bluuebunny/crossref_metadata_2025 huggingface dataset:
Totally Laparoscopic Aortic Surgery: Comparison of the Apron and Retrocolic Techniques in a Porcine Model
Authors: Huynh Hai , Elkouri Stephane , Beaudoin Nathalie , Bruneau Luc , Guimond Cathie , Daniel Véronique , Blair Jean-François
Published: June 2007

This study evaluated the learning curve for a second-year general surgery resident and compared 2 totally laparoscopic aortic surgery techniques in 10 pigs: the transretroperitoneal apron approach and the transperitoneal retrocolic approach. Five end points were compared: success rate, percentage of conversion, time required, laparoscopic anastomosis quality, and learning curve. The first 3 interventions required an open conversion. The last 7 were done without complications. Mean dissection time was significantly higher with the apron approach compared with the retrocolic approach. The total times for operation, clamping, and arteriotomy time were similar. All laparoscopic anastomoses were patent and without stenosis. The initial learning curve for laparoscopic anastomosis was relatively short for a second-year surgery resident. Both techniques resulted in satisfactory exposure of the aorta and similar mean operative and clamping time. Training on an ex vivo laparoscopic box trainer and on an animal model seems to be complementary to decrease laparoscopic anastomosis completion time.
Decreased Ischemic Complications After Endovascular Aortic Aneurysm Repair With Newer Devices
Authors: Maldonado Thomas S. , Ranson Mark E. , Rockman Caron B. , Pua Brad , Cayne Neal S. , Jacobowitz Glenn R. , Adelman Mark A.
Published: June 2007

Ischemic complications after endovascular abdominal aortic aneurysm repair (EVAR) are well-recognized and have been reported to be as high as 9%. The goal of our study was to examine the incidence, management, and outcome of ischemic complications at our institution after EVAR and to compare complications according to graft type and time period. This is a retrospective review of all EVARs performed at our institution from 1993 through 2005 (n = 430). EVAR was performed in asymptomatic patients in most cases. Follow-up consisted of a computed tomography scan and office visit at 1, 6, and 12 months and yearly thereafter. Ischemic complications after EVAR have decreased significantly with the advent of lower-profile devices with easier delivery systems and supported limbs. Simultaneous coil embolization of internal iliac artery at the time of EVAR implant does not appear to increase the risk of pelvic or lower-extremity ischemia, can be done safely, and does not need to be staged.
Restenosis After Carotid Endarterectomy Performed With Routine Intraoperative Duplex Ultrasonography and Arterial Patch Closure: A Contemporary Series
Authors: Schanzer Andres , Hoel Andrew , Owens Christopher D. , Wake Nicole , Nguyen Louis L. , Conte Michael S. , Belkin Michael
Published: June 2007

The restenosis rates of 5% to 15% have been reported after carotid endarterectomy (CEA). We undertook this investigation to determine whether the routine practice of carotid artery patch closure and intraoperative completion duplex ultrasonography would result in lower rates of carotid restenosis after CEA. All consecutive carotid endarterectomies performed between 2000 and 2004 at a single institution were reviewed retrospectively. Patients underwent CEA using a longitudinal arteriotomy, followed by routine patching and intraoperative completion duplex ultrasonography. Only patients with at least one postoperative duplex scan performed at a minimum of 180 days after CEA were included. During the 5-year study period, 407 consecutive carotid endarterectomies were performed, with a combined 30-day stroke and mortality rate of 2.5%; 217 patients (53%) had one or more duplex ultrasound examinations performed at least 180 days after CEA. The mean follow-up duration was 692 days. Of the patients who underwent intraoperative intervention based on the results of the completion duplex study, none experienced restenosis, stroke, or death. CEA that is performed with routine patching and intraoperative duplex completion ultrasonography is a safe, durable operation with restenosis rates below those commonly reported.
Lack of Association Between Chlamydophila Pneumoniae Seropositivity and Abdominal Aortic Aneurysm
Authors: Nyberg Anders , Skagius Elisabet , Nilsson Ingrid , Ljungh Asa , Henriksson Anders E.
Published: June 2007

Chronic Chlamydophila pneumoniae infection has been suggested as a possible contributing factor for the development and expansion of abdominal aortic aneurysm (AAA). The relevance of C pneumoniae involved in the processes underlying aneurysmal rupture is unknown. The aim of this study was to examine the relationship between C pneumoniae seropositivity and AAA rupture. In a case-control study, 119 patients with AAA and 36 matched controls were prospectively investigated with C pneumoniae serology. Patients with ruptured AAA have similar levels of IgG antibodies against C pneumoniae as patients with an electively operated AAA, a small AAA, and controls. In conclusion, this study fails to demonstrate a connection between C pneumoniae seropositivity and AAA rupture.
Hybrid Debranching-Endovascular Repair of Visceral Patch Aneurysm After Thoracoabdominal Aneurysm Repair
Authors: Bakken Andrew M. , Protack Clinton D. , Waldman David L. , Davies Mark G.
Published: June 2007

