bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular architecture of the fruit fly's airway epithelial immune system
Authors: Wagner Christina , Isermann Kerstin , Fehrenbach Heinz , Roeder Thomas 
Published: September 2008

Abstract

Background
Airway epithelial cells not only constitute a physical barrier, but also the first line of defence against airborne pathogens. At the same time, they are constantly exposed to reactive oxygen species. Therefore, airway epithelia cells have to possess a sophisticated innate immune system and a molecular armamentarium to detoxify reactive oxygen species. It has become apparent that deregulation of epithelial innate immunity is a major reason for the development of chronic inflammatory lung diseases. To elucidate the molecular architecture of the innate immune system of airway epithelial cells, we choose the fruit fly Drosophila melanogaster as a model, because it has the simplest type of airways, consisting of epithelial cells only. Elucidating the structure of the innate immune system of this "airway epithelial cell culture" might enable us to understand why deregulatory processes in innate immune signalling cascades lead to long lasting inflammatory events.

Results
All airway epithelial cells of the fruit fly are able to launch an immune response. They contain only one functional signal transduction pathway that converges onto NF-κB factors, namely the IMD-pathway, which is homologous to the TNF-α receptor pathway. Although vital parts of the Toll-pathway are missing, dorsal and dif, the NF-κB factors dedicated to this signalling system, are present. Other pathways involved in immune regulation, such as the JNK- and the JAK/STAT-pathway, are completely functional in these cells. In addition, most peptidoglycan recognition proteins, representing the almost complete collection of pattern recognition receptors, are part of the epithelial cells equipment. Potential effector molecules are different antimicrobial peptides and lysozymes, but also transferrin that can inhibit bacterial growth through iron-depletion. Reactive oxygen species can be inactivated through the almost complete armamentarium of enzymatic antioxidants that has the fly to its disposal.

Conclusion
The innate immune system of the fly's airway epithelium has a very peculiar organization. A great variety of pattern recognition receptors as well as of potential effector molecules are conspicuous, whereas signalling presumably occurs through a single NF-κB activating pathway. This architecture will allow reacting if confronted with different bacterial or fungal elicitors by activation of a multitude of effectors.
A standard procedure for creating a frailty index
Authors: Searle Samuel D , Mitnitski Arnold , Gahbauer Evelyne A , Gill Thomas M , Rockwood Kenneth 
Published: September 2008

AbstractBackgroundFrailty can be measured in relation to the accumulation of deficits using a frailty index. A frailty index can be developed from most ageing databases. Our objective is to systematically describe a standard procedure for constructing a frailty index.MethodsThis is a secondary analysis of the Yale Precipitating Events Project cohort study, based in New Haven CT. Non-disabled people aged 70 years or older (n = 754) were enrolled and re-contacted every 18 months. The database includes variables on function, cognition, co-morbidity, health attitudes and practices and physical performance measures. Data came from the baseline cohort and those available at the first 18-month follow-up assessment.ResultsProcedures for selecting health variables as candidate deficits were applied to yield 40 deficits. Recoding procedures were applied for categorical, ordinal and interval variables such that they could be mapped to the interval 0–1, where 0 = absence of a deficit, and 1= full expression of the deficit. These individual deficit scores were combined in an index, where 0= no deficit present, and 1= all 40 deficits present. The values of the index were well fit by a gamma distribution. Between the baseline and follow-up cohorts, the age-related slope of deficit accumulation increased from 0.020 (95% confidence interval, 0.014–0.026) to 0.026 (0.020–0.032). The 99% limit to deficit accumulation was 0.6 in the baseline cohort and 0.7 in the follow-up cohort. Multivariate Cox analysis showed the frailty index, age and sex to be significant predictors of mortality.ConclusionA systematic process for creating a frailty index, which relates deficit accumulation to the individual risk of death, showed reproducible properties in the Yale Precipitating Events Project cohort study. This method of quantifying frailty can aid our understanding of frailty-related health characteristics in older adults.
The -786T>C promoter polymorphism of the NOS3gene is associated with prostate cancer progression
Authors: Marangoni Karina , Araújo Thaíse G , Neves Adriana F , Goulart Luiz R 
Published: September 2008

Abstract

Background
There is no biological or epidemiological data on the association between NOS3 promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of NOS3 gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage.

