bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ProActivetrial protocol – a randomised controlled trial of the efficacy of a family-based, domiciliary intervention programme to increase physical activity among individuals at high risk of diabetes [ISRCTN61323766]
Authors: Williams Kate , Prevost A Toby , Griffin Simon , Hardeman Wendy , Hollingworth William , Spiegelhalter David , Sutton Stephen , Ekelund Ulf , Wareham Nicholas , Kinmonth Ann Louise 
Published: October 2004

Abstract
Background
Increasing prevalence of obesity and disorders associated with sedentary living constitute a major global public health problem. While previous evaluations of interventions to increase physical activity have involved communities or individuals with established disease, less attention has been given to interventions for individuals at risk of disease.

Methods/design
ProActiveaims to evaluate the efficacy of a theoretical, evidence- and family-based intervention programme to increase physical activity in a sedentary population, defined as being at-risk through having a parental family history of diabetes. Primary care diabetes or family history registers were used to recruit 365 individuals aged 30–50 years, screened for activity level. Participants were assigned by central randomisation to three intervention programmes: brief written advice (comparison group), or a psychologically based behavioural change programme, delivered either by telephone (distance group) or face-to-face in the family home over one year. The protocol-driven intervention programme is delivered by trained facilitators, and aims to support increases in physical activity through the introduction and facilitation of a range of self-regulatory skills (e.g. goal setting). The primary outcome is daytime energy expenditure and its ratio to resting energy expenditure, measured at baseline and one year using individually calibrated heart rate monitoring. Secondary measures include self-report of individual and family activity, psychological mediators of behaviour change, physiological and biochemical correlates, acceptability, and costs, measured at baseline, six months and one year. The primary intention to treat analysis will compare groups at one-year post randomisation. Estimation of the impact on diabetes incidence will be modelled using data from a parallel ten-year cohort study using similar measures.

Discussion
ProActiveis the first efficacy trial of an intervention programme to promote physical activity in a defined high-risk group accessible through primary care. The intervention programme is based on psychological theory and evidence; it introduces and facilitates the use of self-regulatory skills to support behaviour change and maintenance. The trial addresses a range of methodological weaknesses in the field by careful specification and quality assurance of the intervention programme, precise characterisation of participants, year-long follow-up and objective measurement of physical activity. Due to report in 2005, ProActivewill provide estimates of the extent to which this approach could assist at-risk groups who could benefit from changes in behaviours affecting health, and inform future pragmatic trials.
Student evaluation of an OSCE in paediatrics at the University of the West Indies, Jamaica
Authors: Pierre Russell B , Wierenga Andrea , Barton Michelle , Branday J Michael , Christie Celia DC 
Published: October 2004

Abstract
Background
The Faculty of Medical Sciences, University of the West Indies first implemented the Objective Structured Clinical Examination (OSCE) in the final MB Examination in Medicine and Therapeutics during the 2000–2001 academic year. Simultaneously, the Child Health Department initiated faculty and student training, and instituted the OSCE as an assessment instrument during the Child Health (Paediatric) clerkship in year 5. The study set out to explore student acceptance of the OSCE as part of an evaluation of the Child Health clerkship.

Methods
A self-administered questionnaire was completed by successive groups of students immediately after the OSCE at the end of each clerkship rotation. Main outcome measures were student perception of examination attributes, which included the quality of instructions and organisation, the quality of performance, authenticity and transparency of the process, and usefulness of the OSCE as an assessment instrument compared to other formats.

Results
There was overwhelming acceptance of the OSCE in Child Health with respect to the comprehensiveness (90%), transparency (87%), fairness (70%) and authenticity of the required tasks (58–78%). However, students felt that it was a strong anxiety-producing experience. And concerns were expressed regarding the ambiguity of some questions and inadequacy of time for expected tasks.

