bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Men’s Acceptance of Modern Contraceptive Practice: Study in Rural Vietnam
Authors: Ha Bui Thi Thu , Jayasuriya Rohan , Owen Neville
Published: November 2005

Studies have shown family planning adoption is likely to be more effective for women when men are actively involved. The transtheoretical model of behavior change was used to examine men’s involvement in general contraception and intrauterine device (IUD) use by their wives. The study was carried out in rural Vietnam with 651 eligible participants. Cons of IUD use for men in precontemplation and contemplation/preparation were significantly higher than those in the action/maintenance stages, whereas the reverse was true for pros of IUD. The self-efficacy for convincing wife to have IUD in precontemplation was significantly lower than for those in higher stages. Women’s education and ages, spontaneous recall of modern contraceptive method, cons for IUD, and self-efficacy for contraception and for convincing wives to get IUD inserted (or continue use) were significant predictors of men’s readiness to accept IUD. Interventions are targeted to reduce cons and increase self-efficacy for IUD use.
School Tobacco Control Policies Related to Students’ Smoking and Attitudes Toward Smoking: National Survey Results, 1999-2000
Authors: Kumar Revathy , O’Malley Patrick M. , Johnston Lloyd D.
Published: November 2005

The belief that schools can play a powerful role in preventing tobacco use among adolescents has led to the implementation of various tobacco-related polices and practices. This study examines the association between school policies regarding monitoring student behavior, severity of action taken for infraction of policies, and tobacco use by staff, and student smoking behavior and attitudes. Data on students’ smoking behavior and attitudes were obtained from the 1999 and 2000 Monitoring the Future surveys of nationally representative samples of 8th-, 10th-, and 12th-grade students. Data on school policies and practices were obtained from administrators in those same schools. Hierarchical analyses using HLM5 were conducted. Strictness of monitoring was significantly negatively associated with daily cigarette use by middle school students. Permitting staff to smoke was significantly positively associated with students’ daily cigarette use and negatively with their disapproval of cigarette use. Policy implications are discussed.
The Effect of Therapeutic Back Massage in Hypertensive Persons: A Preliminary Study
Authors: Olney Christine M.
Published: November 2005

Hypertension, one of the most pervasive disease processes in the United States, can lead to target organ damage. Although there is no one cause of primary hypertension, the theory of an unchecked long-term stress response continues to be a valid argument. Conversely, eliciting the relaxation response may alter the course of the unchecked stress response. Massage therapists have suggested that their therapy elicits the relaxation response and therefore can decrease blood pressure (BP) and hypertension. This preliminary study tested the effects of a regularly applied back massage on the BP of patients with clinically diagnosed hypertension. In this experimental, pretest-posttest study, a 10-min back massage was given to the experimental group (n = 8), three times a week for 10 sessions. The control group (n = 6) relaxed in the same environment for 10 min, three times a week for 10 sessions. Analysis of variance determined systolic BP changed significantly, F (1, 12) = 17.90, p = .001, between groups over time as did the diastolic BP, F (1, 12) = 8.34, p = .014. Effect size was 2.25 for systolic pressure and 1.56 for diastolic pressure (alpha of .05 and power at .80). This preliminary study suggests that regular massage may lower BP in hypertensive persons.
A handheld chemotherapy symptom management system: results from a preliminary outpatient field trial
Authors: McGee Marilyn Rose , Gray Phil
Published: November 2005

A symptom management system was developed and implemented on personal digital assistants (PDAs) for use by cancer outpatients in their daily management of chemotherapy symptoms. The system allowed patients to record their symptoms at home and send these data to their cancer centre. Patients could view personalized self-care advice and more general medical information. In addition, cancer care nurses were alerted about significantly high symptom scores and could contact the patient by phone. The system was distributed to a group of patients during two of their chemotherapy cycles. Patient interaction with the system was logged, and both patients and cancer nurses were surveyed via questionnaires and interviews in order to assess expectations of and attitudes towards the technology. Comparison was made of the quantitative and qualitative results so obtained. Implications for computer-assisted symptom management and the method of evaluation of such systems are considered.
Commodifying Respectability
Authors: Wright David
Published: November 2005

This article argues for a focus on the relationships between retail managers, workers and the objects that they sell in understanding the production of retail spaces and service interactions as meaningful. Sociological and critical management literatures on the service encounter have emphasized the extent to which retail workers are encouraged to display enthusiasm for the things that they sell as part of the process of selling. Indeed, competitive advantage in large modern retail environments is often premised upon the ‘quality’ of customer service and the genuineness of worker engagement with the customer. This article examines these debates in the context of the UK retail book trade and argues that this emphasis in the literature might neglect the extent to which relationships with symbolic goods in consumer society are not simply benign resources for the creation of reflexive selves. It argues that the notion of reading as a worthwhile or respectable leisure pursuit informs the working practices of the book trade. It demonstrates this through interviews with bookshop managers about processes of selection and recruitment and interviews with managers and workers about relationships with customers. Both of these aspects of retail work are informed by relationships to objects that reflect and produce inequalities in cultural capital. In the discourse of the retail book trade, bookshop workers and customers are presumed to be particular types of people with particular orientations to the products being sold. The embodied cultural capital of workers leads to interactions that implicate the bookshop as a site in which hierarchies of cultural value are produced and reinforced.
Boundary Work
Authors: Goode Jackie , Greatbatch David
Published: November 2005

