bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)–rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study
Authors: Mann Georg , Attarbaschi Andishe , Schrappe Martin , De Lorenzo Paola , Peters Christina , Hann Ian , De Rossi Giulio , Felice Maria , Lausen Birgitte , LeBlanc Thierry , Szczepanski Tomasz , Ferster Alina , Janka-Schaub Gritta , Rubnitz Jeffrey , Silverman Lewis B. , Stary Jan , Campbell Myriam , Li Chi Kong , Suppiah Ram , Biondi Andrea , Vora Ajay , Valsecchi Maria Grazia , Pieters Rob ,   on behalf of the Interfant-99 Study Group
Published: July 2010

To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL+), we compared the outcome of MLL+ patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376 patients with a known MLL status in the trial, 297 (79%) were MLL+. Among the 277 of 297 MLL+ patients (93%) in first remission (CR), there appeared to be a significant difference in disease-free survival (adjusted by waiting time to HSCT) between the 37 (13%) who received HSCT and the 240 (87%) who received chemotherapy only (P = .03). However, the advantage was restricted to a subgroup with 2 additional unfavorable prognostic features: age less than 6 months and either poor response to steroids at day 8 or leukocytes more than or equal to 300 g/L. Ninety-seven of 297 MLL+ patients (33%) had such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only. In summary, HSCT seems to be a valuable option for a subgroup of infant MLL+ acute lymphoblastic leukemia carrying further poor prognostic factors. The trial was registered at www.clinicaltrials.gov as #NCT00015873 and at www.controlled-trials.com as #ISRCTN24251487.
Live imaging of neutrophil motility in a zebrafish model of WHIM syndrome
Authors: Walters Kevin B. , Green Julie M. , Surfus Jill C. , Yoo Sa Kan , Huttenlocher Anna
Published: July 2010

CXCR4 is a G protein–coupled chemokine receptor that has been implicated in the pathogenesis of primary immunodeficiency disorders and cancer. Autosomal dominant gain-of-function truncations of CXCR4 are associated with warts, hypo-gammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a primary immunodeficiency disorder characterized by neutropenia and recurrent infections. Recent progress has implicated CXCR4-SDF1 (stromal cell-derived factor 1) signaling in regulating neutrophil homeostasis, but the precise role of CXCR4-SDF1 interactions in regulating neutrophil motility in vivo is not known. Here, we use the optical transparency of zebrafish to visualize neutrophil trafficking in vivo in a zebrafish model of WHIM syndrome. We demonstrate that expression of WHIM mutations in zebrafish neutrophils induces neutrophil retention in hematopoietic tissue, impairing neutrophil motility and wound recruitment. The neutrophil retention signal induced by WHIM truncation mutations is SDF1 dependent, because depletion of SDF1 with the use of morpholino oligonucleotides restores neutrophil chemotaxis to wounds. Moreover, localized activation of a genetically encoded, photoactivatable Rac guanosine triphosphatase is sufficient to direct migration of neutrophils that express the WHIM mutation. The findings suggest that this transgenic zebrafish model of WHIM syndrome may provide a valuable tool to screen for agents that modify CXCR4-SDF1 retention signals.
Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs)
Authors: Lepelletier Yves , Zollinger Raphaël , Ghirelli Cristina , Raynaud Françoise , Hadj-Slimane Réda , Cappuccio Antonio , Hermine Olivier , Liu Yong-Jun , Soumelis Vassili
Published: July 2010

Microbial infection triggers the endogenous production of immunosuppressive glucocorticoid (GC) hormones and simultaneously activates innate immunity through toll-like receptors (TLRs). How innate immune cells integrate these 2 opposing signals in dictating immunity or tolerance to infection is not known. In this study, we show that human plasmacytoid predendritic cells (pDCs) were highly sensitive to GC-induced apoptosis. Strikingly, they were protected by microbial stimulation through TLR-7 and TLR-9, but not by microbial-independent stimuli, such as interleukin-3, granulocyte macrophage colony-stimulating factor, or CD40-ligand. This protection was dependent on TLR-induced autocrine tumor necrosis factor-α and interferon-α, which collectively increased the expression ratio between antiapoptotic genes (Bcl-2, Bcl-xL, BIRC3, CFLAR) versus proapoptotic genes (Caspase-8, BID, BAD, BAX). In particular, virus-induced Bcl-2 up-regulation was dependent on autocrine interferon-α. Using small interfering RNA technology, we demonstrated that Bcl-2 and CFLAR/c-flip were essential for TLR-induced protection of pDCs from GC-induced caspase-8–mediated apoptosis. Our results demonstrate a novel property of the TLR pathway in regulating the interface between GC and innate immunity and reveal a previously undescribed mechanism of GC resistance.
Proteome-wide survey of phosphorylation patterns affected by nuclear DNA polymorphisms in Arabidopsis thaliana
Authors: Riaño-Pachón Diego Mauricio , Kleessen Sabrina , Neigenfind Jost , Durek Pawel , Weber Elke , Engelsberger Wolfgang R , Walther Dirk , Selbig Joachim , Schulze Waltraud X , Kersten Birgit
Published: July 2010

