bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Real-Time PCR Detects Prolonged Norovirus Excretion in Highly Immunosuppressed Patients and Children
Authors: Henke-Gendo C. , Harste G. , Juergens-Saathoff B. , Mattner F. , Deppe H. , Heim A. 
Published: July 2009

ABSTRACT

Noroviruses (NoV) are a major cause of epidemic nonbacterial gastroenteritis and affect all age groups worldwide. Three of five NoV genogroups, namely, genogroup I (GI), GII, and GIV, are associated with human disease. Unfortunately, these genogroups demonstrate a high degree of sequence diversity, complicating the design of pan-NoV diagnostic PCR tests. To decrease the risk of false-negative test results, we have developed a new one-step real-time TaqMan reverse transcription-PCR protocol. This protocol detects all human NoV genogroups in one reaction with a sensitivity of 400 virus genome equivalents/reaction for both GI and GII. The use of in vitro-transcribed NoV RNA as an external standard allows (semi)quantification of viral loads in samples. In a retrospective analysis of 206 stool samples from 77 patient episodes, the duration of NoV excretion and the amount of virus excreted were determined. Twenty (26.0%) of these episodes lasted longer than 10 days. Univariate risk factor analysis revealed the patient status after organ transplantation (odds ratio [OR], 7.49 [95% confidence interval, 2.06 to 28.32];
P
< 0.001), immunosuppression (OR, 9.19 [95% confidence interval, 2.50 to 35.39];
P
< 0.001), and age of less than 10 years (OR, 4.58 [95% confidence interval, 1.36 to 15.77];
P
= 0.004) as risk factors for a NoV excretion period of more than 10 days. These findings were confirmed by time-dependent Kaplan-Meier analyses, whereas multivariate Cox regression analyses identified immunosuppression as the sole risk factor. Surprisingly, in contrast to the excretion periods, the viral loads in stools did not increase in connection with age or immunosuppressive status. This fact may be one important piece in the pattern of high-level NoV transmissibility and may have an impact on the development of transmission prevention strategies.
Human Immunodeficiency Virus and Leprosy Coinfection in Pune, India
Authors: Vinay Kulkarni , Smita Joshi , Nikhil Gupte , Neeta Gokhale 
Published: July 2009

ABSTRACT
We report eight cases and the incidence of leprosy in human immunodeficiency virus (HIV)-infected individuals after initiation of antiretroviral treatment (ART). The incidence of leprosy in patients on ART was 5.22 per 1,000 person-years (95% confidence interval, 2.25 to 10.28). This high incidence suggests that there should be regular examination of HIV-infected individuals for clinical signs of leprosy.
Detection of Low Levels of Human Immunodeficiency Virus (HIV) May Be Critical for Early Diagnosis of Pediatric HIV Infection by Use of Dried Blood Spots
Authors: Walter Jan , Kuhn Louise , Semrau Katherine , Decker Don W. , Sinkala Moses , Kankasa Chipepo , Thea Donald M. , Bulterys Marc , Ou Chin-Yih , Aldrovandi Grace M. 
Published: July 2009

ABSTRACT
We compared a DNA-based assay with a total nucleic acid-based assay for early detection of infant human immunodeficiency virus (HIV) infection. The codetection of DNA and RNA did not result in an overall higher sensitivity compared to that of DNA alone. Discordant results were associated with low levels of HIV DNA, indicating that the sample amount may be critical.
Wild-Type p53 Enhances Efficiency of Simian Virus 40 Large-T-Antigen-Induced Cellular Transformation
Authors: Hermannstädter Andrea , Ziegler Christine , Kühl Marion , Deppert Wolfgang , Tolstonog Genrich V. 
Published: July 2009

