bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of intra‐operative cell salvage haemolysis in the obstetric and orthopaedic clinical setting, in comparison with allogeneic blood
Authors: Sullivan I. J. , Faulds J. N.
Published: September 2014

SUMMARY

Objectives/Background

Haemolysis is still a re‐occurring theme in intra‐operative cell salvage (ICS) with further haemolysis possibly caused by suction pressure, washing/centrifuging process and aspiration method. Previous investigations, along with manufacturer's reports, state that between 75 and 95% of free haemoglobin (Hb) is removed by the washing and centrifugation process; however, if these results are above the expected levels, excess free Hb may remain after washing.

The aim of this article was to quantify haemolysis levels whilst employing different aspiration methods from skimmed (orthopaedics) and pooled (obstetrics) surgery types and comparing this to allogeneic blood.

Methods/Materials

Samples obtained from 50 allogeneic units and 50 ICS cases (25 obstetric and 25 orthopaedic) were tested for plasma free Hb levels.

Results

Free Hb testing as a marker of haemolysis was greatest in orthopaedic 17·2 g L−1 (range: 1·7–57·0 g L−1), obstetric 2·8 g L−1 (range: 1·0–13·5 g L−1) and allogeneic 0·95 g L−1 (range: 0·2–4·8 g L−1) cases.

Conclusion

ICS involving skimming collection techniques (orthopaedics) had significantly more haemolysis than pooled collections (obstetrics) (P < 0·001). Further analysis of orthopaedic data highlighted a difference between the three machines used with the Haemonetics OrthoPat (Haemonetics Ltd., Watford, UK) significantly higher with a free Hb of 29·8 g L−1 compared with the other two machines 6·7 g L−1 (P < 0·001). On comparison of ICS blood to allogeneic blood, free Hb levels obtained from ICS were significantly higher (P < 0·001).
The Use of Refundable Tax Credits to Increase Low-Income Children’s After-School Physical Activity Level
Authors: Dunton Genevieve , Ebin Vicki J. , Efrat Merav W. , Efrat Rafael , Lane Christianne J. , Plunkett Scott
Published: September 2014

Objective:

The current study investigates the extent to which a refundable tax credit could be used to increase low-income children’s after-school physical activity levels.

Methods:

An experimental study was conducted evaluating the effectiveness of an intervention offering a simulated refundable tax credit to parents of elementary-school-age children (n = 130) for enrollment in after-school physical activity programs. A randomized controlled design was used, with data collected at baseline, immediately following the 4-month intervention (postintervention), and 6 weeks after the end of the intervention (follow-up). Evaluation measures included (1) enrollment rate, time spent, weekly participation frequency, duration of enrollment, and long-term enrollment patterns in after-school physical activity programs and (2) moderate to vigorous physical activity.

Results:

The simulated tax credits did not significantly influence low-income children’s rates of enrollment in after-school physical activity programs, frequency of participation, time spent in after-school physical activity programs, and overall moderate-to-vigorous intensity physical activity at postintervention or follow-up.

Conclusion:

The use of refundable tax credits as incentives to increase participation in after-school physical activity programs in low-income families may have limited effectiveness. Lawmakers might consider other methods of fiscal policy to promote physical activity such as direct payment to after-school physical activity program providers for enrolling and serving a low-income child in a qualified program, or improvements to programming and infrastructure.
Physical Activity Trajectories During Daily Middle School Physical Education
Authors: Burns Ryan D. , Brusseau Timothy A. , Hannon James C.
Published: September 2014

Background:

Optimal levels of moderate-to-vigorous physical activity (MVPA) have been shown to improve health and academic outcomes in youth. Limited research has examined MVPA trajectories throughout a daily middle school physical education (PE) curriculum. The purpose of this study was to examine MVPA trajectories over a daily PE curriculum and the modifying effects of sex, body composition, and cardiorespiratory endurance.

Methods:

One hundred 7th- and 8th-grade students participated in daily PE lessons. There were 66 lessons throughout the semester. MVPA was monitored during each lesson using NL-1000 piezoelectric pedometers. Students were classified into FITNESSGRAM Healthy Fitness Zones using estimated VO2 Max and Body Mass Index (BMI). A population averaged generalized estimating equation was employed to examine MVPA trajectories.

Results:

On average, students’ MVPA decreased over time (β = –0.35, P < .001). Poor student VO2max classification significantly modified the trajectories (β = –0.14, P < .001), however poor BMI classification did not have a modifying effect (β = 0.03, P = .158).

Conclusions:

MVPA decreased in daily PE over time and cardiorespiratory endurance significantly modified the trajectories. The results support that extra efforts have to be made by teachers and students to sustain MVPA behaviors over a semester.
Ramoplanin at Bactericidal Concentrations Induces Bacterial Membrane Depolarization in Staphylococcus aureus
Authors: Cheng Mu , Huang Johnny X. , Ramu Soumya , Butler Mark S. , Cooper Matthew A.
Published: September 2014