Background

Protein phosphorylation is an important post-translational modification influencing many aspects of dynamic cellular behavior. Site-specific phosphorylation of amino acid residues serine, threonine, and tyrosine can have profound effects on protein structure, activity, stability, and interaction with other biomolecules. Phosphorylation sites can be affected in diverse ways in members of any species, one such way is through single nucleotide polymorphisms (SNPs). The availability of large numbers of experimentally identified phosphorylation sites, and of natural variation datasets inArabidopsis thalianaprompted us to analyze the effect of non-synonymous SNPs (nsSNPs) onto phosphorylation sites.

Results

From the analyses of 7,178 experimentally identified phosphorylation sites we found that: (i) Proteins with multiple phosphorylation sites occur more often than expected by chance. (ii) Phosphorylation hotspots show a preference to be located outside conserved domains. (iii) nsSNPs affected experimental phosphorylation sites as much as the corresponding non-phosphorylated amino acid residues. (iv) Losses of experimental phosphorylation sites by nsSNPs were identified in 86A. thalianaproteins, among them receptor proteins were overrepresented.

These results were confirmed by similar analyses of predicted phosphorylation sites inA. thaliana. In addition, predicted threonine phosphorylation sites showed a significant enrichment of nsSNPs towards asparagines and a significant depletion of the synonymous substitution. Proteins in which predicted phosphorylation sites were affected by nsSNPs (loss and gain), were determined to be mainly receptor proteins, stress response proteins and proteins involved in nucleotide and protein binding. Proteins involved in metabolism, catalytic activity and biosynthesis were less affected.

Conclusions

We analyzed more than 7,100 experimentally identified phosphorylation sites in almost 4,300 protein-coding lociin silico, thus constituting the largest phosphoproteomics dataset forA. thalianaavailable to date. Our findings suggest a relatively high variability in the presence or absence of phosphorylation sites between different natural accessions in receptor and other proteins involved in signal transduction. Elucidating the effect of phosphorylation sites affected by nsSNPs on adaptive responses represents an exciting research goal for the future.
Transcriptional regulation of the grape cytochrome P450 monooxygenase gene CYP736B expression in response to Xylella fastidiosa infection
Authors: Cheng Davis W , Lin Hong , Takahashi Yuri , Walker M Andrew , Civerolo Edwin L , Stenger Drake C
Published: July 2010

Background

Plant cytochrome P450 monooxygenases (CYP) mediate synthesis and metabolism of many physiologically important primary and secondary compounds that are related to plant defense against a range of pathogenic microbes and insects. To determine if cytochrome P450 monooxygenases are involved in defense response toXylella fastidiosa(Xf) infection, we investigated expression and regulatory mechanisms of the cytochrome P450 monooxygenaseCYP736Bgene in both disease resistant and susceptible grapevines.

Results

Cloning of genomic DNA and cDNA revealed that theCYP736Bgene was composed of two exons and one intron with GT as a donor site and AG as an acceptor site.CYP736Btranscript was up-regulated in PD-resistant plants and down-regulated in PD-susceptible plants 6 weeks afterXfinoculation. However,CYP736Bexpression was very low in stem tissues at all evaluated time points. 5'RACE and 3'RACE sequence analyses revealed that there were three candidate transcription start sites (TSS) in the upstream region and three candidate polyadenylation (PolyA) sites in the downstream region ofCYP736B. Usage frequencies of each transcription initiation site and each polyadenylation site varied depending on plant genotype, developmental stage, tissue, and treatment. These results demonstrate that expression ofCYP736Bis regulated developmentally and in response toXfinfection at both transcriptional and post-transcriptional levels. Multiple transcription start and polyadenylation sites contribute to regulation ofCYP736Bexpression.

Conclusions

This report provides evidence that the cytochrome P450 monooxygenaseCYP736Bgene is involved in defense response at a specific stage ofXfinfection in grapevines; multiple transcription initiation and polyadenylation sites exist forCYP736Bin grapevine; and coordinative and selective use of transcription initiation and polyadenylation sites play an important role in regulation ofCYP736Bexpression during growth, development and response toXfinfection.
Assessment of FAE1 polymorphisms in three Brassica species using EcoTILLING and their association with differences in seed erucic acid contents
Authors: Wang Nian , Shi Lei , Tian Fang , Ning Huicai , Wu Xiaoming , Long Yan , Meng Jinling
Published: July 2010

Background

FAE1 (fatty acid elongase1) is the key gene in the control of erucic acid synthesis in seeds of Brassica species. Due to oil with low erucic acid (LEA) content is essential for human health and not enough LEA resource could be available, thus new LEA genetic resources are being sought for Brassica breeding. EcoTILLING, a powerful genotyping method, can readily be used to identify polymorphisms in Brassica.