This article explores the joint production and consumption of health information and advice in the context of NHS Direct, the new telephone health information and advice service. NHS Direct is an atypical call centre environment in so far as its core staff (nurses) are highly skilled professionals. These nurses are required to collaborate closely with, and are to some extent dependent upon, non-professional lower skilled staff (call handlers) to define and prioritize their work. This introduces a number of tensions between the two groups. Nurses respond to these tensions by engaging in ‘boundary work’, the micropolitical strategies through which work identities and occupational margins are negotiated, to protect their own status. Call handlers are more subject to the pressures of work ‘speed-up’, highly aware of the risks inherent in their role, but are unable to call upon professional status, either in their resistance to managerial imperatives or in their interactions with health consumers. They are required to manage the tension between offering a safe and high quality service, characterized in their training as ‘professional’, and nurses’ boundary work, which positions them as ‘non-professional’. Here we draw on qualitative research, including call interaction data between call handler and consumer, to show how call handlers’ occupation of the contested territory between professional and non-professional status leaves them wide open to the agency of consumers, as consumers attempt to shape the service in their own interests.
Jesus' Resurrection and Christian Origins: A Response to N.T. Wright
Authors: Goulder Michael
Published: November 2005

While acknowledging Wright's competent handling of a wide range of primary sources, this response takes issue with his conclusions by arguing that the bodily resurrection did not happen and that the Gospel accounts are legendary and at times contradictory. It is also argued that there are two distinct traditions of understanding the resurrection in earliest Christianity, i.e. a more 'spiritual' transformation associated with the Jerusalem church and the bodily resurrection associated with the Pauline churches and represented in narrative form in Mk 16.1-8. This response is divided into the following main areas: ideas of post-mortal life in Judaism; 1 Corinthians 15; the Gospel narratives; and conversion-visions.
Neutrophil adhesion to endothelial cells induced by platelet factor 4 requires sequential activation of Ras, Syk, and JNK MAP kinases
Authors: Kasper Brigitte , Brandt Ernst , Ernst Martin , Petersen Frank
Published: November 2005

Signal transduction mechanisms associated with neutrophil activation by platelet factor 4 (PF4; CXCL4) are as yet poorly characterized. In a recent report, we showed that PF4-induced neutrophil functions (such as adhesion and secondary granule exocytosis) involve the activation of Src-kinases. By analyzing intracellular signals leading to adherence, we here demonstrate by several lines of evidence that in addition to Src-kinases, PF4 signaling involves the monomeric GTPase Ras, the tyrosine kinase Syk, and the MAP kinase JNK. Furthermore, on stimulation, GTPases Rac2 and RhoA were activated, and each was translocated to a different membrane compartment. As shown by inhibitor studies, Rac2 and JNK are located downstream of Syk and Ras. Most intriguingly, the latter 2 elements appear to control the activity of Rac2 and JNK independently of each other at different phases of the activation process. Although a first phase of Rac2 and JNK activation of up to 5 minutes is initiated by Ras, the second phase (5-30 minutes) depends predominantly on the activity of Syk. In summary, we describe that coordinated activity of Syk, Ras, and JNK mediates neutrophil adhesion to endothelial cells and that PF4 induces sequential activation of these elements.
“Maturational” globin switching in primary primitive erythroid cells
Authors: Kingsley Paul D. , Malik Jeffrey , Emerson Rachel L. , Bushnell Timothy P. , McGrath Kathleen E. , Bloedorn Laura A. , Bulger Michael , Palis James
Published: November 2005

Mammals have 2 distinct erythroid lineages. The primitive erythroid lineage originates in the yolk sac and generates a cohort of large erythroblasts that terminally differentiate in the bloodstream. The definitive erythroid lineage generates smaller enucleated erythrocytes that become the predominant cell in fetal and postnatal circulation. These lineages also have distinct globin expression patterns. Our studies in primary murine primitive erythroid cells indicate that βH1 is the predominant β-globin transcript in the early yolk sac. Thus, unlike the human, murine β-globin genes are not up-regulated in the order of their chromosomal arrangement. As primitive erythroblasts mature from proerythroblasts to reticulocytes, they undergo a βH1- to ϵy-globin switch, up-regulate adult β1- and β2-globins, and down-regulate ζ-globin. These changes in transcript levels correlate with changes in RNA polymerase II density at their promoters and transcribed regions. Furthermore, the ϵy- and βH1-globin genes in primitive erythroblasts reside within a single large hyperacetylated domain. These data suggest that this “maturational” βH1- to ϵy-globin switch is dynamically regulated at the transcriptional level. Globin switching during ontogeny is due not only to the sequential appearance of primitive and definitive lineages but also to changes in globin expression as primitive erythroblasts mature in the bloodstream.
Pulmonary function and fuel use: A population survey
Authors: Saha Asim , Mohan Rao N , Kulkarni PK , Majumdar PK , Saiyed HN
Published: November 2005

Background

In the backdrop of conflicting reports (some studies reported adverse outcomes of biomass fuel use whereas few studies reported absence of any association between adverse health effect and fuel use, may be due to presence of large number of confounding variables) on the respiratory health effects of biomass fuel use, this cross sectional survey was undertaken to understand the role of fuel use on pulmonary function.