A visceral patch aneurysm is a significant complication after extensive thoracoabdominal aneurysm repair, and open procedures to correct these lesions are associated with a high perioperative mortality. We report the case of a 6-cm visceral patch aneurysm occurring in a patient with a completely replaced descending and abdominal aorta that was successfully corrected by staged debranching and endovascular repair with a dedicated thoracic endograft. Hybrid procedures are a successful option to treat complex repairs in the reoperative setting. They have the potential to lower perioperative risk and enhance patient care.
Therapeutic Angiogenesis
Authors: Vartanian Shant M. , Sarkar Rajabrata
Published: June 2007

Myocardial ischemia and peripheral vascular disease persist as significant clinical problems despite improved medical, surgical, and endovascular therapies. Advances in our understanding of the biological mechanisms that govern capillary neovascularization and collateral artery growth have enabled molecular therapies for revascularizing ischemic tissues. Generally known as therapeutic angiogenesis, this review summarizes the essential pre-clinical research and the major clinical trials of molecular therapies for ischemic disease. Early clinical experience has established the proof of principle, however, inconsistent and modest improvements in clinical outcomes have exposed the complexity of neovascularization and problems with transitioning basic science to clinical applicability.
The perceptions and experiences of nurses undertaking research in the clinical setting
Authors: Woodward Valerie , Webb Christine , Prowse Morag
Published: June 2007

Nursing research activity by clinicians has increased in volume in the last few years, due to an increased awareness of the importance of evidence-based practice, the shift of nurse education into higher education establishments and the emergence of new nursing roles which demand research activity as a central domain of the role. This paper will report on the results of a study examining nursing research activity in the UK National Health Service and will present data examining the perceptions and experiences of nurses undertaking research. Forty-eight research-active nurses in five NHS organisations were interviewed. Data were analysed using the Framework approach. Four main themes emerged: perceptions of nursing research, NHS influences, support systems and individual influences. Many factors were identified by nurses that influenced their experiences and perceptions, and nurses frequently reported difficulties in being able to conduct research in the clinical area. Dissemination via publication was rare. Personal sacrifices were common and nurses felt that these were not recognised by managers. Nurses undertaking research need more structured support systems and recognition of the value of nursing research. Individualised help from more experienced researchers for support and to disseminate findings is recommended.
Benchmarking research development in nursing: Curran's competitive advantage as a framework for excellence
Authors: James Veronica , Clark Jill Macleod
Published: June 2007

This paper offers a developmental benchmark against which to assess nursing research achievements and excellence. Internationally, the academy of nursing, like other disciplines, has able people fully capable of delivering high-quality research. This raises the question of why, during systematic, peer-review research assessment exercises nursing appears at the bottom of the academic units assessed both in the UK RAE (Research Assessment Exercise, 1992, 1996, 2001) and the New Zealand PBRF (Performance Based Research Fund, 2003). To examine this issue, after tracing the background of the international drive for research excellence and the UK's Research Assessment Exercise (RAE), Curran's analysis of competitive advantage in higher education is introduced as a means of analysing nursing's entry into higher education and the RAE. Together with data comparing the development of nursing with other disciplines, analysis suggests that UK nursing's performance in RAEs was as a new, hard-working, emerging, applied discipline which demonstrated a predictable research trajectory with strong trends of growth in quality and quantity. Recognising that research assessment is both a politically driven, socially constructed competition for scarce resources, and an analysis of the discipline, the conclusion argues that excellence and integrity should form the foundation of a disciplinary identity which incorporates the diversity of the subject. It also notes that without secure research income streams the growth in critical mass of the `knowledge community' and nursing's capacity to contribute to health improvement will remain vulnerable despite strong positive trends.
Intracellular mediators of transforming growth factor β superfamily signaling localize to endosomes in chicken embryo and mouse lenses in vivo
Authors: Rajagopal Ramya , Ishii Shunsuke , Beebe David C
Published: June 2007

Background

Endocytosis is a key regulator of growth factor signaling pathways. Recent studies showed that the localization to endosomes of intracellular mediators of growth factor signaling may be required for their function. Although there is substantial evidence linking endocytosis and growth factor signaling in cultured cells, there has been little study of the endosomal localization of signaling components in intact tissues or organs.

Results

Proteins that are downstream of the transforming growth factor-β superfamily signaling pathway were found on endosomes in chicken embryo and postnatal mouse lenses, which depend on signaling by members of the TGFβ superfamily for their normal development. Phosphorylated Smad1 (pSmad1), pSmad2, Smad4, Smad7, the transcriptional repressors c-Ski and TGIF and the adapter molecules Smad anchor for receptor activation (SARA) and C184M, localized to EEA-1- and Rab5-positive vesicles in chicken embryo and/or postnatal mouse lenses. pSmad1 and pSmad2 also localized to Rab7-positive late endosomes. Smad7 was found associated with endosomes, but not caveolae. Bmpr1a conditional knock-out lenses showed decreased nuclear and endosomal localization of pSmad1. Many of the effectors in this pathway were distributed differently in vivo from their reported distribution in cultured cells.