Results

Seven B. rapa, nine B. oleracea and 101 B. napus accessions were collected for identification of FAE1 polymorphisms. Three polymorphisms were detected in the two FAE1 paralogues of B. napus using EcoTILLING and were found to be strongly associated with differences in the erucic acid contents of seeds. In genomic FAE1 sequences obtained from seven B. rapa accessions, one SNP in the coding region was deduced to cause loss of gene function. Molecular evolution analysis of FAE1 homologues showed that the relationship between the Brassica A and C genomes is closer than that between the A/C genomes and Arabidopsis genome. Alignment of the coding sequences of these FAE1 homologues indicated that 18 SNPs differed between the A and C genomes and could be used as genome-specific markers in Brassica.

Conclusion

This study showed the applicability of EcoTILLING for detecting gene polymorphisms in Brassica. The association between B. napus FAE1 polymorphisms and the erucic acid contents of seeds may provide useful guidance for LEA breeding. The discovery of the LEA resource in B. rapa can be exploited in Brasscia cultivation.
Ultrasonographic detection and assessment of the severity of Crohn's disease recurrence after ileal resection
Authors: Pallotta Nadia , Giovannone Maurizio , Pezzotti Patrizio , Gigliozzi Alessandro , Barberani Fausto , Piacentino Daria , Hassan Naima Abdulkadir , Vincoli Giuseppina , Tosoni Mauro , Covotta Alfredo , Marcheggiano Adriana , Di Camillo Mauro , Corazziari Enrico
Published: July 2010

Background

Recurrence and severity of Crohn's disease mucosal lesions after "curative" ileal resection is assessed at endoscopy. Intramural lesions can be detected as increased wall thickness at Small Intestine Contrast Ultrasonography (SICUS).

Aims. To assess after ileal resection whether: 1) SICUS detects recurrence of Crohn's disease lesions, 2) the intestinal wall thickness measured at the level of ileo-colonic anastomosis predicts the severity of endoscopic lesions, 3) the extension of intramural lesions of the neo-terminal ileum is useful for grading severity of the recurrence, 4) the combined measures of wall thickness of the ileo-colonic anastomosis and of the extension of intramural lesions at level of the neo-terminal ileum may predict the endoscopic Rutgeerts score

Methods

Fifty eight Crohn's disease patients (M 37, age range 19-75 yrs) were prospectively submitted at 6-12 months intervals after surgery to endoscopy and SICUS for a total of 111 observations.

Results

Six months or more after surgery wall thickness of ileo-colonic anastomosis > 3.5 mm identified 100% of patients with endoscopic lesions (p < 0.0001). ROC curve analysis, combining wall thickness of ileo-colonic anastomosis and the extension of intramural lesions of neo-terminal ileum, discriminated (0.95) patients with, from those without, endoscopic lesions. Performing two multiple logistic regression analyses only wall thickness of ileo-colonic anastomosis and extension of neo-terminal ileum intramural lesions were significantly associated with absence or presence of endoscopic lesions. An ordinal polychotomus logistic model, considering all investigated variables, confirmed that only SICUS variables were associated with endoscopic grading of severity.

Conclusions

In patients submitted to ileal resection for Crohn's disease non-invasive Small Intestine Contrast Ultrasonography 1) by assessing thickness of ileo-colonic anastomosis accurately detects initial, minimal Crohn's disease recurrence, and 2) by assessing both thickness of ileo-colonic anastomosis and extension of intramural lesions of neo-terminal ileum grades the severity of the post-surgical recurrence.
Circulating cytokines and procalcitonin in acute Q fever granulomatous hepatitis with poor response to antibiotic and short-course steroid therapy: a case report
Authors: Lai Chung-Hsu , Lin Jiun-Nong , Chang Lin-Li , Chen Yen-Hsu , Lin Hsi-Hsun
Published: July 2010

Background

Q fever is a zoonosis distributed worldwide that is caused by Coxiella burnetii infection and the defervescence usually occurs within few days of appropriate antibiotic therapy. Whether the changes of cytokine levels are associated with acute Q fever with persistent fever despite antibiotic therapy had not been investigated before.

Case Presentation

We report a rare case of acute Q fever granulomatous hepatitis remained pyrexia despite several antibiotic therapy and 6-day course of oral prednisolone. During the 18-month follow-up, the investigation of the serum cytokines profile and procalcitonin (PCT) revealed that initially elevated levels of interleukin-2 (IL-2), IL-8, IL-10, and PCT decreased gradually, but the IL-6 remained in low titer. No evidence of chronic Q fever was identified by examinations of serum antibodies against C. burnetii and echocardiography.