Methods
This study aimed evaluating the NOS3 promoter polymorphisms by PCR-SSCP and sequencing, associating genotypes and haplotypes with NOS3 expression levels through semi-quantitative RT-PCR, and with PCA3 mRNA detection, a specific tumor biomarker, in the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94 BPH.

Results
Three novel SNPs were identified -764A>G, -714G>T and -649G>A in the NOS3 gene promoter region, which together with the -786T>C generated four haplotypes (N, T, C, A). NOS3 gene expression levels were affected by the -786T>C polymorphism, and there was a 2-fold increase in NOS3 levels favored by the incorporation of each C allele. NOS3 levels higher than 80% of the constitutive gene expression level (B2M) presented a 4-fold increase in PCa occurrence.

Conclusion
The -786T>C polymorphism was the most important promoter alteration of the NOS3 gene that may affect the PCa progression, but not its occurrence, and the incorporation of the C allele is associated with increased levels of NOS3 transcripts. The NOS3 transcript levels presented a bimodal behavior in tumor development and may be used as a biomarker together with the PCA3 marker for molecular staging of the prostate cancer.
Country differences in the diagnosis and management of coronary heart disease – a comparison between the US, the UK and Germany
Authors: von dem Knesebeck Olaf , Bönte Markus , Siegrist Johannes , Marceau Lisa , Link Carol , Arber Sara , Adams Ann , McKinlay John 
Published: September 2008

AbstractBackgroundThe way patients with coronary heart disease (CHD) are treated is partly determined by non-medical factors. There is a solid body of evidence that patient and physician characteristics influence doctors' management decisions. Relatively little is known about the role of structural issues in the decision making process. This study focuses on the question whether doctors' diagnostic and therapeutic decisions are influenced by the health care system in which they take place. This non-medical determinant of medical decision-making was investigated in an international research project in the US, the UK and Germany.MethodsVideotaped patients within an experimental study design were used. Experienced actors played the role of patients with symptoms of CHD. Several alternative versions were taped featuring the same script with patients of different sex, age and social status. The videotapes were shown to 384 randomly selected primary care physicians in the three countries under study. The sample was stratified on gender and duration of professional experience. Physicians were asked how they would diagnose and manage the patient after watching the video vignette using a questionnaire with standardised and open-ended questions.ResultsResults show only small differences in decision making between British and American physicians in essential aspects of care. About 90% of the UK and US doctors identified CHD as one of the possible diagnoses. Further similarities were found in test ordering and lifestyle advice. Some differences between the US and UK were found in the certainty of the diagnoses, prescribed medications and referral behaviour. There are numerous significant differences between Germany and the other two countries. German physicians would ask fewer questions, they would order fewer tests, prescribe fewer medications and give less lifestyle advice.ConclusionAlthough all physicians in the three countries under study were presented exactly the same patient, some disparities in the diagnostic and patient management decisions were evident. Since other possible influences on doctors treatment decisions are controlled within the experimental design, characteristics of the health care system seem to be a crucial factor within the decision making process.
Costs and cost-effectiveness of delivering intermittent preventive treatment through schools in western Kenya
Authors: Temperley Matilda , Mueller Dirk H , Njagi J Kiambo , Akhwale Willis , Clarke Siân E , Jukes Matthew CH , Estambale Benson BA , Brooker Simon 
Published: September 2008

