplines will therefore be required at a national and regional level. The implementation of PET/CT training can be achieved more cost-effectively by developing multi-professional learning resources whenever possible. It is intended that the recommendations would be implemented by close co-operation of both public and private healthcare providers together with educational establishments.

Ethanol-induced Regulation of GABA-A Subunit MRNAs in Prefrontal Fields of Cynomolgus Monkeys

Alcoholism, Clinical and Experimental Research. Dec, 2006  |  Pubmed ID: 17117962

Recent evidence indicates that functional impairment of the orbital and medial fields of the prefrontal cortex may underlie the deficits in executive control of behavior that characterize addictive disorders, including alcohol addiction. Moreover, previous studies have indicated that alcohol alters GABA neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting the GABA(A) receptor complex. Given that GABAergic transmission has an integral role in cortical processing, influencing local and interregional communication, understanding alcohol-induced alterations in GABA(A) receptors in prefrontal fields of the primate brain may provide insight into the functional impairment of these brain regions in the alcohol-addicted state and extend our understanding of the molecular consequences of long-term use in these critical brain regions.

Positron Emission Tomography Scans in Postchemotherapy Seminoma Patients with Residual Masses: a Retrospective Review from Indiana University Hospital

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. Dec, 2006  |  Pubmed ID: 17135635

Diagnosis and Management of Cough Executive Summary: ACCP Evidence-based Clinical Practice Guidelines

Chest. Jan, 2006  |  Pubmed ID: 16428686

Global Physiology and Pathophysiology of Cough: ACCP Evidence-based Clinical Practice Guidelines

Chest. Jan, 2006  |  Pubmed ID: 16428691

The anatomy and neurophysiology of cough has been reviewed in the preceding section. The objective of this section is to describe how the varied anatomic components of the respiratory system work in concert to produce an effective cough.

Nonpharmacologic Airway Clearance Therapies: ACCP Evidence-based Clinical Practice Guidelines

Chest. Jan, 2006  |  Pubmed ID: 16428718

Airway clearance may be impaired in disorders associated with abnormal cough mechanics, altered mucus rheology, altered mucociliary clearance, or structural airway defects. A variety of interventions are used to enhance airway clearance with the goal of improving lung mechanics and gas exchange, and preventing atelectasis and infection.

An Event-based Approach for Examining the Effects of Wildland Fire Decisions on Communities

Environmental Management. Apr, 2006  |  Pubmed ID: 16465562

Public concern over the consequences of forest fire to wildland interface communities has led to increased resources devoted to fire suppression, fuel treatment, and management of fire events. The social consequences of the decisions involved in these and other fire-related actions are largely unknown, except in an anecdotal sense, but do occur at a variety of temporal and social organizational scales. These consequences are not limited to the fire event itself. Preparation for the possibility of a fire, actions that suppression agencies take during a fire, and postfire decisions all have consequences, if unknown currently. This article presents an "event-based" approach that can be useful for constructing and systematic discussion about the consequences of wildland fire to human communities. For each of the three major periods within this approach, agencies, communities, and individuals make decisions and take actions that have consequences. The article presents an integrated, temporally based process for examining these consequences, which is similar to others developed in the natural hazards and disaster management literature.

Safety Of, and Biological and Functional Response To, a Novel Metallic Implant for the Management of Focal Full-thickness Cartilage Defects: Preliminary Assessment in an Animal Model out to 1 Year

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. May, 2006  |  Pubmed ID: 16609973

Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC) can cause pain and functional impairment. Affected middle-aged patients respond unpredictably to existing treatments and knee arthroplasty may be required, prompting risk of revision. This study assesses the safety of, and biological and functional response to, a metallic resurfacing implant which may delay or obviate the need for traditional arthroplasty. The anatomic contour of the surgically exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full-thickness osteochondral defect was created. An anchor-based Co-Cr resurfacing implant, matching the mapped articular contour, was implanted. Each goat's contralateral unoperated femorotibial joint was used as a control. Postoperative outcome was assessed by lameness examination, radiography, arthroscopy, synoviocentesis, necropsy, and histology up to 26 (n = 3) or 52 (n = 3) weeks. By postoperative week (POW) 4, goats demonstrated normal range of motion, no joint effusion, and only mild lameness in the operated limb. By POW 26 the animals were sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed moderate synovial inflammation and a chondral membrane extending centrally across the implant surface. Radiographs at POWs 14 to 52 implied implant stability in the operated joints, as well as subchondral bone remodeling and mild exostosis formation in the operated and contralateral unoperated joints of some goats. By POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26 and 52 MFC cartilage was metachromatic and intact in the operated and unoperated femorotibial joints. Proximal tibiae of some operated and unoperated limbs demonstrated limited subchondral bone remodeling and foci of articular cartilage fibrillation and thinning. The chondral membrane crossing the prosthesis possessed a metachromatic matrix containing singular and clustered chondrocytes. Our data imply the safety, biocompatibility, and functionality of the implant. Focal articular damage was documented in the operated joints at POWs 26 and 52, but lesions were much reduced over those previously reported in untreated defects. Expanded animal or preclinical human studies are justified.

Distinct Functional Characteristics of the Lateral/basolateral Amygdala GABAergic System in C57BL/6J and DBA/2J Mice

The Journal of Pharmacology and Experimental Therapeutics. Aug, 2006  |  Pubmed ID: 16651400

It is generally understood that genetic mechanisms contribute to pathological anxiety and that C57BL/6 (B6) and DBA/2J (D2) mice, inbred strains differing markedly in their anxiety-like behaviors, may represent a model system to study these contributions. Because lateral/basolateral amygdala (BLA) GABA(A) receptors help regulate anxiety-like behaviors, we have tested the hypothesis that differences in receptor function/expression may be related to strain-specific differences in experimentally measured anxiety. First, we demonstrated that anxiety-like behaviors in two separate assays were more substantial in D2 mice. Then, using whole-cell electrophysiology of isolated neurons, we found that D2 BLA neurons expressed significantly greater GABA-gated responses than B6 BLA neurons. This was specific for GABA(A) receptors, because N-methyl-d-aspartate-gated responses were similar between strains. At the molecular level, this increased GABA(A) function was associated with higher levels of alpha 2 subunit mRNA expression in D2 BLA. Finally, to understand the ramifications of these functional and molecular biological differences, we examined both electrically evoked GABAergic responses and spontaneous synaptic currents using whole-cell recordings with in vitro slice preparations. Presynaptic GABAergic function was more robust in D2 compared with B6 slices. Together, our findings suggest that genetic mechanisms differentially represented in these two inbred mouse strains lead to robust differences in pre- and postsynaptic aspects of amygdala GABAergic function.

The Native T-type Calcium Current in Relay Neurons of the Primate Thalamus

Neuroscience. Aug, 2006  |  Pubmed ID: 16690211

The generation of thalamic bursts depends upon calcium currents that flow through transiently open (T)-type calcium channels. In this study, we characterized the native T-type calcium current underlying thalamic burst responses in the macaque monkey. Current clamp recordings from lateral geniculate nucleus (LGN) slices showed characteristic burst responses when relay cells were depolarized from relatively hyperpolarized membrane potentials. These bursts could also be elicited by stimulation of excitatory synaptic inputs to LGN cells. Under voltage clamp conditions, the inactivation kinetics of native currents recorded from primate LGN neurons showed consistency with T-type currents recorded in other mammals and in expression systems. Real-time reverse transcriptase PCR performed on RNA isolated from the LGN (including tissues isolated from magnocellular and parvocellular laminae) detected voltage-dependent calcium channel (Ca(v)) 3.1, Ca(v) 3.2, and Ca(v) 3.3 channel transcripts. Ca(v) 3.1 occurred at relatively higher expression than other isoforms, consistent with in situ hybridization studies in rats, indicating that the molecular basis for burst firing in thalamocortical systems is an important conserved property of primate physiology. Since thalamic bursts have been observed during visual processing as well as in a number of CNS disorders, studies of the expression and modulation of these currents at multiple levels are critical for understanding their role in vision and for the discovery of new treatments for disruptions of thalamic rhythms.

Dynamic Changes in Histone H3 Phosphoacetylation During Early Embryonic Stem Cell Differentiation Are Directly Mediated by Mitogen- and Stress-activated Protein Kinase 1 Via Activation of MAPK Pathways

The Journal of Biological Chemistry. Jul, 2006  |  Pubmed ID: 16728397

Embryonic stem (ES) cells are pluripotent cells capable of unlimited self-renewal and differentiation into the three embryonic germ layers under appropriate conditions. Mechanisms for control of the early period of differentiation, involving exit from the pluripotent state and lineage commitment, are not well understood. An emerging concept is that epigenetic histone modifications may play a role during this early period. We have found that upon differentiation of mouse ES cells by removal of the cytokine leukemia inhibitory factor, there is a global increase in coupled histone H3 phosphorylation (Ser-10)-acetylation (Lys-14) (H3 phosphoacetylation). We show that this occurs through activation of both the extracellular signal-regulated kinase (ERK) and p38 MAPK signaling pathways. Early ES cell differentiation is delayed using pharmacological inhibitors of the ERK and p38 pathways. One common point of convergence of these pathways is the activation of the mitogen- and stress-activated protein kinase 1 (MSK1). We show here that MSK1 is the critical mediator of differentiation-induced H3 phosphoacetylation using both the chemical inhibitor H89 and RNA interference. Interestingly, inhibition of H3 phosphoacetylation also alters gene expression during early differentiation. These results point to an important role for both epigenetic histone modifications and kinase pathways in modulating early ES differentiation.

Silk Based Biomaterials to Heal Critical Sized Femur Defects

Bone. Oct, 2006  |  Pubmed ID: 16757219

Bone auto- and allografts have inherent drawbacks, therefore the treatment of non-unions and critical size defects in load bearing long bones would benefit from the use of osteopromotive biodegradable, biocompatible and mechanically durable matrices to enhance migration or delivery of cell populations and/or morphogens/cytokines. Silk fibroin biomaterial scaffolds were evaluated as osteopromotive matrices in critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over 8 weeks in vivo: silk scaffolds (SS) with human mesenchymal stem cells (hMSCs) that had previously been differentiated along an osteoblastic lineage in vitro (group I; pdHMSC/SS); SS with undifferentiated hMSCs (group II; udHMSC/SS); SS alone (group III; SS); and empty defects (group IV). When hMSCs were cultured in vitro in osteogenic medium for 5 weeks, bone formation was characterized with bimodal peak activities for alkaline phosphatase at 2 and 4 weeks. Calcium deposition started after 1 week and progressively increased to peak at 4 weeks, reaching cumulative levels of deposited calcium at 16 mug per mg scaffold wet weight. In vivo osteogenesis was characterized by almost bridged defects with newly formed bone after 8 weeks in group I. Significantly (P < 0.01) greater bone volumes were observed with the pdHMSC/SS (group I) implants than with groups II, III or IV. These three groups failed to induce substantial new bone formation and resulted in the ingrowth of cells with fibroblast-like morphology into the defect zone. The implantation of pdHMSC/SS resulted in significantly (P < 0.05) greater maximal load and torque when compared to the other treatment regimens. The pdHMSC/SS implants demonstrated osteogenic ability in vitro and capacity to thrive towards the healing of critical size femoral segmental defects in vivo. Thus, these new constructs provide an alternative protein-based biomaterial for load bearing applications.

