bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormone receptor‐negative, thyroid transcription factor 1‐positive uterine and ovarian adenocarcinomas: report of a series of mesonephric‐like adenocarcinomas
Authors: McFarland Marie , Quick Charles M , McCluggage W Glenn
Published: October 2015

Aims

To report a series of uterine corpus (n = 7) and ovarian (n = 5) neoplasms which we believe probably represent mesonephric adenocarcinomas based on their characteristic morphology and immunophenotype.

Methods and results

All neoplasms exhibited a relatively constant and characteristic morphological appearance with an admixture of architectural patterns with small glands or tubules, some containing luminal eosinophilic colloid‐like material, typically predominating. Solid and papillary architectures were also often present. The nuclear features were characteristic with atypical angulated clear vesicular nuclei which often exhibited overlapping. All the tumours were ‘flat’ negative with oestrogen receptor and progesterone receptor and all except one exhibited nuclear staining with thyroid transcription factor 1 (TTF1), which was often diffuse. All tumours exhibited wild‐type staining with p53. CD10, calretinin and GATA binding protein 3 (GATA3) were positive in a variable proportion of the neoplasms.

Conclusions

We believe these neoplasms to represent mesonephric adenocarcinomas which have only rarely been reported to arise in the uterine corpus and never in the ovary. We recommend they be termed mesonephric‐like adenocarcinomas until their histogenesis is firmly established.
Virulence of entomopathogenic nematodes and their symbiotic bacteria against the hazelnut weevil Curculio nucum
Authors: Batalla‐Carrera L. , Morton A. , Garcia‐del‐Pino F.
Published: October 2015

The virulence of different entomopathogenic nematode strains of the families Steinernematidae and Heterorhabditidae, isolates from Catalonia (NE Iberian Peninsula), and their symbiotic bacteria was assessed with regard to the larvae and adults of the hazelnut weevil, Curculio nucum L. (Coleoptera: Curculionidae). The nematode strains screened included one Steinernema affine, five Steinernema feltiae, one Steinernema carpocapsae, one Steinernema sp. (a new species not yet described) and one Heterorhabditis bacteriophora. The pathogenicity of all the strains of nematodes was tested on larvae and only four of them on adults of the hazelnut weevil. Larval mortality ranged from 10% with S. affine to 79% with Steinernema sp. Adult mortality was higher in S. carpocapsae, achieving 100% adult weevil mortality. The pathogenicity of the symbiotic bacteria Xenorhabdus bovienii, X. kozodoii, X. nematophila and Photorhabdus luminescens was studied in larvae and adults of C. nucum. In the larvae, X. kozodoii showed a LT50 of 22.7 h, and in the adults, it was 20.5 h. All nematodes species except S. affine tested against larvae showed great potential to control the insect, whereas S. carpocapsae was the most effective for controlling adults.
Improved longitudinal resolution in tomographic diffractive microscopy with an ellipsoidal mirror
Authors: DING C. , TAN Z.
Published: October 2015

Tomographic diffractive microscopy is a technique, which is able to image transparent unstained samples with high resolution. The three‐dimensional distribution of the complex refractive index can be reconstructed quantitatively from the measured scattered fields under various illumination and detection angles, according to the diffraction tomography theorem. We propose a tomographic diffractive microscopy setup with an ellipsoidal mirror as the light collector. We demonstrate analytically and with numerical simulation that this approach permits to obtain images with drastically improved resolution.
Bias in Evaluating Erectile Function in Lifelong Premature Ejaculation Patients with the International Index of Erectile Function—5
Authors: Tang Y. , Wang Y. , Zhu H. , Jiang X. , Gan Y. , Yang J.
Published: October 2015

Introduction

Lifelong premature ejaculation (LPE) is the most important ejaculating dysfunction. Relatively little is known about erectile function in this population.

Aims

We attempted to evaluate the erectile function of patients with LPE using the International Index of Erectile Function—5 (IIEF-5) to determine if it is sufficiently reliable and accurate to make such an assessment.

Methods

A total of 406 patients with LPE were enrolled in our study. The participants voluntarily answered the Premature Ejaculation Diagnostic Tool (PEDT) and IIEF-5 questionnaires and underwent a full history evaluation and clinical examination by doctors. Their answers were converted into data analyzed by a statistic software.

Main Outcome Measures

The patients were diagnosed with LPE based on the diagnostic criteria and PEDT scores. The intravaginal ejaculation latency time was recorded according to patient self-reports. The IIEF-5 was used to evaluate their erectile function. Thorough history and clinical examination helped doctors make more correct diagnoses of erectile dysfunction (ED).

