bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Contributing to Variability of Quantitative Viral PCR Results in Proficiency Testing Samples: a Multivariate Analysis
Authors: Hayden R. T. , Yan X. , Wick M. T. , Rodriguez A. B. , Xiong X. , Ginocchio C. C. , Mitchell M. J. , Caliendo A. M. 
Published: November 2011

ABSTRACT
While viral load testing has gained widespread acceptance, a primary limitation remains the variability of results, particularly between different laboratories. While some work has demonstrated the importance of standardized quantitative control material in reducing this variability, little has been done to explore other important factors in the molecular amplification process. Results of 185 laboratories enrolled in the College of American Pathologists (CAP) 2009 viral load proficiency testing (PT) survey (VLS) were examined. This included 165 labs (89.2%) testing for cytomegalovirus (CMV), 99 (53.5%) for Epstein-Barr virus (EBV), and 64 (34.6%) for BK virus (BKV). At the time of PT, laboratories were asked a series of questions to characterize their testing methods. The responses to these questions were correlated to mean viral load (MVL) and result variability (RV). Contribution of individual factors to RV was estimated through analysis of variance (ANOVA) modeling and the use of backward selection of factors to fit those models. Selection of the quantitative calibrator, commercially prepared primers and probes, and amplification target gene were found most prominently associated with changes in MVL or RV for one or more of the viruses studied. Commercially prepared primers and probes and amplification target gene made the largest contribution to overall variability. Factors contributing to MVL and RV differed among viruses, as did relative contribution of each factor to overall variability. The marked variability seen in clinical quantitative viral load results is associated with multiple aspects of molecular testing design and performance. The reduction of such variability will require a multifaceted approach to improve the accuracy, reliability, and clinical utility of these important tests.
Rapid Genotyping of Cytomegalovirus in Dried Blood Spots by Multiplex Real-Time PCR Assays Targeting the Envelope Glycoprotein gB and gH Genes
Authors: de Vries Jutte J. C. , Wessels Els , Korver Anna M. H. , van der Eijk Annemiek A. , Rusman Lisette G. , Kroes Aloys C. M. , Vossen Ann C. T. M. 
Published: November 2011

ABSTRACT

Genotyping of cytomegalovirus (CMV) is useful to examine potential differences in the pathogenicity of strains and to demonstrate coinfection with multiple strains involved in CMV disease in adults and congenitally infected newborns. Studies on genotyping of CMV in dried blood spots (DBS) are rare and have been hampered by the small amount of dried blood available. In this study, two multiplex real-time PCR assays for rapid gB and gH genotyping of CMV in DBS were developed. Validation of the assays with 39 CMV-positive plasma samples of transplant recipients and 21 urine specimens of congenitally infected newborns was successful in genotyping 100% of the samples, with gB1 and gB3 being the most prevalent genotypes. Multiple gB and gH genotypes were detected in 36% and 33% of the plasma samples, respectively. One urine sample from a newborn with symptomatic congenital CMV was positive for gB1 and gB2. DBS of congenitally infected newborns (
n
= 41) were tested using 9 μl of dried blood, and genotypes were detected in 81% (gB) and 73% (gH) of the samples, with gB3 being the most prevalent genotype. No clear association of specific genotypes with clinical outcome was observed. In conclusion, the CMV gB and gH PCR assays were found to be rapid, sensitive for detecting mixed infections, and suitable for direct usage on DBS. These assays are efficient tools for genotyping of CMV in DBS of congenitally infected newborns.
Epidemiology and Outcomes of Complicated Skin and Soft Tissue Infections in Hospitalized Patients
Authors: Zervos Marcus J. , Freeman Katherine , Vo Lien , Haque Nadia , Pokharna Hiren , Raut Monika , Kim Myoung 
Published: November 2011