Conclusion
Student feedback was invaluable in influencing faculty teaching, curriculum direction and appreciation of student opinion. Further psychometric evaluation will strengthen the development of the OSCE.
Macrophage activation by a DNA/cationic liposome complex requires endosomal acidification and TLR9-dependent and -independent pathways
Authors: Yasuda Kei , Ogawa Yoshiyuki , Yamane Ikuko , Nishikawa Makiya , Takakura Yoshinobu 
Published: October 2004

AbstractPreviously, we showed that bacterial DNA and vertebrate DNA/cationic liposome complexes stimulate potent inflammatory responses in cultured mouse macrophages. In the present study, we examined whether endocytosis and subsequent acidification are associated with these responses. The endocytosis inhibitor, cytochalasin B, reduced tmor necrosis factor α (TNF-α) production by a plasmid DNA (pDNA)/cationic liposome complex. The endosomal acidification inhibitor, monensin, inhibited cytokine production by pDNA or a calf thymus DNA/liposome complex. These results suggest, similarly to CpG motif-dependent responses, that endocytosis and subsequent endosomal acidification are also required for these inflammatory responses. It is intriguing that another inhibitor of endosomal acidification, bafilomycin A, stimulated the production of TNF-α mRNA and its protein after removal of the pDNA/liposome complex and inhibitors, although it inhibited the release of interleukin-6. Similar phenomena were observed in the activation of macrophages by CpG oligodeoxynucleotide, calf thymus DNA, and Escherichia coli DNA complexed with liposomes. Moreover, bafilomycin A also induced a high degree of TNF-α release after stimulation with naked pDNA. These results suggest that bafilomycin A increases TNF-α production induced by DNA at the transcriptional level via an as-yet unknown mechanism. Furthermore, we investigated the contribution of Toll-like receptor 9 (TLR9), the receptor of CpG motifs, to the cell activation by the DNA/cationic liposome complex using the macrophages from TLR9−/− mice. We observed a reduced inflammatory cytokine release from macrophages of TLR9−/− mice compared with wild-type mice. However, the cytokine production was not completely abolished, suggesting that the DNA/cationic liposome complex can induce macrophage activation via TLR9-dependent and -independent pathways.
Linking the “two-hit” response following injury to enhanced TLR4 reactivity
Authors: Murphy Thomas J , Paterson Hugh M , Kriynovich Sara , Zang Yan , Kurt-Jones Evelyn A , Mannick John A , Lederer James A 
Published: October 2004

AbstractSevere injury can initiate an exaggerated systemic inflammatory response and multiple organ failure (MOF) if a subsequent immune stimulus, “second hit”, occurs. Using a mouse thermal injury model, we tested whether changes in innate immune cell reactivity following injury can contribute to the development of heightened inflammation and MOF. Using high-purity Escherichia coli lipopolysaccharide (LPS) to selectively stimulate Toll-like receptor 4 (TLR4), we demonstrate augmented interleukin (IL)-1β, tumor necrosis factor α (TNF-α), and IL-6 production by 1 day but particularly, at 7 days after injury. The in vivo significance of enhanced TLR4 responsiveness was explored by challenging sham or burn mice with LPS at 1 or 7 days after injury and determining mortality along with in vivo cytokine and chemokine levels. Mortality was high (75%) in LPS-challenged burn but not sham mice at 7 days, although not at 1 day, after injury. Death was associated with leukocyte sequestration in the lungs and livers along with increased proinflammatory cytokine and chemokine levels in these organs. Blocking TNF-α activity prevented this mortality, suggesting that excessive TNF-α production contributes to this lethal response. These findings demonstrate the potential lethality of excessive TLR4 reactivity after injury and provide an explanation for the exaggerated inflammatory response to a second hit, which can occur following severe injury.
JAK2 is necessary and sufficient for interferon-γ-induced transcription of the gene encoding gp91PHOX
Authors: Kakar Renu , Kautz Bryan , Eklund Elizabeth A 
Published: October 2004