Results

Of the 406 patients, 70 (17.24%) patients had ED, as confirmed by doctors. IIEF-5 was accurate for the assessment of the erectile function of LPE patients when the cutoff was decreased to 15.5. Question 5 (1.34 ± 0.53) was the main reason for the drop in the total IIEF-5 score. Questions 1 and 5 shared low consistency with the other three IIEF-5 items, thus they lowered the reliability of the IIEF-5 scores. These questions created a confounding bias that decreased the diagnostic threshold of IIEF-5. However, they could not be removed from the IIEF-5 because they did not reduce its diagnostic accuracy in patients with LPE.

Conclusions

Bias from questions 1 and 5 lowered the reliability of the IIEF-5 scores; however, it did not reduce the diagnostic accuracy of the IIEF-5. The recommendation is to edit questions 1 and 5 when they are applied to populations with LPE.
Resolving Semantic Ambiguities in Sentences: Cognitive Processes and Brain Mechanisms
Authors: Vitello Sylvia , Rodd Jennifer M.
Published: October 2015

Functional MRI studies of how the brain processes sentences containing semantically ambiguous words have consistently implicated (i) the left inferior frontal gyrus (LIFG) and (ii) posterior regions of the left temporal lobe in processing high‐ambiguity sentences. This article reviews recent findings on this topic and relates them to (i) psycholinguistic theories about the underlying cognitive processes and (ii) general neuro‐cognitive accounts of the relevant brain regions. We suggest that the LIFG plays a general role in the cognitive control processes that are necessary to select contextually relevant meanings and to reinterpret sentences that were initially misunderstood, but it is currently unclear whether these control processes should best be characterised in terms of specific processes such as conflict resolution and controlled retrieval that are required for high‐ambiguity sentences, or whether its function is better characterised in terms of a more general set of ‘unification’ processes. In contrast to the relatively rapid progress that has been made in understanding the function of the LIFG, we suggest that the contribution of the posterior temporal lobe is less well understood and future work is needed to clarify its role in sentence comprehension.
Colony‐morphology screening uncovers a role for the Pseudomonas aeruginosa nitrogen‐related phosphotransferase system in biofilm formation
Authors: Cabeen Matthew T. , Leiman Sara A. , Losick Richard
Published: October 2015

Pseudomonas aeruginosa is an opportunistic human pathogen whose survival is aided by forming communities known as biofilms, in which cells are encased in a self‐produced matrix. We devised a mutant screen based on colony morphology to identify additional genes with previously unappreciated roles in biofilm formation. Our screen, which identified most known biofilm‐related genes, also uncovered PA14_16550 and PA14_69700, deletions of which abrogated and augmented biofilm formation respectively. We also identified ptsP, which encodes enzyme I of the nitrogen‐regulated phosphotransferase (PTSNtr) system, as being important for cyclic‐di‐GMP production and for biofilm formation. Further experiments showed that biofilm formation is hindered in the absence of phosphotransfer through the PTSNtr, but only in the presence of enzyme II (PtsN), the putative regulatory module of the PTSNtr. These results implicate unphosphorylated PtsN as a negative regulator of biofilm formation and establish one of the first known roles of the PTSNtr in P. aeruginosa.
Atomic force microscopy reveals a dual collagen‐binding activity for the staphylococcal surface protein SdrF
Authors: Herman‐Bausier Philippe , Dufrêne Yves F.
Published: October 2015

Staphylococcus epidermidis causes nosocomial infections by colonizing and forming biofilms on indwelling medical devices. This process involves specific interactions between cell wall‐anchored (CWA) proteins and host proteins adsorbed onto the biomaterial. Here, we have explored the molecular forces by which the S. epidermidis CWA protein serine‐aspartate repeat protein F (SdrF) binds to type I collagen, by means of advanced atomic force microscopy (AFM) techniques. Using single‐cell force spectroscopy, we found that SdrF mediates bacterial adhesion to collagen‐coated substrates through both weak and strong bonds. Single‐molecule force spectroscopy demonstrated that these bonds involve the A and B regions of SdrF, thus revealing that the protein is capable of dual ligand‐binding activity. Both weak and strong bonds showed high dissociation rates, indicating they are much less stable than those formed by the well‐characterized ‘dock, lock and latch’ mechanism. Collectively, our results show that CWA proteins can bind to ligands by novel mechanisms. We anticipate that AFM will greatly contribute to the identification of novel binding partners and binding mechanisms in staphylococcal CWA proteins.
Der Vampir im Warenhaus
Authors: Lubrich Naomi
Published: October 2015

