bluuebunny/crossref_metadata_2025 huggingface dataset:
Home administration of intravenous methylprednisolone for multiple sclerosis relapses: the experience of French multiple sclerosis networks
Authors: Créange A , Debouverie M , Jaillon-Rivière V , Taithe F , Liban D , Moutereau A , Clavelou P , Defer G
Published: June 2009

Background

One single center study has provided support for a home-based approach to the therapeutic management of multiple sclerosis (MS) relapse.

Objective

To report a multicenter series of patients with MS who were treated at home for a relapse with a 3-day course of intravenous methylprednisolone.

Methods

The home administration of intravenous methylprednisolone was coordinated by four MS networks in France; patients with MS with a relapse were referred by their neurologists, and treatment was administered by a local nurse. We analyzed the safety and efficiency of this approach and estimated the related cost savings. Patients completed a patient satisfaction questionnaire.

Results

Eight hundred and seven patients received intravenous methylprednisolone at home. The mean disease duration was 10.3 ± 7.9 years. Treatment was often prescribed by community-based neurologists. The delay between prescription and treatment was 2.8 ± 0.5 days if treatment was initiated at home and 1.9 ± 3.0 days if treatment was initiated in hospital (the subsequent two injections were always administered at home). Home treatment was well tolerated; three serious side effects requiring hospital transfer were observed (anxiety, thoracic oppression, and arrhythmia), which were fully reversible. Overall, 93.8% of patients were satisfied with the treatment approach, and 98% wished to receive future treatment courses at home. The overall cost savings of home-based treatment versus hospital-based treatment were evaluated at EUR1,091,482.

Conclusion

Safety data, patient satisfaction, and economic considerations support home-based treatment of MS relapses with intravenous methylprednisolone, provided strict patient selection criteria are observed and the process is coordinated and closely monitored by an MS network.
The development and validation of the Unidimensional Fatigue Impact Scale (U-FIS)
Authors: Meads DM , Doward LC , McKenna SP , Fisk J. , Twiss J. , Eckert B.
Published: June 2009

Background: The multidimensional assessment of fatigue is complicated by the interrelation of its multiple causes and effects.

Objective: The purpose of the research was to develop a unidimensional assessment of fatigue (U-FIS).

Methods: Data collected with the Fatigue Impact Scale (FIS) were subjected to Rasch analysis to identify potential problems with the scale. Additional items for the U-FIS were generated from interviews with UK MS patients. The U-FIS was tested for face and content validity in patient interviews and included in a validation survey to determine dimensionality (Rasch model), reliability and validity.

Results: The original FIS was not unidimensional when subscale items were combined. The modification of the FIS and addition of a number of items allowed the development of a 22-item unidimensional scale (U-FIS) that was reliable (Cronbach Alpha = 0.96; test-retest = 0.86,) and valid given correlations with the Nottingham Health Profile and ability to distinguish between MS severity groups. There was no significant difference in U-FIS scores according to MS type.

Conclusion: It is valid to conceptualize the functional impact of fatigue as unidimensional. The U-FIS is a reliable and valid questionnaire that will allow the measurement of this construct in clinical studies.
To report or not report? Attitudes held by Norwegian nursing home staff on reporting inadequate care carried out by colleagues
Authors: Malmedal Wenche , Hammervold Randi , Saveman Britt-Inger
Published: June 2009

Aims: The aims of this study are, first, to describe attitudes held by nursing home staff on reporting acts of inadequate care committed by their colleagues, and second, to investigate whether nursing staff have different attitudes depending on age, education, and length of experience of working in the healthcare services. Methods: A questionnaire survey was conducted among nursing staff in 16 nursing homes in the central part of Norway. The response rate was 79% (n=616). Results: A positive attitude towards reporting acts of inadequate care committed by their colleagues was held by the participants in this study. Compared with younger staff, the older staff seemed to be more reluctant to report colleagues, to feel less brave, to be more afraid of what would happen to them if they reported, and to agree that it is best to deal with such matters internally. Regarding education, it seemed that a higher educational level was related with a more positive attitude towards a willingness to report and less fear of negative sanctions. Conclusions: Staff who observe acts of inadequate care committed by colleagues agree that it is their intention to report such incidents. Institutions need to develop and implement mechanisms for understanding and evaluating acts of inadequate care, and staff must be encouraged to speak out on behalf of residents rather than be punished for doing so.
Work life and mental wellbeing of single and non-single working mothers in Scandinavia
Authors: Bull Torill , Mittelmark Maurice B.
Published: June 2009