Ramoplanin is an actinomycetes-derived antibiotic with broad-spectrum activity against Gram-positive bacteria that has been evaluated in clinical trials for the treatment of gastrointestinal vancomycin-resistant enterococci (VRE) and
Clostridium difficile
infections. Recent studies have proposed that ramoplanin binds to bacterial membranes as a C
2
symmetrical dimer that can sequester Lipid II, which causes inhibition of cell wall peptidoglycan biosynthesis and cell death. In this study, ramoplanin was shown to bind to anionic and zwitterionic membrane mimetics with a higher affinity for anionic membranes and to induce membrane depolarization of methicillin-susceptible
Staphylococcus aureus
(MSSA) ATCC 25923 at concentrations at or above the minimal bactericidal concentration (MBC). The ultrastructural effects of ramoplanin on
S. aureus
were also examined by transmission electron microscopy (TEM), and this showed dramatic changes to bacterial cell morphology. The correlation observed between membrane depolarization and bacterial cell viability suggests that this mechanism may contribute to the bactericidal activity of ramoplanin.
Integron-Borne Transmission of VEB-1 Extended-Spectrum β-Lactamase in Pseudomonas aeruginosa in a Tertiary Care Hospital in India
Authors: Maurya Anand Prakash , Talukdar Anupam Das , Chanda Debadatta Dhar , Chakravarty Atanu , Bhattacharjee Amitabha
Published: September 2014

A total 14 clinical isolates of
Pseudomonas aeruginosa
that produced VEB-1 and were susceptible only to polymyxin B were recovered from hospitalized patients. VEB-1 was located within variable regions of the class 1 integron, flanked by resistant genes, and was horizontally transferable as well as carried within the IncP-type plasmid. We conclude that the IncP-type plasmid is responsible for the horizontal transmission of VEB-1-mediated expanded-spectrum cephalosporin resistance in this medical center.
EnhancedIn VitroFormation and Antibiotic Resistance of Nonattached Pseudomonas aeruginosa Aggregates through Incorporation of Neutrophil Products
Authors: Caceres Silvia M. , Malcolm Kenneth C. , Taylor-Cousar Jennifer L. , Nichols David P. , Saavedra Milene T. , Bratton Donna L. , Moskowitz Samuel M. , Burns Jane L. , Nick Jerry A.
Published: September 2014

Pseudomonas aeruginosais a major pathogen in cystic fibrosis (CF) lung disease. Children with CF are routinely exposed toP. aeruginosafrom the natural environment, and by adulthood, 80% of patients are chronically infected.P. aeruginosain the CF airway exhibits a unique biofilm-like structure, where it grows in small clusters or aggregates of bacteria in association with abundant polymers of neutrophil-derived components F-actin and DNA, among other components. These aggregates differ substantially in size and appearance compared to surface-attachedin vitrobiofilm models classically utilized for studies but are believed to share properties of surface-attached biofilms, including antibiotic resistance. However, little is known about the formation and function of surface-independent modes of biofilm growth, how they might be eradicated, and quorum sensing communication. To address these issues, we developed a novelin vitromodel ofP. aeruginosaaggregates incorporating human neutrophil-derived products. Aggregates grownin vitroand those found in CF patients' sputum samples were morphologically similar; viable bacteria were distributed in small pockets throughout the aggregate. ThelasAquorum sensing gene was differentially expressed in the presence of neutrophil products. Importantly, aggregates formed in the presence of neutrophils acquired resistance to tobramycin, which was lost when the aggregates were dispersed with DNase, and antagonism of tobramycin and azithromycin was observed. This novel yet simplein vitrosystem advances our ability to model infection of the CF airway and will be an important tool to study virulence and test alternative eradication strategies againstP. aeruginosa.
Clinical Validation of the Analysis of Fluconazole in Oral Fluid in Hospitalized Children
Authors: van der Elst Kim C. M. , van Alst Manouche , Lub-de Hooge Marjolijn N. , van Hateren Kai , Kosterink Jos G. W. , Alffenaar Jan-Willem C. , Schölvinck Elisabeth H.
Published: September 2014

Fluconazole is a first-line antifungal agent for the treatment and prophylaxis of invasive candidiasis in pediatric patients. Pediatric patients are at risk of suboptimal drug exposure, due to developmental changes in gastrointestinal and renal function, metabolic capacity, and volume of distribution. Therapeutic drug monitoring (TDM) can therefore be useful to prevent underexposure of fluconazole in children and infants. Children, however, often fear needles and can have difficult vascular access. The purpose of this study was to develop and clinically validate a method of analysis to determine fluconazole in oral fluid in pediatric patients. Twenty-one paired serum and oral fluid samples were obtained from 19 patients and were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method after cross-validation between serum and oral fluid. The results were within accepted ranges for accuracy and precision, and samples were stable at room temperature for at least 17 days. A Pearson correlation test for the fluconazole concentrations in serum and oral fluid showed a correlation coefficient of 0.960 (
P
< 0.01). The mean oral fluid-to-serum concentration ratio was 0.99 (95% confidence interval [CI], 0.88 to 1.10) with Bland-Altman analysis. In conclusion, an oral fluid method of analysis was successfully developed and clinically validated for fluconazole in pediatric patients and can be a noninvasive, painless alternative to perform TDM of fluconazole when blood sampling is not possible or desirable. When patients receive prolonged courses of antifungal treatment and use fluconazole at home, this method of analysis can extend the possibilities of TDM for patients at home.
Effect of Suberoylanilide Hydroxamic Acid (SAHA) Administration on the Residual Virus Pool in a Model of Combination Antiretroviral Therapy-Mediated Suppression in SIVmac239-Infected Indian Rhesus Macaques
Authors: Del Prete Gregory Q. , Shoemaker Rebecca , Oswald Kelli , Lara Abigail , Trubey Charles M. , Fast Randy , Schneider Douglas K. , Kiser Rebecca , Coalter Vicky , Wiles Adam , Wiles Rodney , Freemire Brandi , Keele Brandon F. , Estes Jacob D. , Quiñones Octavio A. , Smedley Jeremy , Macallister Rhonda , Sanchez Rosa I. , Wai John S. , Tan Christopher M. , Alvord W. Gregory , Hazuda Daria J. , Piatak Michael , Lifson Jeffrey D.
Published: September 2014