Method

This study was conducted in a village of western India involving 369 randomly selected adult subjects (165 male and 204 female). All the subjects were interviewed and were subjected to pulmonary function test. Analysis of covariance was performed to compare the levels of different pulmonary function test parameters in relation to different fuel use taking care of the role of possible confounding factors.

Results

This study showed that biomass fuel use (especially wood) is an important factor for deterioration of pulmonary function (particularly in female). FEV1 (p < .05), FEV1 % (p < .01), PEFR (p < .05) and FEF25–75 (p < .01) values were significantly lower in biomass fuel using females than nonusers. Comparison of only biomass fuel use vs. only LPG (Liquefied Petroleum Gas) use and only wood vs. only LPG use has showed that LPG is a safer fuel so far as deterioration of pulmonary function is concerned. This study observes some deterioration of pulmonary function in the male subjects also, who came from biomass fuel using families.

Conclusion

This study concluded that traditional biomass fuels like wood have adverse effects on pulmonary function.
Comparison of the systemic inflammatory response syndrome between monomicrobial and polymicrobial Pseudomonas aeruginosa nosocomial bloodstream infections
Authors: Marra Alexandre R , Bearman Gonzalo ML , Wenzel Richard P , Edmond Michael B
Published: November 2005

Background

Some studies of nosocomial bloodstream infection (nBSI) have demonstrated a higher mortality for polymicrobial bacteremia when compared to monomicrobial nBSI. The purpose of this study was to compare differences in systemic inflammatory response and mortality between monomicrobial and polymicrobial nBSI with Pseudomonas aeruginosa.

Methods

We performed a historical cohort study on 98 adults with P. aeruginosa (Pa) nBSI. SIRS scores were determined 2 days prior to the first positive blood culture through 14 days afterwards. Monomicrobial (n = 77) and polymicrobial BSIs (n = 21) were compared.

Results

78.6% of BSIs were caused by monomicrobial P. aeruginosa infection (MPa) and 21.4% by polymicrobial P. aeruginosa infection (PPa). Median APACHE II score on the day of BSI was 22 for MPa and 23 for PPa BSIs. Septic shock occurred in 33.3% of PPa and in 39.0% of MPa (p = 0.64). Progression to septic shock was associated with death more frequently in PPa (OR 38.5, CI95 2.9–508.5) than MPa (OR 4.5, CI95 1.7–12.1). Maximal SIR (severe sepsis, septic shock or death) was seen on day 0 for PPa BSI vs. day 1 for MPa. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that APACHE II score ≥20 at BSI onset, Charlson weighted comorbidity index ≥3, burn injury and respiratory, cardiovascular, renal and hematologic failure were associated with death, while age, malignant disease, diabetes mellitus, hepatic failure, gastrointestinal complications, inappropriate antimicrobial therapy, infection with imipenem resistant P. aeruginosa and polymicrobial nBSI were not. Multivariate analysis revealed that hematologic failure (p < 0.001) and APACHE II score ≥20 at BSI onset (p = 0.005) independently predicted death.

Conclusion

In this historical cohort study of nBSI with P. aeruginosa, the incidence of septic shock and organ failure was high in both groups. Additionally, patients with PPa BSI were not more acutely ill, as judged by APACHE II score prior to blood culture positivity than those with MPa BSI. Using multivariable logistic regression analysis, the development of hematologic failure and APACHE II score ≥20 at BSI onset were independent predictors of death; however, PPa BSI was not.
The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan
Authors: Yang Yun-Liang , Li Shu-Ying , Cheng Hsiao-Hsu , Lo Hsiu-Jung ,   TSARY Hospitals
Published: November 2005

Background

Candida species have various degrees of susceptibility to common antifungal drugs. The extent of resistance to amphotericin B and fluconazole of Candida glabrata isolates causing candidemia has been reported. Active surveillance may help us to monitor the trend of susceptibility to antifungal drugs and to determine if there is an emerging co-resistance to both drugs of Candida species, specifically, of C. glabrata in Taiwan.

Methods

The susceptibilities to amphotericin B and fluconazole of Candida species collected in 1999 and 2002 of the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) were determined by the microdilution method.