In Émile Zolas Roman über ein Kaufhaus, Au Bonheur des Dames (1883), erscheint die Mode in Gestalt einer mysteriösen Allegorie: Sie wird als Vampir inszeniert, der ihren Ort, das titelgebende Warenhaus, heimsucht. Schaufensterauslagen sehen aus wie geopferte Jungfrauen; im Keller ruhen die Waren kalt und steif in Kartons wie in Särgen; wenn sie die Stoffe betasten, fühlen die Kundinnen ihr Blut pulsieren; in den Umkleidekabinen spielen sich orgiastische, sadomasochistische Szenen ab. Anhand historischer Karikaturen hat der Sozialwissenschaftler Eduard Fuchs (1906) gezeigt, daß Vampire, Teufel und andere Monstren lange als Referenzen der Mode dienten. Doch Zola hat in seinem Roman die notorische Figur des Vampirs nicht lediglich fortgeschrieben – er hat sie bekehrt. Denn die sinnlichen Reize seines Kaufhauses wirken durchaus therapeutisch. Sie befriedigen die Kundinnen und machen sie glücklich. Positiv wirkt sich das Geschäft auch auf die Beschäftigten aus, die aus ihm ihre Unabhängigkeit beziehen. Erscheint das „Paradies der Damen“ zunächst als unheimliches Freudenhaus, so entwickelt es sich zu einer realen Utopie: zur Bühne weiblicher Emanzipation.
Self‐esteem trajectories across 25 years and midlife intimate relations
Authors: JOHNSON MATTHEW D. , GALAMBOS NANCY L. , KRAHN HARVEY J.
Published: October 2015

Guided by a life‐span developmental systems approach, this study examined links between self‐esteem assessed over 25 years and adaptive interaction and relationship risk at midlife using data from 341 Canadian adults surveyed (or followed) from ages 18 to 43. Results showed higher self‐esteem at age 18 was associated with more adaptive interactions and lower perceived relationship risk at age 43. A more rapid increase in self‐esteem through the transition to adulthood into midlife (ages 18–43) was also associated with more frequent adaptive interactions and less relationship risk at age 43. These results held after accounting for potential confounding variables. This study is the first to demonstrate self‐esteem trajectories over a quarter century predict midlife intimate relationship functioning.
Sequential renal and bone marrow transplants in a child with Fanconi anemia
Authors: Vincent Carol L. , Primack William A. , Hipps John , Kasow Kimberly A.
Published: October 2015

FA is an autosomal recessive disorder characterized by small stature and renal abnormalities. FA can lead to progressive bone marrow failure, myelodysplastic syndrome, or acute leukemia. Using a multidisciplinary team approach, we managed a 3‐yr‐old boy with FA who simultaneously developed renal and hematopoietic failure. Because renal function was insufficient to support the conditioning regimen for HCT, we performed a deceased donor renal transplant in December 2012 prior to HCT with the known risk of graft‐versus‐graft rejection of the donor kidney. Seven months later he underwent allogeneic HCT. He obtained myeloid engraftment on day +11 and peripheral blood chimerism demonstrated all donor by day +21. He developed asymptomatic CMV reactivation and despite antirejection medications, mild skin graft‐versus‐host disease. He has maintained excellent renal function and remains transfusion independent with full hematopoietic recovery. He has not experienced any renal rejection episodes nor developed donor‐specific antibodies toward his renal donor. Peripheral blood chimerism remains completely HCT donor. He is clinically well, now greater than two and a half yr after renal transplant and two yr after HCT. The continuing close collaboration between the Pediatric Nephrology and Bone Marrow Transplant teams is a major factor in this successful outcome.
Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study
Authors: Brodwall Kristoffer , Leirgul Elisabeth , Greve Gottfried , Vollset Stein Emil , Holmstrøm Henrik , Tell Grethe S. , Øyen Nina
Published: October 2015

Background

The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation‐wide cohort study.

Methods

Information on all births registered in the Medical Birth Registry of Norway, 1994–2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR).

Results

Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early‐onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log‐linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early‐onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early‐onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8).

Conclusions

Early‐onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15‐fold higher if the mother was diagnosed with early‐onset preeclampsia, suggesting common aetiological factors for early‐onset preeclampsia and erroneous fetal heart development.
Caveat Emptor: What Do We Know about Public Administration Evidence and How Do We Know It?
Authors: Isett Kimberley R. , Head Brian W. , VanLandingham Gary
Published: October 2015

This article provides an overview of a new feature in Public Administration Review called Evidence in Public Administration. This feature was created to provide a space in which scholars and practitioners of public administration can meet to engage in a dialogue about evidence in public decision making. In this feature, we will shine a light on the evidence needed to make effective decisions and examinations of the evidence that currently exists for contemporary public sector efforts. We explicitly want to create a resource for both practitioners and scholars to consult when trying to find evidence on a particular topic and to know the limitations and parameters of that evidence. This article lays out the purpose, scope, and rationale for the feature, as well as a call to engage in this endeavor.
Understanding the (Re)Definition of Nationhood in French Cities: A Case of Multiple States and Multiple Republics
Authors: Downing Joseph
Published: October 2015

