Reducing 30-day post gastrostomy insertion mortality with a feeding issues multidisciplinary team meeting.

INTRODUCTION: Decision-making regarding percutaneous endoscopic gastrostomy (PEG) insertion can be complex both medically and ethically. Thirty-day mortality following (PEG) insertion is an important quality indicator for endoscopy accreditation and for service evaluation. It also forms part of the measures assessed within the 'Getting It Right First Time' programme (GIRFT). We aimed to assess the impact of a newly adopted Feeding Issues MDT (FIMDT) and the clinical application of the Royal Free Gastrostomy Score (RFGS). METHOD: We adopted a retrospective observational methodology to assess the impact of a feeding issues MDT within our trust. The included study period ran from January 2016 to December 2019 (4 years). This formed part of a quality improvement (QI) project initiated upon receipt of the GIRFT report for our NHS trust. Statistical analysis and QI methodology was used to interpret and present the data. RESULTS: Two hundred and sixty eight PEG insertions occurred during the study period. 188 PEGs were inserted prior to the start of FIMDT and 45 following its inception. On average there were 66 PEGs performed per year. There was no significant difference in age for those undergoing PEG insertion pre (68 years) and post (69 years) FIMDT adoption. Prior to FIMDT those that died within 30 days post PEG were significantly older than those who did not (p < 0.001), whilst following FIMDT adoption there was no such difference. Prior to FIMDT the 30-day post PEG mortality was 10.64%, whilst following adoption of the FIMDT the mortality rate fell to 6.6% (p = 0.04). The mean number of procedures performed between a 30-day mortality occurring rose from 7.5 to 13.6. Furthermore, the mean number of days between a 30-day post insertion mortality occurring also rose from a mean of 53.0-111.8, pre and post FIMDT adoption. The Royal Free Gastrostomy Score (RFGS) for those discussed at FIMDT and declined for PEG insertion was significantly higher than those accepted for PEG insertion (p = 0.01). Over the entire study period those who died within 30 days following PEG insertion had a significantly greater RFGS (p < 0.0001). CONCLUSION: In our trust the adoption of a FIMDT has significantly reduced the 30-day mortality for PEG insertion. We have also demonstrated the clinical utility to assess mortality risk of the RFGS when making decisions around patient suitability for PEG insertion.

Skeletal muscle plasticity with marathon training in novice runners.

The purpose of this study was to investigate leg muscle adaptation in runners preparing for their first marathon. Soleus and vastus lateralis (VL) biopsies were obtained from six recreational runners (23 ± 1 years, 61 ± 3 kg) before (T1), after 13 weeks of run training (T2), and after 3 weeks of taper and marathon (T3). Single muscle fiber size, contractile function (strength, speed, and power) and oxidative enzyme activity [citrate synthase (CS)] were measured at all three time points, and fiber type distribution was determined before and after the 16-week intervention. Training increased VO(2max) ∼9% (P<0.05). All soleus parameters were unchanged. VL MHC I fiber diameter increased (+8%; P<0.05) from T1 to T2. VL MHC I V(o) (-12%), MHC I power (-22%) and MHC IIa power (-29%) were reduced from T1 to T2 (P<0.05). No changes in VL single fiber contractile properties were observed from T2 to T3. No change was observed in soleus CS activity, whereas VL CS activity increased 66% (P<0.05). Our observations indicate that modest marathon training elicits very specific skeletal muscle adaptations that likely support the ability to perform 42.2 km of continuous running - further strengthening the existing body of evidence for skeletal muscle specificity.

Construct validity of the MAST and AUDIT with multiple offender drunk drivers.

The construct validity of the Michigan Alcoholism Screening Test (MAST) and the Alcohol Use Disorders Identification Test (AUDIT) in screening for current DSM-IV alcohol dependence disorders with persons convicted of multiple offenses of Driving Under the Influence (DUI) is evaluated. These tests were administered to 126 DUI offenders presenting for court-ordered inpatient treatment at an agency. DSM-IV alcohol disorders are evaluated for a representative subset of clients in this program using National Longitudinal Alcohol Epidemiologic Surveys' DSM-IV Alcohol Dependence Diagnostic Criteria and Associated Questionnaire Items. Both instruments exhibit acceptable internal consistency. The MAST and The AUDIT correlate moderately well with each other (r=0.617). The MAST correlates more highly (r=0.602) than the AUDIT (r=0.432) with DSM-IV. Future research should examine if the results reported here apply to other multiple offender DUI programs. It is recommended that such programs employing test instruments evaluate their construct validity in a similar method.