The Role of Histone Acetylation in Regulating Early Gene Expression Patterns During Early Embryonic Stem Cell Differentiation

The Journal of Biological Chemistry. Mar, 2007  |  Pubmed ID: 17204470

We have examined the role of histone acetylation in the very earliest steps of differentiation of mouse embryonic stem cells in response to withdrawal of leukemia inhibitory factor (LIF) as a differentiation signal. The cells undergo dramatic changes in morphology and an ordered program of gene expression changes representing differentiation to all three germ layers over the first 3-5 days of LIF withdrawal. We observed a global increase in acetylation on histone H4 and to a lesser extent on histone H3 over this time period. Treatment of the cells with trichostatin A (TSA), a histone deacetylase inhibitor, induced changes in morphology, gene expression, and histone acetylation that mimicked differentiation induced by withdrawal of LIF. We examined localized histone acetylation in the regulatory regions of genes that were transcriptionally either active in undifferentiated cells, induced during differentiation, or inactive under all treatments. There was striking concordance in the histone acetylation patterns of specific genes induced by both TSA and LIF withdrawal. Increased histone acetylation in local regions correlated best with induction of gene expression. Finally, TSA treatment did not support the maintenance or progression of differentiation. Upon removal of TSA, the cells reverted to the undifferentiated phenotype. We concluded that increased histone acetylation at specific genes played a role in their expression, but additional events are required for maintenance of differentiated gene expression and loss of the pluripotent state.

Strychnine and Taurine Modulation of Amygdala-associated Anxiety-like Behavior is 'state' Dependent

Behavioural Brain Research. Mar, 2007  |  Pubmed ID: 17207866

Strychnine-sensitive glycine receptors are expressed in many adult forebrain regions, yet the biological function of these receptors outside the spinal cord/brainstem is poorly understood. We have recently shown that rat lateral/basolateral amygdala neurons express strychnine-sensitive glycine-gated currents whose pharmacological and molecular characteristics are consistent with those established for classic ligand-gated chloride channels. The current studies were undertaken to establish the behavioral role, if any, of these strychnine-sensitive glycine receptors. Adult Long-Evans male rats were implanted with guide cannulae targeted at the lateral amygdala and were microinjected with standard artificial cerebrospinal fluid with or without various doses of strychnine or taurine. Anxiety-like behaviors were assessed with the elevated plus maze or the light/dark box. In the elevated plus maze, strychnine decreased closed-arm time and increased open-arm time, suggestive of an anxiolytic effect. Similarly, strychnine produced a modest anxiolytic effect in the light/dark box. Post hoc analysis of 'open-arm' time and 'light-side' time indicated that aCSF-treated animals were distributed into two apparent groups that displayed either high or low amounts of anxiety-like behavior in a given apparatus. Surprisingly, the pharmacological effects of both strychnine and taurine in these assays were dependent upon a given animal's behavioral phenotype. Together, these findings are significant because they suggest that the basal 'emotional state' of the animal could influence the behavioral outcome associated with drug application directly into the lateral/basolateral amygdala. Furthermore, our findings also suggest that compounds acting at amygdala strychnine-sensitive glycine receptors may actively modulate this basal anxiety-like state.

Long-term Ethanol Self-administration by the Nonhuman Primate, Macaca Fascicularis, Decreases the Benzodiazepine Sensitivity of Amygdala GABA(A) Receptors

Alcoholism, Clinical and Experimental Research. Jun, 2007  |  Pubmed ID: 17428292

Rodent models of chronic alcohol exposure are typically constrained to relatively short periods of forced ethanol due to the lifespan of these animals. Nonhuman primate models, particularly those employing long-term self-administration, are conceptually more similar to human alcoholic individuals.

Effects of Chronic Alcohol Exposure on Dopamine Uptake in Rat Nucleus Accumbens and Caudate Putamen

Psychopharmacology. Sep, 2007  |  Pubmed ID: 17492432

Existing data strongly suggest that alcohol affects dopamine (DA) neurotransmission in the brain. However, many questions remain about the effects of alcohol on the delicate equilibrium between such neurochemical processes as DA release and uptake. Dysregulation of these processes in the mesolimbic and nigrostriatal systems after chronic alcohol ingestion could be a neuroadaptation contributing to dependence.

BMP-silk Composite Matrices Heal Critically Sized Femoral Defects

Bone. Aug, 2007  |  Pubmed ID: 17553763

Clinical drawbacks of bone grafting prompt the search for alternative bone augmentation technologies such as use of growth and differentiation factors, gene therapy, and cell therapy. Osteopromotive matrices are frequently employed for the local delivery and controlled release of these augmentation agents. Some matrices also provide an osteoconductive scaffold to support new bone growth. In this study, silkworm-derived silk fibroin was evaluated as an osteoconductive matrix for healing critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over eight weeks: silk scaffolds (SS) with recombinant human BMP-2 (rhBMP-2) and human mesenchymal stem cells (HMSC) that had been pre-differentiated along an osteoblastic lineage ex vivo (Group I; pdHMSC/rhBMP-2/SS); SS with rhBMP-2 and undifferentiated HMSCs (Group II; udHMSC/rhBMP-2/SS); SS and rhBMP-2 alone (Group III; rhBMP-2/SS); and empty defects (Group IV). Bi-weekly radiographs revealed a progressive and similar increase in Group I-III mean defect mineralization through post-operative week (POW) 8. Radiographs, dual energy x-ray absorptiometry, and micro-computed tomography confirmed that Groups I-III exhibited similar substantial and significantly (p<0.05) greater defect mineralization at POW 8 than the unfilled Group IV defects which remained void of bone. No significant differences in Groups I-III defect healing at POW 8 were apparent using these same assays or mechanical testing. Histology at POW 8 revealed moderately good bridging of the parent diaphyseal cortices with woven and lamellar bone bridging islands of silk matrix in Groups I and III. Group II defects possessed comparatively less new bone which was most abundant adjacent to the parent bone margins. Elsewhere the silk matrix was more often enveloped by poorly differentiated loose fibrous connective tissue. Group IV defects showed minimal new bone formation. None of the treatment groups attained the mean mineralization or the mean biomechanical strength of identical defects implanted with SS and pdHMSCs alone in a previous study. However, addition of rhBMP-2 to SS prompted more bone than was previously generated using udHMSC/SS or SS alone. These data imply the clinical potential of silk scaffolds and rhBMP-2 as composite osteopromotive implants when used alone or with select stem cell populations. Additional studies in larger species are now warranted.

The Role of Litigation in Midwifery Practice in the United States: Results from a Nationwide Survey of Certified Nurse-midwives/certified Midwives

Journal of Midwifery & Women's Health. Sep-Oct, 2007  |  Pubmed ID: 17826708

Professional liability litigation is playing an increasing role in the practice of women's health care in this country. Although the impact of litigation on obstetricians' practices has been widely documented, data on the effect of litigation on midwifery practice are scant. The authors conducted a nationwide Web-based survey of American College of Nurse-Midwives (ACNM) members about the experience of being involved in litigation. The survey was completed by 600 midwives (17.5% response rate). Of those midwives completing the survey, 152 (25.3%) had been named in a lawsuit at least once during their midwifery careers. The litigation cases had been resolved for 114 (75%) of these respondents at the time of the survey. Forty-one (36%) reported being dropped from the case, even though the litigation continued without their involvement. Another 54 individuals (47.4%) were involved in cases that were settled before going to court, and an additional 10 cases (8.8%) were dropped without a settlement. Of the nine lawsuits (7.9%) that went to court, four favored the plaintiff (3.5%) and five (4.4%) favored the defendant. Future surveys are needed to better define the relationship between the practices of midwives and medical malpractice litigation.

The Evolution of Internet-based Map Server Applications in the United States Department of Agriculture, Veterinary Services

Veterinaria Italiana. Jul-Sep, 2007  |  Pubmed ID: 20422551

The internet is used increasingly as an effective means of disseminating information. For the past five years, the United States Department of Agriculture (USDA) Veterinary Services (VS) has published animal health information in internet-based map server applications, each oriented to a specific surveillance or outbreak response need. Using internet-based technology allows users to create dynamic, customised maps and perform basic spatial analysis without the need to buy or learn desktop geographic information systems (GIS) software. At the same time, access can be restricted to authorised users. The VS internet mapping applications to date are as follows: Equine Infectious Anemia Testing 1972-2005, National Tick Survey tick distribution maps, the Emergency Management Response System-Mapping Module for disease investigations and emergency outbreaks, and the Scrapie mapping module to assist with the control and eradication of this disease. These services were created using Environmental Systems Research Institute (ESRI)'s internet map server technology (ArcIMS). Other leading technologies for spatial data dissemination are ArcGIS Server, ArcEngine, and ArcWeb Services. VS is prototyping applications using these technologies, including the VS Atlas of Animal Health Information using ArcGIS Server technology and the Map Kiosk using ArcEngine for automating standard map production in the case of an emergency.

Chronic Ethanol and Withdrawal Differentially Modulate Pre- and Postsynaptic Function at Glutamatergic Synapses in Rat Basolateral Amygdala

Journal of Neurophysiology. Dec, 2007  |  Pubmed ID: 17898152

Withdrawal anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is long-lasting, can manifest well after the overt physical symptoms of withdrawal, and is frequently associated with relapse in recovering alcoholics. The neurobiological mechanisms governing these withdrawal-associated increases in anxiety are currently unknown. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates the expression of both learned fear and anxiety. Neurotransmitter system alterations within this brain region may therefore contribute to withdrawal-associated anxiety. Because evidence suggests that glutamate-gated neurotransmitter receptors are sensitive to acute ethanol exposure, we examined the effect of chronic intermittent ethanol (CIE) and withdrawal (WD) on glutamatergic synaptic transmission in the BLA. We found that slices prepared from CIE and WD animals had significantly increased contributions by synaptic NMDA receptors. In addition, CIE increased the amplitude of AMPA-receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs), whereas only WD altered the amplitude and kinetics of tetrodotoxin-resistant spontaneous events (mEPSCs). Similarly, the frequency of sEPSCs was increased in both CIE and WD neurons, although only WD increased the frequency of mEPSCs. These data suggest that CIE and WD differentially alter both pre- and postsynaptic properties of BLA glutamatergic synapses. Finally, we show that microinjection of the AMPA-receptor antagonist, DNQX, can attenuate withdrawal-related anxiety-like behavior. Together, our results suggest that increased glutamatergic function may contribute to anxiety expressed during withdrawal from chronic ethanol.