Conclusions

The changes of cytokine levels may be associated with acute Q fever with poor response to treatment and PCT may be an indicator for monitoring the response to treatment.
Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review
Authors: Zhou Yanming , Sui Chengjun , Li Bin , Yin Zhengfeng , Tan Yunchang , Yang Jiamei , Liu Zhenyu
Published: July 2010

Background

This study aimed to assess the efficacy and safety of repeat hepatectomy for recurrent hepatocellular carcinoma (HCC).

Methods

Thirty-seven patients who underwent a curative repeat hepatectomy in our hospital were retrospectively studied. An extensive database literature search was performed to obtain for all relevant studies.

Results

In our series, there were no perioperative deaths during repeat hepatectomy for recurrent HCC. Patients survival after repeat hepatectomy were similar to 429 patients undergoing initial hepatectomy. A computerized search of the Medline and PubMed databases found 29 retrospective studies providing relevant data in 1149 patients were included for appraisal and data extraction. After the repeat hepatectomy, postoperative morbidity ranged from 6.2% to 68.2% with a median per cohort of 23.5 per cent. There were 7 perioperative deaths (0.7 per cent of 993 for whom mortality data were provided). The overall median survival ranged from 21 to 61.5 months, with 1 -, 3 -, and 5-year survival of 69.0% to 100%, 21.0% to 87.0%, and 25.0% to 87.0%, respectively.

Conclusions

Repeat hepatectomy can be performed safely and is associated with long-term survival in a subset of patients with recurrent HCC. However, the findings have to be carefully interpreted due to the lower level of evidence. A randomized controlled study is needed to compare repeat hepatectomy and other modalities for recurrent HCC.
Unusually young age distribution of primary hepatic leiomyosarcoma: case series and review of the adult literature
Authors: Shamseddine Achraf , Faraj Walid , Mukherji Deborah , El Majzoub Nadim , Khalife Mohamed , Soubra Ayman , Shamseddine Ali
Published: July 2010

Background

Primary hepatic leiomyosarcoma is a rare disease diagnosed in older aged adults with a median age of 58 and occasionally in children with a history of immunosuppression.

Methods

From 1998 to 2009, 215 patients were diagnosed with primary hepatic malignancies at our institution, 4 of which were diagnosed with primary hepatic sarcoma (1.8%). Three cases were primary hepatic leiomyosarcomas (LMS) and one case was primary undifferentiated embryonal sarcoma of the liver; median age 30 (range 20-39) years.

Results

One patient is currently 12 months post-resection with no evidence of recurrence. Two patients passed away at 19 days and 22 months from small for size liver and tumor recurrence respectively.

Conclusion

We have presented 3 cases of primary hepatic leiomyosarcoma diagnosed at our institution with an unusually young age distribution and no evidence of immunosuppression. These cases highlight the diagnostic and therapeutic challenges of this rare tumour.
Acute onset lactobacillus endophthalmitis after trabeculectomy: a case report
Authors: Papaconstantinou Dimitris , Georgalas Ilias , Karmiris Themis , Ladas Ioannis , Droutsas Konstantinos , Georgopoulos Gerasimos
Published: July 2010

Introduction

We report a case of early lactobacillus endophthalmitis which occurred ten days after trabeculectomy.

Case presentation

A 76-year-old Caucasian diabetic woman underwent uncomplicated trabeculectomy with a collagen implant as an adjunct, in her left phakic eye, for the treatment of uncontrolled open-angle glaucoma. Ten days post-operatively, our patient complained of left phakic eye discharge pain and visual acuity decreased to "light-perception". The anterior chamber had 3+ cells and flare, and there was also 2 mm layered hypopyon. Vitreous involvement was present obscuring visualization of the fundus. On the same day our patient underwent vitrectomy surgery and intra-vitreal and systemic antibiotics were administered. Vitreous cultures grew Lactobacillus brevis. Our patient responded well to treatment and 30 days after vitrectomy visual acuity improved to 1/10. Six months later our patient underwent cataract surgery. Eight months after initial surgery visual acuity was 2/10 and intra-ocular pressure was 14 mmHg without any anti-glaucoma medication.

Conclusions

This is the first report of acute lactobacillus endophthalmitis in the phakic eye of a diabetic patient after trabeculectomy. Glaucoma surgeons should be aware of the potential for acute post-operative endophthalmitis due to rare microorganisms, such as lactobacillus, in glaucoma filtration surgery, especially in diabetic patients. The literature shows an increased risk of endophthalmitis when anti-metabolites are used in conjunction with trabeculectomy. Perhaps, any type of wound healing modulation, such as collagen or mitomycin-C may increase this risk. However, it is unclear at this time and more studies need to be done. In this single case, vitrectomy combined with intra-vitreal and systemic antibiotics were efficient in limiting the devastating sequels of this complication.
Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells
Authors: Brüning Ansgar , Friese Klaus , Burges Alexander , Mylonas Ioannis
Published: July 2010

Introduction

The HIV protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. Several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. In the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated.