AbstractDuring the inflammatory response, interferon-γ (IFN-γ) increases transcription of the gene encoding gp91PHOX, a respiratory burst oxidase component. This gene (referred to as the CYBB gene) is transcribed in phagocytic cells differentiated beyond the promyelocyte stage, and transcription continues until cell death. Previous investigations identified a positive regulatory element in the proximal CYBB promoter rferred to as the hematopoiesis-associated factor 1 (HAF1)-cis element. This element is activated by a multiprotein complex, which includes the IFN consensus sequence-binding protein (ICSBP). Interaction of this complex with the HAF1-cis element requires ICSBP tyrosine phosphorylation, which is induced by IFN-γ stimulation of phagocytic cells. Previous studies also identified a negative cis element in the CYBB promoter. This element is repressed by the homeodomain protein HoxA10. HoxA10 tyrosine phosphorylation, which occurs in response to IFN-γ, decreases HoxA10 DNA binding and therefore repression of CYBB transcription. In these studies, we determine Janus tyrosine kinase 2 (JAK2) activation is necessary and sufficient for IFN-γ-induced CYBB transcription in phagocytic cells and also for ICSBP and HoxA10 tyrosine phosphorylation. Consistent with these results, we find JAK2 activation is sufficient to induce ICSBP interaction with the HAF1 element and abolish HoxA10 binding to the CYBBrepressor element. Therefore, these findings provide direct demonstration of JAK2 dependence of IFN-γ-induced CYBB transcription. In addition, these results identify a mechanism mediating this effect.
Cardiorespiratory and tissue adenosine responses to hypoxia and reoxygenation in the short-horned sculpinMyoxocephalus scorpius
Authors: MacCormack T. J. , Driedzic W. R. 
Published: October 2004

SUMMARYAdenosine is a product of adenylate phosphate breakdown that can exert protective effects on tissues during energy limitation. Accumulation of cardiac adenosine under hypoxia is well documented in mammals but has not been shown in fish. Adenosine content was measured in heart and brain tissue from short-horned sculpin Myoxocephalus scorpius L. exposed to acute hypoxia and to graded hypoxia and reoxygenation at 8°C. Cardiorespiratory parameters were recorded along with plasma lactate, K+,Ca2+ and Na+ levels and their relationship to adenosine levels investigated. Sculpin exhibited a large bradycardia during hypoxia,with a concomitant drop in cardiac output that recovers fully with reoxygenation. Ventilation rate also declined with hypoxia, suggesting a depression of activity. Plasma lactate concentration was significantly elevated after 4 h at 2.0 mg l-1 dissolved oxygen while K+ levels increased during acute hypoxia. Adenosine levels were maintained in heart under acute and graded hypoxia. Brain levels fluctuated under hypoxia and showed no change with reoxygenation. It is concluded that a depression of cardiac activity in conjunction with an adequate anaerobic metabolism allow sculpin to avoid excessive adenosine accumulation under conditions of moderate hypoxia. Cardiac adenosine levels decreased and plasma K+ levels and heart rate increased significantly at reoxygenation.
Presence and properties of cellulase and hemicellulase enzymes of the gecarcinid land crabs Gecarcoidea natalis and Discoplax hirtipes
Authors: Linton Stuart M. , Greenaway Peter 
Published: October 2004

SUMMARY
Digestive juice from the herbivorous gecarcinid land crabs Gecarcoidea natalis and Discoplax hirtipes exhibited total cellulase activity and activities of two cellulase enzymes; endo-β-1,4-glucanase and β-1,4-glucosidase. These enzymes hydrolysed native cellulose to glucose. The digestive juice of both species also contained laminarinase,licheninase and xylanase, which hydrolysed laminarin, lichenin and xylan,respectively, to component sugars. The pH optima of β-1,4-glucosidase,endo-β-1,4-glucanase and total cellulase from G. natalis were 4–5.5, 5.5 and 5.5–7, respectively. In the digestive juice from D. hirtipes, the corresponding values were 4–7, 5.5–7 and 4–9, respectively. The pH of the digestive juice was 6.69±0.03 for G. natalis and 6.03±0.04 for D. hirtipes and it is likely that the cellulases operate near maximally in vivo. In G. natalis, total cellulase activity and endo-β-1,4-glucanase activity were higher than in D. hirtipes, and the former species can thus hydrolyse cellulose more rapidly. β-1,4-glucosidase from G. natalis was inhibited less by glucono-d-lactone(Ki=11.12 mmol l-1) than was theβ-1,4-glucosidase from D. hirtipes (Ki=4.53 mmol l-1). The greater resistance to inhibition by theβ-1,4-glucosidase from G. natalis may contribute to the efficiency of the cellulase system in vivo by counteracting the effects of product inhibition and possibly dietary tannins. The activity ofβ-1,4-glucosidase in the digestive juice of D. hirtipes was higher than that of G. natalis.
Calcium handling in Sparus auratus: effects of water and dietary calcium levels on mineral composition, cortisol and PTHrP levels
Authors: Abbink Wout , Bevelander Gideon S. , Rotllant Josep , Canario Adelino V. M. , Flik Gert 
Published: October 2004