Mistakes that heterosexual people make when trying to appear non-prejudiced: the view from LGB people.

In two studies, lesbians, gay men and bisexuals were queried concerning mistakes that well-meaning heterosexual people have made when interacting with them. In qualitative, open-ended research, we determined that the most common mistakes concerned heterosexuals' pointing out that they know someone who is gay, emphasizing their lack of prejudice, and relying on stereotypes about gays. Following up with a quantitative, close-ended questionnaire, we determined that the mistakes respondents experienced most often involved heterosexuals (a) relying on stereotypes and (b) ignoring gay issues; the most annoying mistakes were heterosexuals (a) using subtle prejudicial language and (b) not owning up to their discomfort with gay issues. We used two theoretical perspectives, shared reality theory and the contact hypothesis, to analyze the quantitative responses. Implications for intergroup relationships between heterosexual people and gay people are discussed.

Cannabinoid and dopamine interaction in rodent brain: effects on locomotor activity.

We investigated interactions between cannabinoid and dopamine receptor systems in ICR mice. Mice were treated with the cannabinoid agonist levonantradol, the D(1) dopamine agonist 6-Br-APB, or the D(2) dopamine agonist quinelorane, or with combinations of these drugs. In addition, the D(1) antagonist SCH23390 was administered both alone and in combination with levonantradol. Two tests were used to evaluate changes in motor function: the immobility (ring stand) test and the catalepsy (bar) test. Levonantradol increased immobility and catalepsy in a dose-dependant manner. Both the D(2) agonist quinelorane and the D(1) agonist 6-Br-APB were able to attenuate the motor dysfunction caused by levonantradol. Administration of the D(1) antagonist SCH23390 enhanced the effects of levonantradol, producing a leftward shift of the log dose-response curve. These results differ from the augmentation by D(2) agonists of the hypoactivity induced by levonantradol in non-human primates [Meschler JP, Clarkson FA, Mathew PJ, Howlett AC, Madras BK. D(2), but not D(1) dopamine receptor agonists potentiate cannabinoid-induced sedation in nonhuman primates. J Pharmacol Exp Ther 2000;292:952-959], suggesting that conclusions about the interactions between the dopamine and cannabinoid receptor motor systems in rodents may not extend to primates.

Mutations affecting induction of glycolytic and fermentative genes during germination and environmental stresses in Arabidopsis.

Expression of the alcohol dehydrogenase gene (ADH) of Arabidopsis is known to be induced by environmental stresses and regulated developmentally. We used a negative-selection approach to isolate mutants that were defective in regulating the expression of the ADH gene during seed germination; we then characterized three recessive mutants, aar1-1, aar1-2, and aar2-1, which belong to two complementation groups. In addition to their defects during seed germination, mutations in the AAR1 and AAR2 genes also affected anoxic and hypoxic induction of ADH and other glycolytic genes in mature plants. The aar1 and aar2 mutants were also defective in responding to cold and osmotic stress. The two allelic mutants aar1-1and aar1-2 exhibited different phenotypes under cold and osmotic stresses. Based on our results we propose that these mutants are defective in a late step of the signaling pathways that lead to increased expression of the ADH gene and glycolytic genes.

A critique of Bem's "Exotic Becomes Erotic" theory of sexual orientation.

Two critiques of D. J. Bem's (1996) "Exotic Becomes Erotic" (EBE) theory of sexual orientation are presented. First, the core proposition of EBE theory is considered; that is, the idea that adults are erotically attracted to the gender-based class of peers (males or females) who were dissimilar or unfamiliar to them in childhood. Studies cited by Bem and additional research show that EBE theory is not supported by scientific evidence. Second, Bem's claim that his theory applies equally to both sexes is questioned; instead the argument that it neglects and misrepresents women's experiences is made. Bem's conceptualization of erotic desire and his analysis of gender nonconformity illustrate this problem. It is suggested that different theories may be needed to explain the development of men's and women's sexual orientation.