Both theoretical and empirical accounts of the nation have neglected the city as an arena for the (re)definition of national belonging. This article analyses contemporary France to advance theoretical and empirical insights into this process. Rather than presenting France as characterized by a Republican, assimilationist position, this article argues France is better characterized by competing ‘multiple republics’ with numerous definitions of nationhood. This article identifies three mechanisms of the multiple Republic. In Marseille, the municipal administration acts to redefine the secular character of the nation by bringing religion directly into local politics. This use of religion to redefine nationhood is also present in Lyon, with the key difference that it occurs in symbiosis with European governance. Finally, the Nanterre suburb of Paris demonstrates that the local state also uses notions of ethnicity to redefine the French nation as compatible with ethnic difference.
Neutralization of Interleukin‐17 Attenuates Cholestatic Liver Fibrosis in Mice
Authors: Zhang S. , Huang D. , Weng J. , Huang Y. , Liu S. , Zhang Q. , Li N. , Wen M. , Zhu G. , Lin F. , Gu W.
Published: October 2015

Anti‐inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. IL‐17 is critical in inflammation, but the role of IL‐17 in liver fibrosis has not yet been elucidated. In this study, we investigate the role of IL‐17 on bile duct ligation‐induced liver injury and fibrosis in C57BL/6 mice. Animals were sacrificed at designated times, and serum and liver tissues were collected for analysis of liver function and serum IL‐6, IL‐1β, tumour necrosis factor‐alpha (TNF‐α) and transforming growth factor‐β (TGF‐β) levels. IL‐17 blockade with anti‐IL‐17A mAb significantly improved liver function and decreased hepatocellular necrosis, pro‐inflammatory cytokines, neutrophils and macrophages influx. Furthermore, CD3 + and CD8 + lymphocytes, neutrophils and macrophages were found to express IL‐17, and neutrophils are the principal IL‐17‐producing cells after BDL‐induced liver injury. These data indicated that IL‐17 signal contributes to the pathogenesis of cholestatic liver injury and blocked of IL‐17 could potentially benefit patients with cholestatic liver disease.
Endocytosis of Ligand‐Activated Sphingosine 1‐Phosphate Receptor 1 Mediated by the Clathrin‐Pathway
Authors: Reeves Patrick M. , Kang Yuan‐Lin , Kirchhausen Tom
Published: October 2015

We show here that the G protein‐coupled receptor (GPCR) sphingosine 1‐phosphate receptor 1 (S1PR1) activated by its natural lipid ligand S1P or the synthetic agonist FTY720P is rapidly internalized by the clathrin‐dependent endocytic pathway. Depletion of activated S1PR1 from the cell surface relies on clathrin, its endocytic adaptor AP‐2 dynamin and the non‐visual βarrestin 1 and βarrestin 2, suggesting that activated S1PR1 is downregulated from the cell surface using the canonical GPCR entry route.
Improving Accuracy in Arrhenius Models of Cell Death: Adding a Temperature-Dependent Time Delay
Authors: Pearce John A.
Published: October 2015

The Arrhenius formulation for single-step irreversible unimolecular reactions has been used for many decades to describe the thermal damage and cell death processes. Arrhenius predictions are acceptably accurate for structural proteins, for some cell death assays, and for cell death at higher temperatures in most cell lines, above about 55 °C. However, in many cases—and particularly at hyperthermic temperatures, between about 43 and 55 °C—the particular intrinsic cell death or damage process under study exhibits a significant “shoulder” region that constant-rate Arrhenius models are unable to represent with acceptable accuracy. The primary limitation is that Arrhenius calculations always overestimate the cell death fraction, which leads to severely overoptimistic predictions of heating effectiveness in tumor treatment. Several more sophisticated mathematical model approaches have been suggested and show much-improved performance. But simpler models that have adequate accuracy would provide useful and practical alternatives to intricate biochemical analyses. Typical transient intrinsic cell death processes at hyperthermic temperatures consist of a slowly developing shoulder region followed by an essentially constant-rate region. The shoulder regions have been demonstrated to arise chiefly from complex functional protein signaling cascades that generate delays in the onset of the constant-rate region, but may involve heat shock protein activity as well. This paper shows that acceptably accurate and much-improved predictions in the simpler Arrhenius models can be obtained by adding a temperature-dependent time delay. Kinetic coefficients and the appropriate time delay are obtained from the constant-rate regions of the measured survival curves. The resulting predictions are seen to provide acceptably accurate results while not overestimating cell death. The method can be relatively easily incorporated into numerical models. Additionally, evidence is presented to support the application of compensation law behavior to the cell death processes—that is, the strong correlation between the kinetic coefficients, ln{A} and Ea, is confirmed.
Hybrid molecular beam epitaxy for the growth of stoichiometric BaSnO3
Authors: Prakash Abhinav , Dewey John , Yun Hwanhui , Jeong Jong Seok , Mkhoyan K. Andre , Jalan Bharat
Published: October 2015