Conclusion

Based on the findings reported here and data from other signaling systems, we suggest that the localization of activated intracellular mediators of the transforming growth factor-β superfamily to endosomes is important for the regulation of growth factor signaling.
Protein Kinase D regulates several aspects of development in Drosophila melanogaster
Authors: Maier Dieter , Nagel Anja C , Gloc Helena , Hausser Angelika , Kugler Sabrina J , Wech Irmgard , Preiss Anette
Published: June 2007

Background

Protein Kinase D (PKD) is an effector of diacylglycerol-regulated signaling pathways. Three isoforms are known in mammals that have been linked to diverse cellular functions including regulation of cell proliferation, differentiation, motility and secretory transport from the trans-Golgi network to the plasma membrane. In Drosophila, there is a single PKD orthologue, whose broad expression implicates a more general role in development.

Results

We have employed tissue specific overexpression of various PKD variants as well as tissue specific RNAi, in order to investigate the function of the PKD gene in Drosophila. Apart from a wild type (WT), a kinase dead (kd) and constitutively active (SE) Drosophila PKD variant, we also analyzed two human isoforms hPKD2 and hPKD3 for their capacity to substitute PKD activity in the fly. Overexpression of either WT or kd-PKD variants affected primarily wing vein development. However, overexpression of SE-PKD and PKD RNAi was deleterious. We observed tissue loss, wing defects and degeneration of the retina. The latter phenotype conforms to a role of PKD in the regulation of cytoskeletal dynamics. Strongest phenotypes were larval to pupal lethality. RNAi induced phenotypes could be rescued by a concurrent overexpression of Drosophila wild type PKD or either human isoform hPKD2 and hPKD3.

Conclusion

Our data confirm the hypothesis that Drosophila PKD is a multifunctional kinase involved in diverse processes such as regulation of the cytoskeleton, cell proliferation and death as well as differentiation of various fly tissues.
The identity, distribution, and impacts of non-native apple snails in the continental United States
Authors: Rawlings Timothy A , Hayes Kenneth A , Cowie Robert H , Collins Timothy M
Published: June 2007

Background

Since the mid 1990s populations of non-native apple snails (Ampullariidae) have been discovered with increasing frequency in the continental United States. Given the dramatic effects that introduced apple snails have had on both natural habitats and agricultural areas in Southeast Asia, their introduction to the mainland U.S. is cause for concern. We combine phylogenetic analyses of mtDNA sequences with examination of introduced populations and museum collections to clarify the identities, introduced distributions, geographical origins, and introduction histories of apple snails.

Results

Based on sampling to date, we conclude there are five species of non-native apple snails in the continental U.S. Most significantly, we recognize three species within what has been called the channeled apple snail:Pomacea canaliculata(California and Arizona),Pomacea insularum, (Florida, Texas, and Georgia) andPomacea haustrum(Florida). The first established populations ofP. haustrumwere discovered in the late 1970s in Palm Beach County Florida, and have not spread appreciably in 30 years. In contrast, populations ofP. insularumwere established in Texas by 1989, in Florida by the mid to late 1990s, and in Georgia by 2005, and this species continues to spread rapidly. Most introducedP. insularumhaplotypes are a close match to haplotypes from the Río Uruguay near Buenos Aires, indicating cold tolerance, with the potential to spread from Florida, Georgia, and Texas through Louisiana, Alabama, Mississippi, and South Carolina.Pomacea canaliculatapopulations were first discovered in California in 1997. Haplotypes of introducedP. canaliculatamatch native-range haplotypes from near Buenos Aires, Argentina, also indicating cold tolerance and the potential to establish farther north.

Conclusion

The term "channeled apple snail" is descriptive of a morphology found in many apple snail species. It does not identify a single species or a monophyletic group. Clarifying species identifications permits a more accurate assessment of introduction histories and distributions, and provides a very different picture of the tempo and pattern of invasions than was inferred when the three species with channeled sutures were considered one. Matching introduced and native-range haplotypes suggests the potential for range expansion, with implications for native aquatic ecosystems and species, agriculture, and human health.
Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S versus R rats
Authors: Shehata Marlene F , Leenen Frans HH , Tesson Frédérique
Published: June 2007

Background

To test whether epithelial sodium channel (ENaC) genes' variants contribute to salt sensitive hypertension in Dahl rats, we screened ENaC α, β, and γ genes entire coding regions, intron-exon junctions, and the 3' and 5' flanking regions in Dahl S, R and Wistar rats using both Denaturing High Performance Liquid Chromatography (DHPLC) and sequencing.