ABSTRACT

Abortive infection of BALB/c mouse embryo fibroblasts differing in
p53
gene status (p53
+/+
versus p53
−/
−
) with simian virus 40 (SV40) revealed a quantitatively and qualitatively decreased transformation efficiency in p53
−/−
cells compared to p53
+/+
cells, suggesting a supportive effect of wild-type (wt) p53 in the SV40 transformation process. SV40 transformation efficiency also was low in immortalized p53
−/−
BALB/c 10-1 cells but could be restored to approximately the level in immortalized p53
+/+
BALB/c 3T3 cells by reconstituting wt p53, but not mutant p53 (mutp53), expression. Stable expression of large T antigen (LT) in p53
+/+
3T3 cells resulted in full transformation, while LT expression in p53
−/−
10-1 cells could not promote growth in suspension or in soft agar to a significant extent. The helper effect of wt p53 is mediated by its cooperation with LT and resides in the p53 N terminus, as an N-terminally truncated p53 (ΔNp53) could not rescue the p53-null phenotype. The p53 N terminus serves as a scaffold for recruiting transcriptional regulators like p300/CBP and Mdm2 into the LT-p53 complex. Consequently, LT affected global and specific gene expression in p53
+/+
cells significantly more than in p53
−/−
cells. Our data suggest that recruitment of transcriptional regulators into the LT-p53 complex may help to modify cellular gene expression in response to the needs of cellular transformation.
Rho GTPases Modulate Entry of Ebola Virus and Vesicular Stomatitis Virus Pseudotyped Vectors
Authors: Quinn Kathrina , Brindley Melinda A. , Weller Melodie L. , Kaludov Nikola , Kondratowicz Andrew , Hunt Catherine L. , Sinn Patrick L. , McCray Paul B. , Stein Colleen S. , Davidson Beverly L. , Flick Ramon , Mandell Robert , Staplin William , Maury Wendy , Chiorini John A. 
Published: July 2009

ABSTRACT
To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. Candidate genes were identified by using EBOV GP pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cDNA microarray. Transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between RhoC expression and permissivity for EBOV vector transduction. This correlation was not specific for EBOV vector alone as RhoC also correlated highly with transduction of vesicular stomatitis virus GP (VSVG) pseudotyped vector. Levels of RhoC protein in EBOV and VSV permissive and nonpermissive cells were consistent with the cDNA gene array findings. Additionally, vector transduction was elevated in cells that expressed high levels of endogenous RhoC but not RhoA. RhoB and RhoC overexpression significantly increased EBOV GP and VSVG pseudotyped vector transduction but had minimal effect on human immunodeficiency virus (HIV) GP pseudotyped HIV or adeno-associated virus 2 vector entry, indicating that not all virus uptake was enhanced by expression of these molecules. RhoB and RhoC overexpression also significantly enhanced VSV infection. Similarly, overexpression of RhoC led to a significant increase in fusion of EBOV virus-like particles. Finally, ectopic expression of RhoC resulted in increased nonspecific endocytosis of fluorescent dextran and in formation of increased actin stress fibers compared to RhoA-transfected cells, suggesting that RhoC is enhancing macropinocytosis. In total, our studies implicate RhoB and RhoC in enhanced productive entry of some pseudovirions and suggest the involvement of actin-mediated macropinocytosis as a mechanism of uptake of EBOV GP and VSVG pseudotyped viral particles.
Human Immunodeficiency Virus Type 1 V1-to-V5 Envelope Variants from the Chronic Phase of Infection Use CCR5 and Fuse More Efficiently than Those from Early after Infection
Authors: Etemad Behzad , Fellows Angela , Kwambana Brenda , Kamat Anupa , Feng Yang , Lee Sandra , Sagar Manish 
Published: July 2009

ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein modifications over the course of infection have been associated with coreceptor switching and antibody neutralization resistance, but the effect of the changes on replication and host cell receptor usage remains unclear. To examine this question, unique early- and chronic-stage infection envelope V1-toV5 (V1-V5) segments from eight HIV-1 subtype A-infected subjects were incorporated into an isogenic background to construct replication-competent recombinant viruses. In all subjects, viruses with chronic-infection V1-V5 segments showed greater replication capacity than those with early-infection V1-V5 domains in cell lines with high levels of both the CD4 and the CCR5 receptors. Viruses with chronic-infection V1-V5s demonstrated a significantly increased ability to replicate in cells with low CCR5 receptor levels and greater resistance to CCR5 receptor and fusion inhibitors compared to those with early-infection V1-V5 segments. These properties were associated with sequence changes in the envelope V1-V3 segments. Viruses with the envelope segments from the two infection time points showed no significant difference in their ability to infect cells with low CD4 receptor densities, in their sensitivity to soluble CD4, or in their replication capacity in monocyte-derived macrophages. Our results suggest that envelope changes, primarily in the V1-V3 domains, increase both the ability to use the CCR5 receptor and fusion kinetics. Thus, envelope modifications over time within a host potentially enhance replication capacity.
Interaction of the
Tobacco Mosaic Virus
Replicase Protein with a NAC Domain Transcription Factor Is Associated with the Suppression of Systemic Host Defenses
Authors: Wang Xiao , Goregaoker Sameer P. , Culver James N. 
Published: July 2009

ABSTRACT

An interaction between the helicase domain of the
Tobacco mosaic virus
(TMV) 126-/183-kDa replicase protein(s) and the
Arabidopsis thaliana
NAC domain transcription factor ATAF2 was identified via yeast two-hybrid and in planta immunoprecipitation assays. ATAF2 is transcriptionally induced in response to TMV infection, and its overexpression significantly reduces virus accumulation. Proteasome inhibition studies suggest that ATAF2 is targeted for degradation during virus infection. The transcriptional activity of known defense-associated marker genes
PR1
,
PR2
, and
PDF1.2
significantly increase within transgenic plants overexpressing ATAF2. In contrast, these marker genes have reduced transcript levels in ATAF2 knockout or repressor plant lines. Thus, ATAF2 appears to function in the regulation of host basal defense responses. In response to TMV infections,
ATAF2
and
PR1
display increased transcript accumulations in inoculated tissues but not in systemically infected tissues.
ATAF2
and
PR1
transcript levels also increase in response to salicylic acid treatment. However, the salicylic acid treatment of systemically infected tissues did not produce a similar increase in either
ATAF2
or
PR1
transcripts, suggesting that host defense responses are attenuated during systemic virus invasion. Similarly, noninfected ATAF2 knockout or ATAF2 repressor lines display reduced levels of
PR1
transcripts when treated with salicylic acid. Taken together, these findings suggest that the replicase-ATAF2 interaction suppresses basal host defenses as a means to promote systemic virus accumulation.
Hip Arthroscopy for Labral Tears
Authors: Kamath Atul F. , Componovo Roger , Baldwin Keith , Israelite Craig L. , Nelson Charles L. 
Published: July 2009

Background Arthroscopy of the hip joint is a relatively new diagnostic and therapeutic option for labral tears. Purpose More data are needed to characterize the utility and effectiveness of hip arthroscopy and identify patient-related factors that might predict functional outcome. Study Design Case series; Level of evidence, 4. Methods This retrospective study with prospective follow-up examined the clinical outcomes of 52 consecutive patients undergoing hip arthroscopy for labral tears. Outcomes measures included clinical outcome and the modified Harris hip score. Any complications associated with the procedure were recorded. Exclusion criteria included age younger than 18 years or prior ipsilateral hip surgery. Results Mean patient age was 42 years. Mean follow-up was 4.8 years. Twenty-one patients (40.4%) had a traumatic cause of the labral tears. Eight patients (15.4%) had possible secondary gain issues. Four (7.7%) patients suffered transient nerve palsies; in 1 case, the guide wire broke during initial cannulation. Three patients (5.8%) went on to total hip arthroplasty after hip arthroscopy. On multivariate analysis, left-sided surgery, a higher preoperative activity level, and duration of symptoms greater than 18 months were found to be positive predictors of good or excellent outcomes. Smoking and secondary gain issues were significant negative predictors of good or excellent outcomes. Only prior level of activity was a significant positive predictor of return to activity after surgery. A traumatic cause of the labral tear was a significant negative predictor of return to activity. Chondromalacia and osteoarthritis were not significant predictors of negative outcome. Postoperative modified Harris hip score improved 40% from 56.8 preoperatively to 80.4 (P < .001). No cases of patients with secondary gain issues achieved good or excellent outcomes. Overall percentage of good or excellent outcomes was 56%, or 66% when those with secondary gain issues were excluded; 84% of patients were able to return to sports or equivalent level of preoperative recreational activity. Neither preoperative radiographic osteoarthritis nor grade of intraoperative chondromalacia predicted postoperative outcome. Conclusion This series supports the hypothesis that hip arthroscopy provides safe and reliable improvement of labral symptoms in the majority of patients.
Suspected multiple sclerosis – what to do? Evaluation of a patient information leaflet
Authors: Heesen C , Schäffler N , Kasper J , Mühlhauser I , Köpke S 
Published: July 2009