AbstractBackgroundAwareness of the potential impact of malaria among school-age children has stimulated investigation into malaria interventions that can be delivered through schools. However, little evidence is available on the costs and cost-effectiveness of intervention options. This paper evaluates the costs and cost-effectiveness of intermittent preventive treatment (IPT) as delivered by teachers in schools in western Kenya.MethodsInformation on actual drug and non-drug associated costs were collected from expenditure and salary records, government budgets and interviews with key district and national officials. Effectiveness data were derived from a cluster-randomised-controlled trial of IPT where a single dose of sulphadoxine-pyrimethamine and three daily doses of amodiaquine were provided three times in year (once termly). Both financial and economic costs were estimated from a provider perspective, and effectiveness was estimated in terms of anaemia cases averted. A sensitivity analysis was conducted to assess the impact of key assumptions on estimated cost-effectiveness.ResultsThe delivery of IPT by teachers was estimated to cost US$ 1.88 per child treated per year, with drug and teacher training costs constituting the largest cost components. Set-up costs accounted for 13.2% of overall costs (equivalent to US$ 0.25 per child) whilst recurrent costs accounted for 86.8% (US$ 1.63 per child per year). The estimated cost per anaemia case averted was US$ 29.84 and the cost per case ofPlasmodium falciparumparasitaemia averted was US$ 5.36, respectively. The cost per case of anaemia averted ranged between US$ 24.60 and 40.32 when the prices of antimalarial drugs and delivery costs were varied. Cost-effectiveness was most influenced by effectiveness of IPT and the background prevalence of anaemia. In settings where 30% and 50% of schoolchildren were anaemic, cost-effectiveness ratios were US$ 12.53 and 7.52, respectively.ConclusionThis study provides the first evidence that IPT administered by teachers is a cost-effective school-based malaria intervention and merits investigation in other settings.
Rac1 GTPase and the Rac1 exchange factor Tiam1 associate with Wnt-responsive promoters to enhance beta-catenin/TCF-dependent transcription in colorectal cancer cells
Authors: Buongiorno Pinella , Pethe Vaijayanti V , Charames George S , Esufali Susmita , Bapat Bharati 
Published: September 2008

Abstract

Background
β-catenin is a key mediator of the canonical Wnt pathway as it associates with members of the T-cell factor (TCF) family at Wnt-responsive promoters to drive the transcription of Wnt target genes. Recently, we showed that Rac1 GTPase synergizes with β-catenin to increase the activity of a TCF-responsive reporter. This synergy was dependent on the nuclear presence of Rac1, since inhibition of its nuclear localization effectively abolished the stimulatory effect of Rac1 on TCF-responsive reporter activity. We hypothesised that Rac1 plays a direct role in enhancing the transcription of endogenous Wnt target genes by modulating the β-catenin/TCF transcription factor complex.

Results
We employed chromatin immunoprecipitation studies to demonstrate that Rac1 associates with the β-catenin/TCF complex at Wnt-responsive promoters of target genes. This association served to facilitate transcription, since overexpression of active Rac1 augmented Wnt target gene activation, whereas depletion of endogenous Rac1 by RNA interference abrogated this effect. In addition, the Rac1-specific exchange factor, Tiam1, potentiated the stimulatory effects of Rac1 on the canonical Wnt pathway. Tiam1 promoted the formation of a complex containing Rac1 and β-catenin. Furthermore, endogenous Tiam1 associated with endogenous β-catenin, and this interaction was enhanced in response to Wnt3a stimulation. Intriguingly, Tiam1 was recruited to Wnt-responsive promoters upon Wnt3a stimulation, whereas Rac1 was tethered to TCF binding elements in a Wnt-independent manner.

Conclusion
Taken together, our results suggest that Rac1 and the Rac1-specific activator Tiam1 are components of transcriptionally active β-catenin/TCF complexes at Wnt-responsive promoters, and the presence of Rac1 and Tiam1 within these complexes serves to enhance target gene transcription. Our results demonstrate a novel functional mechanism underlying the cross-talk between Rac1 and the canonical Wnt signalling pathway.
Improvement of quality of life, anxiety and depression after surgery in patients with stress urinary incontinence: Results of a longitudinal short-term follow-up
Authors: Innerkofler Petra C , Guenther Verena , Rehder Peter , Kopp Martin , Nguyen-Van-Tam Dominic P , Giesinger Johannes M , Holzner Bernhard 
Published: September 2008

Abstract

Objective
The objective of this study was to compare the effect of incontinence surgery and pelvic floor training on quality of life (QOL), anxiety and depression in patients with stress urinary incontinence (SUI).