ABSTRACTComplicated skin and soft tissue infections (cSSTIs) are among the most rapidly increasing reasons for hospitalization. To describe inpatients with regard to patient characteristics, cSSTI origin, appropriateness of initial antibiotics, and outcomes, we performed a retrospective cohort study in patients hospitalized for cSSTI. To identify independent predictors of outcomes, we performed multivariate analyses. Of 1,096 eligible patients, 48.7% had health care-associated (HCA) cSSTI and 51.3% had community-acquired (CA) cSSTI. After adjustment for baseline variables, hospital length of stay (LOS) was longer for HCA than for CA cSSTI (difference, 2.1 days; 95% confidence interval [CI], 0.8 to 3.5;P< 0.05). Other covariates associated with a longer LOS were need for dialysis (regression coefficient ± standard error, 4.5 ± 1.1) and diabetic wound diagnosis (2.6 ± 1.0) (allP< 0.05). In the subset with culture-positive cSSTI within 24 h of admission, the most common pathogen wasStaphylococcus aureus(298/449 [66.4%]), of which 74.8% (223/298) were methicillin-resistantS. aureus(MRSA). Eighty-three patients (18.5%) received inappropriate initial antibiotics. After adjustment for other variables, the following were associated with inappropriate initial therapy: direct admission to hospital (not via emergency department), cSSTI caused by MRSA or mixed pathogens, and cSSTI caused by pathogens other thanS. aureusor streptococci (allP< 0.05). We did not find an association between inappropriate therapy and outcomes, except in the subset with ulcers (adjusted odds ratio, 11.8; 95% CI, 1.3 to 111.1;P= 0.03). More studies are needed to examine the impact of HCA cSSTI and inappropriate initial therapy on outcomes.
Comparison of the Idaho Technology FilmArray System to Real-Time PCR for Detection of Respiratory Pathogens in Children
Authors: Pierce Virginia M. , Elkan Michael , Leet Marilyn , McGowan Karin L. , Hodinka Richard L. 
Published: November 2011

ABSTRACT

The FilmArray Respiratory Panel (RP) multiplexed nucleic acid amplification test (Idaho Technology, Inc., Salt Lake City, UT) was compared to laboratory-developed real-time PCR assays for the detection of various respiratory viruses and certain bacterial pathogens. A total of 215 frozen archived pediatric respiratory specimens previously characterized as either negative or positive for one or more pathogens by real-time PCR were examined using the FilmArray RP system. Overall agreement between the FilmArray RP and corresponding real-time PCR assays for shared analytes was 98.6% (kappa = 0.92 [95% confidence interval (CI), 0.89 to 0.94]). The combined positive percent agreement was 89.4% (95% CI, 85.4 to 92.6); the negative percent agreement was 99.6% (95% CI, 99.2 to 99.8). The mean real-time PCR threshold cycle (

C
T

) value for specimens with discordant results was 36.46 ± 4.54. Detection of coinfections and correct identification of influenza A virus subtypes were comparable to those of real-time PCR when using the FilmArray RP. The greatest comparative difference in sensitivity was observed for adenovirus; only 11 of 24 (45.8%; 95% CI, 27.9 to 64.9) clinical specimens positive for adenovirus by real-time PCR were also positive by the FilmArray RP. In addition, upon testing 20 characterized adenovirus serotypes prepared at high and low viral loads, the FilmArray RP did not detect serotypes 6 and 41 at either level and failed to detect serotypes 2, 20, 35, and 37 when viral loads were low. The FilmArray RP system is rapid and extremely user-friendly, with results available in just over 1 h with almost no labor involved. Its low throughput is a significant drawback for laboratories receiving large numbers of specimens, as only a single sample can be processed at a time with one instrument.
A Novel Real-Time PCR Method for Determination and Quantification of Each Cytomegalovirus Glycoprotein H Subtype in Clinical Samples
Authors: Ikuta Kazufumi , Ishioka Ken , Sato Yuka , Imamura Takashi , Asano Kimisato , Koyano Shin , Inoue Naoki , Suzutani Tatsuo 
Published: November 2011

ABSTRACT
To investigate reinfection in patients with congenital cytomegalovirus (CMV) infection, we established a CMV subtype-specific real-time quantitative PCR method targeting the CMV gH epitope region that can be used for evaluating pathogenic CMV strains in cases of mixed CMV infection.
Mini-sternotomy for aortic valve replacement reduces the length of stay in the cardiac intensive care unit: meta-analysis of randomised controlled trials
Authors: Khoshbin E , Prayaga S , Kinsella J , Sutherland F W H 
Published: November 2011