Water Deficit Rapidly Stimulates the Activity of a Protein Kinase in the Elongation Zone of the Maize Primary Root.

The mechanisms by which plants detect water deficit and transduce that signal into adaptive responses is unknown. In maize (Zea mays L.) seedlings, primary roots adapt to low water potentials such that substantial rates of elongation continue when shoot growth is completely inhibited. In this study, in-gel protein kinase assays were used to determine whether protein kinases in the elongation zone of the primary root undergo activation or inactivation in response to water deficit. Multiple differences were detected in the phosphoprotein content of root tips of water-stressed compared with well-watered seedlings. Protein kinase assays identified water-deficit-activated protein kinases, including a 45-kD, Ca2+-independent serine/threonine protein kinase. Water-deficit activation of this kinase occurred within 30 min after transplanting seedlings to conditions of low water potential and was localized to the elongation zone, was independent of ABA accumulation, and was unaffected by cycloheximide-mediated inhibition of protein translation. These results provide evidence that the 45-kD protein kinase acts at an early step in the response of maize primary roots to water deficit and is possibly involved in regulating the adaptation of root growth to low water potential.

Effects of light and chloroplast functional state on expression of nuclear genes encoding chloroplast glyceraldehyde-3-phosphate dehydrogenase in long hypocotyl (hy) mutants and wild-type Arabidopsis thaliana.

In a previous study of Arabidopsis thaliana (J. Dewdney, T.R. Conley, M.-C. Shih, H.M. Goodman [1993] Plant Physiol 103: 1115-1121), it was postulated that both blue light receptor- and phytochrome-mediated pathways contribute to regulation of the nuclear genes encoding A and B subunits of glyceraldehyde-3-phosphate dehydrogenase (GAPA and GAPB). Here were report on the involvement of a nuclear gene encoding a putative blue-light receptor (HY4) and of a nuclear gene encoding phytochrome A apoprotein (PHYA) in regulation of the GAPA and GAPB genes in response to blue and far-red light. Continuous light irradiation experiments with the hy4 mutant demonstrate that the HY4 gene product is required for full expression of GAPA, GAPB, and one or more of the nuclear genes encoding small subunits of of ribulose-1,5-bisphosphate carboxylase/oxygenase. Continuous light irradiation and fluence-response studies with the phyA-101 mutant show that phytochrome A functions in far-red light regulation of GAPA, GAPB, nuclear genes encoding small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase, and CAB genes. Phytochromes A and B alone either do not participate in red light-mediated gene regulation or have redundant functions, as shown by analysis of phyA-101 and phyB-1 single mutants. In addition, the hypothesis that chloroplast-nucleus interactions affect GAPA and GAPB gene regulation was tested. Herbicide-mediated photooxidative damage to chloroplasts in A thaliana seedlings strongly decreased the maximum amount of GAPA and GAPB steady-state mRNA detected in continuous-light irradiation experiments. Full expression of the GAPB genes is dependent on the presence of functional chloroplasts.

Rochalimaea species stimulate human endothelial cell proliferation and migration in vitro.

Rochalimaea henselae and R. quintana are associated clinically with proliferative neovascular lesions. The effect of Rochalimaea species on human umbilical vein endothelial cell (HUVEC) proliferation and migration was evaluated in vitro. Cocultivation of Rochalimaea organisms with HUVECs resulted in enhanced HUVEC proliferation. Fibroblast proliferation was unaffected by R. henselae. HUVECs were also stimulated to migrate by Rochalimaea. When R. henselae organisms were disrupted and subjected to centrifugation, the ability to enhance HUVEC proliferation and migration was localized to the particulate, noncytosolic fraction. Trypsin treatment of this fraction diminished its stimulatory activity. These data suggest that the neovascular manifestations of infection with Rochalimaea are likely caused by the production of an angiogenic factor by these bacteria.