Results

Our analysis revealed no sequence variability in the three genes encoding ENaC in Dahl S versus R rats. One homozygous sequence variation predicted to result in a D75E substitution was identified in Dahl and Wistar rat ENaC α compared to Brown Norway. Six and two previously reported polymorphic sites in Brown Norway sequences were lost in Dahl and Wistar rats, respectively. In the 5' flanking regions, we found a deletion of 5GCTs in Dahl and Wistar rat ENaC α gene, five new polymorphic sites in ENaC β and γ genes, one homozygous sequence variation in Dahl and Wistar rat ENaC γ gene, as well as one Dahl rat specific homozygous insertion of -1118CCCCCA in ENaC γ gene. This insertion created additional binding sites for Sp1 and Oct-1. Five and three Brown Norway polymorphic sites were lost in Dahl and Wistar rats, respectively. No sequence variability in ENaC 3' flanking regions was identified in Dahl compared to Brown Norway rats.

Conclusion

The first comprehensive sequence analysis of ENaC genes did not reveal any differences between Dahl S and R rats that were isogenic in the regions screened. Mutations in ENaC genes intronic sequence or in ENaC-regulatory genes might possibly account for increased ENaC activity in Dahl S versus R rats.
Effects of DNA-targeted ionizing radiation produced by 5-[125I]iodo-2'-deoxyuridine on global gene expression in primary human cells
Authors: Sokolov Mykyta V , Neumann Ronald D , Panyutin Igor G
Published: June 2007

Background

This study assesses the whole-genome gene expression changes in a panel of primary human cell lines in response to DNA damage mediated by decay of DNA-incorporated radioiodinated thymidine analog 5-[125I]iodo-2'-deoxyuridine (125I-IUdR). Three normal human cell lines of different origin, namely, gingival fibroblasts AG09319, fetal skin fibroblasts GM05388 and neonatal foreskin epidermal keratinocytes (NHFK) were used in this study. DNA molecules were radiolabeled by incubation of cells in culture in a medium supplemented with either 3.7 kBq/ml or 18.5 kBq/ml of 125I-IUdR for 24 h followed by incubation in IUdR-free medium for additional 24 hours. Each experiment was carried out in quadruplicate. 125I-IUdR uptake was monitored by measuring DNA-associated radioactivity. The whole-genome gene expression changes were evaluated using Agilent Human Whole Genome oligo microarrays containing 44,290 elements representing all known and predicted human genes. DNA microarray dataset was independently partially validated with quantitative real-time PCR (RT-PCR).

Results

AG09319 gingival cells in culture responded to 125I-IUdR treatment by changing the expression level of 335 genes in total, whereas under the same conditions GM05388 and NHFK cells differentially expressed 49 genes and 27 genes, respectively. However, for GM05388 cells the number of differentially expressed genes increases with the rise of 125I-IUdR concentrations in cell culture media. The key up-regulated biological processes in a chosen panel of cell lines concern the regulation of protein kinase activities and/or cell death. Genes repressed in response to 125I-IUdR treatment are involved in cytokinesis, M phase of the cell cycle, chromosome architecture and organization, DNA metabolism, DNA packaging, DNA repair and response to DNA damage. Despite the disparate nature of the gene patterns elicited by 125I-induced DNA damage among the different cell lines, the differentially expressed transcripts reveal strikingly non-random chromosomal distribution in all the cell lines we used.

Conclusion

Our data suggest that DNA-targeted ionizing radiation produced by 125I-IUdR results in changes in expression of only a limited subset of genes in primary human cells. The responsive genes are distributed non-randomly among the chromosomes; and a significant fraction of them is p53-dependent in the transcriptional regulation.
Polymorphism of the FABP2 gene: a population frequency analysis and an association study with cardiovascular risk markers in Argentina
Authors: Gomez Laura C , Real Sebastián M , Ojeda Marta S , Gimenez Sergio , Mayorga Luis S , Roqué María
Published: June 2007

Background

The FABP2 gene encodes for the intestinal FABP (IFABP) protein, which is expressed only in intestinal enterocytes. A polymorphism at codon 54 in exon 2 of the FABP2 gene exchanges an Alanine (Ala), in the small helical region of the protein, for Threonine (Thr). Given the potential physiological role of the Ala54Thr FABP2 polymorphism, we assess in this study the local population frequency and analyze possible associations with five selected markers, i.e. glycemia, total cholesterol, body mass index (BMI), hypertension, and high Cardiovascular Risk Index (CVR index).

Methods

We studied 86 men and 116 women. DNA was extracted from a blood drop for genotype analysis. Allele frequencies were calculated by direct counting. Hardy Weinberg Equilibrium was evaluated using a Chi-square goodness of fit test.

For the polymorphism association analysis, five markers were selected, i.e. blood pressure, Framingham Risk Index, total cholesterol, BMI, and glycemia.

For each marker, the Odds Ratio (OR) was calculated by an online statistic tool.

Results

Our results reveal a similar population polymorphism frequency as in previous European studies, with q = 0.277 (95% confidence limits 0.234–0.323). No significant association was found with any of the tested markers in the context of our Argentine nutritional and cultural habits. We did, however, observe a tendency for increased Cholesterol and high BMI in Thr54 carriers.