Respiratory Muscle Strength in the Physically Active Elderly

Lung. Dec, 2007  |  Pubmed ID: 17917778

Advancing age is associated with a decline in the strength of the skeletal muscles, including those of respiration. Respiratory muscles can be strengthened with nonrespiratory activities. We therefore hypothesized that regular exercise in the elderly would attenuate this age-related decline in respiratory muscle strength. Twenty-four healthy subjects older than 65 years were recruited (11 males and 13 females). A comprehensive physical activity survey was administered, and subjects were categorized as active (n = 12) or inactive (n = 12). Each subject underwent testing of maximum inspiratory and expiratory pressures (PI(max) and PE(max)). Diaphragmatic thickness (tdi) was measured via two-dimensional B-mode ultrasound. There were no significant differences between the active and inactive groups with respect to age (75 vs. 73 years) or body weight (69.1vs. 69.9 kg). There were more women (9) than men (3) in the inactive group. Diaphragm thickness was greater in the active group (0.31 +/- 0.06 cm vs. 0.25 +/- 0.04 cm; p = 0.011). PE(max) and PI(max) were also greater in the active group (130 +/- 44 cm H(2)O vs. 80 +/- 24 cm H(2)O; p = 0.002; and 99 +/- 32 cm H(2)O vs. 75 +/- 14 cm H(2)O; p = 0.03). There was a positive association between PI(max )and tdi (r = 0.43, p = 0.03). Regular exercise was positively associated with diaphragm muscle thickness in this cohort. As PE(max) was higher in the active group, we postulate that recruitment of the diaphragm and abdominal muscles during nonrespiratory activities may be the source of this training effect.

Measurement of Drug Agglomerates in Powder Blending Simulation Samples by Near Infrared Chemical Imaging

International Journal of Pharmaceutics. Feb, 2008  |  Pubmed ID: 17951017

This research note describes a powder blending simulation study conducted using 20-mL scintillation vials and a bench-top rotating mixer on a scale of 2g for each sample. In order to investigate the impact of mean particle size and size distribution on blending behavior of an active pharmaceutical ingredient (API), the drug substance was separated into sieve fractions using the US standard sieves of 60, 80, 100, 200, and 325mesh. Each of the fractions was mixed with two excipients (hydroxypropyl methylcellulose and microcrystalline cellulose) for up to 20min. Then the blending samples were analyzed by a near infrared chemical imaging (NIR-CI) system. The NIR-CI system was able to measure API particles/domains (agglomerates) at 0.001mm(2) and above within a 11.2mmx9.0mm field of view. It was found that blends prepared with larger API particles (60-200 mesh) contain agglomerated API domains > or =0.1mm(2). The blends prepared with finer API particles (< or =325 mesh) show the characteristics of a randomized mixing. This simple and effective method can be used for evaluation of blending behavior for APIs in formulation development.

Monitoring Recovery from Diaphragm Paralysis with Ultrasound

Chest. Mar, 2008  |  Pubmed ID: 18198248

Diaphragmatic paralysis is an uncommon, yet underdiagnosed cause of dyspnea. Data regarding the time course and potential for recovery has come from a few small case series. The methods that have been traditionally employed to diagnose diaphragmatic weakness or paralysis are either invasive or limited in sensitivity and specificity. A new technique utilizing two-dimensional, B-mode ultrasound (US) measurements of diaphragm muscle thickening during inspiration (Deltatdi%) has been validated in the diagnosis of diaphragm paralysis (DP). The purpose of this study was to assess whether serial US evaluation might be utilized to monitor the potential recovery of diaphragm function.

Cough, Basic Science, and the Clinician

Lung. Mar-Apr, 2008  |  Pubmed ID: 18311504

Cough is a major cause of disability and distress worldwide. In June 2007, the First American Cough Conference was held in New York City and covered a spectrum of topics of interest to the basic scientist as well as the clinician. The conference was organized by Dr. Peter Dicpinigaitis and its proceedings are published in the February Supplement of LUNG. This supplement consists of a series of articles that provide a valuable overview of recent advances in our understanding of mechanism, etiology, and treatment of cough and constitute an adjunct to the guidelines recently published by the American College of Chest Physicians, the British Thorax Society, the European Respiratory Society, and the Japanese Respiratory Society.

The Impact of Scientific Information on Ecosystem Management: Making Sense of the Contextual Gap Between Information Providers and Decision Makers

Environmental Management. May, 2008  |  Pubmed ID: 18330619

Scientific information is not always effectively incorporated into decision-making processes. This phenomenon seems to hold even when the information is aligned with an articulated need, is generated according to sound scientific procedures, and is packaged with end-user preferences in mind. We propose that contextual or cultural differences contribute significantly to the misalignment in communication between those who generate information and those who seek information for improved management of natural resources. The solution is to cultivate shared understanding, which in turn relies on acknowledgment and sharing of diverse values and attitudes. This constitutes a difficult challenge in a culturally diverse environment. Whereas cultural diversity represents wealth in experiences, knowledge and perspectives it can constrain the potential to develop the shared understandings necessary for effective integration of new information. This article illustrates how a lack of shared understanding among participants engaged in a resource-management process can produce and perpetuate divergent views of the world, to the extent that information and knowledge flows are ineffective and scientific information, even when requested, cannot be used effectively. Four themes were distilled from interviews with management and scientific staff of a natural resource-management agency in South Africa. The themes are used to illustrate how divergent views embedded in different cultures can discourage alignment of effort toward a common purpose. The article then presents a sense-making framework to illustrate the potential for developing shared understandings in a culturally diverse world.

Light Curable Dental Composites Designed with Colloidal Crystal Reinforcement

Dental Materials : Official Publication of the Academy of Dental Materials. Dec, 2008  |  Pubmed ID: 18499245

Methods to prepare dental composites with a periodic filler arrangement were developed following a strategy of colloidal crystallization. The aims of this study were to determine the influence of suspension medium, silane treatment and amine additive on colloidal particle redispersion and subsequent ordering, and to evaluate the effect of filler ordering on mechanical properties of composites.

Tetracycline Effects on Candida Albicans Virulence Factors

Infectious Diseases in Obstetrics and Gynecology. 2008  |  Pubmed ID: 18528520

To determine if tetracycline, previously reported to increase the probability of developing symptomatic vaginal yeast infections, has a direct effect on Candida albicans growth or induction of virulent phenotypes.

Domiciliary Humidification Improves Lung Mucociliary Clearance in Patients with Bronchiectasis

Chronic Respiratory Disease. 2008  |  Pubmed ID: 18539721

Inspired air humidification has been reported to show some benefit in bronchiectatic patients. We have investigated the possibility that one effect might be to enhance mucociliary clearance. Such enhancement might, if it occurs, help to lessen the risks of recurrent infective episodes. Using a radioaerosol technique, we measured lung mucociliary clearance before and after 7 days of domiciliary humidification. Patients inhaled high flow saturated air at 37 degrees C via a patient-operated humidification nasal inhalation system for 3 h per day. We assessed tracheobronchial mucociliary clearance from the retention of (99m)Tc-labelled polystyrene tracer particles monitored for 6 h, with a follow-up 24-h reading. Ten out of 14 initially recruited patients (age 37-75 years; seven females) completed the study (two withdrew after their initial screening and two prior to the initial clearance test). Seven patients studied were non-smokers; three were ex-smokers (1-9 pack-years). Initial tracer radioaerosol distribution was closely similar between pre- and post-treatment. Following humidification, lung mucociliary clearance significantly improved, the area under the tracheobronchial retention curve decreased from 319 +/- 50 to 271 +/- 46%h (p < 0.07). Warm air humidification treatment improved lung mucociliary clearance in our bronchiectatic patients. Given this finding plus increasing laboratory and clinical interest in humidification mechanisms and effects, we believe further clinical trials of humidification therapy are desirable, coupled with analysis of humidification effects on mucus properties and transport.

Registered Dietitians' Coding Practices and Patterns of Code Use

Journal of the American Dietetic Association. Jul, 2008  |  Pubmed ID: 18589037

Coding, coverage, and reimbursement are vital to the clinical segment of our profession. The objective of this study was to assess understanding and use of the medical nutrition therapy (MNT) procedure codes. Its design was a targeted, cross-sectional, Internet survey. Participants were registered dietitians (RDs) preselected based on Medicare Part B provider status, randomly selected RDs from the American Dietetic Association database based on clinical practice designation, and self-selected RDs. Parameters assessed were knowledge and use of existing MNT and/or alternative procedure codes, barriers to code use/compensation, need for additional codes for existing/emerging services, and practice demographics. Results suggest that MNT is being reimbursed for a variety of diseases and conditions. Many RDs working in clinic settings are undereducated about code use of any kind, reporting that code selection frequently is determined not by the RD providing the service, but by "someone else." Self-employed RDs are less likely to rely on others to administrate paperwork required for reimbursement, including selection of procedure codes for billable nutrition services. Self-employed RDs are more likely to be reimbursed by private or commercial payers and RDs working in clinic settings are more likely to be reimbursed by Medicare; however, the proportion of Medicare providers in both groups is high. RDs must be knowledgeable and accountable for both the business and clinical side of their nutrition practices; using correct codes and following payers' claims processing policies and procedures. This survey and analysis is a first step in understanding the complex web of relationships between clinical practice, MNT code use, and reimbursement.

Mechanical Ventilation and Disuse Atrophy of the Diaphragm

The New England Journal of Medicine. Jul, 2008  |  Pubmed ID: 18596279

Reverse Osmosis Desalting of Inland Brackish Water of High Gypsum Scaling Propensity: Kinetics and Mitigation of Membrane Mineral Scaling

Environmental Science & Technology. Jun, 2008  |  Pubmed ID: 18605546

The potential for mineral scaling that may limit the generation of new potable water resources by reverse osmosis (RO), from inland brackish water of high gypsum scaling propensity, was experimentally explored via flux decline measurements and real-time RO membrane surface imaging. Antagonistic gypsum and calcium carbonate scaling kinetics were demonstrated for high-sulfate brackish water desalting. RO scaling studies with brackish water from the California San Joaquin Valley (approximately 10 000 mg/L total dissolved solids) revealed that membrane gypsum scaling was increasingly retarded with rising bicarbonate concentrations. Crystal growth rate, fractional membrane scale coverage, and flux decline decreased by up to about 63, 78, and 73%, respectively, as the bicarbonate concentration increased, at the membrane surface, from < 0.01 to 7.81 mM, for a gypsum saturation index of 2. Inhibition of gypsum crystal growth was attributed to bicarbonate adsorption onto the crystal surfaces, and CaCO3 scaling was undetected even up to a calcite saturation index of approximately 16. Given the suppression of gypsum scaling by bicarbonate, it is essential to considerthis effect in the conventional practice of pH adjustment to suppress CaCO3 scaling. The present results suggest that antagonistic and synergistic mineral crystallization kinetics effects are important for optimizing scale-control strategies (e.g., acid and antiscalants addition to the RO feed).