Methods
In a prospective longitudinal study, females with proven SUI were asked to complete a set of standardized questionnaires (sociodemographic data sheet, FACT-G, I-QOL, HADS) before and eight weeks after treatment. The comparison groups consisted of a surgical treatment group and a conservative group that underwent supervised pelvic floor training for eight weeks.

Results
From the 67 female patients included in the study a number of 53 patients completed both assessment time points (mean age 57.4, mean years of SUI 7.6). The surgical treatment group consisted of 32 patients of which 21 patients received a modified Burch colposuspension and 11 patients a tension-free mid-urethral tape suspension. The 21 patients in the conservative group attended eight once-weekly supervised pelvic floor training sessions.
After treatment the surgical intervention group showed a significantly higher improvement of QOL (FACT-G and I-QOL) and anxiety (HADS) than the pelvic floor training group.

Conclusion
For female patients with SUI surgery yielded a better outcome than pelvic floor training with regard to quality of life and anxiety.
Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice
Authors: Oyamada Naofumi , Itoh Hiroshi , Sone Masakatsu , Yamahara Kenichi , Miyashita Kazutoshi , Park Kwijun , Taura Daisuke , Inuzuka Megumi , Sonoyama Takuhiro , Tsujimoto Hirokazu , Fukunaga Yasutomo , Tamura Naohisa , Nakao Kazuwa 
Published: September 2008

Abstract

Background
We previously demonstrated that vascular endothelial growth factor receptor type 2 (VEGF-R2)-positive cells induced from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) and these vascular cells construct blood vessel structures in vitro. Recently, we have also established a method for the large-scale expansion of ECs and MCs derived from human ES cells. We examined the potential of vascular cells derived from human ES cells to contribute to vascular regeneration and to provide therapeutic benefit for the ischemic brain.

Methods
Phosphate buffered saline, human peripheral blood mononuclear cells (hMNCs), ECs-, MCs-, or the mixture of ECs and MCs derived from human ES cells were intra-arterially transplanted into mice after transient middle cerebral artery occlusion (MCAo).

Results
Transplanted ECs were successfully incorporated into host capillaries and MCs were distributed in the areas surrounding endothelial tubes. The cerebral blood flow and the vascular density in the ischemic striatum on day 28 after MCAo had significantly improved in ECs-, MCs- and ECs+MCs-transplanted mice compared to that of mice injected with saline or transplanted with hMNCs. Moreover, compared to saline-injected or hMNC-transplanted mice, significant reduction of the infarct volume and of apoptosis as well as acceleration of neurological recovery were observed on day 28 after MCAo in the cell mixture-transplanted mice.

Conclusion
Transplantation of ECs and MCs derived from undifferentiated human ES cells have a potential to contribute to therapeutic vascular regeneration and consequently reduction of infarct area after stroke.
Differential Regulation of Morphine Antinociceptive Effects by Endogenous Enkephalinergic System in the Forebrain of Mice
Authors: Chen Tsung-Chieh , Cheng Ying-Ying , Sun Wei-Zen , Shyu Bai-Chuang 
Published: September 2008