Background Parallel to the establishment of early treatments in multiple sclerosis (MS), new diagnostic criteria have made an earlier diagnosis possible. While there is ongoing discussion about possible benign courses and only partial effective treatments, there have been no attempts today to facilitate shared decision making on diagnostic testing between patients with suspected MS and their physicians. Objective This study describes the development and validation process of a leaflet to be presented to people with suspected MS to engage them in a diagnostic decision-making process. Methods After a qualitative study showing acceptability among five patients, the leaflet was presented to a retrospective cohort ( n = 87 of which 70 replied)) of patients being diagnosed within the last 2 years as well to a prospective cohort of n = 51 patients with symptoms suggestive of MS. Results Approximately 70% of patients in the prospective as well as in the retrospective cohort wanted to be informed about a possible MS before testing, whereas 10% did not. The leaflet did not seem to elicit anxieties. The attitude to undergo diagnostic testing was not influenced by the leaflet, which can be explained by the nonexperimental design of the study. Conclusion Taken together, our findings demonstrate that early information about possible MS is warranted by patients and does not show negative side effects. Further studies on evidence-based patient information in early MS seem necessary.
Process maps in clinical trial quality assurance
Authors: Rosen Daniel H , Johnson Sandra , Kebaabetswe Poloko , Thigpen Michael , Smith Dawn K 
Published: July 2009

Background A process map is a diagram showing the sequential steps and decisions used to accomplish a procedure from start to finish. Process maps are a standard tool in continuous improvement efforts. They have not been used routinely in clinical trials although they are well suited to display trial processes. Purpose We present the use of process maps as a tool to visualize and to monitor the correctness of trial work flows. We show that process maps can be used to assure that trial processes are conducted according to the SOP. Methods We describe how a process map is made. We then derive process maps from two sources: the SOP and trial procedures as currently implemented. We compare these maps to each other, using the SOP maps as the gold standard, to check that work is done according to the written procedures. Results Eight process maps were produced from each source. 172 differences were found between the SOP maps and the walkthrough maps. Differences included the addition of extra steps, order errors, step mistakes, and ambiguities. Limitations These process maps focused only on clinic procedures, so interactions with other trial components were not considered. The maps were made after the trial started, which may have biased their content and use. Conclusion Process maps are a simple tool to check if clinical trial processes are operating as designed and offer an effective means to identify and correct such divergences. Further research should focus on using process maps in the design phase of trials, analyzing the cost to benefit ratio for process maps, and linking the analysis of the process map to monitor queries to quantify the improvement gained from using this technique. Clinical Trials 2009; 6: 373—377. http://ctj.sagepub.com
Challenges in designing a pragmatic clinical trial: the mixed incontinence — medical or surgical approach (MIMOSA) trial experience
Authors: Brubaker Linda , Moalli Pamela , Richter Holly E , Albo Michael , Sirls Larry , Chai Toby , Kraus Stephen R , Norton Peggy , Chang Debuene , Tennstedt Sharon L 
Published: July 2009