SUMMARY
Juvenile gilthead sea bream (Sparus auratus L.; 10–40 g body mass) were acclimatized in the laboratory to full strength (34‰) or dilute (2.5‰) seawater and fed normal, calcium-sufficient or calcium-deficient diet for nine weeks. Mean growth rate, whole-body calcium and phosphorus content and accumulation rates were determined, as well as plasma levels of ionic and total calcium, cortisol and parathyroid hormone related protein (PTHrP; a hypercalcemic hormone in fish). When confronted with limited calcium access (low salinity and calcium-deficient diet), sea bream show growth arrest. Both plasma cortisol and PTHrP increase when calcium is limited in water or diet, and a positive relationship was found between plasma PTHrP and plasma ionic calcium (R2=0.29, N=18, P&lt;0.05). Furthermore, a strong correlation was found between net calcium and phosphorus accumulation (R2=0.92, N=16, P&lt;0.01) and between body mass and whole-body calcium (R2=0.84, N=25, P&lt;0.01) and phosphorus (R2=0.88, N=24, P&lt;0.01)content. Phosphorus accumulation is strongly calcium dependent, as phosphorus accumulation decreases in parallel to calcium accumulation when the diet is calcium deficient but phosphorus sufficient. We conclude that PTHrP and cortisol are involved in the regulation of the hydromineral balance of these fish, with growth-related calcium accumulation as an important target.
Conservation of capa peptide-induced nitric oxide signalling in Diptera
Authors: Pollock Valerie P. , McGettigan James , Cabrero Pablo , Maudlin Ian M. , Dow Julian A. T. , Davies Shireen-A. 
Published: October 2004

SUMMARYIn D. melanogaster Malpighian (renal) tubules, the capa peptides stimulate production of nitric oxide (NO) and guanosine 3′,5′-cyclic monophosphate (cGMP), resulting in increased fluid transport. The roles of NO synthase (NOS), NO and cGMP in capa peptide signalling were tested in several other insect species of medical relevance within the Diptera(Aedes aegypti, Anopheles stephensi and Glossina morsitans) and in one orthopteran out-group, Schistocerca gregaria. NOS immunoreactivity was detectable by immunocytochemistry in tubules from all species studied. D. melanogaster, A. aegypti and A. stephensi express NOS in only principal cells,whereas G. morsitans and S. gregaria show more general NOS expression in the tubule. Measurement of associated NOS activity (NADPH diaphorase) shows that both D. melanogaster capa-1 and the two capa peptides encoded in the A. gambiae genome, QGLVPFPRVamide(AngCAPA-QGL) and GPTVGLFAFPRVamide (AngCAPA-GPT), all stimulate NOS activity in D. melanogaster, A. aegypti, A. stephensi and G. morsitans tubules but not in S. gregaria. Furthermore, capa-stimulated NOS activity in all the Diptera was inhibited by the NOS inhibitor l-NAME. All capa peptides stimulate an increase in cGMP content across the dipteran species, but not in the orthopteran S. gregaria. Similarly, all capa peptides tested stimulate fluid secretion in D. melanogaster, A. aegypti, A. stephensi and G. morsitans tubules but are either without effect or are inhibitory on S. gregaria. Consistent with these results, the Drosophila capa receptor was shown to be expressed in Drosophila tubules, and its closest Anopheles homologue was shown to be expressed in Anopheles tubules. Thus, we provide the first demonstration of physiological roles for two putative A. gambiae neuropeptides. We also demonstrate neuropeptide modulation of fluid secretion in tsetse tubule for the first time. Finally, we show the generality of capa peptide action, to stimulate NO/cGMP signalling and increase fluid transport, across the Diptera, but not in the more primitive Orthoptera.
Ontogeny of the gut motility control system in zebrafishDanio rerioembryos and larvae
Authors: Holmberg Anna , Schwerte Thorsten , Pelster Bernd , Holmgren Susanne 
Published: October 2004