Characterization of cis-acting elements in light regulation of the nuclear gene encoding the A subunit of chloroplast isozymes of glyceraldehyde-3-phosphate dehydrogenase from Arabidopsis thaliana.

We have characterized cis-acting elements involved in light regulation of the nuclear gene (GapA) encoding the A subunit of chloroplast glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in Arabidopsis thaliana. Our results show that a 1.1-kb promoter fragment of the GapA gene is sufficient to confer light inducibility and organ specificity in transgenic Nicotiana tabacum (tobacco) plants, using the beta-glucuronidase gene of Escherichia coli as the reporter gene. Deletion analysis indicates that the -359 to -110 bp region of the GapA gene is necessary for light responsiveness. Within this region there are three copies of a decamer repeat (termed the Gap box) having the consensus sequence 5'-CAAATGAA(A/G)A-3', which has not been characterized in the promoter regions of other light-regulated genes. A deletion (to -247) producing loss of one copy of these elements from the GapA promoter reduces light induction by two- to threefold compared with a promoter deletion (to -359) with all three Gap boxes present, while deletion of all three Gap boxes (to -110) abolishes light induction completely. Gel mobility shift experiments using tobacco nuclei as the source of nuclear proteins show that GapA promoter fragments that contain these repeats bind strongly to a factor in the nuclear extract and that binding can be abolished by synthetic competitors consisting only of a monomer or dimer of the Gap box. Furthermore, a trimer, dimer, and monomer of the Gap box show binding activity and, like the authentic GapA promoter-derived probes, show binding activities that are correlated with Gap box copy number. These results strongly suggest that these repeats play important roles in light regulation of the GapA gene of A. thaliana.

Effects of blue and red light on expression of nuclear genes encoding chloroplast glyceraldehyde-3-phosphate dehydrogenase of Arabidopsis thaliana.

We have characterized the effects of different light spectra on expression of the nuclear genes (GapA and GapB) encoding chloroplast glyceraldehyde-3-phosphate dehydrogenase in Arabidopsis thaliana. Steady-state mRNA levels for both genes in etiolated seedlings increased after a short exposure to red or blue light. However, these increases could not be reversed by immediate far-red light following the initial light treatment. In mature plants, a short light pulse, regardless of its spectrum, had no apparent effect on GapA or GapB mRNA levels in dark-adapted plants. In contrast, continuous exposure to red, blue, or white light resulted in increases of GapA and GapB mRNA levels, with blue and white light being far more efficient than red light. Similarly, continuous exposure of etiolated seedlings to red, blue, or white light also resulted in increased GapA and GapB mRNA levels. In addition, we show that illumination of red light-saturated Arabidopsis plants with continuous blue light results in further increases of GapA and GapB mRNA levels. Based on these results, we conclude that both blue light photoreceptor- and phytochrome-mediated pathways are involved in light regulation of GapA and GapB genes in Arabidopsis, with blue light acting as the dominant regulator.

Splenic abscess due to Peptostreptococcus spp. as a complication of cardiac catheterization.

We describe the development of a splenic abscess, due in part to Peptostreptococcus, as a complication of cardiac catheterization. The etiologies of splenic abscess should include Peptostreptococcus, and splenic abscesses should be added to the list of complications of cardiac catheterization.

Thermodynamics and stoicheiometry of the binding of substrate analogues to uricase.

The subunit composition, metal content, substrate-analogue binding and thermal stability of Aspergillus flavus uricase were determined. A. flavus uricase is a tetramer and contains no copper, iron or any other common prosthetic group. Analytical-gel-filtration and equilibrium-dialysis experiments showed one binding site per subunit for urate analogues. The free energy of xanthine binding was -30.5 kJ (-7.3 kcal)/mol of subunit by equilibrium dialysis and -30.1 kJ (-7.2 kcal)/mol of subunit by microcalorimetry. The enthalpy change for xanthine binding was -15.9 kJ (-3.8 kcal)/mol of subunit when determined from the temperature-dependence of the equilibrium constant and -18.0 kJ (-4.3 kcal)/mol of subunit when measured microcalorimetrically. The thermal inactivation rate of A. flavus uricase increases as protein concentration is decreased. This concentration-dependent instability is not due to subunit dissociation.