Background: This study examined levels and predictors of mental wellbeing in Scandinavian working single and non-single mothers, with a special focus on financial stress, job characteristics and work—family conflict. Methods: The European Social Survey Round 2 (2005) provided questionnaire data from 73 single and 432 non-single working mothers in Denmark, Sweden and Norway. Respondents answered questions about the outcome variables life satisfaction, happiness, and positive affect, and predictor variables financial stress, job characteristics, work—family conflict, and social support. Hierarchical multiple regression was used to assess the relationships between predictor variables and mental wellbeing outcomes. Results: Single working mothers scored significantly lower on life satisfaction and happiness, but not on positive affect, than did non-single mothers. Financial stress was higher in the single mother group. There were no significant differences in levels of enriching or stressful job characteristics, or in levels of social support. While financial stress and work—family conflict were important predictors in both groups, the relationship between financial stress and wellbeing was far stronger in the single mother group. Confidant support was a significant predictor only in the single mother group, and social participation only in the non-single mothers group. Conclusions: This study suggests that the Scandinavian welfare democracies have not yet been successful in relieving the financial pressure experienced by single working mothers. Development of efficient financial support systems should be prioritized. Ways to reduce work—family conflict in both single and non-single mothers in Scandinavia should also be given increased attention.
Inflammatory Abdominal Aortic Aneurysms (IAAA): Past and Present
Authors: Paravastu Sharath C.V. , Murray David , Ghosh Jonathan , Serracino-Inglott Ferdinand , Smyth J. Vincent , Walker Michael G.
Published: June 2009

Aim: The aim of the study is to determine whether presentation and outcomes of inflammatory abdominal aortic aneurysms (IAAA) have changed over the last five decades. Methods: Comparison of current outcomes (January 2001 to December 2007) with results of the earliest report from our unit in 1972. Results: In contemporary series, 421 patients underwent AAA repair; 38 (9%) were IAAA. In 58% patients, IAAA was an incidental finding, whereas 42% patients were symptomatic with abdominal or back pain. Of those, 32% were ruptured IAAA. Male-to-female ratio was 12:1. Thirty-day mortality was 13%; elective 11.5%; emergency 17%. Comparison with 1972 study showed no change in the incidence and gender predilection. Presentation as an incidental finding and rupture increased 4- and 2-folds, respectively. Conclusion: The incidence and gender predilection of IAAA have remained unchanged. The 4-fold increase in the presentation as an incidental finding reflects current trends in patient evaluation.
Thoracic Outlet Syndrome Associated With a Large Cervical Rib
Authors: De Martino Randall R. , Stone David H. , Beck Adam W. , Walsh Daniel B.
Published: June 2009

This case illustrates the anatomic impact of a large cervical rib as an etiology for thoracic outlet syndrome. Current management remains predicated on astute diagnosis, multidisciplinary therapy including, physical therapy, scalene muscle blockade, and surgical decompression in appropriate cases.
Effect of Hospital Volume on In-Hospital Mortality for Renal Artery Bypass
Authors: Modrall J. Gregory , Rosero Eric B. , Smith Stephen T. , Arko Frank R. , Valentine R. James , Clagett G. Patrick , Timaran Carlos H.
Published: June 2009

Background: A recent report determined that the nationwide mortality for renal artery bypass (RAB) is surprisingly high—10%. We hypothesized that operative mortality for RAB is related to the volume of such operations performed in each center. Methods: The Nationwide Inpatient Sample was analyzed to identify patients undergoing RAB for the years 2000-2005. In-hospital mortality for RAB was compared between hospitals. Results: During the study period, RAB was performed on 7413 patients with an overall in-hospital mortality of 9.6%. The multivariate logistic regression analyses revealed that after adjusting for surgical risk, increasing hospital volume was significantly associated with decreased in-hospital mortality for RAB (odds ratio 0.98; 95% confidence interval, 0.96-0.99; P = .015). Conclusions: Patient risk profile and hospital volume are critical determinants of in-hospital mortality for RAB, which should be factored into decision making for patients requiring intervention for renovascular disease.
Is Infrainguinal Percutaneous Atherectomy Better Suited for Certain Arteries Than Others?
Authors: Kolakowski Stephen , Calligaro Keith D. , Dougherty Matthew J.
Published: June 2009