Results

The antifungal susceptibilities of 342 and 456 isolates collected from 11 hospitals participating in both TSARY 1999 and TSARY 2002, respectively, have been determined. The resistance rate to amphotericin B has increased from 0.3% in the TSARY1999 to 2.2% in the TSARY 2002. In contrast, the resistance rate to fluconazole has decreased from 8.8% to 2.2%. Nevertheless, significantly more C. glabrata isolates were not susceptible to fluconazole in the TSARY 2002 (47.4%) than that in the TSARY 1999 (20.8%). There were 9.8% and 11% of C. glabrata isolates having susceptible-dose dependent and resistant phenotype to fluconazole in the TSARY 1999, verse 45.3% and 2.1% in the TSARY 2002.

Conclusion

There was an increase of resistance rate to amphotericin B in C. glabrata. On the other hand, although the resistance rate to fluconazole has decreased, almost half of C. glabrata isolates were not susceptible to this drug. Hence, continuous monitoring the emerging of co-resistance to both amphotericin B and fluconazole of Candida species, specifically, of C. glabrata, will be an important early-warning system.
Surface pretreatment for prolonged survival of cemented tibial prosthesis components: full- vs. surface-cementation technique
Authors: Marx Rudolf , Qunaibi Mutaz , Wirtz Dieter Christian , Niethard Fritz Uwe , Mumme Thorsten
Published: November 2005

Background

One of few persisting problems of cemented total knee arthroplasty (TKA) is aseptic loosening of tibial component due to degradation of the interface between bone cement and metallic tibial shaft component, particularly for surface cemented tibial components. Surface cementation technique has important clinical meaning in case of revision and for avoidance of stress shielding. Degradation of the interface between bone cement and bone may be a secondary effect due to excessive crack formation in bone cement starting at the opposite metallic surface.

Methods

This study was done to prove crack formation in the bone cement near the metallic surface when this is not coated. We propose a newly developed coating process by PVD layering with SiOxto avoid that crack formation in the bone cement. A biomechanical model for vibration fatigue test was done to simulate the physiological and biomechanical conditions of the human knee joint and to prove excessive crack formation.

Results

It was found that coated tibial components showed a highly significant reduction of cement cracking near the interface metal/bone cement (p < 0.01) and a significant reduction of gap formation in the interface metal-to-bone cement (p < 0.05).

Conclusion

Coating dramatically reduces hydrolytic- and stress-related crack formation at the prosthesis interface metal/bone cement. This leads to a more homogenous load transfer into the cement mantle which should reduce the frequency of loosening in the interfaces metal/bone cement/bone. With surface coating of the tibial component it should become possible that surface cemented TKAs reveal similar loosening rates as TKAs both surface and stem cemented. This would be an important clinical advantage since it is believed that surface cementing reduces metaphyseal bone loss in case of revision and stress shielding for better bone health.
23 years of the discovery of Helicobacter pylori: Is the debate over?
Authors: Ahmed Niyaz
Published: November 2005

The Gram negative curved bacillus H. pylori has become the prize bug of all times. Barry Marshall and Robin Warren the two discoverers of this organism have been awarded with this year's Nobel Prize. The Nobel committee at the Karolinska Institute of Sweden has selected this paradigm shift discovery of 1982 as the most impacting in medical sciences. This award has surprised many as the Nobel assembly has selected this 'Robert Koch styled medical detective work' for the prize as compared to many outstanding basic research stories on the waitlist. This editorial briefly touches the significant impact of H. pylori on gastroduodenal management and the path forward as the bug has become quite controversial in recent times.
Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector
Authors: Sasaki Makoto , Mathis J Michael , Jennings Merilyn H , Jordan Paul , Wang Yuping , Ando Tomoaki , Joh Takashi , Alexander J Steven
Published: November 2005

Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.
Apical membrane P2Y4 purinergic receptor controls K+ secretion by strial marginal cell epithelium
Authors: Marcus Daniel C , Liu Jianzhong , Lee Jun Ho , Scherer Elias Q , Scofield Margaret A , Wangemann Philine
Published: November 2005

Background

It was previously shown that K+secretion by strial marginal cell epithelium is under the control of G-protein coupled receptors of the P2Y family in the apical membrane. Receptor activation by uracil nucleotides (P2Y2, P2Y4or P2Y6) leads to a decrease in the electrogenic K+secretion. The present study was conducted to determine the subtype of the functional purinergic receptor in gerbil stria vascularis, to test if receptor activation leads to elevation of intracellular [Ca2+] and to test if the response to these receptors undergoes desensitization.

Results

The transepithelial short circuit current (Isc) represents electrogenic K+secretion and was found to be decreased by uridine 5'-triphosphate (UTP), adenosine 5'-triphosphate (ATP) and diadenosine tetraphosphate (Ap4A) but not uridine 5'-diphosphate (UDP) at the apical membrane of marginal cells of the gerbil stria vascularis. The potencies of these agonists were consistent with rodent P2Y4and P2Y2but not P2Y6receptors. Activation caused a biphasic increase in intracellular [Ca2+] that could be partially blocked by 2-aminoethoxy-diphenyl borate (2-APB), an inhibitor of the IP3 receptor and store-operated channels. Suramin (100 μM) did not inhibit the effect of UTP (1 μM). The ineffectiveness of suramin at the concentration used was consistent with P2Y4but not P2Y2. Transcripts for both P2Y2and P2Y4were found in the stria vascularis. Sustained exposure to ATP or UTP for 15 min caused a depression of Isc that appeared to have two components but with apparently no chronic desensitization.