Conclusion

This is the first study to look at the population frequency of the Thr54 allele in Argentina. The obtained result does not differ from previously reported frequencies in European populations. Moreover, we found no association between the Thr54 allele and any of the five selected markers. The observed tendency to increased total cholesterol and elevated BMI in Thr54 carriers, even though not significant for p < 0.1 could be worth of further investigation to establish whether the Thr54 variant should be taken into consideration in cardiovascular prevention strategies.
Impact of pharmaceutical promotion on prescribing decisions of general practitioners in Eastern Turkey
Authors: Vancelik Serhat , Beyhun Nazim E , Acemoglu Hamit , Calikoglu Oksan
Published: June 2007

Background

Commercial sources of information are known to have greater influence than scientific sources on general practitioners' (GPs) prescribing behavior in under developed and developing countries. The study aimed to determine the self-reported impact of pharmaceutical promotion on the decision-making process of prescription of GPs in Eastern Turkey.

Methods

A cross-sectional, exploratory survey was performed among 152 GPs working in the primary health centers and hospitals in Erzurum province of Eastern Turkey in 2006. A self-administered structured questionnaire was used. The questionnaire included questions regarding sociodemographics, number of patients per day, time per patient, frequency of sales representative visits to GPs, participation of GPs in training courses on prescribing (in-service training, drug companies), factors affecting prescribing decision, reference sources concerning prescribing and self-reported and self-rated effect of the activities of sales representatives on GPs prescribing decisions.

Results

Of 152 subjects, 53.3% were male and 65.8% were working at primary health care centers, respectively. Mean patient per day was 58.3 ± 28.8 patients per GP. For majority of the GPs (73.7%), the most frequent resource used in case of any problems in prescribing process was drug guides of pharmaceutical companies. According to self-report of the GPs, their prescribing decisions were affected by participation in any training activity of drug companies, frequent visits by sales representatives, high number of patient examinations per day and low year of practice (p < 0.05 for all).

Conclusion

The results of this study suggest that for the majority of the GPs, primary reference sources concerning prescribing was commercial information provided by sales representatives of pharmaceutical companies, which were reported to be highly influential on their decision-making process of prescribing by GPs. Since this study was based on self-report, the influence reported by the GPs may have been underestimated.
Prevalence of and risk factors for different measures of low back pain among female nursing aides in Taiwanese nursing homes
Authors: Feng Chao-Kang , Chen Mei-Lien , Mao I-Fang
Published: June 2007

Background

Although low back pain (LBP) among nursing staff, especially in nursing aides (NAs), has been a major health problem around the world, there is limited information on its prevalence in Taiwan. In addition, various measurements have been used to determine LBP; understanding the risk factors for each measurement of LBP is essential for prevention. This study aimed to assess the prevalence of and risk factors for different measures of LBP among NAs in Taiwan.

Methods

A cross-sectional study was conducted among 244 female NAs from 31 nursing homes in central Taiwan. A self-administered questionnaire, including the Nordic questionnaire and the Karasek's job content questionnaire, was used to collect data regarding five different measures of LBP and about demographic, physical and psychosocial factors. Also, on-site observation at the workplace was conducted to measure the frequency of five high risk patient-handling tasks.

Results

Based on the subjects' reports on the previous twelve months, the prevalence rates for pain lasting for at least one day, seeking of medical care, intense pain, sick leave, and chronic pain were 66.0%, 43.9%, 38.1%, 10.7%, and 8.6%, respectively. While multiple logistic regression analyses indicated that the risk factors varied with different measures of LBP, at least one high risk patient-handling task and one psychosocial factor were observed to be associated each LBP related measure. Three risk factors, including manual transfer of patients between bed/wheelchair and bath cart, perceived physical exertion, and psychological demands, were consistently associated with different measures of LBP. Besides, age was found to be associated with an increased risk of only chronic pain.

Conclusion

The prevalence of LBP among NAs in Taiwan is high and should be actively addressed. Certain manual patient-transfer tasks and psychological demands seemed to play more important roles in severe LBP (such as care seeking, intense pain, and sick leave) than in minor LBP (pain lasting for at least one day). Because different LBP related measures might be involved with different etiological risk factors, any LBP reduction interventions that aim to improve ergonomic and psychosocial work environments for NAs should take this information into consideration.
The effect of amino acid deletions and substitutions in the longest loop of GFP
Authors: Flores-Ramírez Gabriela , Rivera Manuel , Morales-Pablos Alfredo , Osuna Joel , Soberón Xavier , Gaytán Paul
Published: June 2007

Background

The effect of single and multiple amino acid substitutions in the green fluorescent protein (GFP) from Aequorea victoria has been extensively explored, yielding several proteins of diverse spectral properties. However, the role of amino acid deletions in this protein -as with most proteins- is still unknown, due to the technical difficulties involved in generating combinatorial in-phase amino acid deletions on a target region.