Objective: We analyzed our results with percutaneous rotational atherectomy catheters and specifically examined whether they were more likely to be associated with a successful outcome when used to treat smaller diameter vessels such as infrapopliteal (IP) arteries compared to larger diameter femoropopliteal (FP) arteries and infrainguinal arterial autogenous vein grafts (GRAFTS). Material and Methods: Between January 1, 2005, and December 31, 2006, athrectomies were performed on 32 patients for claudication (14), gangrene (9), rest pain (4), and failing GRAFTS (5). Treated vessels included 14 superficial femoral, 1 popliteal, 5 anterior tibial, 4 posterior tibial, and 3 peroneal arteries along with 5 failing GRAFTS. All procedures were performed by vascular surgeons in an endovascular operating suite using a mobile C-arm. Results for larger diameter vessels including FP arteries and GRAFTS were combined (FP + BYPASSES) and compared to results of IP artery lesions. Follow-up averaged 10 weeks (range, 0.5-34 weeks). Results: Length of treated lesions averaged 4.2 cm (range, 1—15 cm) for FP + GRAFT lesions (9 occlusions, 11 stenoses) versus 1.8 cm (1-4 cm) for IP lesions (6 occlusions, 6 stenoses; P = ns). Procedural success rate based on postoperative segmental pressures, pulse volume recordings, and duplex ultrasound was 70% (14/20) for FP + GRAFTS versus 83% (10/12) for IP lesions (P = .03). Need for concomitant adjunctive balloon angioplasty to treat residual stenosis tended to be higher for FP + GRAFT lesions (40% [8/20]) compared to IP lesions (25% [3/12]; P = ns). During follow-up, 25% (5/20) of FP + GRAFTS lesions required reintervention (3 balloon angioplasties, 1 thrombectomy, 1 GRAFT pseudoaneurysm) versus none for the IP lesions (P = .03). Limb salvage rates were 90% (18/20) for FP + GRAFT lesions versus 100% (12/12) for IP lesions during this short follow-up. Conclusions: These preliminary results suggest that short segment IP arterial stenoses and occlusions can be successfully treated with atherectomy catheters with a lower rate of reintervention during short-term follow-up, less need for concomitant adjunctive balloon angioplasty and a lower complication rate compared to FP + graft lesions.
Newton’s Law to the Rescue: Therapeutic Effects of Gravity Aiding the Management of a Migratory Venous Foreign Body—A Case Report
Authors: Nesargikar Prabhu Nanjundeshwar , Grannell Mark , Hinwood David , Orme Richard , Houghton Andrew
Published: June 2009

The management of intravascular metallic foreign bodies (FB) can be difficult and challenging. We report a case of a migrating FB, initially within the femoral vein which subsequently migrated to the intrahepatic venacava. Following a change of posture, the metallic FB moved with gravity against the normal venous blood flow to the left renal vein. It was finally fixed in position in a peripheral branch of the renal vein using an intravascular stent. Employing gravity as a therapeutic intervention and the technique used in isolating the FB has not, to our knowledge, been reported before. A case is described, and the literature is reviewed.
Reduced Sway During Dual Task Balance Performance Among People With Stroke at 6 and 12 Months After Discharge From Hospital
Authors: Hyndman Dorit , Pickering Ruth M. , Ashburn Ann
Published: June 2009

Background. Cognitive motor interference has been linked to poor recovery and falls. Little is known about recovery of dual-task balance ability poststroke. Methods. In this experimental study, postural sway was examined while standing on a force plate in preferred stance, with feet together, and with eyes closed, at 6 and 12 months postdischarge from hospital. Sway was assessed in isolation and while participants performed a cognitive (shopping list) task. Results . Seventy-six people with stroke (mean age 67 years; range, 21-91 years) took part. Fifty-four completed both assessments. When compared with the single task, sway during the dual-task condition was significantly lower in both the medial lateral (ML) and anterior posterior (AP) directions (both P < .0001). Sway in both directions was influenced by the difficulty of the balance task (both P < .0001). There was a trend of reduced sway at the 12-month assessment compared with the 6-month assessment: significant only in the ML direction ( P = .0056). Repeat fallers swayed more than non—repeat fallers, with increases of 48% and 44% in the ML ( P = .0262) and AP ( P = .0134) directions, respectively. No significant variation in the dual-task reduction in sway was found: the dual-task effect was remarkably consistent over all the conditions tested, particularly in the AP direction. Conclusions. Sway decreased under dual-task conditions and changed as the difficulty of the balance task changed. Stroke fallers swayed more than nonfallers and there was evidence of a reduction in sway over time, particularly in the ML direction.
The Use of En Bloc Infant Kidneys for Adult Kidney Transplants
Authors: Digiacinto Dora , Mayes Candace , Bagley Jennifer
Published: June 2009

The increasing need for cadaveric kidneys has caused the criteria for acceptable donor kidneys to include younger and older donors. Researchers have been studying the use of infant kidneys as a source for adult transplant. When used as a pair, infant kidneys transplanted into an adult have been found to filter an adult volume of blood. Sonographers will be asked to evaluate this type of transplant. Understanding the specific features of the transplant will aid in that process.
How I treat mantle cell lymphoma
Authors: Ghielmini Michele , Zucca Emanuele
Published: June 2009

Mantle cell lymphoma is included in the World Health Organization classification as distinct lymphoma subtype characterized by the t(11;14)(q13;q32) translocation, which results in overexpression of Cyclin D1. The clinical presentation often includes extranodal involvement, particularly of the bone marrow and gut. The prognosis of patients with mantle cell lymphoma (median overall survival, 3-5 years) is poorest among B-cell lymphoma patients, even though a prospectively difficult to identify subgroup can survive for years with little or no treatment. Conventional chemotherapy is not curative but obtains frequent remissions (60%-90%) which are usually shorter (1-2 years) compared with other lymphoma entities. Very intensive regimens, including autologous and allogeneic stem cell transplantation, seem required to improve the outcome, but with the median age of diagnosis being 60 years or more, such approaches are feasible only in a limited proportion of patients. The possibility of treating patients based on prognostic factors needs to be investigated prospectively.
Repression of BMI1 in normal and leukemic human CD34+ cells impairs self-renewal and induces apoptosis
Authors: Rizo Aleksandra , Olthof Sandra , Han Lina , Vellenga Edo , de Haan Gerald , Schuringa Jan Jacob
Published: June 2009