Owing to its high room-temperature electron mobility and wide bandgap, BaSnO3 has recently become of significant interest for potential room-temperature oxide electronics. A hybrid molecular beam epitaxy (MBE) approach for the growth of high-quality BaSnO3 films is developed in this work. This approach employs hexamethylditin as a chemical precursor for tin, an effusion cell for barium, and a radio frequency plasma source for oxygen. BaSnO3 films were thus grown on SrTiO3 (001) and LaAlO3 (001) substrates. Growth conditions for stoichiometric BaSnO3 were identified. Reflection high-energy electron diffraction (RHEED) intensity oscillations, characteristic of a layer-by-layer growth mode were observed. A critical thickness of ∼1 nm for strain relaxation was determined for films grown on SrTiO3 using in situ RHEED. Scanning transmission electron microscopy combined with electron energy-loss spectroscopy and energy dispersive x-ray spectroscopy confirmed the cube-on-cube epitaxy and composition. The importance of precursor chemistry is discussed in the context of the MBE growth of BaSnO3.
CAN-flip: A Pilot Gymnastics Program for Children With Cerebral Palsy
Authors: Cook Olivia , Frost Gail , Twose Donna , Wallman Linda , Falk Bareket , Galea Victoria , Adkin Allan , Klentrou Panagiota
Published: October 2015

This pilot study examined whether an adapted gymnastics program, CAN-flip, could be a feasible activity for children with cerebral palsy (CP) leading to improvements in muscle fitness, motor performance, and physical self-perception. Four girls and 1 boy (9.8 ± 1.3 yr) with CP participated in this multiple-baseline acrosssubjects design and were randomly assigned to start either the 6-wk gymnastics or the 6-wk control period. Muscle strength, neuromuscular activation, range of motion, gross motor performance, balance, and physical self-perception were assessed at baseline, after the first 6-wk period, and at the conclusion of the study. The gymnastics program comprised two 1-hr individualized classes per week. All participants were able to complete the gymnastics classes without injury and showed improvement in specific gymnastics skills. In addition, 3 of the 5 participants registered for regular gymnastics classes after the study, demonstrating the program’s usability as a link to inclusive gymnastic classes.
Dying to impress the immune system
Authors: Mueller Kristen L.
Published: October 2015

Active signaling in dying cells determines their immunogenicity.
Understanding empathy
Authors: Gough Nancy R.
Published: October 2015

An opioid antagonist blocks both placebo-induced analgesia and placebo-induced reduction in empathy for pain of another.
Molecule Targeting Glucosyltransferase Inhibits Streptococcus mutans Biofilm Formation and Virulence
Authors: Ren Zhi , Cui Tao , Zeng Jumei , Chen Lulu , Zhang Wenling , Xu Xin , Cheng Lei , Li Mingyun , Li Jiyao , Zhou Xuedong , Li Yuqing
Published: October 2015

Dental plaque biofilms are responsible for numerous chronic oral infections and cause a severe health burden. Many of these infections cannot be eliminated, as the bacteria in the biofilms are resistant to the host's immune defenses and antibiotics. There is a critical need to develop new strategies to control biofilm-based infections. Biofilm formation inStreptococcus mutansis promoted by major virulence factors known as glucosyltransferases (Gtfs), which synthesize adhesive extracellular polysaccharides (EPS). The current study was designed to identify novel molecules that target Gtfs, thereby inhibitingS. mutansbiofilm formation and having the potential to prevent dental caries. Structure-based virtual screening of approximately 150,000 commercially available compounds against the crystal structure of the glucosyltransferase domain of the GtfC protein fromS. mutansresulted in the identification of a quinoxaline derivative, 2-(4-methoxyphenyl)-N-(3-{[2-(4-methoxyphenyl)ethyl]imino}-1,4-dihydro-2-quinoxalinylidene)ethanamine, as a potential Gtf inhibitor.In vitroassays showed that the compound was capable of inhibiting EPS synthesis and biofilm formation inS. mutansby selectively antagonizing Gtfs instead of by killing the bacteria directly. Moreover, thein vivoanti-caries efficacy of the compound was evaluated in a rat model. We found that the compound significantly reduced the incidence and severity of smooth and sulcal-surface cariesin vivowith a concomitant reduction in the percentage ofS. mutansin the animals' dental plaque (P< 0.05). Taken together, these results represent the first description of a compound that targets Gtfs and that has the capacity to inhibit biofilm formation and the cariogenicity ofS. mutans.
Antimicrobial Susceptibilities of Aerobic and Facultative Gram-Negative Bacilli from Intra-abdominal Infections in Patients from Seven Regions in China in 2012 and 2013
Authors: Zhang Hui , Yang Qiwen , Liao Kang , Ni Yuxing , Yu Yunsong , Hu Bijie , Sun Ziyong , Huang Wenxiang , Wang Yong , Wu Anhua , Feng Xianju , Luo Yanping , Hu Zhidong , Chu Yunzhuo , Chen Shulan , Cao Bin , Su Jianrong , Gui Bingdong , Duan Qiong , Zhang Shufang , Shao Haifeng , Kong Haishen , Badal Robert E. , Xu Yingchun
Published: October 2015