Conclusion

The results support the conclusion that regulation of K+secretion across strial marginal cell epithelium occurs by P2Y4receptors at the apical membrane. The apparent lack of desensitization of the response is consistent with two processes: a rapid-onset phosphorylation of KCNE1 channel subunit and a slower-onset of regulation by depletion of plasma membrane PIP2.
A mathematical model of the euglycemic hyperinsulinemic clamp
Authors: Picchini Umberto , De Gaetano Andrea , Panunzi Simona , Ditlevsen Susanne , Mingrone Geltrude
Published: November 2005

Background

The Euglycemic Hyperinsulinemic Clamp (EHC) is the most widely used experimental procedure for the determination of insulin sensitivity, and in its usual form the patient is followed under insulinization for two hours. In the present study, sixteen subjects with BMI between 18.5 and 63.6 kg/m2 were studied by long-duration (five hours) EHC.

Results

From the results of this series and from similar reports in the literature it is clear that, in obese subjects, glucose uptake rates continue to increase if the clamp procedure is prolonged beyond the customary 2 hours. A mathematical model of the EHC, incorporating delays, was fitted to the recorded data, and the insulin resistance behaviour of obese subjects was assessed analytically. Obese subjects had significantly less effective suppression of hepatic glucose output and higher pancreatic insulin secretion than lean subjects. Tissue insulin resistance appeared to be higher in the obese group, but this difference did not reach statistical significance.

Conclusion

The use of a mathematical model allows a greater amount of information to be recovered from clamp data, making it easier to understand the components of insulin resistance in obese vs. normal subjects.
"Near-miss" obstetric events and maternal deaths in Sagamu, Nigeria: a retrospective study
Authors: Oladapo Olufemi T , Sule-Odu Adewale O , Olatunji Adetola O , Daniel Olusoji J
Published: November 2005

Aim

To determine the frequency of near-miss (severe acute maternal morbidity) and the nature of near-miss events, and comparatively analysed near-miss morbidities and maternal deaths among pregnant women managed over a 3-year period in a Nigerian tertiary centre.

Methods

Retrospective facility-based review of cases of near-miss and maternal death which occurred between 1 January 2002 and 31 December 2004. Near-miss case definition was based on validated disease-specific criteria, comprising of five diagnostic categories: haemorrhage, hypertensive disorders in pregnancy, dystocia, infection and anaemia. The near-miss morbidities were compared with maternal deaths with respect to demographic features and disease profiles. Mortality indices were determined for various disease processes to appreciate the standard of care provided for life-threatening obstetric conditions. The maternal death to near-miss ratios for the three years were compared to assess the trend in the quality of obstetric care.

Results

There were 1501 deliveries, 211 near-miss cases and 44 maternal deaths. The total near-miss events were 242 with a decreasing trend from 2002 to 2004. Demographic features of cases of near-miss and maternal death were comparable. Besides infectious morbidity, the categories of complications responsible for near-misses and maternal deaths followed the same order of decreasing frequency. Hypertensive disorders in pregnancy and haemorrhage were responsible for 61.1% of near-miss cases and 50.0% of maternal deaths. More women died after developing severe morbidity due to uterine rupture and infection, with mortality indices of 37.5% and 28.6%, respectively. Early pregnancy complications and antepartum haemorrhage had the lowest mortality indices. Majority of the cases of near-miss (82.5%) and maternal death (88.6%) were unbooked for antenatal care and delivery in this hospital. Maternal mortality ratio for the period was 2931.4 per 100,000 deliveries. The overall maternal death to near-miss ratio was 1: 4.8 and this remained relatively constant over the 3-year period.

Conclusion

The quality of care received by critically ill obstetric patients in this centre is suboptimal with no evident changes between 2002 and 2004. Reduction of the present maternal mortality ratio may best be achieved by developing evidence-based protocols and improving the resources for managing severe morbidities due to hypertension and haemorrhage especially in critically ill unbooked patients. Tertiary care hospitals in Nigeria could also benefit from evaluation of their standard of obstetric care by including near-miss investigations in their maternal death enquiries.
Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 3: Discussion and Conclusion
Authors: Hohoff Ariane , Rabe Heike , Ehmer Ulrike , Harms Erik
Published: November 2005

Background

It has been hypothesized that prematurity and adjunctive neonatal care is 'a priori' a risk for disturbances of palatal and orofacial development which increases the need for later orthodontic or orthognathic treatment. As results on late consequences of prematurity are consistently contradictory, the necessity exists for a fundamental analysis of existing methodologies, confounding factors, and outcomes of studies on palatal development in preterm and low birthweight infants.