High expression of BMI1 in acute myeloid leukemia (AML) cells is associated with an unfavorable prognosis. Therefore, the effects of down-modulation of BMI1 in normal and leukemic CD34+ AML cells were studied using a lentiviral RNA interference approach. We demonstrate that down-modulation of BMI1 in cord blood CD34+ cells impaired long-term expansion and progenitor-forming capacity, both in cytokine-driven liquid cultures as well as in bone marrow stromal cocultures. In addition, long-term culture-initiating cell frequencies were dramatically decreased upon knockdown of BMI1, indicating an impaired maintenance of stem and progenitor cells. The reduced progenitor and stem cell frequencies were associated with increased expression of p14ARF and p16INK4A and enhanced apoptosis, which coincided with increased levels of intracellular reactive oxygen species and reduced FOXO3A expression. In AML CD34+ cells, down-modulation of BMI1 impaired long-term expansion, whereby self-renewal capacity was lost, as determined by the loss of replating capacity of the cultures. These phenotypes were also associated with increased expression levels of p14ARF and p16INK4A. Together our data indicate that BMI1 expression is required for maintenance and self-renewal of normal and leukemic stem and progenitor cells, and that expression of BMI1 protects cells against oxidative stress.
Soy consumption and risk of COPD and respiratory symptoms: a case-control study in Japan
Authors: Hirayama Fumi , Lee Andy H , Binns Colin W , Zhao Yun , Hiramatsu Tetsuo , Tanikawa Yoshimasa , Nishimura Koichi , Taniguchi Hiroyuki
Published: June 2009

Background

To investigate the relationship between soy consumption, COPD risk and the prevalence of respiratory symptoms, a case-control study was conducted in Japan.

Methods

A total of 278 eligible patients (244 men and 34 women), aged 50–75 years with COPD diagnosed within the past four years, were referred by respiratory physicians, while 340 controls (272 men and 68 women) were recruited from the community. All participants underwent spirometric measurements of respiratory function. Information on demographics, lifestyle characteristics and habitual food consumption was obtained using a structured questionnaire.

Results

Total soy consumption was positively correlated with observed lung function measures. The mean soy intake was significantly higher among controls (59.98, SD 50.23 g/day) than cases (44.84, SD 28.5 g/day). A significant reduction in COPD risk was evident for highest versus lowest quartile of daily intake of total soybean products, with adjusted odds ratio (OR) 0.392, 95% CI 0.194–0.793, p for trend 0.001. Similar decreases in COPD risk were associated with frequent and higher intake of soy foods such as tofu and bean sprouts, whereas respiratory symptoms were inversely associated with high consumption of soy foods, especially for breathlessness (OR 0.989, 95% CI 0.982–0.996).

Conclusion

Increasing soy consumption was associated with a decreased risk of COPD and breathlessness.
Lymphocyte apoptosis in murine Pneumocystis pneumonia
Authors: Shi Xin , LeCapitaine Nicole J , Rudner Xiaowen L , Ruan Sanbao , Shellito Judd E
Published: June 2009

Background

Apoptosis of lymphocytes is important in the termination of an immune response to infection but has also been shown to have detrimental effects in animal models of systemic infection and sepsis. We sought to characterize lymphocyte apoptosis in an animal model of pneumonia due toPneumocystis murina, an infection localized to the lungs.

Methods

Control mice and mice depleted of CD4+ lymphocytes were inoculated withPneumocystis. Apoptosis of lung and spleen lymphocytes was assayed by flow cytometry and PCR assay of apoptotic proteins.

Results

In control mice, apoptosis of lung lymphocytes was maximal just after the infection was cleared from lung tissue and then declined. However, in CD4-depleted mice, apoptosis was also upregulated in recruited lymphocytes in spite of progressive infection. In splenic lymphocytes, apoptosis was observed early at 1 week after inoculation and then declined. Apoptosis of lung lymphocytes in control mice was associated with a decrease in mRNA for Bcl-2 and an increase in mRNA for Bim. In CD4-depleted mice, lavaged CD8+ cells did change intracellular Bcl-2 but showed increased mRNA for Bim.

Conclusion

Apoptosis of both pulmonary and extrapulmonary lymphocytes is part of the normal host response toPneumocystisbut is also triggered in CD4-deficient animals with progressive infection. In normal mice apoptosis of pulmonary lymphocytes may serve to terminate the immune response in lung tissue. Apoptosis of lung lymphocytes takes place via both the intrinsic and extrinsic apoptotic pathways and is associated with changes in both pro- and anti-apoptotic proteins.
Protection from pulmonary ischemia-reperfusion injury by adenosine A2A receptor activation
Authors: Sharma Ashish K , Linden Joel , Kron Irving L , Laubach Victor E
Published: June 2009

Background

Lung ischemia-reperfusion (IR) injury leads to significant morbidity and mortality which remains a major obstacle after lung transplantation. However, the role of various subset(s) of lung cell populations in the pathogenesis of lung IR injury and the mechanisms of cellular protection remain to be elucidated. In the present study, we investigated the effects of adenosine A2Areceptor (A2AAR) activation on resident lung cells after IR injury using an isolated, buffer-perfused murine lung model.