Methods

The effects of nelfinavir and tamoxifen on the human breast cancer cell lines MCF7, T47 D, MDA-MB-453, and MDA-MB-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(ADP-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3B expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level).

Results

Nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. The concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 μg/ml to 6 μg/ml when combined with tamoxifen. At a concentration of 6 μg/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (BiP) upregulation (MCF7, T47D), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3B upregulation (MDA-MB-453). Although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 μg/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32%, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir.

Conclusions

The results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. Moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. We therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option.
Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock
Authors: Taccone Fabio Silvio , Laterre Pierre-François , Dugernier Thierry , Spapen Herbert , Delattre Isabelle , Wittebole Xavier , De Backer Daniel , Layeux Brice , Wallemacq Pierre , Vincent Jean-Louis , Jacobs Frédérique
Published: July 2010

Introduction

Altered pharmacokinetics (PK) in critically ill patients can result in insufficient serum β-lactam concentrations when standard dosages are administered. Previous studies on β-lactam PK have generally excluded the most severely ill patients, or were conducted during the steady-state period of treatment. The aim of our study was to determine whether the first dose of piperacillin-tazobactam, ceftazidime, cefepime, and meropenem would result in adequate serum drug concentrations in patients with severe sepsis and septic shock.

Methods

Open, prospective, multicenter study in four Belgian intensive care units. All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom treatment with the study drugs was indicated, were included. Serum concentrations of the antibiotics were determined by high-pressure liquid chromatography (HPLC) before and 1, 1.5, 4.5 and 6 or 8 hours after administration.

Results

80 patients were treated with piperacillin-tazobactam (n = 27), ceftazidime (n = 18), cefepime (n = 19) or meropenem (n = 16). Serum concentrations remained above 4 times the minimal inhibitory concentration (T > 4 × MIC), corresponding to the clinical breakpoint for Pseudomonas aeruginosa defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), for 57% of the dosage interval for meropenem (target MIC = 8 μg/mL), 45% for ceftazidime (MIC = 32 μg/mL), 34% for cefepime (MIC = 32 μg/mL), and 33% for piperacillin-tazobactam (MIC = 64 μg/mL). The number of patients who attained the target PK profile was 12/16 for meropenem (75%), 5/18 for ceftazidime (28%), 3/19 (16%) for cefepime, and 12/27 (44%) for piperacillin-tazobactam.

Conclusions

Serum concentrations of the antibiotic after the first dose were acceptable only for meropenem. Standard dosage regimens for piperacillin-tazobactam, ceftazidime and cefepime may, therefore, be insufficient to empirically cover less susceptible pathogens in the early phase of severe sepsis and septic shock.
A Study of the Effect of Global Track Stiffness and Its Variations on Track Performance: Simulation and Measurement
Authors: Li M X D , Berggren E G
Published: July 2010

This article investigates the effect of vertical track stiffness, and its variations along the track, on track performance with focus on dynamic responses of the track due to parametric excitations. Two approaches for calculating global track stiffness, a static one based on Zimmermann's theory and a dynamic one based on the track model used in the dynamic vehicle-track interaction program Dynamisk Interaktion mellan Fordon och Farbana (DIFF), are discussed. A rolling stiffness measurement vehicle has been developed at Banverket, and measurements have been carried out over hundreds of kilometres of track. This article presents a statistical analysis of the collected results and provides information of track stiffness and its variation on typical Swedish tracks.
The Effect of Stem Structure on Stress Distribution of a Custom-Made Hip Prosthesis
Authors: Li X , Li D , Lian Q , Guo H , Jin Z
Published: July 2010

A custom-made hip is essential for the initial stability and longevity which correspond to an optimal stress distribution, since a standard hip cannot always satisfy every patient's need. In order to find out the designing principles of a custom-made hip, a patient's personal features on which the design was based were acquired. In this study, an integrated finite element model of the hip (including ilium, acetabular cup, femoral head, femoral stem, and femur) was created based on the computed tomography (CT) images of this patient. A series model with different stem length, cross-section, and collodiaphyseal angle were analysed under both static and quasi-static loading conditions. Comparing the stress distribution on each part of the hip prosthesis with that of the natural hip before replacement, the optimal stem structure for this patient was found. In addition, the changes of interspace between acetabular cup and femoral head were measured according to dynamic CT images on the healthy side of this patient during a gait cycle. Results correspond to the trail of the maximum contact stress sites, which were mainly located on the superolateral surface of the acetabular cup. This custom-design method can also be adopted for other patients.
Mechanobiology of bone healing and regeneration: in vivo models
Authors: Epari D R , Duda G N , Thompson M S
Published: July 2010

