bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro
Antifungal Susceptibility Testing of Candida Isolates with the EUCAST Methodology, a New Method for ECOFF Determination
Authors: Meletiadis J. , Curfs-Breuker I. , Meis J. F. , Mouton J. W. 
Published: January 2017

ABSTRACT

The
in vitro
susceptibilities of 1,099 molecularly identified clinical
Candida
isolates against 8 antifungal drugs were determined using the EUCAST microdilution method. A new simple, objective, and mathematically solid method for determining epidemiological cutoff values (ECOFFs) was developed by derivatizing the MIC distribution and determining the derivatized ECOFF (dECOFF) as the highest MIC with the maximum second derivative. The dECOFFs were similar (95% agreement within 1 dilution) to the EUCAST ECOFFs. Overall, low non-wild-type/resistance rates were found. The highest rates were found for azoles with
C. parapsilosis
(2.7 to 9.8%),
C. albicans
(7%), and
C. glabrata
(1.7 to 2.3%) and for echinocandins with
C. krusei
(3.3%),
C. albicans
(1%), and
C. tropicalis
(1.7%).
Synergistic Interactions of MmpL3 Inhibitors with Antitubercular Compounds
In Vitro
Authors: Li Wei , Sanchez-Hidalgo Andrea , Jones Victoria , de Moura Vinicius Calado Nogueira , North E. Jeffrey , Jackson Mary 
Published: January 2017

ABSTRACT

A number of inhibitors of the essential
Mycobacterium tuberculosis
mycolic acid transporter, MmpL3, are currently under development as potential novel antituberculosis agents. Using the checkerboard method to study the interaction profiles of various antituberculosis drugs or experimental compounds with two different chemotypes inhibiting this transporter (indolcarboxamides and adamantyl ureas), we showed that MmpL3 inhibitors act synergistically with rifampin, bedaquiline, clofazimine, and β-lactams.
Targeting Alpha Toxin To Mitigate Its Lethal Toxicity in Ferret and Rabbit Models of Staphylococcus aureus Necrotizing Pneumonia
Authors: Diep Binh An , Hilliard Jamese J. , Le Vien T. M. , Tkaczyk Christine , Le Hoan N. , Tran Vuvi G. , Rao Renee L. , Dip Etyene Castro , Pereira-Franchi Eliane P. , Cha Paulyn , Jacobson Scott , Broome Rosemary , Cheng Lily I. , Weiss William , Prokai Laszlo , Nguyen Vien , Stover C. Ken , Sellman Bret R. 
Published: January 2017

ABSTRACT

The role broad-spectrum antibiotics play in the spread of antimicrobial resistance, coupled with their effect on the healthy microbiome, has led to advances in pathogen-specific approaches for the prevention or treatment of serious bacterial infections. One approach in clinical testing is passive immunization with a monoclonal antibody (MAb) targeting alpha toxin for the prevention or treatment of
Staphylococcus aureus
pneumonia. Passive immunization with the human anti-alpha toxin MAb, MEDI4893*, has been shown to improve disease outcome in murine
S. aureus
pneumonia models. The species specificity of some
S. aureus
toxins necessitates testing anti-
S. aureus
therapeutics in alternate species. We developed a necrotizing pneumonia model in ferrets and utilized an existing rabbit pneumonia model to characterize MEDI4893* protective activity in species other than mice. MEDI4893* prophylaxis reduced disease severity in ferret and rabbit pneumonia models against both community-associated methicillin-resistant
S. aureus
(MRSA) and hospital-associated MRSA strains. In addition, adjunctive treatment of MEDI4893* with either vancomycin or linezolid provided enhanced protection in rabbits relative to the antibiotics alone. These results confirm that MEDI4893 is a promising candidate for immunotherapy against
S. aureus
pneumonia.
Survival of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 in Human Blood
Authors: DeLeo Frank R. , Kobayashi Scott D. , Porter Adeline R. , Freedman Brett , Dorward David W. , Chen Liang , Kreiswirth Barry N. 
Published: January 2017