Methods

To assess the protective effects of A2AAR activation, three groups of C57BL/6J mice were studied: a sham group (perfused for 2 hr with no ischemia), an IR group (1 hr ischemia + 1 hr reperfusion) and an IR+ATL313 group where ATL313, a specific A2AAR agonist, was included in the reperfusion buffer after ischemia. Lung injury parameters and pulmonary function studies were also performed after IR injury in A2AAR knockout mice, with or without ATL313 pretreatment. Lung function was assessed using a buffer-perfused isolated lung system. Lung injury was measured by assessing lung edema, vascular permeability, cytokine/chemokine activation and myeloperoxidase levels in the bronchoalveolar fluid.

Results

After IR, lungs from C57BL/6J wild-type mice displayed significant dysfunction (increased airway resistance, pulmonary artery pressure and decreased pulmonary compliance) and significant injury (increased vascular permeability and edema). Lung injury and dysfunction after IR were significantly attenuated by ATL313 treatment. Significant induction of TNF-α, KC (CXCL1), MIP-2 (CXCL2) and RANTES (CCL5) occurred after IR which was also attenuated by ATL313 treatment. Lungs from A2AAR knockout mice also displayed significant dysfunction, injury and cytokine/chemokine production after IR, but ATL313 had no effect in these mice.

Conclusion

Specific activation of A2AARs provides potent protection against lung IR injury via attenuation of inflammation. This protection occurs in the absence of circulating blood thereby indicating a protective role of A2AAR activation on resident lung cells such as alveolar macrophages. Specific A2AAR activation may be a promising therapeutic target for the prevention or treatment of pulmonary graft dysfunction in transplant patients.
Ab initio and homology based prediction of protein domains by recursive neural networks
Authors: Walsh Ian , Martin Alberto JM , Mooney Catherine , Rubagotti Enrico , Vullo Alessandro , Pollastri Gianluca
Published: June 2009

Background

Proteins, especially larger ones, are often composed of individual evolutionary units, domains, which have their own function and structural fold. Predicting domains is an important intermediate step in protein analyses, including the prediction of protein structures.

Results

We describe novel systems for the prediction of protein domain boundaries powered by Recursive Neural Networks. The systems rely on a combination of primary sequence and evolutionary information, predictions of structural features such as secondary structure, solvent accessibility and residue contact maps, and structural templates, both annotated for domains (from the SCOP dataset) and unannotated (from the PDB). We gauge the contribution of contact maps, and PDB and SCOP templates independently and for different ranges of template quality. We find that accurately predicted contact maps are informative for the prediction of domain boundaries, while the same is not true for contact maps predicted ab initio. We also find that gap information from PDB templates is informative, but, not surprisingly, less than SCOP annotations. We test both systems trained on templates of all qualities, and systems trained only on templates of marginal similarity to the query (less than 25% sequence identity). While the first batch of systems produces near perfect predictions in the presence of fair to good templates, the second batch outperforms or match ab initio predictors down to essentially any level of template quality.

We test all systems in 5-fold cross-validation on a large non-redundant set of multi-domain and single domain proteins. The final predictors are state-of-the-art, with a template-less prediction boundary recall of 50.8% (precision 38.7%) within ± 20 residues and a single domain recall of 80.3% (precision 78.1%). The SCOP-based predictors achieve a boundary recall of 74% (precision 77.1%) again within ± 20 residues, and classify single domain proteins as such in over 85% of cases, when we allow a mix of bad and good quality templates. If we only allow marginal templates (max 25% sequence identity to the query) the scores remain high, with boundary recall and precision of 59% and 66.3%, and 80% of all single domain proteins predicted correctly.

Conclusion

The systems presented here may prove useful in large-scale annotation of protein domains in proteins of unknown structure. The methods are available as public web servers at the address: http://distill.ucd.ie/shandy/ and we plan on running them on a multi-genomic scale and make the results public in the near future.
Construction and sequence sampling of deep-coverage, large-insert BAC libraries for three model lepidopteran species
Authors: Wu Chengcang , Proestou Dina , Carter Dorothy , Nicholson Erica , Santos Filippe , Zhao Shaying , Zhang Hong-Bin , Goldsmith Marian R
Published: June 2009

Background

Manduca sexta, Heliothis virescens, and Heliconius erato represent three widely-used insect model species for genomic and fundamental studies in Lepidoptera. Large-insert BAC libraries of these insects are critical resources for many molecular studies, including physical mapping and genome sequencing, but not available to date.