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum β-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused byEscherichia coli(46.3%) andKlebsiella pneumoniae(19.7%). Rates of ESBL-producingE. coli(P= 0.031),K. pneumoniae(P= 0.017), andProteus mirabilis(P= 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective againstP. mirabilis(<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptibleE. coliandK. pneumoniaewere higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused byE. coliorK. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.
Genomic Characteristics of NDM-Producing Enterobacteriaceae Isolates in Australia and Their
bla
NDM
Genetic Contexts
Authors: Wailan Alexander M. , Paterson David L. , Kennedy Karina , Ingram Paul R. , Bursle Evan , Sidjabat Hanna E.
Published: October 2015

bla
NDM
has been reported in different
Enterobacteriaceae
species and on numerous plasmid replicon types (Inc). Plasmid replicon typing, in combination with genomic characteristics of the bacterial host (e.g., sequence typing), is used to infer the spread of antimicrobial resistance determinants between genetically unrelated bacterial hosts. The genetic context of
bla
NDM
is heterogeneous. In this study, we genomically characterized 12 NDM-producing
Enterobacteriaceae
isolated in Australia between 2012 and 2014:
Escherichia coli
(
n
= 6),
Klebsiella pneumoniae
(
n
= 3),
Enterobacter cloacae
(
n
= 2) and
Providencia rettgeri
(
n
= 1). We describe their
bla
NDM
genetic contexts within Tn
125
, providing insights into the acquisition of
bla
NDM
into
Enterobacteriaceae
. IncFII-type (
n
= 7) and IncX3 (
n
= 4) plasmids were the most common plasmid types found. The IncHI1B (
n
= 1) plasmid was also identified. Five different
bla
NDM
genetic contexts were identified, indicating four particular plasmids with specific
bla
NDM
genetic contexts (NGCs), three of which were IncFII plasmids (FII-A to -C). Of note, the
bla
NDM
genetic context of
P. rettgeri
was not conjugative. Epidemiological links between our NDM-producing
Enterobacteriaceae
were established by their acquisition of these five particular plasmid types. The combination of different molecular and genetic characterization methods allowed us to provide insight into the spread of plasmids transmitting
bla
NDM
.
Impact of a Cross-Kingdom Signaling Molecule of Candida albicans on Acinetobacter baumannii Physiology
Authors: Kostoulias Xenia , Murray Gerald L. , Cerqueira Gustavo M. , Kong Jason B. , Bantun Farkad , Mylonakis Eleftherios , Khoo Chen Ai , Peleg Anton Y.
Published: October 2015

Multidrug-resistant (MDR)
Acinetobacter baumannii
is an opportunistic human pathogen that has become highly problematic in the clinical environment. Novel therapies are desperately required. To assist in identifying new therapeutic targets, the antagonistic interactions between
A. baumannii
and the most common human fungal pathogen,
Candida albicans
, were studied. We have observed that the
C. albicans
quorum-sensing molecule, farnesol, has cross-kingdom interactions, affecting the viability of
A. baumannii
. To gain an understanding of its mechanism, the transcriptional profile of
A. baumannii
exposed to farnesol was examined. Farnesol caused dysregulation of a large number of genes involved in cell membrane biogenesis, multidrug efflux pumps (AcrAB-like and AdeIJK-like), and
A. baumannii
virulence traits such as biofilm formation (
csuA
,
csuB
, and
ompA
) and motility (
pilZ
and
pilH
). We also observed a strong induction in genes involved in cell division (
minD
,
minE
,
ftsK
,
ftsB
, and
ftsL
). These transcriptional data were supported by functional assays showing that farnesol disrupts
A. baumannii
cell membrane integrity, alters cell morphology, and impairs virulence characteristics such as biofilm formation and twitching motility. Moreover, we showed that
A. baumannii
uses efflux pumps as a defense mechanism against this eukaryotic signaling molecule. Owing to its effects on membrane integrity, farnesol was tested to see if it potentiated the activity of the membrane-acting polymyxin antibiotic colistin. When coadministered, farnesol increased sensitivity to colistin for otherwise resistant strains. These data provide mechanistic understanding of the antagonistic interactions between diverse pathogens and may provide important insights into novel therapeutic strategies.
Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage
Authors: Sanchez Ana B. , Varano Giuseppe P. , de Rozieres Cyrus M. , Maung Ricky , Catalan Irene C. , Dowling Cari C. , Sejbuk Natalia E. , Hoefer Melanie M. , Kaul Marcus
Published: October 2015

HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.
RNA Helicase Important for Listeria monocytogenes Hemolytic Activity and Virulence Factor Expression
Authors: Netterling Sakura , Bäreclev Caroline , Vaitkevicius Karolis , Johansson Jörgen
Published: October 2015

RNA helicases have been shown to be important for the function of RNA molecules at several levels, although their putative involvement in microbial pathogenesis has remained elusive. We have previously shown that
Listeria monocytogenes
DExD-box RNA helicases are important for bacterial growth, motility, ribosomal maturation, and rRNA processing. We assessed the importance of the RNA helicase Lmo0866 (here named CshA) for expression of virulence traits. We observed a reduction in hemolytic activity in a strain lacking CshA compared to the wild type. This phenomenon was less evident in strains lacking other RNA helicases. The reduced hemolysis was accompanied by lower expression of major listerial virulence factors in the Δ
cshA
strain, mainly listeriolysin O, but also to some degree the actin polymerizing factor ActA. Reduced expression of these virulence factors in the strain lacking CshA did not, however, correlate with a decreased level of the virulence regulator PrfA. When combining the Δ
cshA
knockout with a mutation creating a constitutively active PrfA protein (PrfA*), the effect of the Δ
cshA
knockout on LLO expression was negated. These data suggest a role for the RNA helicase CshA in posttranslational activation of PrfA. Surprisingly, although the expression of several virulence factors was reduced, the Δ
cshA
strain did not demonstrate any reduced ability to infect nonphagocytic cells compared to the wild-type strain.
The Trk Potassium Transporter Is Required for RsmB-Mediated Activation of Virulence in the Phytopathogen Pectobacterium wasabiae
Authors: Valente Rita S. , Xavier Karina B.
Published: October 2015

Pectobacterium wasabiae
(previously known as
Erwinia carotovora
) is an important plant pathogen that regulates the production of plant cell wall-degrading enzymes through an
N
-acyl homoserine lactone-based quorum sensing system and through the GacS/GacA two-component system (also known as ExpS/ExpA). At high cell density, activation of GacS/GacA induces the expression of RsmB, a noncoding RNA that is essential for the activation of virulence in this bacterium. A genetic screen to identify regulators of RsmB revealed that mutants defective in components of a putative Trk potassium transporter (
trkH
and
trkA
) had decreased
rsmB
expression. Further analysis of these mutants showed that changes in potassium concentration influenced
rsmB
expression and consequent tissue damage in potato tubers and that this regulation required an intact Trk system. Regulation of
rsmB
expression by potassium via the Trk system occurred even in the absence of the GacS/GacA system, demonstrating that these systems act independently and are both required for full activation of RsmB and for the downstream induction of virulence in potato infection assays. Overall, our results identified potassium as an essential environmental factor regulating the Rsm system, and the consequent induction of virulence, in the plant pathogen
P. wasabiae
.

IMPORTANCE
Crop losses from bacterial diseases caused by pectolytic bacteria are a major problem in agriculture. By studying the regulatory pathways involved in controlling the expression of plant cell wall-degrading enzymes in
Pectobacterium wasabiae
, we showed that the Trk potassium transport system plays an important role in the regulation of these pathways. The data presented further identify potassium as an important environmental factor in the regulation of virulence in this plant pathogen. We showed that a reduction in virulence can be achieved by increasing the extracellular concentration of potassium. Therefore, this work highlights how elucidation of the mechanisms involved in regulating virulence can lead to the identification of environmental factors that can influence the outcome of infection.
Identification of the PhoB Regulon and Role of PhoU in the Phosphate Starvation Response of Caulobacter crescentus
Authors: Lubin Emma A. , Henry Jonathan T. , Fiebig Aretha , Crosson Sean , Laub Michael T.
Published: October 2015

An ability to sense and respond to changes in extracellular phosphate is critical for the survival of most bacteria. For
Caulobacter crescentus
, which typically lives in phosphate-limited environments, this process is especially crucial. Like many bacteria,
Caulobacter
responds to phosphate limitation through a conserved two-component signaling pathway called PhoR-PhoB, but the direct regulon of PhoB in this organism is unknown. Here we used chromatin immunoprecipitation-DNA sequencing (ChIP-Seq) to map the global binding patterns of the phosphate-responsive transcriptional regulator PhoB under phosphate-limited and -replete conditions. Combined with genome-wide expression profiling, our work demonstrates that PhoB is induced to regulate nearly 50 genes under phosphate-starved conditions. The PhoB regulon is comprised primarily of genes known or predicted to help
Caulobacter
scavenge for and import inorganic phosphate, including 15 different membrane transporters. We also investigated the regulatory role of PhoU, a widely conserved protein proposed to coordinate phosphate import with expression of the PhoB regulon by directly modulating the histidine kinase PhoR. However, our studies show that it likely does not play such a role in
Caulobacter
, as PhoU depletion has no significant effect on PhoB-dependent gene expression. Instead, cells lacking PhoU exhibit striking accumulation of large polyphosphate granules, suggesting that PhoU participates in controlling intracellular phosphate metabolism.