Results

In this study, the region I129-L142 of superglo GFP (sgGFP), corresponding to the longest loop of the protein and located far away from the central chromophore, was subjected to a random amino acid deletion approach, employing an in-house recently developed mutagenesis method termed Codon-Based Random Deletion (COBARDE). Only two mutants out of 16384 possible variant proteins retained fluorescence: sgGFP-Δ I129 and sgGFP-Δ D130. Interestingly, both mutants were thermosensitive and at 30°C sgGFP-Δ D130 was more fluorescent than the parent protein. In contrast with deletions, substitutions of single amino acids from residues F131 to L142 were well tolerated. The substitution analysis revealed a particular importance of residues F131, G135, I137, L138, H140 and L142 for the stability of the protein.

Conclusion

The behavior of GFP variants with both amino acid deletions and substitutions demonstrate that this loop is playing an important structural role in GFP folding. Some of the amino acids which tolerated any substitution but no deletion are simply acting as "spacers" to localize important residues in the protein structure.
Toll-like receptor 4 deficiency: Smaller infarcts, but nogain in function
Authors: Kim Se-Chan , Ghanem Alexander , Stapel Heidi , Tiemann Klaus , Knuefermann Pascal , Hoeft Andreas , Meyer Rainer , Grohé Christian , Knowlton Anne A , Baumgarten Georg
Published: June 2007

Backgound

It has been reported that Toll-like receptor 4 (TLR4) deficiency reduces infarct size after myocardial ischemia/reperfusion (MI/R). However, measurement of MI/R injury was limited and did not include cardiac function. In a chronic closed-chest model we assessed whether cardiac function is preserved in TLR4-deficient mice (C3H/HeJ) following MI/R, and whether myocardial and systemic cytokine expression differed compared to wild type (WT).

Results

Infarct size (IS) in C3H/HeJ assessed by TTC staining after 60 min ischemia and 24h reperfusion was significantly smaller than in WT. Despite a smaller infarct size, echocardiography showed no functional difference between C3H/HeJ and WT. Left-ventricular developed pressure measured with a left-ventricular catheter was lower in C3H/HeJ (63.0 ± 4.2 mmHg vs. 77.9 ± 1.7 mmHg in WT, p < 0.05). Serum cytokine levels and myocardial IL-6 were higher in WT than in C3H/HeJ (p < 0.05). C3H/HeJ MI/R showed increased myocardial IL-1β and IL-6 expression compared to their respective shams (p < 0.05), indicating TLR4-independent cytokine activation due to MI/R.

Conclusion

These results demonstrate that, although a mutant TLR4 signaling cascade reduces myocardial IS and serum cytokine levels, it does not preserve myocardial function. The change in inflammatory response, secondary to a non-functional TLR-4 receptor, may contribute to the observed dichotomy between infarct size and function in the TLR-4 mutant mouse.
Differential scanning calorimetry study of glycerinated rabbit psoas muscle fibres in intermediate state of ATP hydrolysis
Authors: Dergez Timea , Lőrinczy Dénes , Könczöl Franciska , Farkas Nelli , Belagyi Joseph
Published: June 2007

Background

Thermal denaturation experiments were extended to study the thermal behaviour of the main motor proteins (actin and myosin) in their native environment in striated muscle fibres. The interaction of actin with myosin in the highly organized muscle structure is affected by internal forces; therefore their altered conformation and interaction may differ from those obtained in solution. The energetics of long functioning intermediate states of ATP hydrolysis cycle was studied in muscle fibres by differential scanning calorimetry (DSC).

Results

SETARAM Micro DSC-II was used to monitor the thermal denaturation of the fibre system in rigor and in the presence of nucleotide and nucleotide analogues. The AM.ADP.Pi state of the ATP hydrolysis cycle has a very short lifetime therefore, we mimicked the different intermediate states with AMP.PNP and/or inorganic phosphate analogues Vi and AlF4 or BeFx. Studying glycerol-extracted muscle fibres from the rabbit psoas muscle by DSC, three characteristic thermal transitions were detected in rigor. The thermal transitions can be assigned to myosin heads, myosin rods and actin with transition temperatures (Tm) of 52.9 ± 0.7°C, 57.9 ± 0.7°C, 63.7 ± 1.0°C. In different intermediate states of the ATP hydrolysis mimicked by nucleotide analogues a fourth thermal transition was also detected which is very likely connected with nucleotide binding domain of myosin and/or actin filaments. This transition temperature Tm4 depended on the mimicked intermediate states, and varied in the range of 66°C – 77°C.