Results

We report the construction and characterization of six large-insert BAC libraries for the three species and sampling sequence analysis of the genomes. The six BAC libraries were constructed with two restriction enzymes, two libraries for each species, and each has an average clone insert size ranging from 152–175 kb. We estimated that the genome coverage of each library ranged from 6–9 ×, with the two combined libraries of each species being equivalent to 13.0–16.3 × haploid genomes. The genome coverage, quality and utility of the libraries were further confirmed by library screening using 6~8 putative single-copy probes. To provide a first glimpse into these genomes, we sequenced and analyzed the BAC ends of ~200 clones randomly selected from the libraries of each species. The data revealed that the genomes are AT-rich, contain relatively small fractions of repeat elements with a majority belonging to the category of low complexity repeats, and are more abundant in retro-elements than DNA transposons. Among the species, the H. erato genome is somewhat more abundant in repeat elements and simple repeats than those of M. sexta and H. virescens. The BLAST analysis of the BAC end sequences suggested that the evolution of the three genomes is widely varied, with the genome of H. virescens being the most conserved as a typical lepidopteran, whereas both genomes of H. erato and M. sexta appear to have evolved significantly, resulting in a higher level of species- or evolutionary lineage-specific sequences.

Conclusion

The high-quality and large-insert BAC libraries of the insects, together with the identified BACs containing genes of interest, provide valuable information, resources and tools for comprehensive understanding and studies of the insect genomes and for addressing many fundamental questions in Lepidoptera. The sample of the genomic sequences provides the first insight into the constitution and evolution of the insect genomes.
Discovery of cis-elements between sorghum and rice using co-expression and evolutionary conservation
Authors: Wang Xi , Haberer Georg , Mayer Klaus FX
Published: June 2009

Background

The spatiotemporal regulation of gene expression largely depends on the presence and absence ofcis-regulatory sites in the promoter. In the economically highly important grass family, our knowledge of transcription factor binding sites and transcriptional networks is still very limited. With the completion of the sorghum genome and the available rice genome sequence, comparative promoter analyses now allow genome-scale detection of conservedcis-elements.

Results

In this study, we identified thousands of phylogenetic footprints conserved between orthologous rice and sorghum upstream regions that are supported by co-expression information derived from three different rice expression data sets. In a complementary approach,cis-motifs were discovered by their highly conserved co-occurrence in syntenic promoter pairs. Sequence conservation and matches to known plant motifs support our findings. Expression similarities of gene pairs positively correlate with the number of motifs that are shared by gene pairs and corroborate the importance of similar promoter architectures for concerted regulation. This strongly suggests that these motifs function in the regulation of transcript levels in rice and, presumably also in sorghum.

Conclusion

Our work provides the first large-scale collection ofcis-elements for rice and sorghum and can serve as a paradigm forcis-element analysis through comparative genomics in grasses in general.
249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients
Authors: Nogueira Jeronimo A , Ono-Nita Suzane K , Nita Marcelo E , de Souza Marcelo MT , do Carmo Eliane P , Mello Evandro S , Scapulatempo Cristovan , Paranaguá-Vezozzo Denise C , Carrilho Flair J , Alves Venancio AF
Published: June 2009

Background

Ser-249 TP53 mutation (249Ser) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249Ser mutation in HCC from patients in Brazil.

Methods

We studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249Ser mutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR.

Results

249Ser mutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249Ser mutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249Ser mutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249Ser mutation (OR = 2.415, 95% CI = 1.001 – 5.824, p = 0.05). The mean size of 249Ser HCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249Ser mutation.

Conclusion

Our results indicate that 249Ser mutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.
Are immigrant populations aware about their oral health status? A study among immigrants from Ethiopia
Authors: Zini Avi , Vered Yuval , Sgan-Cohen Harold D
Published: June 2009

Background

Evidence from Western countries indicates that there are fundamental discrepancies between self-perceived illness of immigrants and the provision of health care, according to the Western bio-medical health service model. These need to be understood in the planning and implementation stages of public health care programs for new immigrants. The objectives of the present study were to investigate self-perceived versus clinically diagnosed dental and periodontal health status among immigrants from Ethiopia.

Methods

During 2004–2005, dental and periodontal health status was recorded among 340 Ethiopian immigrants, utilizing the DMFT and CPI indices. Additionally, participants were interviewed using a questionnaire which included perceived dental and periodontal health status. Sensitivity and specificity levels of this perception were calculated and compared with the published scientific literature.

Results

Regarding dental caries, according to the three operational cut-off points, sensitivity ranged from 70% to 81%, and specificity ranged from 56% to 67%. Regarding periodontal status, 75% of the subjects clinically diagnosed with periodontal pockets self-perceived a "bad" health status of gums (sensitivity) and 54% of the subjects diagnosed without periodontal pockets, reported a "good" health status of gums (specificity). These indications of perception levels were higher than a previous study conducted among native born Israelis.