Nonhuman primate models are needed for evaluations of proposed strategies targeting residual virus that persists in HIV-1-infected individuals receiving suppressive combination antiretroviral therapy (cART). However, relevant nonhuman primate (NHP) models of cART-mediated suppression have proven challenging to develop. We used a novel three-class, six-drug cART regimen to achieve durable 4.0- to 5.5-log reductions in plasma viremia levels and declines in cell-associated viral RNA and DNA in blood and tissues of simian immunodeficiency virus SIVmac239-infected Indian-origin rhesus macaques, then evaluated the impact of treatment with the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA; Vorinostat) on the residual virus pool.Ex vivoSAHA treatment of CD4+T cells obtained from cART-suppressed animals increased histone acetylation and viral RNA levels in culture supernatants. cART-suppressed animals each received 84 total doses of oral SAHA. We observed SAHA dose-dependent increases in acetylated histones with evidence for sustained modulation as well as refractoriness following prolonged administration.In vivovirologic activity was demonstrated based on the ratio of viral RNA to viral DNA in peripheral blood mononuclear cells, a presumptive measure of viral transcription, which significantly increased in SAHA-treated animals. However, residual virus was readily detected at the end of treatment, suggesting that SAHA alone may be insufficient for viral eradication in the setting of suppressive cART. The effects observed were similar to emerging data for repeat-dose SAHA treatment of HIV-infected individuals on cART, demonstrating the feasibility, utility, and relevance of NHP models of cART-mediated suppression forin vivoassessments of AIDS virus functional cure/eradication approaches.
Random Mutagenesis of the Multidrug Transporter AcrB from Escherichia coli for Identification of Putative Target Residues of Efflux Pump Inhibitors
Authors: Schuster Sabine , Kohler Samay , Buck Annika , Dambacher Christine , König Armin , Bohnert Jürgen A. , Kern Winfried V.
Published: September 2014

Efflux is an important mechanism of bacterial multidrug resistance (MDR), and the inhibition of MDR pumps by efflux pump inhibitors (EPIs) could be a promising strategy to overcome MDR. 1-(1-Naphthylmethyl)-piperazine (NMP) and phenylalanine-arginine-β-naphthylamide (PAβN) are model EPIs with activity in various Gram-negative bacteria expressing AcrB, the major efflux pump of
Escherichia coli
, or similar homologous pumps of the resistance-nodulation-cell division class. The aim of the present study was to generate
E. coli
AcrB mutants resistant to the inhibitory action of the two model EPIs and to identify putative EPI target residues in order to better understand mechanisms of pump inhibition. Using an
in vitro
random mutagenesis approach focusing on the periplasmic domain of AcrB, we identified the double mutation G141D N282Y, which substantially compromised the synergistic activity of NMP with linezolid, was associated with similar intracellular linezolid concentrations in the presence and absence of NMP, and did not impair the intrinsic MICs of various pump substrates and dye accumulation. We propose that these mutations near the outer face of the distal substrate binding pocket reduce NMP trapping. Other residues found to be relevant for efflux inhibition by NMP were G288 and A279, but mutations at these sites also changed the susceptibility to several pump substrates. Unlike with NMP, we were unable to generate AcrB periplasmic domain mutants with resistance or partial resistance to the EPI activity of PAβN, which is consistent with the modes of action of PAβN differing from those of NMP.
Mechanisms of Tigecycline Resistance among Klebsiella pneumoniae Clinical Isolates
Authors: Sheng Zi-Ke , Hu Fupin , Wang Weixia , Guo Qinglan , Chen Zhijun , Xu Xiaogang , Zhu Demei , Wang Minggui
Published: September 2014

Of 26 tigecycline-nonsusceptible
Klebsiella pneumonia
e (TNSKP) clinical isolates, 25 had nonsynonymous mutations in
ramR
and/or
acrR
(23 in
ramR
and 10 in
acrR
). Eight TNSKP isolates possessed overexpression of
ramA
,
acrB
,
rarA
, and
oqxB
simultaneously, while 8 and 1 TNSKP strains had upregulation of
ramA
and
acrB
and of
rarA
and
oqxB
, respectively. Thus, resistance mechanisms of 9 TNSKP isolates cannot be explained by the present pathways. This study underscores the role of RamA in TNSKP and suggests the presence of novel tigecycline resistance mechanisms.
Molecular and Structural Basis for the Roles of Hepatitis C Virus Polymerase NS5B Amino Acids 15, 223, and 321 in Viral Replication and Drug Resistance
Authors: Lam Angela M. , Edwards Thomas E. , Mosley Ralph T. , Murakami Eisuke , Bansal Shalini , Lugo Christopher , Bao Haiying , Otto Michael J. , Sofia Michael J. , Furman Phillip A.
Published: September 2014