ABSTRACT

Klebsiella pneumoniae
is a prominent cause of nosocomial infections worldwide. Bloodstream infections caused by carbapenem-resistant
K. pneumoniae
, including the epidemic lineage known as multilocus sequence type 258 (ST258), are difficult to treat, and the rate of mortality from such infections is high. Thus, it is imperative that we gain a better understanding of host defense against this pathogen as a step toward developing novel therapies. Here we tested the hypothesis that the resistance of ST258 to bactericidal components of human blood, such as serum complement, is linked to virulence capacity in the context of bacteremia. There was significant variance in the survival of ST258 clinical isolates in heparinized human blood or normal human serum. The rate of survival of ST258 isolates in human blood was, in general, similar to that in normal human serum, suggesting a prominent role for complement (rather than leukocytes) in the healthy host defense against ST258 isolates and related organisms. Indeed, deposition of serum complement—the C5b to C9 (C5b-C9) membrane attack complex—onto the surface of ST258 isolates accompanied serum bactericidal activity. Human serum treated with pharmacological inhibitors of complement, depleted of antibody, or heated at 56°C for 30 min had significantly reduced or absent bactericidal activity. In contrast to heparinized blood from humans, that from BALB/c mice lacked bactericidal activity toward the ST258 isolates tested, but the virulence of these ST258 isolates in a mouse bacteremia model was inexplicably limited. Our data highlight the importance of the complement system in host defense against ST258 bacteremia, and we propose that there is the potential to enhance complement-mediated bactericidal activity using an antibody-based approach.
Fluorescent Lead(IV) Sulfide Nanoparticles Synthesized by Idiomarina sp. Strain PR58-8 for Bioimaging Applications
Authors: Srivastava Pallavee , Kowshik Meenal 
Published: January 2017

ABSTRACT

The fabrication of nanoparticles by microorganisms presents a “green” method for generating biocompatible nanomaterials. We discovered the intracellular biosynthesis of fluorescent lead(IV) sulfide nanoparticles by the moderate halophile,
Idiomarina
sp. strain PR58-8. The bacterium tolerated up to 8 mM Pb(NO
3
)
2
during growth. Non-protein thiols dose-dependently increased in response to metal exposure, which suggests they are involved in the growth of PbS
2
crystals and lead detoxification. Using X-ray diffraction, transmission electron microscopy (TEM), high-resolution TEM, and energy dispersive analysis of X-rays, the nanoparticles were characterized as spherical β-PbS
2
nanoparticles (PbS
2
NPs) with a tetragonal crystal lattice, a crystallite domain size of 2.38 nm, and an interplanar distance of 0.318 nm. A narrow symmetric emission spectrum with a Gaussian distribution and an emission maximum at 386 nm was obtained when the particles were excited at 570 nm. The PbS
2
NPs exhibited a large Stokes' shift (8,362 cm
−1
) and a relatively high quantum yield (67%). These properties, along with fluorescence that was maintained in various microenvironments and their biocompatibility, make these nanoparticles excellent candidates for bioimaging. The particles were internalized by HeLa cells and evenly distributed within the cytoplasm, exhibiting their potential for
in situ
bioimaging applications. The “as-synthesized” lead(IV) sulfide nanoparticles may provide expanded opportunities for targeted bioimaging via modifying the surface of the particles.

IMPORTANCE
This article reports the intracellular synthesis of fluorescent lead(IV) sulfide nanoparticles (PbS
2
NPs) by a microorganism. All previous reports on the microbial synthesis of lead-based nanoparticles are on lead(II) sulfide that exhibits near-infrared fluorescence, requiring expensive instrumentation for bioimaging. Bioimaging using PbS
2
NPs can be achieved using routine epifluorescence microscopes, as it fluoresces in the visible range. The research on PbS
2
nanoparticles to date is on their chemical synthesis employing toxic precursors, extreme pH, pressure, and temperature, resulting in cytotoxic products. In this context, the synthesis of PbS
2
nanoparticles by
Idiomarina
sp. strain PR58-8, described in this work, occurs at ambient temperature and pressure and results in the generation of biocompatible nanoparticles with no hazardous by-products. The excellent fluorescence properties that these particles exhibit, as well as their abilities to easily penetrate the cells and evenly distribute within the cytoplasm, make them exceptional candidates for bioimaging applications. This study demonstrated the synthesis and fluorescence bioimaging application of microbially synthesized PbS
2
nanoparticles.
Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques
Authors: Ellis Amy , Balgeman Alexis , Rodgers Mark , Updike Cassaundra , Tomko Jaime , Maiello Pauline , Scanga Charles A. , O'Connor Shelby L. 
Published: January 2017