Ethanol Inhibition of Kainate Receptor-mediated Excitatory Neurotransmission in the Rat Basolateral Nucleus of the Amygdala

Neuropharmacology. Oct, 2008  |  Pubmed ID: 18617194

The neurobiological mechanisms governing alcohol-induced alterations in anxiety-like behaviors are not fully understood. Given that the amygdala is a major emotional center in the brain and regulates the expression of both learned fear and anxiety, neurotransmitter systems within the basolateral amygdala represent likely mechanisms governing the anxiety-related effects of acute ethanol exposure. It is well established that, within the glutamatergic system, N-methyl-d-aspartate (NMDA)-type receptors are particularly sensitive to intoxicating concentrations of ethanol. However, recent evidence suggests that kainate-type glutamate receptors are sensitive to ethanol as well. Therefore, we examined the effect of acute ethanol on kainate receptor (KA-R)-mediated synaptic transmission in the basolateral amygdala (BLA) of Sprague-Dawley rats. Acute ethanol decreased KA-R-mediated excitatory postsynaptic currents (EPSCs) in the BLA in a concentration-dependent manner. Ethanol also inhibited currents evoked by focal application of the kainate receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), and ethanol inhibition of kainate EPSCs was not associated with a change in paired-pulse ratio, suggesting a postsynaptic mechanism of ethanol action. The neurophysiological consequences of this acute sensitivity were tested by measuring ethanol's effects on KA-R-dependent modulation of synaptic plasticity. Acute ethanol, like the GluR5-specific antagonist (R,S)-3-(2-carboxybenzyl)willardiine (UBP 296), robustly diminished ATPA-induced increases in synaptic efficacy. Lastly, to better understand the relationship between KA-R activity and anxiety-like behavior, we bilaterally microinjected ATPA directly into the BLA. We observed an increase in measures of anxiety-like behavior, assessed in the light/dark box, with no change in locomotor activity. This evidence suggests that kainate receptors in the BLA are inhibited by pharmacologically relevant concentrations of ethanol and may contribute to some of the acute anxiolytic effects of this drug.

Symptoms of Attention-deficit/hyperactivity Disorder, Overeating, and Body Mass Index in Men

Eating Behaviors. Dec, 2008  |  Pubmed ID: 18928919

The high prevalence of obesity currently poses a global health crisis. Previous research has identified a novel link between obesity and Attention-Deficit/Hyperactivity Disorder (AD(H)D). Davis, Levitan, Smith, Tweed and Curtis [Davis, C., Levitan, R. D., Smith, M., Tweed, S., & Curtis, C. (2006). Associations among overeating, overweight, and attention deficit/hyperactivity disorder: A structural equation modeling approach. Eating Behaviors, 7, 266-274] recently tested a structural equation model predicting that AD(H)D symptoms foster overeating and subsequently contribute to the variation in Body Mass Index (BMI) in a sample of healthy adult females. The data were an excellent fit to the model.

Education Level Moderates Learning on Two Versions of the Iowa Gambling Task

Journal of the International Neuropsychological Society : JINS. Nov, 2008  |  Pubmed ID: 18954486

The Iowa Gambling Task (IGT) is the major plank of behavioral support for the Somatic Marker Hypothesis--a prominent theory of emotionally-based decision making. Despite its widespread use, some have questioned the ecological and discriminative validity of the IGT because a substantial proportion of neurologically-normal adults display a response pattern indistinguishable from those with ventromedial prefrontal cortical brain lesions. In a large sample of healthy adults, we examined the statistical influence of several demographic variables on two versions of the IGT, with the specific prediction that educational attainment would moderate learning across trials. Results confirmed a highly significant effect of education. On the commonly used original version of the IGT, performance tended to improve more rapidly, and reach a higher eventual positive score, as the level of education increased. Age and gender were nonsignificant effects in the model, and Caucasians had slightly better IGT performance than their non-Caucasian counterparts. Conclusions are that education level, among neurologically-normal adults, should be treated as a stratification or matching variable in case-control research using this task.

Discovery and Analysis of Bartonella Henselae Antigens for Use in Clinical Serologic Assays

Diagnostic Microbiology and Infectious Disease. Jan, 2008  |  Pubmed ID: 17889484

The antibody response to Bartonella henselae has been studied in a number of mammals; however, the human response needs to be further studied. After natural infection, humans have antibody reactivity to a large number of B. henselae proteins. We used a proteomic approach to identify antigenic proteins of B. henselae to determine their capacity to elicit a human antibody response. Comparing patient sera by Western blot analysis demonstrated significant amounts of reactivity to B. henselae. The immunofluorescence assay (IFA)-positive sera identified several protein spots of interest. However, a consistent reactivity to a single spot by all sera was not observed. Three of these spots demonstrated reactivity in 71%, 64%, and 64% of positive sera tested with negligible reactivity to the negative sera. These proteins were identified as GroES, BepA, and GroEL. Most IFA-positive sera demonstrated reactivity to GroES, GroEL, and BepA. The usefulness of these proteins for a clinical serologic assay is discussed.

Differential Involvement of M1-type and M4-type Muscarinic Cholinergic Receptors in the Dorsomedial Striatum in Task Switching

Neurobiology of Learning and Memory. Feb, 2008  |  Pubmed ID: 17709264

Previous experiments have demonstrated that the rat dorsomedial striatum is one brain area that plays a crucial role in learning when conditions require a shift in strategies. Further evidence indicates that muscarinic cholinergic receptors in this brain area support adaptations in behavioral responses. Unknown is whether specific muscarinic receptor subtypes in the dorsomedial striatum contribute to a flexible shift in response patterns. The present experiments investigated whether blockade of M1-type and/or M4-type cholinergic receptors in the dorsomedial striatum underlie place reversal learning. Experiment 1 investigated the effects of the M1-type muscarinic cholinergic antagonist, muscarinic-toxin 7 (MT-7) infused into the dorsomedial striatum in place acquisition and reversal learning. Experiment 2 investigated the effects of the M4-type muscarinic cholinergic antagonist, muscarinic-toxin 3 (MT-3) injected into the dorsomedial striatum in place acquisition and reversal learning. All testing occurred in a modified cross-maze across two consecutive sessions. Bilateral injections of MT-7 into the dorsomedial striatum at 1 or 2 microg, but not 0.05 microg impaired place reversal learning. Analysis of the errors revealed that MT-7 at 1 and 2 microg significantly increased regressive errors, but not perseverative errors. An injection of MT-7 2 microg into the dorsomedial striatum prior to place acquisition did not affect learning. Experiment 2 revealed that dorsomedial striatal injections of MT-3 (0.05, 1 or 2 microg) did not affect place acquisition or reversal learning. The findings suggest that activation of M1-type muscarinic cholinergic receptors in the dorsomedial striatum, but not M4-type muscarinic cholinergic receptors facilitate the flexible shifting of response patterns by maintaining or learning a new choice pattern once selected.

Early Social Isolation in Male Long-Evans Rats Alters Both Appetitive and Consummatory Behaviors Expressed During Operant Ethanol Self-administration

Alcoholism, Clinical and Experimental Research. Feb, 2009  |  Pubmed ID: 19032581

Postweaning social isolation in rats produces profound and long-lasting cognitive and behavioral deficits in adult animals. Importantly, this housing manipulation alters sensitivity to a number of drugs of abuse including ethanol. However, most studies with ethanol have utilized continuous or limited home-cage access to examine interactions between juvenile social experience and drinking. More recently, social isolation was shown to increased ethanol responding in a "dipper" model of self-administration (Deehan et al., 2007). In the current study, we utilize a "sipper" operant self-administration model to distinguish the effects of isolation rearing on ethanol seeking- and drinking-related behaviors.

Treatment of Chordomas with CyberKnife: Georgetown University Experience and Treatment Recommendations

Neurosurgery. Feb, 2009  |  Pubmed ID: 19165073

To determine the efficacy and safety of chordoma treatment with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (CK/SRS).

Chronic Ethanol and Withdrawal Effects on Kainate Receptor-mediated Excitatory Neurotransmission in the Rat Basolateral Amygdala

Alcohol (Fayetteville, N.Y.). Feb, 2009  |  Pubmed ID: 19185207

Withdrawal (WD) anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is extensive, long-lasting, and develops well after the obvious physical symptoms of acute WD. The neurobiological mechanisms underlying this prolonged WD-induced anxiety are not well understood. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates the expression of anxiety. New evidence suggests that increased glutamatergic function in the BLA may contribute to WD-related anxiety following chronic ethanol exposure. Recent evidence also suggests that kainate-type ionotropic glutamate receptors are inhibited by intoxicating concentrations of acute ethanol. This acute sensitivity suggests potential (KA-R) contributions by these receptors to the increased glutamatergic function seen during chronic exposure. Therefore, we examined the effect of chronic intermittent ethanol (CIE) and WD on KA-R-mediated synaptic transmission in the BLA of Sprague-Dawley rats. Our study showed that CIE, but not WD, increased synaptic responses mediated by KA-Rs. Interestingly, both CIE and WD occluded KA-R-mediated synaptic plasticity. Finally, we found that BLA field excitatory postsynaptic potential responses were increased during CIE and WD via a mechanism that is independent of glutamate release from presynaptic terminals. Taken together, these data suggest that KA-Rs might contribute to postsynaptic increases in glutamatergic synaptic transmission during CIE and that the mechanisms responsible for the expression of KA-R-dependent synaptic plasticity might be engaged by chronic ethanol exposure and WD.

Multidisciplinary Reports of Nursing Home Mistreatment

Journal of the American Medical Directors Association. Mar, 2009  |  Pubmed ID: 19233057

The purpose of this research was to learn about nursing home employees' knowledge and perspectives on mandatory reporting of elder abuse.

Idiopathic Diaphragmatic Paralysis: Bell's Palsy of the Diaphragm?

Lung. May-Jun, 2009  |  Pubmed ID: 19277778

Idiopathic diaphragm paralysis is probably more common and responsible for more morbidity than generally appreciated. Bell's palsy, or idiopathic paralysis of the seventh cranial nerve, may be seen as an analogous condition. The roles of zoster sine herpete and herpes simplex have increasingly been recognized in Bell's palsy, and there are some data to suggest that antiviral therapy is a useful adjunct to steroid therapy. Thus, we postulated that antiviral therapy might have a positive impact on the course of acute idiopathic diaphragm paralysis which is likely related to viral infection.

Taking a Risk Perception Approach to Improving Beach Swimming Safety

International Journal of Behavioral Medicine. 2009  |  Pubmed ID: 19288204

Beach swimming is generally associated with a healthy lifestyle, yet the risk of drowning is universally significant.

In Situ Measurement of Permeability

The Journal of the Acoustical Society of America. Apr, 2009  |  Pubmed ID: 19354349

Permeability of a porous material with a fluid interface is shown to be related to the propagation of the slow longitudinal wave. The propagation threshold of the slow longitudinal wave occurs when the wave number is higher than the critical wave number, k(cr). Measuring k(cr) can provide the intrinsic permeability of a porous interface. The ability to detect a change in k(cr) due to differences in pore size and fluid viscosity is demonstrated. This measurement is demonstrated in a model material with two pore sizes and two fluid viscosities. The results suggest opportunities to extend the method to a range of materials of scientific and technical importance.