Resistance to the 2′-F-2′-
C
-methylguanosine monophosphate nucleotide hepatitis C virus (HCV) inhibitors PSI-352938 and PSI-353661 was associated with a combination of amino acid changes (changes of S to G at position 15 [S15G], C223H, and V321I) within the genotype 2a nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase. To understand the role of these residues in viral replication, we examined the effects of single and multiple point mutations on replication fitness and inhibition by a series of nucleotide analog inhibitors. An acidic residue at position 15 reduced replicon fitness, consistent with its proximity to the RNA template. A change of the residue at position 223 to an acidic or large residue reduced replicon fitness, consistent with its proposed proximity to the incoming nucleoside triphosphate (NTP). A change of the residue at position 321 to a charged residue was not tolerated, consistent with its position within a hydrophobic cavity. This triple resistance mutation was specific to both genotype 2a virus and 2′-F-2′-
C
-methylguanosine inhibitors. A crystal structure of the NS5B S15G/C223H/V321I mutant of the JFH-1 isolate exhibited rearrangement to a conformation potentially consistent with short primer-template RNA binding, which could suggest a mechanism of resistance accomplished through a change in the NS5B conformation, which was better tolerated by genotype 2a virus than by viruses of other genotypes.
Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection
Authors: Nett Jeniel E. , Brooks Erin G. , Cabezas-Olcoz Jonathan , Sanchez Hiram , Zarnowski Robert , Marchillo Karen , Andes David R.
Published: September 2014

Indwelling urinary catheters are commonly used in the management of hospitalized patients.
Candida
can adhere to the device surface and propagate as a biofilm. These
Candida
biofilm communities differ from free-floating
Candida
, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated
Candida albicans
biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat,
Candida
proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of
C. albicans
cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of
Candida
biofilms in the urinary tract.
Bicarbonate Increases Binding Affinity of Vibrio cholerae ToxT to Virulence Gene Promoters
Authors: Thomson Joshua J. , Withey Jeffrey H.
Published: September 2014

The major
Vibrio cholerae
virulence gene transcription activator, ToxT, is responsible for the production of the diarrhea-inducing cholera toxin (CT) and the major colonization factor, toxin coregulated pilus (TCP). In addition to the two primary virulence factors mentioned, ToxT is responsible for the activation of accessory virulence genes, such as
aldA
,
tagA
,
acfA
,
acfD
,
tcpI
, and
tarAB
. ToxT activity is negatively modulated by bile and unsaturated fatty acids found in the upper small intestine. Conversely, previous work identified another intestinal signal, bicarbonate, which enhances the ability of ToxT to activate production of CT and TCP. The work presented here further elucidates the mechanism for the enhancement of ToxT activity by bicarbonate. Bicarbonate was found to increase the activation of ToxT-dependent accessory virulence promoters in addition to those that produce CT and TCP. Bicarbonate is taken up into the
V. cholerae
cell, where it positively affects ToxT activity by increasing DNA binding affinity for the virulence gene promoters that ToxT activates regardless of toxbox configuration. The increase in ToxT binding affinity in the presence of bicarbonate explains the elevated level of virulence gene transcription.
Defect in the Formation of 70S Ribosomes Caused by Lack of Ribosomal Protein L34 Can Be Suppressed by Magnesium
Authors: Akanuma Genki , Kobayashi Ako , Suzuki Shota , Kawamura Fujio , Shiwa Yuh , Watanabe Satoru , Yoshikawa Hirofumi , Hanai Ryo , Ishizuka Morio
Published: September 2014

To elucidate the biological functions of the ribosomal protein L34, which is encoded by the
rpmH
gene, the
rpmH
deletion mutant of
Bacillus subtilis
and two suppressor mutants were characterized. Although the Δ
rpmH
mutant exhibited a severe slow-growth phenotype, additional mutations in the
yhdP
or
mgtE
gene restored the growth rate of the Δ
rpmH
strain. Either the disruption of
yhdP
, which is thought to be involved in the efflux of Mg
2+
, or overexpression of
mgtE
, which plays a major role in the import of Mg
2+
, could suppress defects in both the formation of the 70S ribosome and growth caused by the absence of L34. Interestingly, the Mg
2+
content was lower in the Δ
rpmH
cells than in the wild type, and the Mg
2+
content in the Δ
rpmH
cells was restored by either the disruption of
yhdP
or overexpression of
mgtE. In vitro
experiments on subunit association demonstrated that 50S subunits that lacked L34 could form 70S ribosomes only at a high concentration of Mg
2+
. These results showed that L34 is required for efficient 70S ribosome formation and that L34 function can be restored partially by Mg
2+
. In addition, the Mg
2+
content was consistently lower in mutants that contained significantly reduced amounts of the 70S ribosome, such as the Δ
rplA
(L1) and Δ
rplW
(L23) strains and mutant strains with a reduced number of copies of the
rrn
operon. Thus, the results indicated that the cellular Mg
2+
content is influenced by the amount of 70S ribosomes.
Staphylococcus aureus Alters Growth Activity, Autolysis, and Antibiotic Tolerance in a Human Host-Adapted Pseudomonas aeruginosa Lineage
Authors: Michelsen Charlotte Frydenlund , Christensen Anne-Mette Juel , Bojer Martin Saxtorph , Høiby Niels , Ingmer Hanne , Jelsbak Lars
Published: September 2014