SUMMARYUsing digital motion analysis, the ontogeny of the cholinergic, tachykinin and pituitary adenylate cyclase-activating polypeptide (PACAP) control systems was studied in zebrafish Danio rerio larvae, in vivo. For the first time we show that the regular propagating anterograde waves that occur in the zebrafish larval gut before and around the onset [at 5–6 days post fertilization (d.p.f.)] of feeding are modulated by acetylcholine or atropine, PACAP and NKA (neurokinin A). At 3 d.p.f., when no spontaneous motility has developed, application of acetylcholine did not affect the gut. However, at 4 d.p.f., acetylcholine increased and atropine reduced the frequency of propagating anterograde waves. At 5 d.p.f., NKA increased and PACAP reduced the wave frequency. This suggests that both excitatory and inhibitory pathways develop at an early stage in the gut, independent of exogenous feeding. Immunohistochemistry established the presence of gut neurons expressing PACAP and NKA in the proximal part of the developing gut from the first stage investigated (2 d.p.f.) and before regular motility was observed. 1 d.p.f. (PACAP) or 2 d.p.f. (NKA) stages later the whole gut was innervated. This supports physiological results that gut motility is under neuronal control during the period when regular motility patterns develop.
The effect of substrate on the efficacy of seismic courtship signal transmission in the jumping spider Habronattus dossenus (Araneae:Salticidae)
Authors: Elias Damian O. , Mason Andrew C. , Hoy Ronald R. 
Published: October 2004

SUMMARY
The jumping spider Habronattus dossenusGriswold 1987 (Salticidae)communicates using seismic signals during courtship and can be found on rocks,sand and leaf litter. We examined the filtering properties of, and tested the efficacy of male courtship signals on, these natural substrates. These substrates have drastically different filtering properties at the distances at which the males court. Rocks sharply attenuated all frequencies, with considerable variability among different rocks. Desert sand showed band-pass properties, attenuating frequencies contained in the animal's signal. Leaf litter passed all frequencies and was the most favourable signalling environment. In behavioural trials, the proportion of males mating successfully was significantly higher on leaf litter than on rocks or desert sand. Males did not modify their courtship behaviour on different substrates. Therefore, the effectiveness of male courtship seismic signals appears to be strongly constrained by the available substratum resources.
Elevated intra-abdominal pressure limits venous return during exercise inVaranus exanthematicus
Authors: Munns Suzanne L. , Hartzler Lynn K. , Bennett Albert F. , Hicks James W. 
Published: October 2004

SUMMARYThe effects of treadmill exercise on components of the cardiovascular(venous return, heart rate, arterial blood pressure) and respiratory systems(minute ventilation, tidal volume, breathing frequency, oxygen consumption,carbon dioxide production) and intra-abdominal pressure were investigated in the Savannah monitor lizard, Varanus exanthematicus B., at 35°C. Compared with resting conditions, treadmill exercise significantly increased lung ventilation, gular pumping, intra-abdominal pressure, mean arterial blood pressure and venous return (blood flow in the post caval vein). However,venous return declines at high levels of activity, and mean arterial pressure and venous return did not attain peak values until the recovery period,immediately following activity. Elevating intra-abdominal pressure in resting lizards (via saline infusion) resulted in significant reductions in venous return when the transmural pressure of the post caval vein became negative (i.e. when intra-abdominal pressure exceeded central venous pressure). Together these results suggest that increments in intra-abdominal pressure compress the large abdominal veins and inhibit venous return. During locomotion, the physical compression of the large abdominal veins may represent a significant limitation to cardiac output and maximal oxygen consumption in lizards.
The Activity of Class I and II Alcohol Dehydrogenase Isoenzymes in the Sera of Patients with Liver Tumours
Authors: Chrostek Lech , Szmitkowski Maciej 
Published: October 2004

Abstract
We have measured the activity of class I and II alcohol dehydrogenase isoenzymes in the sera of patients with liver tumours, using class-specific fluorogenic naphthaldehydes as substrates. The activity of the tested isoenzymes was unchanged in primary tumours and significantly increased (class I) in metastatic liver tumours. The total enzyme activity was also increased (3-fold) in this group of patients. The elevated activity of class I isoenzymes in secondary tumours seems to be caused by the enzyme released from primary cells originating in the other organs, but increased total enzyme activity measured with chromogenic substrates may be proof of the presence of other classes of isoenzymes. These results show that the elevated class I isoenzymes and total enzyme activity in the sera of patients with liver tumours may indicate the metastatic origin of these tumours.