The Role of the Media in Influencing Children's Nutritional Perceptions

Qualitative Health Research. May, 2009  |  Pubmed ID: 19380500

Recently the mass media environment of children, in particular food advertising, has come under scrutiny as a contributing factor in the increasing prevalence of childhood obesity. Focus groups were used to explore how children's appraisals of various forms of media inform their health-related perceptions about eating and nutrition. Ninety participants aged 10 to 12 years were recruited from schools throughout Auckland, New Zealand. Schools were randomly selected from among those rated with low, medium, and high socioeconomic status. Results show that the media is a key factor shaping how young people conceptualize healthy eating and healthy bodies. Mass media food messages were not seen as a credible source of health information; rather, they assist in constructing and reinforcing dominant misconceptions about food, healthy eating, and nutrition. Nutritional messages embedded in both health promotion and advertising were perceived to be conflicting and ambiguous, and might serve to undermine the trustworthiness of health promotion initiatives.

Outdoor Workers' Perceptions of the Risks of Excess Sun-exposure

Journal of Occupational Health. 2009  |  Pubmed ID: 19590155

To describe the pattern of associations with sunscreen use of sun protection attitudes and knowledge in a large sample of New Zealand outdoor workers. We also examined the relationship between perceived skin type and perceived risk of developing skin cancer.

Natural History of Mesenteric Venous Thrombosis in Patients Treated with Vitamin K Antagonists: a Multi-centre, Retrospective Cohort Study

Thrombosis and Haemostasis. Sep, 2009  |  Pubmed ID: 19718470

Knowledge on the natural history of mesenteric vein thrombosis (MVT) and of the efficacy and safety of long-term oral anticoagulant therapy (OAT) in this setting is based on small uncontrolled series of patients with a limited follow-up. It was the aim of the study to assess the natural history of MVT in a cohort of patients treated with OAT. The charts of all MVT patients currently attending or who have attended four anticoagulation clinics were reviewed. Information on risk factors, treatment, recurrence, major bleeding and mortality was collected. Seventy-seven patients (mean age 49.2 years; 45 males) were included with a median follow-up of 36 months (range 2-204 months). Forty-six patients were treated with long-term OAT. Seven patients had venous thromboembolism (VTE) recurrence (5 splanchnic vein thromboses and two pulmonary emboli) for an incidence rate of 23.4 events /1,000 year patients. In two patients recurrent VTE occurred during OAT, for an incidence rate of 10.5 events /1,000 year patient. Five patients had VTE recurrence when OAT was suspened for an incidence rate of 45.9 events /1,000 year patient. Two patients (2.6%) had a major bleeding event. 97.3% of patients were alive at one year, and seven patients (9.1%) died during follow up. In conclusion, patients with MTV seem to have a low risk of recurrent VTE while receiving OAT. This risk appears increased after treatment is stopped.

Incidence and Predictors of Bleeding or Thrombosis After Polypectomy in Patients Receiving and Not Receiving Anticoagulation Therapy

Journal of Thrombosis and Haemostasis : JTH. Dec, 2009  |  Pubmed ID: 19719825

To assess the effect of warfarin anticoagulation therapy (AC) on the incidence of colon bleeding after elective colonoscopy with polypectomy and to identify independent predictors of post-polypectomy colon bleeding.

The Pain That Binds Us: Midwives' Experiences of Loss and Adverse Outcomes Around the World

Health Care for Women International. Nov, 2009  |  Pubmed ID: 19809903

Although much has been written about helping women and their families cope with loss related to childbearing, little exists in the literature to guide and support the midwives who witness these losses. We conducted qualitative interviews globally with 22 midwives from nations located on six different continents to begin exploring common themes of experiences and coping methods of midwives involved in adverse perinatal outcomes. The concept of critical incident stress (CIS) is presented as a framework for understanding practitioner reactions that occur after adverse outcomes. Implications for practice, education, and continued research are addressed.

Breathing Pattern and Ventilatory Control in Chronic Tetraplegia

Lung. Nov-Dec, 2009  |  Pubmed ID: 19820994

Blunted ventilatory responses to carbon dioxide indicate that respiratory control is impaired when ventilation is stimulated in individuals with tetraplegia; however, respiratory control during resting breathing has not been extensively studied in this population. Our objective was to evaluate respiratory control and sigh frequency during resting breathing in persons with tetraplegia. A prospective, two-group comparative study was performed. Breathing pattern was assessed in ten outpatients with chronic tetraplegia and eight age- and gender-matched able-bodied controls. Subjects were noninvasively monitored for 1 h, while seated and at rest. Tidal volume (V(T)) was calculated from the sum of the anteroposterior displacements of the rib cage and abdomen and the axial displacement of the chest wall. Inspiratory time (T(I)), V(T), and the ratio of V(T) to inspiratory time (V(T)/T(I)) were calculated breath by breath. A sigh was defined as any breath greater than two or more times an individual's mean V(T). Minute ventilation, V(T)/T(I), and sigh frequency were reduced in tetraplegia compared with controls (5.24 +/- 1.15 vs. 7.16 +/- 1.29 L/min, P < 0.005; 208 +/- 45 vs. 284 +/- 47 ml/s, P < 0.005; and 11 +/- 7 vs. 42 +/- 19 sighs/h, P < 0.0005, respectively). V(T)/T(I) was associated with sigh frequency in both groups (tetraplegia: R = 0.88; P = 0.001 and control: R = 0.70; P < 0.05). We concluded that reductions in minute ventilation, V(T)/T(I), and sigh frequency suggest that respiratory drive is diminished during resting breathing in subjects with tetraplegia. These findings extend prior observations of disordered respiratory control during breathing stimulated by CO(2) in tetraplegia to resting breathing.

Neurobiological Mechanisms Contributing to Alcohol-stress-anxiety Interactions

Alcohol (Fayetteville, N.Y.). Nov, 2009  |  Pubmed ID: 19913194

This article summarizes the proceedings of a symposium that was presented at a conference entitled "Alcoholism and Stress: A Framework for Future Treatment Strategies." The conference was held in Volterra, Italy on May 6-9, 2008 and this symposium was chaired by Jeff L. Weiner. The overall goal of this session was to review recent findings that may shed new light on the neurobiological mechanisms that underlie the complex relationships between stress, anxiety, and alcoholism. Dr. Danny Winder described a novel interaction between D1 receptor activation and the corticotrophin-releasing factor (CRF) system that leads to an increase in glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Dr. Marisa Roberto presented recent data describing how protein kinase C epsilon, ethanol, and CRF interact to alter GABAergic inhibition in the central nucleus of the amygdala. Dr. Jeff Weiner presented recent advances in our understanding of inhibitory circuitry within the basolateral amygdala (BLA) and how acute ethanol exposure enhances GABAergic inhibition in these pathways. Finally, Dr. Brian McCool discussed recent findings on complementary glutamatergic and GABAergic adaptations to chronic ethanol exposure and withdrawal in the BLA. Collectively, these investigators have identified novel mechanisms through which neurotransmitter and neuropeptide systems interact to modulate synaptic activity in stress and anxiety circuits. Their studies have also begun to describe how acute and chronic ethanol exposure influence excitatory and inhibitory synaptic communication in these pathways. These findings point toward a number of novel neurobiological targets that may prove useful for the development of more effective treatment strategies for alcohol use disorders.

A PAR-SUMOnious Mechanism of NEMO Activation

Molecular Cell. Nov, 2009  |  Pubmed ID: 19917242

In this issue of Molecular Cell, Stilmann et al. (2009) demonstrate a new mode of prosurvival NF-kappaB activation through the formation of a PARP-1-poly(ADP-ribose) signaling scaffold in response to DNA damage.

Keeping Kids Smokefree: Rationale, Design, and Implementation of a Community, School, and Family-based Intervention to Modify Behaviors Related to Smoking Among Māori and Pacific Island Children in New Zealand

International Quarterly of Community Health Education. 2009-2010  |  Pubmed ID: 20860980

Despite a concerted, sustained and comprehensive tobacco control effort, smoking is prevalent among young people in New Zealand, particularly for Māori and Pacific Island teenagers. Many took up smoking in their pre-teen years. New Zealand research has shown that daily smoking by children aged 14-15 years is strongly influenced by parental smoking. The Keeping Kids Smokefree study is investigating whether changing parental smoking behavior and attitudes via a community-partnership approach with parents, schools, and local health providers can reduce smoking initiation by 11-12 year olds. It is a quasi-experimental trial involving four schools in an urban area of high social deprivation with large numbers of Māori and Pacific Islands families. Schools were allocated to intervention or control and the intervention was developed through a process of engagement with the schools, parents of children and local healthcare organizations. This article describes the rationale, context, methodology and methods involved in establishing the study. Building Māori and Pacific Islander research capacity was a secondary objective of the study.

Development of PyrF-based Genetic System for Targeted Gene Deletion in Clostridium Thermocellum and Creation of a Pta Mutant

Applied and Environmental Microbiology. Oct, 2010  |  Pubmed ID: 20693441

We report development of a genetic system for making targeted gene knockouts in Clostridium thermocellum, a thermophilic anaerobic bacterium that rapidly solubilizes cellulose. A toxic uracil analog, 5-fluoroorotic acid (5-FOA), was used to select for deletion of the pyrF gene. The ΔpyrF strain is a uracil auxotroph that could be restored to a prototroph via ectopic expression of pyrF from a plasmid, providing a positive genetic selection. Furthermore, 5-FOA was used to select against plasmid-expressed pyrF, creating a negative selection for plasmid loss. This technology was used to delete a gene involved in organic acid production, namely pta, which encodes the enzyme phosphotransacetylase. The C. thermocellum Δpta strain did not produce acetate. These results are the first examples of targeted homologous recombination and metabolic engineering in C. thermocellum, a microbe that holds an exciting and promising future in the biofuel industry and development of sustainable energy resources.

Glutamate Plasticity in the Drunken Amygdala: the Making of an Anxious Synapse

International Review of Neurobiology. 2010  |  Pubmed ID: 20813244

Plasticity at glutamatergic synapses is believed to be the cellular correlate of learning and memory. Classic fear conditioning, for example, is dependent upon NMDA-type glutamate receptor activation in the lateral/basolateral amygdala followed by increased synaptic expression of AMPA-type glutamate receptors. This review provides an extensive comparison between the initiation and expression of glutamatergic plasticity during learning/memory and glutamatergic alterations associated with chronic ethanol exposure and withdrawal. The parallels between these neuro-adaptive processes suggest that long-term ethanol exposure might "chemically condition" amygdala-dependent fear/anxiety via the increased function of pre- and post-synaptic glutamate signaling.

Is Human Seasonality Implicated in the Risk Profile for Obesity?