Interactions among members of polymicrobial infections or between pathogens and the commensal flora may determine disease outcomes.
Pseudomonas aeruginosa
and
Staphylococcus aureus
are important opportunistic human pathogens and are both part of the polymicrobial infection communities in human hosts. In this study, we analyzed the
in vitro
interaction between
S. aureus
and a collection of
P. aeruginosa
isolates representing different evolutionary steps of a dominant lineage, DK2, that have evolved through decades of growth in chronically infected patients. While the early adapted
P. aeruginosa
DK2 strains outcompeted
S. aureus
during coculture on agar plates, we found that later
P. aeruginosa
DK2 strains showed a commensal-like interaction, where
S. aureus
was not inhibited by
P. aeruginosa
and the growth activity of
P. aeruginosa
was enhanced in the presence of
S. aureus
. This effect is mediated by one or more extracellular
S. aureus
proteins greater than 10 kDa, which also suppressed
P. aeruginosa
autolysis and prevented killing by clinically relevant antibiotics through promoting small-colony variant (SCV) formation. The commensal interaction was abolished with
S. aureus
strains mutated in the
agr
quorum sensing system or in the SarA transcriptional virulence regulator, as well as with strains lacking the proteolytic subunit, ClpP, of the Clp protease. Our results show that during evolution of a dominant cystic fibrosis lineage of
P. aeruginosa
, a commensal interaction potential with
S. aureus
has developed.
The Cysteine Desulfhydrase CdsH Is Conditionally Required for Sulfur Mobilization to the Thiamine Thiazole in Salmonella enterica
Authors: Palmer Lauren D. , Leung Man Him , Downs Diana M.
Published: September 2014

Thiamine pyrophosphate is a required coenzyme that contains a mechanistically important sulfur atom. In
Salmonella enterica
, sulfur is trafficked to both thiamine biosynthesis and 4-thiouridine biosynthesis by the enzyme ThiI using persulfide (R-S-S-H) chemistry. It was previously reported that a
thiI
mutant strain could grow independent of exogenous thiamine in the presence of cysteine, suggesting there was a second mechanism for sulfur mobilization. Data reported here show that oxidation products of cysteine rescue the growth of a
thiI
mutant strain by a mechanism that requires the transporter YdjN and the cysteine desulfhydrase CdsH. The data are consistent with a model in which sulfide produced by CdsH reacts with cystine (Cys-S-S-Cys),
S
-sulfocysteine (Cys-S-SO
3
−
), or another disulfide to form a small-molecule persulfide (R-S-S-H). We suggest that this persulfide replaced ThiI by donating sulfur to the thiamine sulfur carrier protein ThiS. This model describes a potential mechanism used for sulfur trafficking in organisms that lack ThiI but are capable of thiamine biosynthesis.
Human Herpesvirus 8 Induces Polyfunctional B Lymphocytes That Drive Kaposi’s Sarcoma
Authors: Knowlton Emilee R. , Rappocciolo Giovanna , Piazza Paolo , Lepone Lauren M. , Nadgir Sagar V. , Bullotta Arlene , Berendam Stella J. , Li Jun , Reinhart Todd A. , Jenkins Frank J. , Rinaldo Charles R.
Published: September 2014

Kaposi’s sarcoma (KS) is an unusual neoplasia wherein the tumor consists primarily of endothelial cells infected with human herpesvirus 8 (HHV-8; Kaposi’s sarcoma-associated herpesvirus) that are not fully transformed but are instead driven to excess proliferation by inflammatory and angiogenic factors. This oncogenic process has been postulated but unproven to depend on a paracrine effect of an abnormal excess of host cytokines and chemokines produced by HHV-8-infected B lymphocytes. Using newly developed measures for intracellular detection of lytic cycle proteins and expression of cytokines and chemokines, we show that HHV-8 targets a range of naive B cell, IgM memory B cell, and plasma cell-like populations for infection and induction of interleukin-6, tumor necrosis factor alpha, macrophage inhibitory protein 1α, macrophage inhibitory protein 1β, and interleukin-8in vitroand in the blood of HHV-8/HIV-1-coinfected subjects with KS. These B cell lineage subsets that support HHV-8 infection are highly polyfunctional, producing combinations of 2 to 5 of these cytokines and chemokines, with greater numbers in the blood of subjects with KS than in those without KS. Our study provides a new paradigm of B cell polyfunctionality and supports a key role for B cell-derived cytokines and chemokines produced during HHV-8 infection in the development of KS.

IMPORTANCEKaposi’s sarcoma (KS) is the most common cancer in HIV-1-infected persons and is caused by one of only 7 human cancer viruses, i.e., human herpesvirus 8 (HHV-8). It is unclear how this virus causes neoplastic transformation. Development and outgrowth of endothelial cell lesions characteristic of KS are hypothesized to be dependent on virus replication and multiple immune mediators produced by the KS cells and inflammatory cells, yet the roles of these viral and cell factors have not been defined. The present study advances our understanding of KS in that it supports a central role for HHV-8 infection of B cells inducing multiple cytokines and chemokines that can drive development of the cancer. Notably, HIV-1-infected individuals who developed KS had greater numbers of such HHV-8-infected, polyfunctional B cells across a range of B cell phenotypic lineages than did HHV-8-infected persons without KS. This intriguing production of polyfunctional immune mediators by B cells serves as a new paradigm for B cell function and classification.
Ancient-Pathogen Genomics: Coming of Age?
Authors: Whatmore Adrian M.
Published: September 2014