BackgroundMini-sternotomy for isolated aortic valve replacement aims to reduce operative trauma hastening recovery and improving the cosmetic outcome of cardiac surgery. The short-term clinical benefits from the mini-sternotomy are presumed to arise because the incision is less extensive and the lower half of the chest cage remains intact. The basic conduct of virtually all other aspects of the aortic valve replacement procedure remains the same. Therefore, similar long-term outcomes are to be expected.ObjectivesTo conduct a meta-analysis of the only available randomised controlled trials (RCT) in the published English literature.Data sourcesElectronic search for relevant publications in MEDLINE, EMBASE and CENTRAL databases were performed. Four studies met the criteria.Study eligibility criteriaRCT comparing minimally invasive (inverted C or L (J)-shaped) hemi-sternotomy versus conventional sternotomy for adults undergoing isolated aortic valve replacement using standard cardiopulmonary bypass technique.MethodsOutcome measures were the length of positive pressure ventilation, blood loss, intensive care unit (ICU) and hospital stay.ResultsThe length of ICU stay was significantly shorter by 0.57 days in favour of the mini-sternotomy group (CI −0.95 to −0.2; p=0.003). There was no advantage in terms of duration of ventilation (CI −3.48 to 0.36; p=0.11). However, there was some evidence to suggest a reduction in blood loss and the length of stay in hospital in the mini-sternotomy group. This did not prove to be statistically significant (154.17 ml reduction (CI −324.51 to 16.17; p=0.08) and 2.03 days less (CI −4.12 to 0.05; p=0.06), respectively).LimitationsThis study includes a relatively small number of subjects (n=220) and outcome variables. The risk of bias was not assessed during this meta-analysis.ConclusionMini-sternotomy for isolated aortic valve replacement significantly reduces the length of stay in the cardiac ICU. Other short-term benefits may include a reduction in blood loss or the length of hospital stay.
Incidence, time and determinants of tuberculosis treatment default in Yaounde, Cameroon: a retrospective hospital register-based cohort study
Authors: Pefura Yone Eric Walter , Kengne André Pascal , Kuaban Christopher 
Published: November 2011

ObjectivesHigh rates of antituberculosis treatment discontinuation have been reported in some areas of Africa. The aim of this study was to determine the rate, time to and determinants of antituberculosis treatment default in Yaounde.DesignThis was a retrospective cohort study based on hospital registers. Tuberculosis treatment default or antituberculosis treatment discontinuation was defined as any interruption of treatment for at least 2 months following treatment initiation. Sociodemographic and clinical predictors of treatment discontinuation were investigated with the use of Cox regressions models.SettingThis study was carried out in the tuberculosis diagnosis and treatment centre at Yaounde Jamot Hospital, which serves as a referral centre for tuberculosis and respiratory diseases for the capital city of Cameroon (Yaounde) and surrounding areas.ParticipantsAll (1688) patients started on antituberculosis treatment at the centre between January and December 2009 were enrolled. Outcome measures were antituberculosis treatment default and time to treatment default.ResultsOf the 1688 included patients, 337 (20%) defaulted from treatment, 86 (5.1%) died, treatment failed in 6 (0.4%) and 104 (6.2%) were transferred. Therefore, treatment was successfully completed in 1154 (68.4%) patients. Median duration to treatment discontinuation was 90 days (IQR 30–150), and 62% of treatment discontinuation occurred during the continuation phase. Hospitalisation during the intensive phase (adjusted HR 0.69; 95% CI 0.54 to 0.89) and non-consenting for HIV screening (1.65; 1.24 to 2.21) were the main determinants of defaulting from treatment in multivariable analysis.ConclusionsThe default incidence rate is relatively high in this centre and treatment discontinuation occurs frequently during the continuation phase of treatment. Action is needed to improve adherence to treatment when received on an ambulatory basis, to clarify the association between HIV testing and antituberculosis treatment default, and to identify other potential determinants of treatment discontinuation in this setting.
Republished original viewpoint: Complaints, shame and defensive medicine
Authors: Cunningham Wayne , Wilson Hamish 
Published: November 2011

ABSTRACT
While the complaints process is intended to improve healthcare, some doctors appear to practise defensive medicine after receiving a complaint. This response occurs in countries that use a tort-based medicolegal system as well as in countries with less professional liability. Defensive medicine is based on avoiding malpractice liability rather than considering a risk–benefit analysis for both investigations and treatment. There is also evidence that this style of practice is low quality in terms of decision-making, cost and patient outcomes. Western medical practice is based on biomedicine: determining medical failure using the underlying, taken-for-granted assumptions of biomedicine can potentially contribute to a response of shame after an adverse outcome or a complaint. Shame is implicated in the observable changes in practising behaviour after receipt of a complaint. Identifying and responding to shame is required if doctors are to respond to a complaint with an overall improvement in clinical practice. This will eventually improve the outcomes of the complaints process.
Cardiac autonomic function in acutely nitric oxide deficient hypertensive rats: role of the sympathetic nervous system and oxidative stress
Authors: Chaswal Meenakshi , Das Shobha , Prasad Jagdish , Katyal Anju , Fahim Mohammad 
Published: November 2011