Eating Behaviors. Dec, 2010  |  Pubmed ID: 20850068

Although seasonality might once have been a successful energy conservation strategy for people living in temperate regions, this physiological phenomenon may now foster accumulating annual weight gain and thereby feature in the risk profile for obesity. We tested the hypothesis that seasonality relates to BMI, and that this association is mediated by a preference for carbohydrates and the tendency to binge eat. In a sample of men and women, gender significantly moderated the relationship between seasonality and BMI. In men, the relationship was positive, but these two variables did not co-vary in women. Reasons why seasonality is positively associated with BMI only in men are not immediately apparent. It is possible that other gender-specific risk factors for overeating may contribute to these findings.

Robotic Surgery of the Infratemporal Fossa Utilizing Novel Suprahyoid Port

The Laryngoscope. Sep, 2010  |  Pubmed ID: 20583114

To develop a minimally invasive technique for robotic access to the infratemporal fossa and describe use of a novel suprahyoid port placement.

Association of Parent and Best Friend Smoking with Stage of Adolescent Tobacco Smoking

The New Zealand Medical Journal. Nov, 2010  |  Pubmed ID: 21326402

Compare the effect of parental and best friend smoking across the stages of adolescent smoking, from being a never smoker susceptible to smoking, to being a daily smoker

Nurses' Experiences, Expectations, and Preferences for Mind-body Practices to Reduce Stress

BMC Complementary and Alternative Medicine. 2011  |  Pubmed ID: 21481259

Most research on the impact of mind-body training does not ask about participants' baseline experience, expectations, or preferences for training. To better plan participant-centered mind-body intervention trials for nurses to reduce occupational stress, such descriptive information would be valuable.

Shortness of Breath in Parkinson's Disease

Parkinsonism & Related Disorders. Jul, 2011  |  Pubmed ID: 21514208

The SLH-domain Protein BslO is a Determinant of Bacillus Anthracis Chain Length

Molecular Microbiology. Jul, 2011  |  Pubmed ID: 21585566

The Gram-positive pathogen Bacillus anthracis grows in characteristic chains of individual, rod-shaped cells. Here, we report the cell-separating activity of BslO, a putative N-acetylglucosaminidase bearing three N-terminal S-layer homology (SLH) domains for association with the secondary cell wall polysaccharide (SCWP). Mutants with an insertional lesion in the bslO gene exhibit exaggerated chain lengths, although individual cell dimensions are unchanged. Purified BslO complements this phenotype in trans, effectively dispersing chains of bslO-deficient bacilli without lysis and localizing to the septa of vegetative cells. Compared with the extremely long chain lengths of csaB bacilli, which are incapable of binding proteins with SLH-domains to SCWP, bslO mutants demonstrate a chaining phenotype that is intermediate between wild-type and csaB. Computational simulation suggests that BslO effects a non-random distribution of B. anthracis chain lengths, implying that all septa are not equal candidates for separation.

The Promise of Symptom-targeted Intervention to Manage Depression in Dialysis Patients

Nephrology News & Issues. May, 2011  |  Pubmed ID: 21608458

Research with tens of thousands of dialysis patients has established a link between depression, health-related quality of life scores, survival, and hospitalizations. In fact, physical and mental functioning scores are as predictive of death and hospitalization as Kt/V and albumin. Some models for managing depression in the dialysis clinic have been developed. These models address barriers to accessing community mental health services. They also promote collaboration between the nephrology social worker and nephrologist to assurethat patients receive counseling and/or antidepressant medications when they need them. Part 1 of this article will introduce a promising new method designed for nephrology social workers to help patients manage depression. This method, known as symptom-targeted intervention (STI), can be used in brief intervals with patients while they are receiving dialysis treatments to help reduce depressive symptoms and improve quality of life. The second part of this article, which will appear in the June issue of Nephrology News & Issues, will report the outcomes of a 17-state pilot study in which more than 45 nephrology social workers used brief, focused STI methods with more than 75 patients in the dialysis clinic setting. The impact of STI on depression and quality of life in this sample will be explored as well as how those outcomes may impact hospitalizations, improve patient survival, and contain costs in a bundled reimbursement environment.

Young Adults' Interpretations of Tobacco Brands: Implications for Tobacco Control

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Oct, 2011  |  Pubmed ID: 21622495

Marketers have long recognized the power and importance of branding, which creates aspirational attributes that increase products' attractiveness. Although brand imagery has traditionally been communicated via mass media, packaging's importance in promoting desirable brand-attribute associations has increased. Knowledge of how groups prone to smoking experimentation interpret tobacco branding would inform the debate over plain packaging currently occurring in many countries.

Ethanol and Water Adsorption in Methanol-derived ZIF-71

Chemical Communications (Cambridge, England). Aug, 2011  |  Pubmed ID: 21709911

A room temperature method for synthesizing zeolitic imidizolate framework 71 (ZIF-71) is described. The methanol-based synthesis results in >95% yields (based on Zn) and produces crystals with 70% greater surface area than reported earlier. Ethanol uptake into the ZIF compares favorably with a recent modeling-based study. Water uptake was significantly higher than model predictions.

Chinese Peoples' Perceptions of Colorectal Cancer Screening: a New Zealand Perspective

The New Zealand Medical Journal. Mar, 2011  |  Pubmed ID: 21725410

A national cancer screening programme requires a level of perceived acceptability of the procedure among the target population groups to be successful (that is, achieve a high uptake rate). In this study we explored Chinese immigrants' attitudes and perceptions towards colorectal cancer screening.

Driving Kids to Smoke? Children's Reported Exposure to Smoke in Cars and Early Smoking Initiation

Addictive Behaviors. Nov, 2011  |  Pubmed ID: 21733632

The health risks associated with second hand smoke (SHS) are well-known. However, little is known about exposure to SHS in cars and risk of smoking uptake. This paper investigates the association between pre-adolescents reported exposure to smoking in cars and prevalence of early stage smoking activity. Data from Keeping Kids Smokefree baseline surveys of students were used to investigate smoking status and reported exposure to smoking in cars. Log binomial regression analyses were used to investigate if reported exposure to SHS in cars was associated with smoking prevalence. 83% of 5676 students invited took part. After controlling for all variables reported exposure to smoking in cars and homes were significantly associated with increased risk of initiated smoking (RR 1.87, 95% CI 1.43-2.44, and RR 1.5, 95% CI 1.13-1.97, respectively). Exposure to smoking in cars was substantially and significantly associated with risk of current smoking (RR 3.21, 95% CI 1.45-7.08). Early smoking uptake is associated with students' reported exposure to smoking in cars which confirms the importance of protecting children from SHS. Smoking in cars is under parental control and therefore modifiable. Moreover, children's reports of SHlS exposure offer a simple way of identifying families who can be targeted for tobacco control interventions.

Part 2. The Promise of Symptom-targeted Intervention to Manage Depression in Dialysis Patients: Improving Mood and Quality of Life Outcomes

Nephrology News & Issues. Jun, 2011  |  Pubmed ID: 21736132

The Practice Outcome Evaluation of using Symptom Targeted Intervention (STI) to manage depressed mood in dialysis patients reviewed social worker experiences and observations using STI. The evaluation was guided by the following questions: 1. What is the feasibility of STI in nephrology social work? 2. What is nephrology social worker comfort level with clinical assessment, intervention, and tracking? 3. What is the potential efficacy of STI on reducing depression? Initial results suggest that STI enhances existing nephrology social work skills in identifying, treating, and tracking outcomes of patient issues requiring clinical intervention. Most social workers spent 1.5 hours over a six-week period using STI techniques to address symptoms of depression with a patient. This rather short period of intervention led to a reported improvement in PCS and MCS scores of 51.6% and 61.3% of patients, respectively, and improvement in CES-D scores in 72.1% of patients. While this practice outcome evaluation is limited by how social workers were selected and the small number of patients, it demonstrates options for further study of the efficacy of STI in reducing depression. The brief time invested in training holds promise for impacting nephrology social work and improving patient and dialysis clinics' outcomes.

A Co4O4 "cubane" Water Oxidation Catalyst Inspired by Photosynthesis

Journal of the American Chemical Society. Aug, 2011  |  Pubmed ID: 21739983

Herein we describe the molecular Co(4)O(4) cubane complex Co(4)O(4)(OAc)(4)(py)(4) (1), which catalyzes efficient water oxidizing activity when powered by a standard photochemical oxidation source or electrochemical oxidation. The pH dependence of catalysis, the turnover frequency, and in situ monitoring of catalytic species have revealed the intrinsic capabilities of this core type. The catalytic activity of complex 1 and analogous Mn(4)O(4) cubane complexes is attributed to the cubical core topology, which is analogous to that of nature's water oxidation catalyst, a cubical CaMn(4)O(5) cluster.

Nursing Sabbatical in the Acute Care Setting: What is the Evidence?

Nursing Forum. Jul-Sep, 2011  |  Pubmed ID: 21806630

To review and examine the literature supporting a professional sabbatical, a potentially viable and innovative change strategy that could renew, revitalize, and retain nursing staff practicing in the acute care setting.

Stability Studies of Extracellular Domain Two of Neural-cadherin

Biochimica Et Biophysica Acta. Dec, 2011  |  Pubmed ID: 21843662

Neural- (NCAD) and epithelial- (ECAD) cadherin are calcium-dependent cell-adhesive molecules, and are localized at excitatory and inhibitory synapses respectively. They play an important role in synaptogenesis, synapse maintenance and plasticity. The extracellular region plays a critical role in cadherin-mediated cell adhesion, and has five tandemly repeated ectodomains (EC1-EC5). Calcium binding is required for dimer formation between first two N-terminal domains (EC1-EC2). Despite similarity in the primary structure, the extracellular domains of NCAD and ECAD have different intrinsic stability, dimerization affinity and kinetics of disassembly. To investigate the origin of these differences, we are characterizing the modular domains individually. Here, we report studies of NCAD2, EC2 of NCAD. This domain is important for calcium binding and is the physical linkage between the dimerization interface in EC1 and the membrane proximal modular domains. Thermal-denaturation studies show that NCAD2 is less stable than ECAD2 and less influenced by the adjoining 7-residue, N- and C-terminal linker segments. In addition the NCAD2 constructs are less influenced by added salt. This difference is likely due to variation in the overall number and distribution of charges on these anionic proteins. Our studies indicate that despite their sequence similarity and apparently passive role in adhesive dimer formation, EC2 of E- and N-cadherins are distinctly different and may contribute to the differences in energetics and kinetics of dimerization.

The Use of the 'rollie' in New Zealand: Preference for Loose Tobacco Among an Ethnically Diverse Low Socioeconomic Urban Population

The New Zealand Medical Journal. Jul, 2011  |  Pubmed ID: 21946960

To examine the prevalence of and reasons for smoking roll-your-own (RYO) cigarettes in a population of South Auckland adults.

A Cross-sectional Study of Opinions Related to the Tobacco Industry and Their Association with Smoking Status Amongst 14-15 Year Old Teenagers in New Zealand

The New Zealand Medical Journal. Jul, 2011  |  Pubmed ID: 21946961

New Zealand has been at the forefront of tobacco control and can boast an impressive range of tobacco control intervention. To date, tobacco control policy and interventions have directed very little attention to the tobacco industry because they concentrate on reducing demand for tobacco. In addition, the tobacco industry does not have a bold profile in the mass media. Given this low profile of the tobacco industry and the predominance of measures to reduce demand we were interested in teenage perceptions of the tobacco industry in New Zealand.