Background: Mice lacking the preproenkephalin ( ppENK) gene are hyperalgesic and show more anxiety and aggression than wild-type (WT) mice. The marked behavioral changes in ppENK knock-out (KO) mice appeared to occur in supraspinal response to painful stimuli. However the functional role of enkephalins in the supraspinal nociceptive processing and their underlying mechanism is not clear. The aim of present study was to compare supraspinal nociceptive and morphine antinociceptive responses between WT and ppENK KO mice. Results: The genotypes of bred KO mice were confirmed by PCR. Met-enkephalin immunoreactive neurons were labeled in the caudate-putamen, intermediated part of lateral septum, lateral globus pallidus, intermediated part of lateral septum, hypothalamus, and amygdala of WT mice. Met-enkephalin immunoreactive neurons were not found in the same brain areas in KO mice. Tail withdrawal and von Frey test results did not differ between WT and KO mice. KO mice had shorter latency to start paw licking than WT mice in the hot plate test. The maximal percent effect of morphine treatments (5 mg/kg and 10 mg/kg, i.p.) differed between WT and KO mice in hot plate test. The current source density (CSD) profiles evoked by peripheral noxious stimuli in the primary somatosenstory cortex (S1) and anterior cingulate cortex (ACC) were similar in WT and KO mice. After morphine injection, the amplitude of the laser-evoked sink currents was decreased in S1 while the amplitude of electrical-evoked sink currents was increased in the ACC. These differential morphine effects in S1 and ACC were enhanced in KO mice. Facilitation of synaptic currents in the ACC is mediated by GABA inhibitory interneurons in the local circuitry. Percent increases in opioid receptor binding in S1 and ACC were 5.1% and 5.8%, respectively. Conclusion: The present results indicate that the endogenous enkephalin system is not involved in acute nociceptive transmission in the spinal cord, S1, and ACC. However, morphine preferentially suppressed supraspinal related nociceptive behavior in KO mice. This effect was reflected in the potentiated differential effects of morphine in the S1 and ACC in KO mice. This potentiation may be due to an up-regulation of opioid receptors. Thus these findings strongly suggest an antagonistic interaction between the endogenous enkephalinergic system and exogenous opioid analgesic actions in the supraspinal brain structures.
Severe adult ileosigmoid intussusception prolapsing from the rectum: A case report
Authors: Chen Rongrong , Zhao Haitao , Sang Xinting , Mao Yilei , Lu Xin , Yang Yifan 
Published: September 2008

Abstract
Intussusception is a pediatric condition that rarely presents in adults. In this article, we report a case of a 36 year-old man initially presenting with abdominal pain and rectal prolapse, however, surgical reduction of the rectal prolapse did no relief his symptoms. Physical examination, abdominal plain film, barium enema and colonoscopy confirmed the presence of a large intra-abdominal mass, but the origin of the mass was revealed only upon laparotomy. During the surgery, it was noted that the ileum and the sigmoid colon was connected by a 15 cm × 12cm mass, covered by an extremely dilated intestinal tissue. The resected tissue pathology demonstrated a 9 cm × 6 cm × 5 cm submucosal lipoma at the ileocecal junction without evidence of malignancy. The patient's post-surgical course was uneventful. Diagnostic and therapeutic problems related to adult intussusception are reviewed.
The 'cardiac-lung mass' artifact: an echocardiographic sign of lung atelectasis and/or pleural effusion
Authors: Karabinis Andreas , Saranteas Theodosios , Karakitsos Dimitrios , Lichtenstein Daniel , Poularas John , Yang Clifford , Stefanadis Christodoulos 
Published: September 2008

Abstract
Introduction
We conducted an ultrasound study to investigate echocardiographic artifacts in mechanically ventilated patients with lung pathology.

Methods
A total of 205 mechanically ventilated patients who exhibited lung atelectasis and/or pleural effusion were included in this 36-month study. The patients underwent lung echography and transthoracic echocardiography, with a linear 5 to 10 MHz and with a 1.5 to 3.6 MHz wide-angle phased-array transducer, respectively. Patients were examined by two experienced observers who were blinded to each other's interpretation.

Results
A total of 124 patients (60,48%) were hospitalized because of multiple trauma; 60 patients (29,26%) because of respiratory insufficiency, and 21 (10,24%) because of recent postoperative surgery. The mean duration ( ± standard deviation) of hospitalization was 35 ± 27 days. An intracardiac artifact was documented in 17 out of 205 patients (8.29%) by echocardiography. It was visible only in the apical views, whereas subsequent transesophageal echocardiography revealed no abnormalities. The artifact consisted of a mobile component that exhibited, on M-mode, a pattern of respiratory variation similar to the lung 'sinusoid sign'. Lung echography revealed lung atelectasis and/or pleural effusion adjacent to the heart, and a similar M-mode pattern was observed. The artifact was recorded within the left cardiac chambers in 11 cases and within the right cardiac chambers in six.

Conclusions
Lung atelectasis and/or pleural effusion may create a mirror image, intracardiac artifact in mechanically ventilated patients. The latter was named the 'cardiac-lung mass' artifact to underline the important diagnostic role of both echocardiography and lung echography in these patients.

Trial registration
This trial is ISRCTN registered: ISRCTN 49216096.