Method

A search of the literature was conducted based on Cochrane search strategies including sources in English, German, and French. Original data were recalculated from studies which primarily dealt with both preterm and term infants. The extracted data, especially those from non-English paper sources, were provided unfiltered in tables for comparison (Parts 1 and 2).

Results

Morphology assessment of the infant palate is subject to non-standardized visual and metrical measurements. Most methodologies are inadequate for measuring a three-dimensional shape. Several confounding factors were identified as causes contributing to disturbances of palatal and orofacial development.

Conclusion

Taking into account the abovementioned shortcomings, the following conclusions may be drawn for practitioners and prospective investigators of clinical studies. 1) The lack of uniformity in the anatomical nomenclature of the infant's palate underlines the need for a uniform definition. 2) Metrically, non-intubated preterm infants do not exhibit different palatal width or height compared to matched term infants up to the corrected age of three months. Beyond that age, no data on the subject are currently available. 3) Oral intubation does not invariably alter palatal morphology of preterm and low birthweight infants. 4) The findings on palatal grooving, height, and asymmetry as a consequence of orotracheal intubation up to the age of 11 years are inconsistent. 5) Metrically, the palates of orally intubated infants remain narrower posteriorly, beginning at the second deciduous molar, until the age of 11 years. Beyond that age, no data on the subject are currently available. 6) There is a definite need for further, especially metrical, longitudinal and controlled trials on palatal morphology of preterm and low birthweight infants with reliable measuring techniques. 7) None of the raised confounding factors for developmental disturbances may be excluded until evident results are presented. Thus, early orthodontic and logopedic control of formerly premature infants is recommended up to the late mixed dentition stage.
Regulatory polymorphisms in extracellular matrix protease genes and susceptibility to rheumatoid arthritis: a case-control study
Authors: Rodriguez-Lopez Julio , Perez-Pampin Eva , Gomez-Reino Juan J , Gonzalez Antonio
Published: November 2005

Many extracellular matrix (ECM) proteases seem to be important in rheumatoid arthritis (RA) and regulation of their transcription levels is a critical mechanism for controlling their activity. We have investigated, therefore, whether the best-characterized single nucleotide polymorphisms (SNPs) affecting transcription of the ECM proteases that have been related with joint pathology are associated with RA susceptibility. Nine SNPs in eight genes were selected by bibliographic search, including SNPs in the genes encoding matrix metalloproteinase (MMP)1, MMP2, MMP3, MMP7, MMP9, MMP13, plasminogen activator, tissue type (PLAT) and PAI-1. They were studied in a case-control setting that included 550 RA patients and 652 controls of Spanish ancestry from a single center. Genotyping was performed by single-base extension. Only two of the nine SNPs showed significant association with RA susceptibility. RA patients showed increased frequencies of the -7351 T allele of the gene encoding PLAT (36.4% versus 32.1% in controls, p = 0.026) and the -1306 T allele of the gene encoding MMP2 (24.5% versus 20.3% in controls, p = 0.013). These two alleles seemed to cooperate according to an additive model with respect to increased RA susceptibility (p = 0.004), and they were the low-expression alleles of the respective SNPs in a PLAT enhancer and the MMP2 promoter. These findings are in agreement with previous data suggesting that these two ECM proteases have a protective role in RA pathology. Confirmation of these associations will be needed to support these hypotheses. The remaining SNPs did not show association, either individually or collectively. Therefore, although regulatory SNPs in ECM proteases did not show any major effect on RA susceptibility, it was possible to find modest associations that, if replicated, will have interesting implications in the understanding of RA pathology.
The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage
Authors: Bekpen Cemalettin , Hunn Julia P , Rohde Christoph , Parvanova Iana , Guethlein Libby , Dunn Diane M , Glowalla Eva , Leptin Maria , Howard Jonathan C
Published: November 2005

Background

Members of the p47 (immunity-related GTPases (IRG) family) GTPases are essential, interferon-inducible resistance factors in mice that are active against a broad spectrum of important intracellular pathogens. Surprisingly, there are no reports of p47 function in humans.

Results

Here we show that the p47 GTPases are represented by 23 genes in the mouse, whereas humans have only a single full-length p47 GTPase and an expressed, truncated presumed pseudo-gene. The human full-length gene is orthologous to an isolated mouse p47 GTPase that carries no interferon-inducible elements in the promoter of either species and is expressed constitutively in the mature testis of both species. Thus, there is no evidence for a p47 GTPase-based resistance system in humans. Dogs have several interferon-inducible p47s, and so the primate lineage that led to humans appears to have lost an ancient function. Multiple p47 GTPases are also present in the zebrafish, but there is only a tandem p47 gene pair in pufferfish.