Conclusion

Minority ethnic groups should not be prejudicially regarded as less knowledgeable. This is illustrated by the unexpected high level of oral health status perception in the present population. Oral health promotion initiatives among immigrants should be based upon optimal descriptive data in order to accomplish the inherent social commitment to these diverse populations.
Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial
Authors: Claessen Susanne JJ , Hazes Johanna MW , Huisman Margriet AM , van Zeben Derkjen , Luime Jolanda J , Weel Angelique EAM
Published: June 2009

Background

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.

Methods

A multicenter stratified randomized single-blind controlled trial is currently being performed in patients 18 years or older with recent-onset arthritis. Eight hundred ten patients are being stratified according to the likelihood of their developing persistent arthritis. In patients with a high probability of persistent arthritis, we will study combination Disease Modifying Antirheumatic Drug therapy compared to monotherapy methotrexate. In patients with an intermediate probability of persistent arthritis, we will study Disease Modifying Antirheumatic Drug of various intensities. In patients with a low probability, we will study non-steroidal anti-inflammatory drugs, hydroxychloroquine and a single dose of corticosteroids. If disease activity is not sufficiently reduced, treatment will be adjusted according to a step-up protocol. If remission is achieved for at least six months, medication will be tapered off. Patients will be followed up every three months over two years.

Discussion

This is the first rheumatological study to base treatment in early arthritis on a prediction rule. Treatment will be stratified according to the probability of persistent arthritis, and different combinations of treatment per stratum will be evaluated. Treatment will be started early, and patients will not need to meet the ACR-criteria for rheumatoid arthritis.

Trial registration

This trial has been registered in Current Controlled Trials with the ISRCTN26791028.
Factors affecting plasmid production in Escherichia coli from a resource allocation standpoint
Authors: Cunningham Drew S , Koepsel Richard R , Ataai Mohammad M , Domach Michael M
Published: June 2009

Background

Plasmids are being reconsidered as viable vector alternatives to viruses for gene therapies and vaccines because they are safer, non-toxic, and simpler to produce. Accordingly, there has been renewed interest in the production of plasmid DNA itself as the therapeutic end-product of a bioprocess. Improvement to the best current yields and productivities of such emerging processes would help ensure economic feasibility on the industrial scale. Our goal, therefore, was to develop a stoichiometric model ofEscherichia colimetabolism in order to (1) determine its maximum theoretical plasmid-producing capacity, and to (2) identify factors that significantly impact plasmid production.

Results

Such a model was developed for the production of a high copy plasmid under conditions of batch aerobic growth on glucose minimal medium. The objective of the model was to maximize plasmid production. By employing certain constraints and examining the resulting flux distributions, several factors were determined that significantly impact plasmid yield. Acetate production and constitutive expression of the plasmid's antibiotic resistance marker exert negative effects, while low pyruvate kinase (Pyk) flux and the generation of NADPH by transhydrogenase activity offer positive effects. The highest theoretical yield (592 mg/g) resulted under conditions of no marker or acetate production, nil Pyk flux, and the maximum allowable transhydrogenase activity. For comparison, when these four fluxes were constrained to wild-type values, yields on the order of tens of mg/g resulted, which are on par with the best experimental yields reported to date.

Conclusion

These results suggest that specific plasmid yields can theoretically reach 12 times their current experimental maximum (51 mg/g). Moreover, they imply that abolishing Pyk activity and/or transhydrogenase up-regulation would be useful strategies to implement when designing host strains for plasmid production; mutations that reduce acetate production would also be advantageous. The results further suggest that using some other means for plasmid selection than antibiotic resistance, or at least weakening the marker's expression, would be beneficial because it would allow more precursor metabolites, energy, and reducing power to be put toward plasmid production. Thus far, the impact of eliminating Pyk activity has been explored experimentally, with significantly higher plasmid yields resulting.
Respiratory viral infections detected by multiplex PCR among pediatric patients with lower respiratory tract infections seen at an urban hospital in Delhi from 2005 to 2007
Authors: Bharaj Preeti , Sullender Wayne M , Kabra Sushil K , Mani Kalaivani , Cherian John , Tyagi Vikas , Chahar Harendra S , Kaushik Samander , Dar Lalit , Broor Shobha
Published: June 2009

Background

Acute lower respiratory tract infections (ALRI) are the major cause of morbidity and mortality in young children worldwide. Information on viral etiology in ALRI from India is limited. The aim of the present study was to develop a simple, sensitive, specific and cost effective multiplex PCR (mPCR) assay without post PCR hybridization or nested PCR steps for the detection of respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses (PIV1–3) and human metapneumovirus (hMPV). Nasopharyngeal aspirates (NPAs) were collected from children with ALRI ≤ 5 years of age. The sensitivity and specificity of mPCR was compared to virus isolation by centrifugation enhanced culture (CEC) followed by indirect immunofluorescence (IIF).