The potentially debilitating zoonotic disease brucellosis is thought to have been a scourge of mankind throughout history. New work by Kay et al. [mBio 5(4):e01337-14, 2014] adds to evidence for this by exploiting the huge advances in next-generation sequencing technology and applying shotgun metagenomics to a calcified nodule obtained from a 14th-century skeleton from Sardinia. While not the first DNA-based confirmation of
Brucella
in medieval DNA samples, Kay et al.’s study goes much further than previous reports based on single gene fragments in that it allows a full-genome reconstruction and thus facilitates meaningful comparative analysis of relationships with extant
Brucella
strains. These analyses confirm the close relationship of the genome to contemporary isolates from the western Mediterranean, illustrating the continuity of this lineage in the region over centuries. The study, along with recent studies characterizing other ancient-pathogen genomes, confirms that shotgun metagenomics offers us a powerful tool to fully characterize pathogens from ancient samples. Such studies promise to revolutionize our understanding of the nature of infectious disease in these materials and of the wider picture of the emergence, evolution, and spread of bacterial pathogens over history.
The long-term course of patients undergoing alternative and integrative therapy for lumbar disc herniation: 3-year results of a prospective observational study
Authors: Shin Joon-Shik , Lee Jinho , Kim Me-riong , Shin Byung-Cheul , Lee Myeong Soo , Ha In-Hyuk
Published: September 2014

Objectives

This study aimed to assess the efficacy and safety of an integrative complementary and alternative medicine (CAM) approach in the management of lumbar herniated disc (LHD) with sciatic pain and investigate pain relapse, use of medical care and surgery rates in patients who actively chose non-surgical CAM treatment for LHD.

Study design/Setting

This prospective observational study was undertaken at a Korean medicine hospital outpatient setting in Korea.

Participants

A total of 128 consecutive patients with LHD with a numeric rating scale for leg pain of ≥5 completed 6 months of CAM treatment after recruitment from November 2006, and 73/128 participants (57%) attended follow-up 3 years later.

Interventions

6 months of CAM treatment (herbal medicine, acupuncture, bee venom pharmacopuncture, and Chuna manipulation).

Primary outcome measures

Visual analogue scale (VAS) for low back and leg pain, Oswestry Disability Index (ODI), and Short Form (SF)-36 Health Survey.

Secondary outcome measures

Neurological impairment (muscular weakness, sensory loss, Straight Leg Raise test), MRIs, recurrence of low back pain and/or radiating pain, and use of medical care.

Results

92 patients could be assessed for surgical state, of whom 4 replied that they had received surgery. 73 patients attended the 3-year follow-up. The baseline VAS of back pain (4.37±2.70) decreased after treatment (0.90±1.01; p<0.001) and was maintained at 3 years (1.12±1.64; p=0.19). The baseline VAS of leg pain (7.57±1.40) also decreased on treatment (0.82±1.18; p<0.001) and was sustained at 3 years (0.99±1.58; p=0.34). ODI scores declined from 40.74±16.15 to 9.84±9.67 (p<0.001), then decreased further to 6.30±7.19 (p<0.01). SF-36 scores increased from 34.96±13.30 to 69.20±14.96 (p<0.001), reaching 76.19±14.45 (p<0.001) at 3 years. 37 patients reported recurrence of pain and most chose CAM treatment for management of relapse symptoms.

Conclusions

Although the absence of a control group prevents validation of effectiveness, many patients showed favourable long-term outcomes.

Trial registration number

ClinicalTrials.gov Identifier:NCT01989403.
Improving care for patients whose recovery is uncertain. The AMBER care bundle: design and implementation
Authors: Carey Irene , Shouls Susanna , Bristowe Katherine , Morris Michelle , Briant Linda , Robinson Carole , Caulkin Ruth , Griffiths Mathew , Clark Kieron , Koffman Jonathan , Hopper Adrian
Published: September 2014

Introduction

Despite preferences to the contrary, 53% of deaths in England occur in hospital. Difficulties in managing clinical uncertainty can result in delayed recognition that a person may be approaching the end of life, and a failure to address his/her preferences. Planning and shared decision-making for hospital patients need to improve where an underlying condition responds poorly to acute medical treatment and there is a risk of dying in the next 1–2 months. This paper suggests an approach to improve this care.

Intervention

A care bundle (the AMBER care bundle) was designed by a multiprofessional development team, which included service users, utilising the model for improvement following an initial scoping exercise. The care bundle includes two identification questions, four subsequent time restricted actions and systematic daily follow-up.

Clinical impact

This paper describes the development and implementation of a care bundle. From August 2011 to July 2012, 638 patients received care supported by the AMBER care bundle. In total 42.8% died in hospital and a further 14.5% were readmitted as emergencies within 30 days of discharge. Clinical outcome measures are in development.

Conclusions

It has been possible to develop a care bundle addressing a complex area of care which can be a lever for cultural change. The implementation of the AMBER care bundle has the potential to improve care of clinically uncertain hospital patients who may be approaching the end of life by supporting their recognition and prompting discussion of their preferences. Outcomes associated with its use are currently being formally evaluated.
Social media and palliative medicine: a retrospective 2-year analysis of global Twitter data to evaluate the use of technology to communicate about issues at the end of life
Authors: Nwosu Amara Callistus , Debattista Maria , Rooney Claire , Mason Stephen
Published: September 2014

Background

Social media describes technological applications which are used to exchange information in a virtual environment. The use of social media is increasing, in professional and social contexts, on a variety of platforms such as Twitter; however, the scope and breadth of its use to discuss end-of-life care has not previously been reported.

Aims

To determine the frequency, sentiment and trend of Twitter ‘tweets’ containing palliative care-related identifiers (hashtags) and/or phrases sent by users over a 2-year period.

Methods

A 2-year retrospective analysis of Twitter posts (tweets), between the 1 August 2011 to 31 July 2013, using a social media analytics tool: TopsyPro. Thirteen search terms were identified and analysed for tweet volume, frequency, sentiment and acceleration.