Conclusion

According to DSC measurements, strongly and weakly binding states of myosin to actin were significantly different. In the presence of ADP only a moderate change of the DSC pattern was detected in comparison with rigor, whereas in ADP.Pi state trapped by Vi, AlF4 or BeFx a remarkable stabilization was detected on the myosin head and actin filament which is reflected in a 3.0 – 10.0°C shift in Tm to higher temperature. A similar effect was observed in the case of the nonhydrolyzable AMP.PNP analogue. Differential DSC measurements suggest that stabilization actin structure in the intermediate states of ATP hydrolysis may play an additional role in actin-myosin interaction.
Where should Momma go? Current nursing home performance measurement strategies and a less ambitious approach
Authors: Phillips Charles D , Hawes Catherine , Lieberman Trudy , Koren Mary Jane
Published: June 2007

Background

Nursing home performance measurement systems are practically ubiquitous. The vast majority of these systems aspire to rank order all nursing homes based on quantitative measures of quality. However, the ability of such systems to identify homes differing in quality is hampered by the multidimensional nature of nursing homes and their residents. As a result, the authors doubt the ability of many nursing home performance systems to truly help consumers differentiate among homes providing different levels of quality. We also argue that, for consumers, performance measurement models are better at identifying problem facilities than potentially good homes.

Discussion

In response to these concerns we present a proposal for a less ambitious approach to nursing home performance measurement than previously used. We believe consumers can make better informed choice using a simpler system designed to pinpoint poor-quality nursing homes, rather than one designed to rank hundreds of facilities based on differences in quality-of-care indicators that are of questionable importance. The suggested performance model is based on five principles used in the development of the Consumers Union 2006 Nursing Home Quality Monitor.

We can best serve policy-makers and consumers by eschewing nursing home reporting systems that present information about all the facilities in a city, a state, or the nation on a website or in a report. We argue for greater modesty in our efforts and a focus on identifying only the potentially poorest or best homes. In the end, however, it is important to remember that information from any performance measurement website or report is no substitute for multiple visits to a home at different times of the day to personally assess quality.
Bismarck or Beveridge: a beauty contest between dinosaurs
Authors: van der Zee Jouke , Kroneman Madelon W
Published: June 2007

Background

Health systems delivery systems can be divided into two broad categories: National Health Services (NHS) on the one hand and Social Security (based) Health care systems (SSH) on the other hand. Existing literature is inconclusive about which system performs best. In this paper we would like to improve the evidence-base for discussion about pros and cons of NHS-systems versus SSH-system for health outcomes, expenditure and population satisfaction.

Methods

In this study we used time series data for 17 European countries, that were characterized as either NHS or SSH country. We used the following performance indicators: For health outcome: overall mortality rate, infant mortality rate and life expectancy at birth. For health care costs: health care expenditure per capita in pppUS$ and health expenditure as percentage of GDP. Time series dated from 1970 until 2003 or 2004, depending on availability. Sources were OECD health data base 2006 and WHO health for all database 2006. For satisfaction we used the Eurobarometer studies from 1996, 1998 and 1999.

Results

SSH systems perform slightly better on overall mortality rates and life expectancy (after 1980). For infant mortality the rates converged between the two types of systems and since 1980 no differences ceased to exist.

SSH systems are more expensive and NHS systems have a better cost containment. Inhabitants of countries with SSH-systems are on average substantially more satisfied than those in NHS countries.

Conclusion

We concluded that the question 'which type of system performs best' can be answered empirically as far as health outcomes, health care expenditures and patient satisfaction are concerned. Whether this selection of indicators covers all or even most relevant aspects of health system comparison remains to be seen. Perhaps further and more conclusive research into health system related differences in, for instance, equity should be completed before the leading question of this paper can be answered. We do think, however, that this study can form a base for a policy debate on the pros and cons of the existing health care systems in Europe.
Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model
Authors: Oflazoglu Ezogelin , Elliott Mark , Takita Hiroshi , Ferrone Soldano , Henderson Robert A , Repasky Elizabeth A
Published: June 2007

Background

The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs), has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed.

Methods

To address questions related to thein vivointeraction of human lung tumor cells and immune effector cells, we obtained an HLA class I+lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer.

Results

The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific mannerin vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumorsin vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumorsin vivowithout the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface.

Conclusion

These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, thein vivomodel described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular immunotherapy as effector cells seek and destroy areas of tumor growth and for testing strategies to improve clinical effectiveness.
A German national prevalence study on the cost of intensive care: an evaluation from 51 intensive care units
Authors: Moerer Onnen , Plock Enno , Mgbor Uchenna , Schmid Alexandra , Schneider Heinz , Wischnewsky Manfred Bernd , Burchardi Hilmar
Published: June 2007

Introduction

Intensive care unit (ICU) costs account for up to 20% of a hospital's costs. We aimed to analyse the individual patient-related cost of intensive care at various hospital levels and for different groups of disease.

Methods

Data from 51 ICUs all over Germany (15 primary care hospitals and 14 general care hospitals, 10 maximal care hospitals and 12 focused care hospitals) were collected in an observational, cross-sectional, one-day point prevalence study by two external study physicians (January–October 2003). All ICU patients (length of stay > 24 hours) treated on the study day were included. The reason for admission, severity of illness, surgical/diagnostic procedures, resource consumption, ICU/hospital length of stay, outcome and ICU staffing structure were documented.