Mechanical boundary conditions are well known to influence the regeneration of bone and mechanobiology is the study of how mechanical or physical stimuli regulate biological processes. In vivo models have been applied over many years to investigate the effects of mechanics on bone healing. Early models have focused on the influence of mechanical stability on healing outcome, with an interest in parameters such as the magnitude of interfragmentary movement, the rate and timing of application of micromotion and the number of loading cycles. As measurement techniques have been refined, there has been a shift in orders of magnitude from investigations targeted at the organ level to those targeted at the tissue level and beyond. An understanding of how mechanics influences tissue differentiation during repair and regeneration crucially requires spatial and temporal knowledge of both the local mechanical environment in the healing tissue and a characterization of the tissues formed over the course of regeneration. Owing to limitations in the techniques available to measure the local mechanical conditions during repair directly, simulation approaches, such as the finite element method, are an integral part of the mechanobiologist's toolkit, while histology remains the gold standard in the characterization of the tissue formed. However, with rapid advances occurring in imaging modalities and methods to characterize tissue properties, new opportunities exist to better understand the role of mechanics in the biology of bone regeneration. Combined with developments in molecular biology, mechanobiology has the potential to offer exciting, new regenerative treatments for bone healing.
Does Mixing Acute Medical Admissions with Burn Patients Increase Infective Complications from Paediatric Thermal Injuries?
Authors: Shaban Fadlo , Stewart Ken , Kalima Pota
Published: July 2010

Objectives

In the winter of 2005-2006 the management at our children's hospital elected to admit ‘overspill’ acute medical admissions to the ward used for plastic surgery and burns for logistical reasons. This study was conducted to assess the effects of that change on the incidence of infective complications in thermally injured patients.

Design

We conducted a retrospective study by reviewing the case-notes. The data gathered included days on IV fluids and antibiotics, transfer to the Paediatric Intensive Care Unit (PICU), microbiology and a ‘septic signs score’ – based on pyrexia, irritability, diarrhoea/vomiting, wound colonization, bacteraemia. We compared the study winter (when mixed with the medical admissions) to the two preceding winters (control).

Setting

Royal Hospital of Sick Children in Edinburgh.

Participants

Seventy-three patients were studied, 23 in the sample winter and 50 in the two preceding control winters.

Main outcome measures

The outcomes studied were the maximum ‘septic signs score’; patients with a score ≥3; wound colonization; PICU admission; days on antibiotics and IV fluids.

Results

A statistically significant increase in patients with septic episodes was demonstrated by an increase in the mean septic signs score (0.66 to 1.48, p = 0.044) and the number of patients with a score ≥3 (4% to 22%, p = 0.017). Other analysed variables did not reach statistical significance although the raw data suggested a trend.

Conclusion

It was concluded that there is an association between mixing acute medical admissions with thermally injured patients and an increase in the incidence of infective complications in the latter group.
The Impact of Article Titles on Citation Hits: An Analysis of General and Specialist Medical Journals
Authors: Jacques Thomas S , Sebire Neil J
Published: July 2010

Objectives

Most published articles are not cited and citation rates depend on many variables. We hypothesized that specific features of journal titles may be related to citation rates.

Design

We reviewed the title characteristics of the 25 most cited articles and the 25 least cited articles published in 2005 in general and specialist medical journals including the Lancet, BMJ and Journal of Clinical Pathology. The title length and construction were correlated to the number of times the papers have been cited to May 2009.

Setting

Retrospective review of a scientific database.

Participants

None.

Main outcome measures

Citation rate.

Results

The number of citations was positively correlated with the length of the title, the presence of a colon in the title and the presence of an acronym. Factors that predicted poor citation included reference to a specific country in the title.

Conclusions

These data suggest that the construction of an article title has a significant impact on frequently the paper is cited. We hypothesize that this may be related to the way electronic searches of the literature are undertaken.
Comparison of the Application of Low Concentration and 80% Phenol Solution in Pilonidal Sinus Disease
Authors: Sakçak İbrahim , Avşar Fatih Mehmet , Coşgun Erdal
Published: July 2010

Objectives

Many conservative methods have been applied in the treatment of pilonidal sinus disease (PSD). The most commonly used conservative treatment is 80% phenol solution. Our observations demonstrated that 80% phenol solution caused much destruction in the sacrococcygeal region.

Design

In this study low concentrations of phenol were used with the aim of reducing the unwanted side-effects of high-concentration phenol without reducing the therapeutic effects.

Participants

We treated 112 patients (18 women, 94 men) with PSD using phenol solution. Patients were divided into two groups: Group A was treated with a 40% solution of phenol solution, and Group B was treated with an 80% solution of phenol solution.

Setting

All patients were treated on an outpatient basis. One mL of low (40%) or high (80%) concentration phenol solution was injected into the main sinus orifice. During the check it was observed and noted whether there was skin necrosis, fatty tissue necrosis or abscesses.