We evaluated the role of the sympathetic nervous system and oxidative stress in hemodynamic and autonomic control after acute inhibition of the synthesis of nitric oxide, using intravenous (i.v.) injection of 30 mg·kg–1 NG-nitro-l-arginine methyl ester (L-NAME) in adult Wistar rats. Baroreflex sensitivity (BRS) and heart rate variability (HRV) were measured as indices of cardiac autonomic control, before and after L-NAME treatment in rats with intact autonomic innervation, and in rats with chemical sympathectomy by 6-hydroxydopamine. Serum malondialdehyde (MDA) was measured as a marker of oxidative stress. In control rats, L-NAME treatment resulted in a significant rise in blood pressure, augmentation of BRS, and enhanced serum MDA. HRV showed an attenuation of total spectral power and high frequency spectral power, along with a rise of the low to high frequency ratio (LF:HF). Administration of L-NAME produced a pressor response even in sympathectomised rats, but augmented BRS was not observed, and the high frequency spectral power showed an increase, in addition to a significant decline of LF:HF and serum MDA. We therefore conclude that even though pressor response was unaffected, reversal of cardiac autonomic responses and decline in oxidative stress following sympathectomy in L-NAME-treated rats reflects a significant role for sympathetic innervation in acute L-NAME-induced hypertension.
Relaxant and contractile responses of detrusor muscle strips obtained from bladder outlet-obstructed rats treated with doxazosin enantiomers
Authors: Wang Miao , Ren Xue-Jiao , Zhao Qing-Hua , Lin Li-Xin , Wang Xue , Zhao Yan , Ren Lei-Ming 
Published: November 2011

(–)Doxazosin, one of (±)doxazosin enantiomers, was speculated to have a pharmacological enantioselectivity between the cardiovascular system and the urinary system by comparison with (+)doxazosin. Therefore, to evaluate the potential benefits of (–)doxazosin in the treatment of benign prostate hyperplasia, we compared the effects of the 3 agents, using rat mesenteric artery preparations and obstructed bladder strips. Concentration–response curves for carbachol (contractile response) and isoprenaline (relaxant response) in detrusor muscle strips of the bladder outlet obstruction (BOO) rats were shifted to the left, with significant increases in the Emax values, and significant decreases in the EC50 values by comparison with the sham-operated rats (P < 0.05, n = 10). The enhanced responses in detrusor muscle strips of the BOO rats treated with (±)doxazosin and its enantiomers at 3 mg·(kg body mass)–1·day–1 for 2 weeks returned to normal levels, and the 3 agents inhibited the enhanced responses to carbachol and isoprenaline to the same extent. On the other hand, the 3 agents uncompetitively inhibited the vasoconstrictive response curves for NA in the rat isolated mesenteric artery, and the pKB value of (–)doxazosin at vascular α1-adrenoceptors was significantly smaller (P < 0.05, n = 6) than that of (+)doxazosin or (±)doxazosin. In conclusion, although (–)doxazosin inhibits vascular functional α1-adrenoceptors more weakly than (+)doxazosin, both agents equally ameliorate the enhanced responses in detrusor muscle of BOO rats, suggesting that the chiral carbon atom in the molecular structure of doxazosin does not affect its beneficial effects in the bladder smooth muscle of BOO rats.
Effect of DETA-NONOate and papaverine on vasodilation of human internal mammary artery
Authors: Rahimi Nastaran , Dehpour Ahmad R. , Javadi-Paydar Mehrak , Sohanaki Hamid , Rabbani Shahram , Ansari Mohammad , Tafti Seyed Hossein Ahmadi 
Published: November 2011

In this study, the relaxatory effect of DETA-NONOate is compared with that of papaverine on isolated human internal mammary artery. We investigated the inhibitory effects of DETA-NONOate and papaverine on phenylephrine-induced contractile response in internal mammary artery segments. The internal mammary artery segments, taken from methodologically matched patients who underwent coronary artery bypass grafting, were prepared, placed in an organ bath, and contracted with phenylephrine (10−9 to 10−4 mol/L) to investigate their relaxatory response to DETA-NONOate or papaverine. Phenylephrine dose–response contraction was obtained after 1, 2, and 3 h in segments pre-incubated with DETA-NONOate or papaverine for 30 min. The EC50 that presented for internal mammary artery segments incubated with DETA-NONOate was 3.523 ± 1.2696 × 10–7 mol/L, and for papaverine was 3.467 ± 1.2145 × 10–6 mol/L. In segments pre-incubated with DETA-NONOate, the contractile response to phenylephrine was suppressed in the first 2 h post-incubation, compared with control responsive groups (p < 0.05), but this inhibition was revoked after 3 h post-incubation. We showed that DETA-NONOate has a more significant relaxative effect by comparison with papaverine; moreover, continuous and long-lasting nitric oxide production by DETA-NONOate might be of great importance for the outcome from coronary artery bypass grafting, when internal mammary artery is used as a conduit.
Ultrasound molecular imaging of arterial thrombi with novel microbubbles modified by cyclic RGD in vitro and in vivo
Authors: Liao Yulin , Yang Li , Huang Ruizhu , Wu Juefei , Xie Jiajia , Bundhoo Kaviraj , Liu Ying , Hu Guangquan , Liu Cheng , Bin Jianping 
Published: November 2011