Habit Learning is Associated with Major Shifts in Frequencies of Oscillatory Activity and Synchronized Spike Firing in Striatum

Proceedings of the National Academy of Sciences of the United States of America. Oct, 2011  |  Pubmed ID: 21949388

Rhythmic brain activity is thought to reflect, and to help organize, spike activity in populations of neurons during on-going behavior. We report that during learning, a major transition occurs in task-related oscillatory activity in the ventromedial striatum, a striatal region related to motivation-dependent learning. Early on as rats learned a T-maze task, bursts of 70- to 90-Hz high-γ activity were prominent during T-maze runs, but these gradually receded as bursts of 15- to 28-Hz β-band activity became pronounced. Populations of simultaneously recorded neurons synchronized their spike firing similarly during both the high-γ-band and β-band bursts. Thus, the structure of spike firing was reorganized during learning in relation to different rhythms. Spiking was concentrated around the troughs of the β-oscillations for fast-spiking interneurons and around the peaks for projection neurons, indicating alternating periods of firing at different frequencies as learning progressed. Spike-field synchrony was primarily local during high-γ-bursts but was widespread during β-bursts. The learning-related shift in the probability of high-γ and β-bursting thus could reflect a transition from a mainly focal rhythmic inhibition during early phases of learning to a more distributed mode of rhythmic inhibition as learning continues and behavior becomes habitual. These dynamics could underlie changing functions of the ventromedial striatum during habit formation. More generally, our findings suggest that coordinated changes in the spatiotemporal relationships of local field potential oscillations and spike activity could be hallmarks of the learning process.

Identifying Speech, Language and Communication Needs Among Children and Young People in Residential Care

International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists. Nov-Dec, 2011  |  Pubmed ID: 22026568

There are claims that elevated levels of speech, language and communication needs (SLCN) exist among looked-after children and young people, and that their needs remain largely undetected and unmet. Scarce empirical evidence exists to support these assertions.

"Punching Above Its Weight": Why New Zealand Must Maintain Leadership in Global Health

The New Zealand Medical Journal. Nov, 2011  |  Pubmed ID: 22072168

As a small island nation, with a population of only 4.4 million, and geographically isolated from the centres of global power, New Zealand could be seen as of marginal relevance to the global health agenda. This paper argues that New Zealand has been and should remain a player in global health, even if current fiscal constraints may suggest otherwise. Involvement fits with our responsibilities and commitments in the Pacific region and our wider interests, including ethical international trade, security, global alliances and the fundamental protection of health.

Preoperative Embolization of the Inferior Petrosal Sinus in Surgery for Glomus Jugulare Tumors

Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. Dec, 2011  |  Pubmed ID: 22072258

To compare the outcomes of surgery for glomus tumors involving the jugular foramen with and without preoperative venous embolization of the inferior petrosal sinus (IPS).

Showcasing Differences Between Quality Improvement, Evidence-based Practice, and Research

Journal of Continuing Education in Nursing. Feb, 2011  |  Pubmed ID: 20672761

The literature confirms that much confusion exists regarding the terms quality improvement (QI), evidence-based practice (EBP), and research. A multifaceted approach was used to provide clarity regarding these three equally important concepts. First, the authors present a synthesis of the literature that discusses differences between QI, EBP, and research. Second, the authors introduce a newly created comparative table that synthesizes current literature and showcases differences between QI, EBP, and research. Finally, the authors highlight uses of the comparative table within multiple settings.

Tobacco Promotion in the Pacific: the Current State of Tobacco Promotion Bans and Options for Accelerating Progress

Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health. Jan, 2011  |  Pubmed ID: 21169600

Tobacco consumption is a major contributor to the burden of chronic noncommunicable disease within the Pacific region. Low and lower-middle income countries are acutely vulnerable to exploitation by the tobacco industry as they often lack the resources and capacity to implement protective tobacco control policies. The Framework Convention on Tobacco Control, which has been signed by 14 Pacific Island Countries and Territories, was introduced in 2004 to guide the priorities for tobacco control policy implementation. Legislation, tobacco industry documents, and peer-reviewed journals were evaluated to assess the current status of tobacco advertising bans of the 8 low and lower-middle income countries within the Pacific region. RESULTS: identified that of the 8 Pacific countries reviewed, 3 had comprehensive tobacco advertising bans that prohibit tobacco advertisements in 5 to 7 forms of media, and the remaining 5 countries have weak tobacco advertising bans that provide no protection for youth against tobacco advertising. This research reveals the need for resources to support the introduction of effective policies around tobacco advertising in the low and lower-middle income countries within the Pacific region.

Strengthening Health Research Capacity from Within Samoa

Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health. Jan, 2011  |  Pubmed ID: 21169603

This article reflects on the challenges of strengthening health research capacity from within Samoa. It examines the status of health research and related curricula in Samoa and discusses the outcomes of a new postgraduate applied social and health research methods course taught in Samoa for the first time from 5 January to 12 February 2010 by the Department of Preventive and Social Medicine, University of Otago in collaboration with the Centre for Samoan Studies, National University of Samoa. The article argues that collaborative health research courses such as this methods paper can fill a curriculum gap in New Zealand and Samoa and contribute directly toward strengthening Samoa health research capacity in ways that benefit both Samoa and New Zealand. This initiative can be a flagship for strategies operating from within Samoa that can build real win-win type partnerships. These can be ably led by Samoans for the ultimate development of an affordable and sustainable quality health and education infrastructure for Samoa.

Ethanol Modulation of Synaptic Plasticity

Neuropharmacology. Dec, 2011  |  Pubmed ID: 21195719

Synaptic plasticity in the most general terms represents the flexibility of neurotransmission in response to neuronal activity. Synaptic plasticity is essential both for the moment-by-moment modulation of neural activity in response to dynamic environmental cues and for long-term learning and memory formation. These temporal characteristics are served by an array of pre- and post-synaptic mechanisms that are frequently modulated by ethanol exposure. This modulation likely makes significant contributions to both alcohol abuse and dependence. In this review, I discuss the modulation of both short-term and long-term synaptic plasticity in the context of specific ethanol-sensitive cellular substrates. A general discussion of the available preclinical, animal-model based neurophysiology literature provides a comparison between results from in vitro and in vivo studies. Finally, in the context of alcohol abuse and dependence, the review proposes potential behavioral contributions by ethanol modulation of plasticity.

Chronic Ethanol and Withdrawal Differentially Modulate Lateral/basolateral Amygdala Paracapsular and Local GABAergic Synapses

The Journal of Pharmacology and Experimental Therapeutics. Apr, 2011  |  Pubmed ID: 21209156

Withdrawal-related anxiety is cited as a major contributor to relapse in recovering alcoholics. Changes in lateral/basolateral amygdala (BLA) neurotransmission could directly influence anxiety-like behaviors after chronic ethanol exposure and withdrawal. We have shown that these treatments enhance BLA glutamatergic function and neurotransmission. However, the BLA GABAergic system tightly controls the expression of anxiety-like behavior, and additional neuroadaptations in this system are potentially important as well. The intrinsic BLA GABAergic system consists of at least two populations of interneurons: local feed-back interneurons scattered throughout the region and feed-forward interneurons concentrated within groups found in the lateral/paracapsular region of the BLA. In the present study, we found that withdrawal from chronic ethanol robustly decreased presynaptic function at feed-forward GABA synapses but did not alter neurotransmitter release from local interneurons. Differential presynaptic changes at these synapses were complemented by decreased zolpidem sensitivity at feed-forward synapses and decreased midazolam sensitivity at local synapses. Consistent with this, chronic ethanol/withdrawal decreased expression of GABA α1-subunit total protein and increased surface expression of α4-subunit protein. We also found transient increases in GABA-receptor-associated protein levels and persistent increases in γ2-subunit and gephyrin proteins that would suggest alterations in GABA(A) receptor trafficking that might help regulate changes in α4-subunit localization. These data together suggest that chronic ethanol and withdrawal differentially modulate local and lateral paracapsular cell GABAergic synapses via distinct presynaptic and postsynaptic mechanisms. These findings extend our understanding of the neurobiological mechanisms governing changes in anxiety-like behavior after chronic ethanol exposure and withdrawal.

Do Parents Have Any Influence over How Young People Appraise Tobacco Images in the Media?

The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine. Feb, 2011  |  Pubmed ID: 21257116

Socio-cultural factors, including media and family, play an important role in introducing and reinforcing pro-smoking intentions. Tendencies to appraise smokers in media in positive, negative, and empathic ways may play a role in the social and familial dynamics influencing smoking intentions.

Dopamine D3-like Receptors Modulate Anxiety-like Behavior and Regulate GABAergic Transmission in the Rat Lateral/basolateral Amygdala

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Apr, 2011  |  Pubmed ID: 21270771

Central among the brain regions that regulate fear/anxiety behaviors is the lateral/basolateral amygdala (BLA). BLA output is tightly controlled by the relative activity of two populations of inhibitory GABAergic interneurons, local feedback cells distributed throughout the nucleus, and feedforward cells found along the lateral paracapsular border of this subdivision. Recent studies suggest that dopamine (DA) can modulate the BLA GABAergic system, thus linking fear/anxiety states with mesolimbic reward/attentional processes. However, the precise dopaminergic mechanisms regulating the activity of the two BLA GABAergic neuron populations have not been fully explored. We therefore examined the effects of DA D3-like receptors on BLA-dependent anxiety-like behavior and neurophysiology. After confirming the presence of D3-like receptors within the BLA, we found that microinjection of a D3-selective antagonist into the BLA decreased anxiety-like behavior expressed in both the light/dark transition test and the elevated plus maze. Consistent with this, we found that in vitro D3-like receptor activation selectively inhibits synaptic transmission at both BLA feedback and feedforward GABAergic interneuron populations, with no effect on glutamatergic transmission. This inhibition of GABAergic transmission is a result of a D3-like receptor-mediated, dynamin-dependent process that presumably reflects endocytosis of postsynaptic GABA(A) receptors found on principal BLA neurons. Because environmental cues alter both DA release and relative activity states of the BLA, our data strongly suggest that DA, potentially acting through D3-like receptors, may suppress the relative contribution by inhibitory processes in the BLA and modify the expression of BLA-related behaviors.