ABSTRACTNonhuman primates can be used to study host immune responses toMycobacterium tuberculosis. Mauritian cynomolgus macaques (MCMs) are a unique group of animals that have limited major histocompatibility complex (MHC) genetic diversity, such that MHC-identical animals can be infected withM. tuberculosis. Two MCMs homozygous for the relatively common M1 MHC haplotype were bronchoscopically infected with 41 CFU of theM. tuberculosisErdman strain. Four other MCMs, which had at least one copy of the M1 MHC haplotype, were infected with a lower dose of 3 CFUM. tuberculosis. All animals mounted similar T-cell responses to CFP-10 and ESAT-6. Two epitopes in CFP-10 were characterized, and the MHC class II alleles restricting them were determined. A third epitope in CFP-10 was identified but exhibited promiscuous restriction. The CFP-10 and ESAT-6 antigenic regions targeted by T cells in MCMs were comparable to those seen in cases of humanM. tuberculosisinfection. Our data lay the foundation for generating tetrameric molecules to study epitope-specific CD4 T cells inM. tuberculosis-infected MCMs, which may guide future testing of tuberculosis vaccines in nonhuman primates.
The Fatty Acid Regulator FadR Influences the Expression of the Virulence Cascade in the El Tor Biotype of Vibrio cholerae by Modulating the Levels of ToxT via Two Different Mechanisms
Authors: Kovacikova Gabriela , Lin Wei , Taylor Ronald K. , Skorupski Karen 
Published: January 2017

ABSTRACT

FadR is a master regulator of fatty acid (FA) metabolism that coordinates the pathways of FA degradation and biosynthesis in enteric bacteria. We show here that a Δ
fadR
mutation in the El Tor biotype of
Vibrio cholerae
prevents the expression of the virulence cascade by influencing both the transcription and the posttranslational regulation of the master virulence regulator ToxT. FadR is a transcriptional regulator that represses the expression of genes involved in FA degradation, activates the expression of genes involved in unsaturated FA (UFA) biosynthesis, and also activates the expression of two operons involved in saturated FA (SFA) biosynthesis. Since FadR does not bind directly to the
toxT
promoter, we determined whether the regulation of any of its target genes indirectly influenced ToxT. This was accomplished by individually inserting a double point mutation into the FadR-binding site in the promoter of each target gene, thereby preventing their activation or repression. Although preventing FadR-mediated activation of
fabA
, which encodes the enzyme that carries out the first step in UFA biosynthesis, did not significantly influence either the transcription or the translation of ToxT, it reduced its levels and prevented virulence gene expression. In the mutant strain unable to carry out FadR-mediated activation of
fabA
, expressing
fabA
ectopically restored the levels of ToxT and virulence gene expression. Taken together, the results presented here indicate that
V. cholerae
FadR influences the virulence cascade in the El Tor biotype by modulating the levels of ToxT via two different mechanisms.

IMPORTANCE
Fatty acids (FAs) play important roles in membrane lipid homeostasis and energy metabolism in all organisms. In
Vibrio cholerae
, the causative agent of the acute intestinal disease cholera, they also influence virulence by binding into an N-terminal pocket of the master virulence regulator, ToxT, and modulating its activity. FadR is a transcription factor that coordinately controls the pathways of FA degradation and biosynthesis in enteric bacteria. This study identifies a new link between FA metabolism and virulence in the El Tor biotype by showing that FadR influences both the transcription and posttranslational regulation of the master virulence regulator ToxT by two distinct mechanisms.
Recurrent hierarchical patterns and the fractal distribution of fossil localities
Authors: Plotnick Roy E. 
Published: January 2017