Main outcome measures

The mean age was 27.4 years (6-44). The median length of symptoms was seven months (0.5-132). In the 2.8 years (1-6) of mean follow-up period, the disease recurred in 13 (11.6%) patients.

Results

This treatment procedure was well-tolerated by all the patients except for those who had unwanted results. No patients in group A had skin necrosis, and only one had abscesses. In group B two patients had abscesses, and three had skin necrosis. Fatty tissue necrosis was seen in one patient in Group A and in five patients in Group B. Recurrence rates were four (7.4%) cases in Group A and nine (15.5%) cases in Group B.

Conclusions

It is possible to treat patients in a shorter time with a considerably smaller loss of working time, since the destruction of peripilonidal adipose tissue and skin is less. Therefore, the use of low-concentration phenol solution is an option to be considered in the treatment of PSD.
Factors Influencing Foundation Programme Choice among Medical Students
Authors: Patel Shelain , Colaco Henry B , Hossain Fahad S
Published: July 2010

Objectives

The advent of Modernising Medical Careers has replaced the traditional pre-registration house officer (PRHO) year and first year of senior house officer (SHO) training with a combined foundation programme. The aim of this study was to find out the factors influencing choice of foundation programme among medical students.

Design

Prospective survey.

Setting

Three medical schools based in England.

Main outcome measures

A questionnaire was formulated containing the reasons for choosing a foundation programme with students asked to rank their choices.

Results

There were 46 replies. The most important factors identified were geographical location (score 154) and combination of specialties (score 178). The least important factors was the reputation of consultants (score 525) and opportunities for research (score 530).

Conclusions

The factors influencing choice of foundation programme are not dissimilar to the choice of PRHO year despite the different emphasis in training which it offers.
Smoking Habits and Beliefs About Smoking in Elderly Patients With COPD During Hospitalisation
Authors: Bjarnason Nina H. , Mikkelsen Kim L. , Tønnesen Philip
Published: July 2010

To study beliefs about smoking and COPD, and motivation for smoking discontinuation we recruited 100 COPD patients during admission for exacerbation. They were asked about motivation to quit smoking and about disease understanding. We compared their survival with that of 324 COPD patients and with survival of age-matched Danes. Forty-five smokers, 50 ex-smokers and five never-smokers were included. Mean value of age was 77.5 years, number of years smoking was 51.8, and FEV1 was 0.79 L. Most patients were not certain about the association between smoking and COPD. Only 16% thought that their smoking had caused COPD and 24% thought that they would not suffer from COPD, had they not smoked. Three out of the six motivation questions could be included in a mutual quantitative scale (alpha = 0.76). Thirty per cent (r = 0.55, p = .005) of the variation in the motivation scale score was explained by number of years with smoking (negative association), number of cigarettes smoked per day (positive association) and BMI (negative association). Mortality was lower than in the reference population (RR = 0.63, p = .005), but higher than in age-matched Danes. Many patients are not certain about the association between smoking and COPD. We developed a smoking cessation motivation scale based on three questions.
Smoking Cessation Rates After a Nurse-Led Inpatient Smoking Cessation Intervention
Authors: Meysman Marc , Boudrez Hedwig , Nackaerts Kris , Dieriks Björn , Indemans Rudy , Vermeire Paul
Published: July 2010

Objective: To evaluate the effectiveness of inpatient brief counselling by a smoking cessation nurse compared to usual care (no advice). Methods: The subjects (n = 381, 245 men and 136 women) studied were in-patients, in four Flemish University Hospitals, who were daily smokers. Patients were randomised between 2005 and June 2006. Patients were allocated to an experimental group (EG) or to a control group (CG). Allocation and smoking cessation interventions of patients were stage-matched according to their stage of change as defined by Prochaska and Diclemente. Smoking cessation advice was administered by a qualified smoking cessation nurse. Results: The six-month self-reported continuous abstinence in the EG in 28/178 patients (15.7%) compared to the CG where 14/180 patients were abstinent (7.7%) was significantly better. The effect was most pronounced in the subgroup over 40 years old in the preparation and action stage. In this cohort in the EG, 44% of patients were abstinent at six months compared to 18%in the CG. All patients tended to smoke less after a hospitalisation. Conclusion: The intervention by a smoking cessation nurse during hospitalisation seems effective and is most rewarding in the smokers > 40 years old, and who were well motivated to stop.
Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy
Authors: Giavoli Claudia , Ferrante Emanuele , Profka Eriselda , Olgiati Luca , Bergamaschi Silvia , Ronchi Cristina L , Verrua Elisa , Filopanti Marcello , Passeri Elena , Montefusco Laura , Lania Andrea G , Corbetta Sabrina , Arosio Maura , Ambrosi Bruno , Spada Anna , Beck-Peccoz Paolo
Published: July 2010

Objective

A common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy.