Conclusion

Mice and humans must deploy their immune resources against vacuolar pathogens in radically different ways. This carries significant implications for the use of the mouse as a model of human infectious disease. The absence of the p47 resistance system in humans suggests that possession of this resistance system carries significant costs that, in the primate lineage that led to humans, are not outweighed by the benefits. The origin of the vertebrate p47 system is obscure.
Genome-wide gene expression in response to parasitoid attack in Drosophila
Authors: Wertheim Bregje , Kraaijeveld Alex R , Schuster Eugene , Blanc Eric , Hopkins Meirion , Pletcher Scott D , Strand Michael R , Partridge Linda , Godfray H Charles J
Published: November 2005

Background

Parasitoids are insect parasites whose larvae develop in the bodies of other insects. The main immune defense against parasitoids is encapsulation of the foreign body by blood cells, which subsequently often melanize. The capsule sequesters and kills the parasite. The molecular processes involved are still poorly understood, especially compared with insect humoral immunity.

Results

We explored the transcriptional response to parasitoid attack in Drosophila larvae at nine time points following parasitism, hybridizing five biologic replicates per time point to whole-genome microarrays for both parasitized and control larvae. We found significantly different expression profiles for 159 probe sets (representing genes), and we classified them into 16 clusters based on patterns of co-expression. A series of functional annotations were nonrandomly associated with different clusters, including several involving immunity and related functions. We also identified nonrandom associations of transcription factor binding sites for three main regulators of innate immune responses (GATA/srp-like, NF-κB/Rel-like and Stat), as well as a novel putative binding site for an unknown transcription factor. The appearance or absence of candidate genes previously associated with insect immunity in our differentially expressed gene set was surveyed.

Conclusion

Most genes that exhibited altered expression following parasitoid attack differed from those induced during antimicrobial immune responses, and had not previously been associated with defense. Applying bioinformatic techniques contributed toward a description of the encapsulation response as an integrated system, identifying putative regulators of co-expressed and functionally related genes. Genome-wide studies such as ours are a powerful first approach to investigating novel genes involved in invertebrate immunity.
Chipper: discovering transcription-factor targets from chromatin immunoprecipitation microarrays using variance stabilization
Authors: Gibbons Francis D , Proft Markus , Struhl Kevin , Roth Frederick P
Published: November 2005

Chromatin immunoprecipitation combined with microarray technology (Chip2) allows genome-wide determination of protein-DNA binding sites. The current standard method for analyzing Chip2 data requires additional control experiments that are subject to systematic error. We developed methods to assess significance using variance stabilization, learning error-model parameters without external control experiments. The method was validated experimentally, shows greater sensitivity than the current standard method, and incorporates false-discovery rate analysis. The corresponding software ('Chipper') is freely available. The method described here should help reveal an organism's transcription-regulatory 'wiring diagram'.
Pleiotropic functions of a conserved insect-specific Hox peptide motif
Authors: Hittinger Chris Todd , Stern David L. , Carroll Sean B.
Published: November 2005

The proteins that regulate developmental processes in animals have generally been well conserved during evolution. A few cases are known where protein activities have functionally evolved. These rare examples raise the issue of how highly conserved regulatory proteins with many roles evolve new functions while maintaining old functions. We have investigated this by analyzing the function of the `QA' peptide motif of the Hox protein Ultrabithorax (Ubx), a motif that has been conserved throughout insect evolution since its establishment early in the lineage. We precisely deleted the QA motif at the endogenous locus via allelic replacement in Drosophila melanogaster. Although the QA motif was originally characterized as involved in the repression of limb formation, we have found that it is highly pleiotropic. Curiously, deleting the QA motif had strong effects in some tissues while barely affecting others, suggesting that QA function is preferentially required for a subset of Ubx target genes. QA deletion homozygotes had a normal complement of limbs, but, at reduced doses of Ubx and the abdominal-A (abd-A) Hox gene, ectopic limb primordia and adult abdominal limbs formed when the QA motif was absent. These results show that redundancy and the additive contributions of activity-regulating peptide motifs play important roles in moderating the phenotypic consequences of Hox protein evolution, and that pleiotropic peptide motifs that contribute quantitatively to several functions are subject to intense purifying selection.
A requirement for membrane cholesterol in the β-arrestin- and clathrin-dependent endocytosis of LPA1 lysophosphatidic acid receptors
Authors: Urs Nikhil M. , Jones Kymry T. , Salo Paul D. , Severin Jamie E. , Trejo JoAnn , Radhakrishna Harish
Published: November 2005