Results

A total of 683.5K tweets containing a combination of 13 palliative care terms were analysed. The tweet volume for all terms increased by 62.3% between 2011–2012 (262.5K) and 2012–2013 (421K). The most popular terms include ‘end-of-life’ (210K), #hpm (114K) and ‘palliative care’ (93.8K). Sentiment was high with 89% of tweets rated more positive than all other tweets sent on Twitter during this period. The term ‘Liverpool Care Pathway’ experienced the highest percentage increase in tweets (55% increase) reaching a peak in July 2013.

Conclusions

A lot of discussion about palliative care is taking place on Twitter, and the majority of this is positive. Social media presents a novel opportunity for engagement and ongoing dialogue with public and professional groups.
Grading of breast cancer on needle core biopsy: does a reduction in mitotic count threshold improve agreement with grade on excised specimens?
Authors: Dhaliwal Catharine Ann , Graham Catriona , Loane Joseph
Published: September 2014

Background

Accurate assessment of invasive breast cancer grade on needle core biopsy (NCB) is important as it guides treatment.

Aim

To assess the agreement between grade of invasive cancer on NCB and excision and determine whether altering the mitotic count score threshold on NCB improves it.

Methods

Pathology slides from patients with an NCB diagnosis of invasive breast cancer who underwent subsequent breast conservation surgery in 2012 were reviewed. Mitotic counts were assessed and tumour grade agreement between NCB and excision evaluated. The mitotic count thresholds were altered and grade agreement was reassessed.

Results

In 283/359 (79%) cases, there was concurrence on histological grade between NCB and excision. Reduction in mitotic count thresholds did not improve either overall tumour grade agreement or agreement within any subgroup of patients.

Conclusions

In our experience, the current mitotic count score thresholds are appropriate and should be maintained.
A real-time prospective evaluation of clinical pharmaco-economic impact of diagnostic label of ‘penicillin allergy’ in a UK teaching hospital
Authors: Li M , Krishna M T , Razaq S , Pillay D
Published: September 2014

Aims

To perform a pharmaco-economic analysis of prescribing alternative antibiotics in patients with a diagnostic label of ‘penicillin allergy’ and assess whether collation of information from a structured history and liaison with the family physician could reduce costs.

Methods

A prospective pro-forma-based interview of randomly selected in-patients and their family physician was used to assess the validity of the diagnostic label of ‘penicillin allergy’. Cost analysis of prescription of alternative antibiotics was performed and compared with first-line agents.

Results

102 patients were assessed and only 40% (n=41) were found to have a history consistent with penicillin hypersensitivity, 40% (n=41) were likely ‘not allergic’ and 20% (n=20) had ‘indeterminate’ reactions. Total cost of antibiotics prescribed for patients with penicillin allergy was 1.82–2.58-fold higher than for first-line antibiotics.

Conclusions

Obtaining a structured history from the patient and family physician alone can enable an accurate identification of penicillin allergy status. Total acquisition cost of second-line antibiotics is higher than if these patients were prescribed first-line antibiotics.
Women's experiences of endometriosis: a systematic review and synthesis of qualitative research
Authors: Young Kate , Fisher Jane , Kirkman Maggie
Published: September 2014

Background

Endometriosis is experienced by approximately 10% of women worldwide; it is associated with significant burden on the woman, her family, and society.

Aim

The aim of this systematic review was to synthesise the available qualitative literature to increase our understanding of the effects of endometriosis on women's lives.

Methods

Seven social science and medical databases (PubMed, Medline, CINAHL, Web of Science, ScienceDirect, PsycInfo and Embase) and Google Scholar were searched for peer-reviewed papers published in English of research using qualitative methods.

Results and conclusions

Eighteen papers reporting 11 studies met the inclusion criteria. Participant numbers ranged from 15 to 61 women, all recruited from support groups and specialised clinics. Studies were conducted in high-income, Anglophone countries. The review identified four prominent themes: Life, Symptoms, Medical Experience, and Self. Women's reported experiences demonstrated opportunities for enhancing current clinical practice, including improved education about endometriosis for health professionals, the need to take a comprehensive approach to pain treatment, and initiating appropriate discussion of the impact on sex life. Significant evidence gaps were identified: there was inadequate investigation of women's experiences of endometriosis-associated infertility and of the impact of reduced social participation on perceived support and emotional well-being, and limited or no inclusion of the experiences of adolescent and post-menopausal women, women from low socioeconomic backgrounds, women who do not identify as Caucasian, and non-heterosexual women.
Systematic Review of Traditional Chinese Medicine for Depression in Parkinson's Disease
Authors: Zhang Yi , Wang Zhen-Zhen , Sun Hong-Mei , Li Ping , Li Yun-Feng , Chen Nai-Hong
Published: September 2014

Depression is the most common non-motor symptom of Parkinson's disease (PD). Recent clinical trials have evaluated the effectiveness of traditional Chinese medicine (TCM) in the treatment of depression in PD (dPD). However, the results are conflicting rather than conclusive. To investigate the effectiveness of TCM for the treatment of dPD, a systematic review was conducted. Literature searches and collections were performed to identify studies addressing the treatment of TCM for dPD. The methodological quality and risk of bias in all studies included were evaluated. Weighted mean difference (WMD) with 95% confidence interval (CI) was used as the effect measure. Finally, a total of 10 studies involving 582 patients were identified. The pooled results revealed that TCM combined with conventional drugs significantly improved the total scores of the unified Parkinson's disease rating scale (WMD = -7.35, 95% CI: -11.24 to -3.47) and the score of the Hamilton rating scale for depression (HAM-D) (WMD = -4.19, 95% CI: -5.14 to -3.24) compared with conventional drug, respectively. Conclusively, there is evidence that TCM may be beneficial to the treatment of dPD in spite of the methodological weakness of the included studies.
Sub-Volt Fully Balanced Differential Difference Amplifier
Authors: Khateb Fabian , Kumngern Montree , Vlassis Spyridon , Psychalinos Costas , Kulej Tomasz
Published: September 2014