Abstract
Understanding the spatial structure of fossil localities is critical for interpreting Earth system processes based on their geographic distribution. Coordinates of marine and terrestrial sites in the conterminous United States for 17 time bins were analyzed using point pattern statistics. Lacunarity analysis shows that the spatial distributions of sites are fractal for almost every studied interval, indicating that clumping of localities occurs at multiple scales. Random hierarchical multiplicative processes provide a theoretical null model for the distribution of collecting sites, consistent with their occurrence being a complex product of numerous biological, geological, and anthropogenic processes acting at many spatial and temporal scales. Mechanistic models for the formation, preservation, and exposure of fossil localities and other geologic entities can be tested using point pattern and related spatial statistics.
Protocol of a randomised controlled, open-label trial of ex vivo normothermic perfusion versus static cold storage in donation after circulatory death renal transplantation
Authors: Hosgood Sarah A , Saeb-Parsy Kourosh , Wilson Colin , Callaghan Christopher , Collett Dave , Nicholson Michael L 
Published: January 2017

IntroductionEx vivo normothermic perfusion (EVNP) is a novel technique that reconditions the kidney and restores renal function prior to transplantation. Phase I data from a series of EVNP in extended criteria donor kidneys have established the safety and feasibility of the technique in clinical practice.Methods and analysisThis is a UK-based phase II multicentre randomised controlled trial to assess the efficacy of EVNP compared with the conventional static cold storage technique in donation after circulatory death (DCD) kidney transplantation. 400 patients receiving a kidney from a DCD donor (categories III and IV, controlled) will be recruited into the study. On arrival at the transplant centre, kidneys will be randomised to receive either EVNP (n=200) or remain in static cold storage (n=200). Kidneys undergoing EVNP will be perfused with an oxygenated packed red cell solution at near body temperature for 60 min prior to transplantation. The primary outcome measure will be determined by rates of delayed graft function (DGF) defined as the need for dialysis in the first week post-transplant. Secondary outcome measures include incidences of primary non-function, the duration of DGF, functional DGF defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplant, creatinine reduction ratio days 2 and 5, length of hospital stay, rates of biopsy-proven acute rejection, serum creatinine and estimated glomerular filtration rate at 1, 3, 6 and 12 months post-transplant and patient and allograft survival. The EVNP assessment score will be recorded and the level of fibrosis and inflammation will also be measured using tissue, blood and urine samples. Ethics and dissemination. The study has been approved by the National Health Service (NHS) Health Research Authority Research Ethics Committee. The results are expected to be published in 2020.Trial registration numberISRCTN15821205; Pre-results.
E-therapies in England for stress, anxiety or depression: what is being used in the NHS? A survey of mental health services
Authors: Bennion M R , Hardy G , Moore R K , Millings A 
Published: January 2017

ObjectiveTo document the range of web and smartphone apps used and recommended for stress, anxiety or depression by the National Health Service (NHS) in England.DesignThe study was conducted using Freedom of Information (FOI) requests and systematic website searches.Data sourcesData were collected via FOI requests to NHS services between 13 February 2015 and 31 March 2015, and searches conducted on NHS apps library websites between 26 March 2015 and 2 November 2015.Data collection/extraction methodsData were compiled from responses to: (1) FOI requests sent to all Improving Access to Psychological Therapies (IAPT) services and NHS Mental Health Trusts in England and (2) NHS apps library search results.ResultsA total of 61 (54.95%) out of the then 111 IAPT service providers responded, accounting for 191 IAPT services, and all 51 of the then NHS Mental Health Trusts responded. The results were that 13 different web apps and 35 different smartphone apps for depression, anxiety or stress were available through either referral services or the online NHS Apps Libraries. The apps used and recommended vary by area and by point of access (online library/IAPT/trust).ConclusionsFuture research is required to establish the evidence base for the apps that are being used in the NHS in England. There is a need for service provision to be based on evidence and established guidelines.
Vection Latency Is Reduced by Bone-Conducted Vibration and Noisy Galvanic Vestibular Stimulation
Authors: Weech Séamas , Troje Nikolaus F. 
Published: January 2017