IMPORTANCE
The transcription factor PhoB is widely conserved throughout the bacterial kingdom, where it helps organisms respond to phosphate limitation by driving the expression of a battery of genes. Most of what is known about PhoB and its target genes is derived from studies of
Escherichia coli
. Our work documents the PhoB regulon in
Caulobacter crescentus
, and comparison to the regulon in
E. coli
reveals significant differences, highlighting the evolutionary plasticity of transcriptional responses driven by highly conserved transcription factors. We also demonstrated that the conserved protein PhoU, which is implicated in bacterial persistence, does not regulate PhoB activity, as previously suggested. Instead, our results favor a model in which PhoU affects intracellular phosphate accumulation, possibly through the high-affinity phosphate transporter.
Dispersal from Microbial Biofilms
Authors: Barraud Nicolas , Kjelleberg Staffan , Rice Scott A.
Published: October 2015

One common feature of biofilm development is the active dispersal of cells from the mature biofilm, which completes the biofilm life cycle and allows for the subsequent colonization of new habitats. Dispersal is likely to be critical for species survival and appears to be a precisely regulated process that involves a complex network of genes and signal transduction systems. Sophisticated molecular mechanisms control the transition of sessile biofilm cells into dispersal cells and their coordinated detachment and release in the bulk liquid. Dispersal cells appear to be specialized and exhibit a unique phenotype different from biofilm or planktonic bacteria. Further, the dispersal population is characterized by a high level of heterogeneity, reminiscent of, but distinct from, that in the biofilm, which could potentially allow for improved colonization under various environmental conditions. Here we review recent advances in characterizing the molecular mechanisms that regulate biofilm dispersal events and the impact of dispersal in a broader ecological context. Several strategies that exploit the mechanisms controlling biofilm dispersal to develop as applications for biofilm control are also presented.
Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya
Authors: Brooker Simon J , Mwandawiro Charles S , Halliday Katherine E , Njenga Sammy M , Mcharo Carlos , Gichuki Paul M , Wasunna Beatrice , Kihara Jimmy H , Njomo Doris , Alusala Dorcas , Chiguzo Athuman , Turner Hugo C , Teti Caroline , Gwayi-Chore Claire , Nikolay Birgit , Truscott James E , Hollingsworth T Déirdre , Balabanova Dina , Griffiths Ulla K , Freeman Matthew C , Allen Elizabeth , Pullan Rachel L , Anderson Roy M
Published: October 2015

Introduction

In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal?

Methods and analysis

Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision—termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence ofAscaris lumbricoidesandTrichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system.

Ethics and dissemination

Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a dedicated web site.

Trial registration number

NCT02397772.
Expectations and perceptions of care among victims of sexual assault who first seek care from emergency, primary care and gynaecological doctors
Authors: Denis Céline , Seyller Marie , Chariot Patrick
Published: October 2015

Background

The role of health professionals is pivotal in providing support to victims of sexual assault. Our aim was to identify patient expectations of doctors after a sexual assault and to assess how they rated the doctors’ responses.

Methods

We conducted a prospective observational study (May 2010–December 2012) involving victims of sexual assault (age >10 years) in a Department of Forensic Medicine near Paris, France. The patients included were those who had first sought care from a doctor prior to arriving at the Department of Forensic Medicine. Victims were asked by questionnaire and interviewed by the forensic physician about medical consultations before arriving at the Department, their expectations about those consultations and their feelings about the quality of support provided. Each patient's feelings were rated on a five-point scale.

Results

Among 1112 victims reporting sexual assault, 232 previously had a consultation, and were included in the study. Patients expected trauma care in 44% of cases, and received it in 40% (p=0.42), psychological support in 31% of cases, and received it in 21% (p=0.02), gynaecological care in 28%, and received it in 31% (p=0.52) and forensic support in 21%, and received it in 54% (p<0.001). The patients more frequently considered the provided support to be crucial when they received both forensic support and trauma care, psychological support or gynaecological care than when they only received trauma care, psychological support or gynaecological care (25% vs 3%, p=0.001).

Conclusions

Physicians who are the first medical provider to see a patient after a sexual assault often fail to meet patients’ expectations, particularly with regard to psychological support. Care received was perceived as best when physicians provided both forensic support and trauma care, psychological support or gynaecological care.