Lysophosphatidic acid (LPA) stimulates heterotrimeric G protein signaling by activating three closely related receptors, termed LPA1, LPA2 and LPA3. Here we show that in addition to promoting LPA1 signaling, membrane cholesterol is essential for the association of LPA1 with β-arrestin, which leads to signal attenuation and clathrin-dependent endocytosis of LPA1. Reduction of clathrin heavy chain expression, using small interfering RNAs, inhibited LPA1 endocytosis. LPA1 endocytosis was also inhibited in β-arrestin 1 and 2-null mouse embryo fibroblasts (β-arrestin 1/2 KO MEFs), but was restored upon re-expression of wild-type β-arrestin 2. β-arrestin attenuates LPA signaling as LPA1-dependent phosphoinositide hydrolysis was significantly elevated in β-arrestin 1/2 KO MEFs and was reduced to wild-type levels upon re-expression of wild-type β-arrestin. Interestingly, extraction of membrane cholesterol with methyl-β-cyclodextrin inhibited LPA1 signaling, β-arrestin membrane recruitment and LPA1 endocytosis. Cholesterol repletion restored all of these functions. However, neither the stimulation of phosphoinositide hydrolysis by the M1 acetylcholine receptor nor its endocytosis was affected by cholesterol extraction. LPA treatment increased the detergent resistance of LPA1 and this was inhibited by cholesterol extraction, suggesting that LPA1 localizes to detergent-resistant membranes upon ligand stimulation. These data indicate that although LPA1 is internalized by clathrin- and β-arrestin dependent endocytosis, membrane cholesterol is critical for LPA1 signaling, membrane recruitment of β-arrestins and LPA1 endocytosis.
Downregulation of the HERG (KCNH2) K+ channel by ceramide: evidence for ubiquitin-mediated lysosomal degradation
Authors: Chapman Hugh , Ramström Cia , Korhonen Laura , Laine Mika , Wann Kenneth T. , Lindholm Dan , Pasternack Michael , Törnquist Kid
Published: November 2005

The HERG (KCNH2) potassium channel underlies the rapid component of the delayed rectifier current (Ikr), a current contributing to the repolarisation of the cardiac action potential. Mutations in HERG can cause the hereditary forms of the short-QT and long-QT syndromes, predisposing to ventricular arrhythmias and sudden cardiac death. HERG is expressed mainly in the cell membrane of cardiac myocytes, but has also been identified in cell membranes of a range of other cells, including smooth muscle and neurones. The mechanisms regulating the surface expression have however not yet been elucidated. Here we show, using stable HERG-expressing HEK 293 cells, that ceramide evokes a time-dependent decrease in HERG current which was not attributable to a change in gating properties of the channel. Surface expression of the HERG channel protein was reduced by ceramide as shown by biotinylation of surface proteins, western blotting and immunocytochemistry. The rapid decline in HERG protein after ceramide stimulation was due to protein ubiquitylation and its association with lysosomes. The results demonstrate that the surface expression of HERG is strictly regulated, and that ceramide modifies HERG currents and targets the protein for lysosomal degradation.
The Wnt signalling effector Dishevelled forms dynamic protein assemblies rather than stable associations with cytoplasmic vesicles
Authors: Schwarz-Romond Thomas , Merrifield Christien , Nichols Benjamin J. , Bienz Mariann
Published: November 2005

Dishevelled is a crucial effector upstream in the Wnt signalling pathway, but the molecular mechanism by which it transduces the Wnt signal remains elusive. Dishevelled is a cytoplasmic protein with a strong tendency to form puncta, which correlates with its potent activity in stimulating Wnt signal transduction when overexpressed. These puncta are thought to reflect cytoplasmic vesicles. However, we show here that the mammalian Dishevelled protein Dvl2 does not colocalise with known vesicle markers for clathrin-mediated or clathrin-independent endocytic pathways. Furthermore, Dvl2 puncta do not stain with lipid dyes, indicating that these puncta do not contain membranes. Instead, our evidence from live imaging by TIRF microscopy of Dvl2 tagged with green fluorescent protein (GFP-Dvl2) revealed that these puncta move in and out of the evanescent field near the plasma membrane in an undirected fashion, and that they can grow by collision and fusion. Furthermore, high-resolution confocal microscopy and photobleaching experiments indicate that the GFP-Dvl2 puncta are protein assemblies; there is a constant exchange of GFP-Dvl2 between puncta and a diffuse cytoplasmic pool, which, therefore, are in a dynamic equilibrium with each other. The same is true for the DIX domain of Dvl2 itself and also for Axin-GFP, which equilibrates between the punctate and cytosolic pools. Our evidence indicates that Dvl2 and Axin puncta are dynamic protein assemblies rather than cytoplasmic vesicles.
Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta
Authors: Smalley Matthew J. , Signoret Nathalie , Robertson David , Tilley Alan , Hann Anthony , Ewan Ken , Ding Yanning , Paterson Hugh , Dale Trevor C.
Published: November 2005

Dishevelled family proteins are multidomain intracellular transducers of Wnt signals. Ectopically expressed mammalian Dishevelled 2 (Dvl-2) activates downstream signalling and localises to cytoplasmic puncta. It has been suggested that these Dvl-2-containing structures correspond to intracellular vesicles and may be involved in the Wnt signal transduction process. We report that cytoplasmic puncta are primarily formed in cells expressing Dvl-2 at high levels. Lower levels of expression can activate signalling without forming puncta. The structures do not localise with markers of the early or late endocytic pathway and time-lapse analysis demonstrates that Dvl-2 puncta move in a random fashion over short distances but do not originate from the plasma membrane. Based on our findings, we propose that Dvl-2 puncta are protein aggregates that are not required for signalling.