Background Mixed urinary incontinence (MUI) is a common, bothersome condition in women. In MUI, the two subtypes of urinary incontinence that coexist are treated differently; stress urinary incontinence (SUI) is primarily treated surgically while urge urinary incontinence (UUI) is primarily treated medically. There is no evidence to guide the treatment for women with significant bother from both incontinence subtypes. Therefore, investigators of the Urinary Incontinence Treatment Network (UITN) designed and initiated a randomized clinical trial comparing outcomes for two distinct initial treatment approaches for women with mixed urinary incontinence (MUI): therapy initiated with surgery versus therapy initiated with nonsurgical treatment. Purpose The aim of this manuscript is to describe the challenges in planning and implementing this randomized clinical trial. Methods The mixed incontinence: medical or surgical approach (MIMOSA) trial was designed as a practical or pragmatic clinical trial to establish the relative efficacy of two specific treatment approaches. The design presented many challenging decisions including: (1) selection of practical paradigm; (2) refining inclusion/ exclusion criteria to offer equipoise; (3) selection of feasibility sample size; (4) recruitment challenges for two divergent treatment approaches (medical vs. surgical), and (5) resolution of ethical and methodological issues. Results MIMOSA recruitment was planned in two phases, starting with a 5-month pilot and feasibility phase followed by a full trial contingent on the outcome of the first phase. The feasibility portion of the MIMOSA trial started in November 2008. 1198 subjects were screened and approached forstudy enrollment, but only 27 consented to randomization. The feasibility study was halted due to lack of enrollment in March 2009. Limitations The challenges of this trial included a lack of information from subjects who did not enroll, increasing the difficulty of interpreting the feasibility phase. Conclusions Successful recruitment to a randomized trial that compares significantly different treatment approaches poses a challenge. Clinical Trials 2009; 6: 355—364. http://ctj.sagepub.com
Strategies and ethical considerations for the recruitment of young men who have sex with men: challenges of a vaccination trial in Mexico
Authors: Gutiérrez-Luna Arturo , Angeles-Llerenas Angelica , Wirtz Veronika J , Del Río Asunción Álvarez , Zamilpa-Mejía Laura , Aranda-Flores Carlos , Viramontes Jose Luis , Lazcano-Ponce Eduardo 
Published: July 2009

Background The importance of recruiting and retaining study participants from minority groups is well recognized; however, there are no established rules for recruitment as its success depends on the setting and population. Purpose To describe and analyze recruitment strategies, ethical considerations, and recruitment outcomes from a study to evaluate the efficacy the Human Papilloma Virus vaccine in young men who have sex with men (MSM). Methods The recruitment settings were university and community sites in the state of Morelos, Mexico. Eligibility requirement were men between 18 and 23 years old, who were free of anal-genital lesions as confirmed by clinical exploration, HIV negative, with no history of sexual relations with female partners and with fewer than five male lifetime sexual partners. Recruitment goals were 25 study participants in a four and a half month period. In addition to traditional recruitment strategies (flyers and media advertising, specific training of the recruitment team and adequate choice of recruitment sites)—engagement of local leaders in the MSM community formed a crucial part of the strategy. Special consideration was given to confidentiality and respect for study participants and a Bill of Participant Rights was developed as an explicit commitment to respect and acceptance. Results In total 723 MSM were initially contacted, 243 filled out the recruitment questionnaire, of which 151 met the criteria to be invited to the clinical examination. After clinical examination and interviews with the recruitment team, 131 fulfilled the inclusion criteria, of whom 73 were enrolled in the study — nearly triple the recruitment goal. Among the initial recruitment strategies (application of the screening questionnaire) attending meetings with MSM activist organizations was the most successful (326), followed by recruitment at bars and dance clubs (107). Limitations The recruitment strategies should be formally evaluated for their effectiveness to identify those which are most successful. In addition, future studies should consider the evaluation of study participants’ perceptions of the recruitment strategies. Conclusions Recruiting MSM in a developing country such as Mexico presented multiple challenges. We recommend that future studies actively engage the local MSM community and pay special attention to designing recruitment strategies that guarantee the confidentiality of and respect for participants.