Results

From April 2005–March 2007, 301 NPAs were collected from children attending the outpatient department or admitted to the ward of All India Institute of Medical Sciences hospital at New Delhi, India. Multiplex PCR detected respiratory viruses in 106 (35.2%) of 301 samples with 130 viruses of which RSV was detected in 61, PIV3 in 22, PIV2 in 17, hMPV in 11, PIV1 in 10 and influenza A in 9 children. CEC-IIF detected 79 viruses only. The sensitivity of mPCR was 0.1TCID50 for RSV and influenza A and 1TCID50 for hMPV, PIV1, PIV2, PIV3 and Influenza B. Mixed infections were detected in 18.8% of the children with viral infections, none detected by CEC-IIF. Bronchiolitis was significantly associated with both total viral infections and RSV infection (p < 0.05). History of ARI in family predisposed children to acquire viral infection (p > 0.05).

Conclusion

Multiplex PCR offers a rapid, sensitive and reasonably priced diagnostic method for common respiratory viruses.
Modeling AIDS survival after initiation of antiretroviral treatment by Weibull models with changepoints
Authors: Yiannoutsos Constantin T
Published: June 2009

Background

Mortality of HIV‐infected patients initiating antiretroviral therapy in the developing world is very high immediately after the start of ART therapy and drops sharply thereafter. It is necessary to use models of survival time that reflect this change.

Methods

In this endeavor, parametric models with changepoints such as Weibull models can be useful in order to explicitly model the underlying failure process, even in the case where abrupt changes in the mortality rate are present. Estimation of the temporal location of possible mortality changepoints has important implications on the effective management of these patients. We briefly describe these models and apply them to the case of estimating survival among HIV‐infected patients who are initiating antiretroviral therapy in a care and treatment programme in sub‐Saharan Africa.

Results

As a first reported data‐driven estimate of the existence and location of early mortality changepoints after antiretroviral therapy initiation, we show that there is an early change in risk of death at three months, followed by an intermediate risk period lasting up to 10 months after therapy.

Conclusion

By explicitly modelling the underlying abrupt changes in mortality risk after initiation of antiretroviral therapy we are able to estimate their number and location in a rigorous, data‐driven manner. The existence of a high early risk of death after initiation of antiretroviral therapy and the determination of its duration has direct implications for the optimal management of patients initiating therapy in this setting.
Genome analysis and genome-wide proteomics of Thermococcus gammatolerans, the most radioresistant organism known amongst the Archaea
Authors: Zivanovic Yvan , Armengaud Jean , Lagorce Arnaud , Leplat Christophe , Guérin Philippe , Dutertre Murielle , Anthouard Véronique , Forterre Patrick , Wincker Patrick , Confalonieri Fabrice
Published: June 2009

Background

Thermococcus gammatolerans was isolated from samples collected from hydrothermal chimneys. It is one of the most radioresistant organisms known amongst the Archaea. We report the determination and annotation of its complete genome sequence, its comparison with other Thermococcales genomes, and a proteomic analysis.

Results

T. gammatolerans has a circular chromosome of 2.045 Mbp without any extra-chromosomal elements, coding for 2,157 proteins. A thorough comparative genomics analysis revealed important but unsuspected genome plasticity differences between sequenced Thermococcus and Pyrococcus species that could not be attributed to the presence of specific mobile elements. Two virus-related regions, tgv1 and tgv2, are the only mobile elements identified in this genome. A proteogenome analysis was performed by a shotgun liquid chromatography-tandem mass spectrometry approach, allowing the identification of 10,931 unique peptides corresponding to 951 proteins. This information concurrently validates the accuracy of the genome annotation. Semi-quantification of proteins by spectral count was done on exponential- and stationary-phase cells. Insights into general catabolism, hydrogenase complexes, detoxification systems, and the DNA repair toolbox of this archaeon are revealed through this genome and proteome analysis.

Conclusions

This work is the first archaeal proteome investigation done at the stage of primary genome annotation. This archaeon is shown to use a large variety of metabolic pathways even under a rich medium growth condition. This proteogenomic study also indicates that the high radiotolerance of T. gammatolerans is probably due to proteins that remain to be characterized rather than a larger arsenal of known DNA repair enzymes.
A discussion of bias in magnetotelluric responses
Authors: Pomposiello M. Cristina , Booker John R. , Favetto Alicia
Published: June 2009

Magnetic-field noise biases magnitudes of magnetotelluric response functions such as resistivity, impedance, and the induction vector (tipper). This is particularly severe in the so-called dead band between about 1- and [Formula: see text] periods. The standard approach to remove these biases is to use a magnetic remote reference. In cases where this is unavailable or does not work because noise is correlated at the local and remote sites, it is possible to extract unbiased estimates using an inversion algorithm that predicts the magnitude from the phase. However, an important condition for this to be successful is that phase estimates are unbiased. Phase can be biased if parallel components of the electric and magnetic fields are correlated. This arises when the structure is 3D or when a 2D response is estimated in coordinates not parallel to strike. Improvements in electric field measurements make electric field references a viable option for estimating low-bias responses up to periods approaching [Formula: see text].