Results

Altogether 453 patients were included. ICU (hospital) mortality was 12.1% (15.7%). The reason for admission and the severity of illness differed between the hospital levels of care, with a higher amount of unscheduled surgical procedures and patients needing mechanical ventilation in maximal care hospital and focused care hospital facilities. The mean total costs per day were €791 ± 305 (primary care hospitals, €685 ± 234; general care hospitals, €672 ± 199; focused care hospitals, €816 ± 363; maximal care hospitals, €923 ± 306), with the highest cost in septic patients (€1,090 ± 422). Differences were associated with staffing, the amount of prescribed drugs/blood products and diagnostic procedures.

Conclusion

The reason for admission, the severity of illness and the occurrence of severe sepsis are directly related to the level of ICU cost. A high fraction of costs result from staffing (up to 62%). Specialized and maximum care hospitals treat a higher proportion of the more severely ill and most expensive patients.
Correcting for sequence biases in present/absent calls
Authors: Schuster Eugene F , Blanc Eric , Partridge Linda , Thornton Janet M
Published: June 2007

The probe sequence of short oligonucleotides in Affymetrix microarray experiments can have a significant influence on present/absent calls of probesets with absent target transcripts. Probesets enriched for central Ts and depleted of central As in the perfect-match probes tend to be falsely classified as having present transcripts. Correction of non-specific binding for both perfect-match and mismatch probes using probe-sequence models can partially remove the probe-sequence bias and result in better performance of the MAS 5.0 algorithm.
Estimation and correction of non-specific binding in a large-scale spike-in experiment
Authors: Schuster Eugene F , Blanc Eric , Partridge Linda , Thornton Janet M
Published: June 2007

Background

The availability of a recently published large-scale spike-in microarray dataset helps us to understand the influence of probe sequence in non-specific binding (NSB) signal and enables the benchmarking of several models for the estimation of NSB. In a typical microarray experiment using Affymetrix whole genome chips, 30% to 50% of the probes will apparently have absent target transcripts and show only NSB signal, and these probes can have significant repercussions for normalization and the statistical analysis of the data if NSB is not estimated correctly.

Results

We have found that the MAS5 perfect match-mismatch (PM-MM) model is a poor model for estimation of NSB, and that the Naef and Zhang sequence-based models can reasonably estimate NSB. In general, using the GC robust multi-array average, which uses Naef binding affinities, to calculate NSB (GC-NSB) outperforms other methods for detecting differential expression. However, there is an intensity dependence of the best performing methods for generating probeset expression values. At low intensity, methods using GC-NSB outperform other methods, but at medium intensity, MAS5 PM-MM methods perform best, and at high intensity, MAS5 PM-MM and Zhang's position-dependent nearest-neighbor (PDNN) methods perform best.

Conclusion

A combined statistical analysis using the MAS5 PM-MM, GC-NSB and PDNN methods to generate probeset values results in an improved ability to detect differential expression and estimates of false discovery rates compared with the individual methods. Additional improvements in detecting differential expression can be achieved by a strict elimination of empty probesets before normalization. However, there are still large gaps in our understanding of the Affymetrix GeneChip technology, and additional large-scale datasets, in which the concentration of each transcript is known, need to be produced before better models of specific binding can be created.
Contextual Control of Choice Performance
Authors: HADDON JOSEPHINE E. , KILLCROSS SIMON
Published: June 2007

Abstract:  An important aspect of decision making is the ability of responses to be controlled by different cues in different situations or contexts, especially when there is conflict between alternative responses or actions.Recently, a context‐dependent biconditional task has been developed for rats that mimic some aspects of response conflict seen in human cognitive paradigms, such as the Stroop task. In this task, contextual cues are used to disambiguate conflicting response information provided by audiovisual compound stimuli. Here we review current findings that investigate some of the behavioral, neurobiological, and neurochemical mechanisms that underlie this use of contextual or task‐setting information to resolve response conflict, and discuss future ways in which this research can be extended.
A Computational Model of Craving and Obsession
Authors: REDISH A. DAVID , JOHNSON ADAM
Published: June 2007

Abstract:  If addictions and problematic behaviors arise from interactions between drugs, reward sequences, and natural learning sytems, then an explanation of clinically problematic conditions (such as the self‐administration of drugs or problem gambling) requires an understanding of the neural systems that have evolved to allow an agent to make decisions. We hypothesize a unified decision‐making system consisting of three components—a situation recognition system, a flexible, planning‐capable system, and an inflexible, habit‐like system. In this article, we present a model of the planning‐capable system based on a planning process arising from experimentally observed look‐ahead dynamics in the hippocampus enabling a forward search of possibilities and an evaluation process in the nucleus accumbens. Based on evidence that opioid signaling can provide hedonic evalutation of an achieved outcome, we hypothesize that similar opioid‐signaling processes evaluate the value of expected outcomes. This leads to a model of craving, based on the recognition of a path to a high‐value outcome, and obsession, based on a value‐induced limitation of the search process. This theory can explain why opioid antagonists reduce both hedonic responses and craving.