SummaryDespite immense potential, ultrasound molecular imaging (UMI) of arterial thrombi remains very challenging because the high-shear arterial flow limits binding of site-targeted microbubbles to the thrombi. The linear Arg-Gly-Asp (RGD) peptides have been successfully applied to evaluate venous, atrial, and arteriolar thrombi, but have thus far failed in the detection of arterial thrombi. Cyclic RGD (Arg-Gly-Asp-D-Phe-Cys) is a cyclic conformation of linear RGD peptides, which has much higher binding-affinity and selectivity for binding to the glycoprotein (GP) IIb/IIIa receptor than its linear counterpart and thus is likely to be an optimal targeted molecular probe for ultrasound molecular imaging of arterial thrombi. In this study, we sought to assess the feasibility of a novel microbubble conjugated with cyclic RGD (Mb-cyclic RGD) in UMI of arterial thrombi in vitro and in vivo. As expected, Mb-cyclic RGD had greater GP IIb/IIIa-targeted binding capability in all shear stress conditions. In addition, the shear stress at half-maximal detachment of Mb-cyclic RGD was 5.7-fold higher than that of microbubbles with nonspecific peptide (Mb-CON) (p<0.05). Mb-cyclic RGD enhanced the echogenicity of the platelet-rich thrombus in vitro whereas Mb-CON did not produce enhancement. In the in vivo setting, optimal signal enhancement of the abdominal aortic thrombus was displayed with Mb-cyclic RGD in all cases. Mean video intensity of the abdominal aortic thrombi with Mb-cyclic RGD was 3.2-fold higher than that with Mb-CON (p<0.05). The novel Mb-cyclic RGD facilitated excellent visualisation of arterial thrombi using UMI and showed great promise for clinical applications.
Receptor activator of NF-κB ligand (RANKL) increases the release of neutrophil products associated with coronary vulnerability
Authors: Bertolotto Maria , Lenglet Sébastien , Vuilleumier Nicolas , Galan Katia , Pagano Sabrina , Braunersreuther Vincent , Pelli Graziano , Pistoia Vito , Bianchi Giovanna , Cittadini Giuseppe , Viviani Giorgio Luciano , Pende Aldo , Roux-Lombard Pascale , Thomas Aurélien , Staub Christian , Ratib Osman , Dallegri Franco , Quercioli Alessandra , Mach François , Schindler Thomas Helmut , Montecucco Fabrizio 
Published: November 2011

SummaryThe “blood vulnerability”, resulting from the complex balance between serum molecules and inflammatory cell atherosclerotic activities, is a major determinant in the evaluation of the “global patient cardiovascular vulnerability”. In the present study, we focused on the role of the soluble receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL, a potential marker of coronary calcification and vulnerability) in the release of neutrophilic proteases. Then, the association between these mediators and the degree of coronary calcification (assessed by coronary calcium score [CCS]) was investigated in 20 subjects (aged ≥65 years) asymptomatic for cardiovascular disease. Results showed that RANKL dose-dependently induced matrix metalloprotease (MMP)-8 and MMP-9 release from human primary neutrophils cultured in Teflon dishes (suspension condition, mimicking cells circulating in the blood stream). Conversely, when adherent to polystyrene, neutrophils became unresponsive to RANKL. RANKL did not influence the release of other neutrophilic products in suspension and adherence cultures as well as neutrophil migration. RANKL-induced release of MMPs was dependent on the activation of defined intracellular signalling pathways (PI3K/Akt and ERK1/2). In asymptomatic subjects, serum levels of RANKL, MMP-8 and MMP-9 positively correlated with CCS, reflecting a potential relationship between circulating RANKL and coronary calcification. In conclusion, RANKL increased the release of neutrophilic products potentially related to the “blood” vulnerability via defined intracellular pathways. Serum levels of RANKL might represent a potential biomarker of coronary calcification and related cardiovascular risk.