This paper presents a new CMOS structure for a fully balanced differential difference amplifier (FB-DDA) designed to operate from a sub-volt supply. This structure employs the bulk-driven quasi-floating-gate (BD-QFG) technique to achieve the capability of an ultra-low voltage operation and an extended input voltage range. The proposed BD-QFG FB-DDA is suitable for ultra-low-voltage low-power applications. The circuit is designed with a single supply of 0.5 V and consumes only 357 nW of power. The proposed circuit was simulated in a 0.18-μm TSMC CMOS technology and the simulation results prove its functionality and attractive parameters. An application example of a state variable filter is also presented to confirm the usefulness of the proposed BD-QFG FB-DDA.
AN ELECTRODE MODIFIED WITH AuNPs/GRAPHENE NANOCOMPOSITES FILM FOR THE DETERMINATION OF METHYL PARATHION RESIDUES
Authors: MAO YALI , FA HUANBAO , CHENG YANMEI , DU YANQIU , YIN WEI , HOU CHANGJUN , HUO DANQUN , ZHANG DONG
Published: September 2014

A novel sensitive and elective electrochemical sensor was developed to detect methyl parathion (MP) based on a glassy carbon electrode (GCE) modified with gold nanoparticles ( AuNPs )/graphene nanocomposites film. The AuNPs were modified onto graphene sheets using NaBH 4 as a reductant. The obtained AuNPs /graphene nanocomposites were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The electrochemical behavior of MP and interference studies were then investigated. Compared with metal ions and nitroaromatic compounds, which exist in environmental samples, the AuNPs /graphene/GCE exhibited high adsorption and strong affinity toward MP. Under optimized conditions, the oxidation peak current of MP was linear to its concentration within the range of 4.0 × 10-7–8.0 × 10-5 M, with a detection limit ( S/N = 3) of 8.5 × 10-8 M. These results indicated that the AuNPs /graphene nanocomposites displayed a synergic effect involving the catalytic characteristics of graphene and AuNPs nanocomposites, which can effectively improve the electrochemical properties of MP. Furthermore, the AuNPs also enhanced sensor sensitivity to MP. Therefore, the AuNPs /graphene/GCE could be a promising sensor for the fast, sensitive and selective detection of MP in real samples.
Continuous fabrication platform for highly aligned polymer films
Authors: Loomis James , Ghasemi Hadi , Huang Xiaopeng , Thoppey Nagarajan , Wang Jianjian , Tong Jonathan K. , Xu Yanfei , Li Xiaobo , Lin Cheng-Te , Chen Gang
Published: September 2014

Superior mechanical and thermal properties in bulk polymers can be achieved by aligning the molecular chains through drawing-induced plastic deformation. Although highly aligned polymer films (HAPFs) are in demand, current fabrication methods are limited to manual, lab-scale batch processes. Here we report a continuous fabrication platform for HAPFs consisting of a three-step sol-gel extrusion, structure freezing and drying, and mechanical drawing process. First, a polymer-solvent solution is subjected to a high shear, high temperature, Couette flow extrusion into a thin film, resulting in initial chain disentanglement. Next, the extruded disentangled structure is frozen using a liquid N 2-cooled substrate, and then solvent is removed from polymer gel through ambient evaporation. Finally, dried films are mechanically drawn within a heated enclosure using a constant-force adaptive-thickness drawing system. The performance of this platform has been confirmed by fabricating polyethylene HAPFs with > 99% crystallinity and draw ratios up to 100× (creating continuous films > 15 m in length).
Emerging Issues in Public Health Genomics
Authors: Roberts J. Scott , Dolinoy Dana C. , Tarini Beth A.
Published: September 2014

This review highlights emerging areas of interest in public health genomics. First, we describe recent advances in newborn screening (NBS), with a focus on the practice and policy implications of current and future efforts to expand NBS programs (e.g., via next-generation sequencing). Next, we detail research findings from the rapidly progressing field of epigenetics and epigenomics, highlighting ways in which our emerging understanding in these areas could guide future intervention and research efforts in public health. We close by considering various ethical, legal, and social issues posed by recent developments in public health genomics; these include policies to regulate access to personal genomic information, the need to enhance genetic literacy in both health professionals and the public, and challenges in ensuring that the benefits (and burdens) of genomic discoveries and applications are equitably distributed. We also note needs for future genomic research that integrates across basic and social sciences.
On a New Three-Step Class of Methods and Its Acceleration for Nonlinear Equations
Authors: Lotfi T. , Mahdiani K. , Noori Z. , Khaksar Haghani F. , Shateyi S.
Published: September 2014

A class of derivative-free methods without memory for approximating a simple zero of a nonlinear equation is presented. The proposed class uses four function evaluations per iteration with convergence order eight. Therefore, it is an optimal three-step scheme without memory based on Kung-Traub conjecture. Moreover, the proposed class has an accelerator parameter with the property that it can increase the convergence rate from eight to twelve without any new functional evaluations. Thus, we construct a with memory method that increases considerably efficiency index from81/4≈1.681to121/4≈1.861. Illustrations are also included to support the underlying theory.