Studies of the illusory sense of self-motion elicited by a moving visual surround (‘vection’) have revealed key insights about how sensory information is integrated. Vection usually occurs after a delay of several seconds following visual motion onset, whereas self-motion in the natural environment is perceived immediately. It has been suggested that this latency relates to the sensory mismatch between visual and vestibular signals at motion onset. Here, we tested three techniques with the potential to reduce sensory mismatch in order to shorten vection onset latency: noisy galvanic vestibular stimulation (GVS) and bone conducted vibration (BCV) at the mastoid processes, and body vibration applied to the lower back. In Experiment 1, we examined vection latency for wide field visual rotations about the roll axis and applied a burst of stimulation at the start of visual motion. Both GVS and BCV reduced vection latency by two seconds compared to the control condition, whereas body vibration had no effect on latency. In Experiment 2, the visual stimulus rotated about the pitch, roll, or yaw axis and we found a similar facilitation of vection by both BCV and GVS in each case. In a control experiment, we confirmed that air-conducted sound administered through headphones was not sufficient to reduce vection onset latency. Together the results suggest that noisy vestibular stimulation facilitates vection, likely due to an upweighting of visual information caused by a reduction in vestibular sensory reliability.
Dynamics of Reversed Urban Breeze Circulation
Authors: Seo Jaemyeong Mango , Ganbat Gantuya , Baik Jong-Jin 
Published: January 2017

Abstract
The urban breeze circulation (UBC) is a thermally forced mesoscale circulation that is characterized by low-level inward flow toward the urban center, updrafts near the urban center, upper-level outward flows, and weak downdrafts outside the urban area. Previous numerical modeling studies indicate that in the early morning the direction of the UBC can be reversed. Here, the dynamics of a reversed UBC is studied in the context of the response of the atmosphere to specified thermal forcing, which represents diurnally varying urban heating. For this, a linearized, two-dimensional, hydrostatic, Boussinesq airflow system in a rotating frame with specified thermal forcing is solved using the Fourier transform method. The occurrence of a reversed UBC in the early morning is confirmed. The Coriolis parameter affects the strength and vertical structure of the UBC, whose role is similar to that of the coefficient of Rayleigh friction and Newtonian cooling. The occurrence condition, strength, and vertical structure of a reversed UBC are examined. The Coriolis force as well as urban heating alters the occurrence time of the reversed UBC. For a strongly viscous system, a reversed UBC occurs only in high latitudes with low occurrence possibility. A simple oscillation-type model for the horizontal velocity is constructed to get some dynamical insights into a reversed UBC. The analysis results also show that the Coriolis force alters the occurrence time of the reversed UBC.
Culturally Targeted Strategies for Diabetes Prevention in Minority Population
Authors: Lagisetty Pooja A. , Priyadarshini Shubadra , Terrell Stephanie , Hamati Mary , Landgraf Jessica , Chopra Vineet , Heisler Michele 
Published: January 2017

Purpose The purpose of this study is to (a) assess the effectiveness of culturally tailored diabetes prevention interventions in minority populations and (b) develop a novel framework to characterize 4 key domains of culturally tailored interventions. Prevention strategies specifically tailored to the culture of ethnic minority patients may help reduce the incidence of diabetes. Methods We searched PubMed, EMBASE, and CINAHL for English-language, randomized controlled trials (RCTs) or quasi-experimental (QE) trials testing culturally tailored interventions to prevent diabetes in minority populations. Two reviewers independently extracted data and assessed risk of bias. Inductive thematic analysis was used to develop a framework with 4 domains (FiLLM: Facilitating [ie, delivering] Interventions Through Language, Location, and Message). The framework was used to assess the overall effectiveness of culturally tailored interventions. Results Thirty-four trials met eligibility criteria. Twelve studies were RCTs, and 22 were QE trials. Twenty-five out of 34 studies (74%) that used cultural tailoring demonstrated significantly improved A1C, fasting glucose, and/or weight loss. Of the 25 successful interventions, 21 (84%) incorporated at least 3 culturally targeted domains. Seven studies used all 4 domains and were all successful. The least utilized domain was delivery (4/34) of the intervention’s key educational message. Conclusions Culturally tailoring interventions across the 4 domains of facilitators, language, location, and messaging can be effective in improving risk factors for progression to diabetes among ethnic minority groups. Future studies should evaluate how specific tailoring approaches work compared to usual care as well as comparative effectiveness of each tailoring domain.