The Anxiolytic-like Profile of the Nociceptin Receptor Agonist, Endo-8-[bis(2-chlorophenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxamide (SCH 655842): Comparison of Efficacy and Side Effects Across Rodent Species

European Journal of Pharmacology. Jul, 2011  |  Pubmed ID: 21545797

The endogenous opioid-like peptide, nociceptin, produces anxiolytic-like effects that are mediated via the nociceptin (NOP) receptor. Similarly, synthetic, non-peptide NOP agonists produce robust anxiolytic-like effects although these effects are limited by marked side effects. In the present studies, the effects of a novel NOP receptor agonist, SCH 655842, were examined in rodent models sensitive to anxiolytic drugs and tests measuring potential adverse affects. Oral administration of SCH 655842 produced robust, anxiolytic-like effects in three species, i.e., rat, guinea pig, and mouse. Specifically, SCH 655842 was effective in rat conditioned lick suppression (3-10 mg/kg) and fear-potentiated startle (3-10 mg/kg) tests, a guinea pig pup vocalization test (1-3 mg/kg), as well as in mouse Geller-Seifter (30 mg/kg) and marble burying (30 mg/kg) tests. The anxiolytic-like effect of SCH 655842 in the conditioned lick suppression test was attenuated by the NOP antagonist, J-113397. In mice, SCH 655842 reduced locomotor activity and body temperature at doses similar to the anxiolytic-like dose and these effects were absent in NOP receptor knockout mice. In rats, SCH 655842 did not produce adverse behavioral effects up to doses of 70-100 mg/kg. Pharmacokinetic studies in the rat confirmed dose-related increases in plasma and brain levels of SCH 655842 across a wide oral dose range. Taken together, SCH 655842 may represent a NOP receptor agonist with improved tolerability compared to other members of this class although further studies are necessary to establish whether this extends to higher species.

Health of Pacific Islanders: Achievements and Challenges

Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health. Jan, 2011  |  Pubmed ID: 21169595

Impact of National Smokefree Environments Laws on Teachers, Schools and Early Childhood Centres

Health Promotion Journal of Australia : Official Journal of Australian Association of Health Promotion Professionals. Dec, 2011  |  Pubmed ID: 22497058

New Zealand's (NZ) smokefree legislation, implemented on 1 January 2004, requires that all school and early childhood centre buildings and grounds are 100% smokefree; one aim being to prevent young people being influenced by seeing people (including teachers) smoke there. This study, conducted in 2008, investigated teachers'smoking behaviour and perceived adherence to the legislation.

Smoking is Rank! But, Not As Rank As Other Drugs and Bullying Say New Zealand Parents of Pre-adolescent Children

Health Promotion Journal of Australia : Official Journal of Australian Association of Health Promotion Professionals. Dec, 2011  |  Pubmed ID: 22497067

Despite the established risks associated with smoking, 21% of New Zealand adults smoke. Prevalence among Māori (indigenous) and Pacific Island New Zealanders is disproportionately high. Prevention of smoking initiation is a key component of tobacco control. Keeping Kids Smokefree--a quasi-experimental trial--aimed to do this by changing parental smoking behaviour and attitudes. However, little is known about parents' attitudes to smoking in comparison with other concerns.

Media Reporting of Global Health Issues and Events in New Zealand Daily Newspapers

Health Promotion Journal of Australia : Official Journal of Australian Association of Health Promotion Professionals. Dec, 2011  |  Pubmed ID: 22497068

In the context of a globalised world, reports on health that extend personal or country borders have increasing relevance. Media can promote opportunities to identify and address gaps in important global health issues. In light of the potential role of media as an advocacy tool for global health, we examined how global health issues are represented in mainstream media in New Zealand.

Using Monosodium Glutamate to Initiate Ethanol Self-administration in Inbred Mouse Strains

Addiction Biology. Jan, 2012  |  Pubmed ID: 21054690

Voluntary oral ethanol consumption in rodents is generally limited by strong taste-aversion in these species. Historically, this has been overcome by combining ethanol with a sweetener, typically sucrose or saccharine, and then slowly 'fading' away the sweetener. While useful in most instances, this approach has not proven as successful for some inbred strains of mice (e.g. DBA/2J) despite consistent evidence in the literature that these same strains express strong conditioned place preference for intraperitoneal- or intragastric-administered ethanol. Importantly, DBA/2J mice express a polymorphism in a 'sweet' taste receptor subunit gene that reduces the potency of sweet substances in these mice. We hypothesized that the presence of this polymorphism might help explain the contrasting behavioral findings of weak voluntary oral ethanol consumption following sucrose-fade yet robust conditioned place preference for ethanol in this strain. To test this, we compared ethanol consumption initiated by either a 'traditional' sucrose-fade or a fade from an alternative tastant, monosodium glutamate (MSG). We found that in both C57BL/6J and DBA/2J mice, the MSG-fade produced robust increases in home cage ethanol consumption relative to the traditional sucrose-fade. This increased ethanol intake following MSG-fade was evident across a range of ethanol concentrations. Our findings suggest the potential utility of the MSG-fade to establish stable voluntary oral ethanol consumption in mice, particularly ethanol 'non-preferring' strains such as DBA/2J and lend additional support to the notion that ethanol consumption in DBA/2J mice is limited by pronounced taste aversion.

Statistical Strategies to Quantify Respiratory Sinus Arrhythmia: Are Commonly Used Metrics Equivalent?

Biological Psychology. Feb, 2012  |  Pubmed ID: 22138367

Three frequently used RSA metrics are investigated to document violations of assumptions for parametric analyses, moderation by respiration, influences of nonstationarity, and sensitivity to vagal blockade. Although all metrics are highly correlated, new findings illustrate that the metrics are noticeably different on the above dimensions. Only one method conforms to the assumptions for parametric analyses, is not moderated by respiration, is not influenced by nonstationarity, and reliably generates stronger effect sizes. Moreover, this method is also the most sensitive to vagal blockade. Specific features of this method may provide insights into improving the statistical characteristics of other commonly used RSA metrics. These data provide the evidence to question, based on statistical grounds, published reports using particular metrics of RSA.

Tobacco Branding, Plain Packaging, Pictorial Warnings, and Symbolic Consumption

Qualitative Health Research. May, 2012  |  Pubmed ID: 22203384

We use brand association and symbolic consumption theory to explore how plain cigarette packaging would influence the identities young adults cocreate with tobacco products. Group discussions and in-depth interviews with 86 young adult smokers and nonsmokers investigated how participants perceive tobacco branding and plain cigarette packaging with larger health warnings. We examined the transcript data using thematic analysis and explored how removing tobacco branding and replacing this with larger warnings would affect the symbolic status of tobacco brands and their social connotations. Smokers used tobacco brand imagery to define their social attributes and standing, and their connection with specific groups. Plain cigarette packaging usurped this process by undermining aspirational connotations and exposing tobacco products as toxic. Replacing tobacco branding with larger health warnings diminishes the cachet brand insignia creates, weakens the social benefits brands confer on users, and represents a potentially powerful policy measure.

Editorial: Furthering Our Understanding of Cough

Lung. Feb, 2012  |  Pubmed ID: 22258422

Youth Opinions of Tobacco Control in New Zealand: Support for Specific Measures and the Relationship with Smoking Behaviors Among 14-15-year-olds

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Apr, 2012  |  Pubmed ID: 22311958

The purpose of this study was to assess the attitudes of young people toward tobacco control and explore the association between these attitudes and both smoking intentions and behavior.

Graphic Warning Labels on Plain Cigarette Packs: Will They Make a Difference to Adolescents?

Social Science & Medicine (1982). Apr, 2012  |  Pubmed ID: 22385817

Graphic warning labels and plain cigarette packaging are two initiatives developed to increase quit behaviour among smokers. Although a little is known about how adolescents interpret graphic warning labels, very few studies have examined how plain cigarette packaging would affect adolescents' perceptions of cigarette smoking and smoking behaviour. We explored how teens interpret and respond to graphic warning labels and the plain packaging of cigarettes, to assess the potential these strategies may offer in deterring smoking initiation. Twelve focus group interviews with a sample of 80 14-16 year old students from a diverse range of schools in Auckland, New Zealand were undertaken between June and August 2009. Textual analysis revealed that graphic warning labels may influence adolescents by reiterating a negative image of smokers. Graphic warning on a plain cigarette pack increased the attention paid to graphic warning labels and the overall perceptions of harm caused by cigarette smoking, and reduced the social appeal of cigarette smoking. This research offers evidence on how adolescents are appraising and interpreting graphic warning labels, and explores how dominant appraisals may affect the role graphic warning labels play in preventing smoking. Not only would plain cigarette packaging enhance the salience and impact of graphic warning labels, but it would potentially bolster the overall message that cigarette smoking is harmful. In the context of a comprehensive tobacco control programme, graphic warning labels on plain cigarette packaging present an explicit message about the risks (to health and image) associated with cigarette smoking.

Chronic Intermittent Ethanol and Withdrawal Differentially Modulate Basolateral Amygdala AMPA-type Glutamate Receptor Function and Trafficking

Neuropharmacology. Jun, 2012  |  Pubmed ID: 22387532

The amygdala plays a critical role in the generation and expression of anxiety-like behaviors including those expressed following withdrawal (WD) from chronic intermittent ethanol (CIE) exposure. In particular, the BLA glutamatergic system controls the expression of both innate and pathological anxiety. Recent data suggests that CIE and WD may functionally alter this system in a manner that closely parallels memory-related phenomena like long-term potentiation (LTP). We therefore specifically dissected CIE/WD-induced changes in glutamatergic signaling using electrophysiological and biochemical approaches with a particular focus on the plasticity-related components of this neurotransmitter system. Our results indicate that cortical glutamatergic inputs arriving at BLA principal via the external capsule undergo predominantly post-synaptic alterations in AMPA receptor function following CIE and WD. Biochemical analysis revealed treatment-dependent changes in AMPA receptor surface expression and subunit phosphorylation that are complemented by changes in total protein levels and/or phosphorylation status of several key, plasticity-associated protein kinases such as calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC). Together, these data show that CIE- and WD-induced changes in BLA glutamatergic function both functionally and biochemically mimic plasticity-related states. These mechanisms likely contribute to long-term increases in anxiety-like behavior following chronic ethanol exposure.

Dysfunction of the Diaphragm

The New England Journal of Medicine. Mar, 2012  |  Pubmed ID: 22397655

DNA Damage-dependent NF-κB Activation: NEMO Turns Nuclear Signaling Inside Out

Immunological Reviews. Mar, 2012  |  Pubmed ID: 22435563

Summary:  The dimeric transcription factor nuclear factor κB (NF-κB) functions broadly in coordinating cellular responses during inflammation and immune reactions, and its importance in the pathogenesis of cancer is increasingly recognized. Many of the signal transduction pathways that trigger activation of cytoplasmic NF-κB in response to a broad array of immune and inflammatory stimuli have been elaborated in great detail. NF-κB can also be activated by DNA damage, though relatively less is known about the signal transduction mechanisms that link DNA damage in the nucleus with activation of NF-κB in the cytoplasm. Here, we focus on the conserved signaling pathway that has emerged that promotes NF-κB activation following DNA damage. Post-translational modification of NF-κB essential modulator (NEMO) plays a central role in linking the cellular DNA damage response to NF-κB via the ataxia telangiectasia mutated (ATM) kinase. Accumulating evidence suggests that DNA damage-dependent NF-κB activation may play significant biological roles, particularly during lymphocyte differentiation and progression of human malignancies.