Design

Prospective study of GHD patients evaluated before and during short- (1 year,n=100) and long-term (5 years,n=50) rhGH therapy.

Methods

Effects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant.

Results

The different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low-density lipoprotein cholesterol was also observed.

Conclusion

The functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults.
A Ubiquitin E2 Variant Protein Acts in Axon Termination and Synaptogenesis in Caenorhabditis elegans
Authors: Trujillo Gloriana , Nakata Katsunori , Yan Dong , Maruyama Ichi N , Jin Yishi
Published: July 2010

In the developing nervous system, cohorts of events regulate the precise patterning of axons and formation of synapses between presynaptic neurons and their targets. The conserved PHR proteins play important roles in many aspects of axon and synapse development from C. elegans to mammals. The PHR proteins act as E3 ubiquitin ligases for the dual-leucine-zipper-bearing MAP kinase kinase kinase (DLK MAPKKK) to regulate the signal transduction cascade. In C. elegans, loss-of-function of the PHR protein RPM-1 (Regulator of Presynaptic Morphology-1) results in fewer synapses, disorganized presynaptic architecture, and axon overextension. Inactivation of the DLK-1 pathway suppresses these defects. By characterizing additional genetic suppressors of rpm-1, we present here a new member of the DLK-1 pathway, UEV-3, an E2 ubiquitin-conjugating enzyme variant. We show that uev-3 acts cell autonomously in neurons, despite its ubiquitous expression. Our genetic epistasis analysis supports a conclusion that uev-3 acts downstream of the MAPKK mkk-4 and upstream of the MAPKAPK mak-2. UEV-3 can interact with the p38 MAPK PMK-3. We postulate that UEV-3 may provide additional specificity in the DLK-1 pathway by contributing to activation of PMK-3 or limiting the substrates accessible to PMK-3.
A Principled Approach to Deriving Approximate Conditional Sampling Distributions in Population Genetics Models with Recombination
Authors: Paul Joshua S , Song Yun S
Published: July 2010

The multilocus conditional sampling distribution (CSD) describes the probability that an additionally sampled DNA sequence is of a certain type, given that a collection of sequences has already been observed. The CSD has a wide range of applications in both computational biology and population genomics analysis, including phasing genotype data into haplotype data, imputing missing data, estimating recombination rates, inferring local ancestry in admixed populations, and importance sampling of coalescent genealogies. Unfortunately, the true CSD under the coalescent with recombination is not known, so approximations, formulated as hidden Markov models, have been proposed in the past. These approximations have led to a number of useful statistical tools, but it is important to recognize that they were not derived from, though were certainly motivated by, principles underlying the coalescent process. The goal of this article is to develop a principled approach to derive improved CSDs directly from the underlying population genetics model. Our approach is based on the diffusion process approximation and the resulting mathematical expressions admit intuitive genealogical interpretations, which we utilize to introduce further approximations and make our method scalable in the number of loci. The general algorithm presented here applies to an arbitrary number of loci and an arbitrary finite-alleles recurrent mutation model. Empirical results are provided to demonstrate that our new CSDs are in general substantially more accurate than previously proposed approximations.
The Effective Size of Populations Infected With Cytoplasmic Sex-Ratio Distorters
Authors: Engelstädter Jan
Published: July 2010

Many arthropod species are infected with maternally inherited endosymbionts that induce a shift in the sex ratio of their hosts by feminizing or killing males (cytoplasmic sex-ratio distorters, or SRDs). These endosymbionts can have profound impacts on evolutionary processes of their hosts. Here, I derive analytical expressions for the coalescent effective size Ne of populations that are infected with SRDs. Irrespective of the type of SRD, Ne for mitochondrial genes is given by the number of infected females. For nuclear genes, the effective population size generally decreases with increasing prevalence of the SRD and can be considerably lower than the actual size of the population. For example, with male-killing bacteria that have near perfect maternal transmission, Ne is reduced by a factor that is given to a good approximation by the proportion of uninfected individuals in the population. The formulae derived here also yield the effective size of populations infected with mutualistic endosymbionts or maternally inherited bacteria that induce cytoplasmic incompatibility, although in these cases, the reduction in Ne is expected to be less severe than for cytoplasmic SRDs.
Neonatology and the Environment: Early Exposure to Airborne Environmental Toxicants
Authors: Rauh Virginia A. , Horton Megan K. , Miller Rachel L. , Whyatt Robin M. , Perera Frederica
Published: July 2010

Environmental contaminants pose a threat to infant neurodevelopment. We discuss evidence for the potentially harmful impact of fetal and early childhood exposure to polycyclic aromatic hydrocarbons (PAHs), environmental tobacco smoke (ETS), and organophosphorus (OP) insecticides. We focus on effects resulting from chronic and low-level exposure during the prenatal period and early childhood, when the brain still is undergoing rapid developmental changes.