bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Mode of Action of a Plant Natural Product Targeting Human Fungal Pathogens
Authors: Dorsaz Stéphane , Snäkä Tiia , Favre-Godal Quentin , Maudens Pierre , Boulens Nathalie , Furrer Pascal , Ebrahimi Samad Nejad , Hamburger Matthias , Allémann Eric , Gindro Katia , Queiroz Emerson Ferreira , Riezman Howard , Wolfender Jean-Luc , Sanglard Dominique 
Published: July 2017

ABSTRACT

Candida albicans
is a major cause of fungal diseases in humans, and its resistance to available drugs is of concern. In an attempt to identify novel antifungal agents, we initiated a small-scale screening of a library of 199 natural plant compounds (i.e., natural products [NPs]).
In vitro
susceptibility profiling experiments identified 33 NPs with activity against
C. albicans
(MIC
50
s ≤ 32 μg/ml). Among the selected NPs, the sterol alkaloid tomatidine was further investigated. Tomatidine originates from the tomato (
Solanum lycopersicum
) and exhibited high levels of fungistatic activity against
Candida
species (MIC
50
s ≤ 1 μg/ml) but no cytotoxicity against mammalian cells. Genome-wide transcriptional analysis of tomatidine-treated
C. albicans
cells revealed a major alteration (upregulation) in the expression of ergosterol genes, suggesting that the ergosterol pathway is targeted by this NP. Consistent with this transcriptional response, analysis of the sterol content of tomatidine-treated cells showed not only inhibition of Erg6 (C-24 sterol methyltransferase) activity but also of Erg4 (C-24 sterol reductase) activity. A forward genetic approach in
Saccharomyces cerevisiae
coupled with whole-genome sequencing identified 2 nonsynonymous mutations in
ERG6
(amino acids D249G and G132D) responsible for tomatidine resistance. Our results therefore unambiguously identified Erg6, a C-24 sterol methyltransferase absent in mammals, to be the main direct target of tomatidine. We tested the
in vivo
efficacy of tomatidine in a mouse model of
C. albicans
systemic infection. Treatment with a nanocrystal pharmacological formulation successfully decreased the fungal burden in infected kidneys compared to the fungal burden achieved by the use of placebo and thus confirmed the potential of tomatidine as a therapeutic agent.
Effects of Isavuconazole on the Plasma Concentrations of Tacrolimus among Solid-Organ Transplant Patients
Authors: Rivosecchi Ryan M. , Clancy Cornelius J. , Shields Ryan K. , Ensor Christopher R. , Shullo Michael A. , Falcione Bonnie A. , Venkataramanan Raman , Nguyen M. Hong 
Published: July 2017

ABSTRACT
We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, the tacrolimus concentration/dose ratio normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction. A 1.3-fold decrease in tacrolimus daily dose was required to maintain desired tacrolimus levels. There was considerable interpatient variability in the magnitude of the drug interaction. Tacrolimus doses should not be adjusted uniformly but, rather, be guided by therapeutic drug monitoring.
Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation
Authors: Wi Jin , Noh Hayeon , Min Kyoung Lok , Yang Seungwon , Jin Byung Hak , Hahn Jongsung , Bae Soo Kyung , Kim Jiseon , Park Min Soo , Choi Donghoon , Chang Min Jung 
Published: July 2017

ABSTRACT
The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 h using a trough concentration target of >10 μg/ml for mild to moderate infections and a trough concentration target of >15 μg/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)
A Novel 6-Benzyl Ether Benzoxaborole Is Active against Mycobacterium tuberculosis
In Vitro
Authors: Patel Nipul , O'Malley Theresa , Zhang Yong-Kang , Xia Yi , Sunde Bjorn , Flint Lindsay , Korkegian Aaron , Ioerger Thomas R. , Sacchettini Jim , Alley M. R. K. , Parish Tanya 
Published: July 2017

ABSTRACT

We identified a novel 6-benzyl ether benzoxaborole with potent activity against
Mycobacterium tuberculosis
. The compound had an MIC of 2 μM in liquid medium. The compound was also able to prevent growth on solid medium at 0.8 μM and was active against intracellular bacteria (50% inhibitory concentration [IC
50
] = 3.6 μM) without cytotoxicity against eukaryotic cells (IC
50
> 100 μM). We isolated resistant mutants (MIC ≥ 100 μM), which had mutations in Rv1683, Rv3068c, and Rv0047c.
Assessment of Clinical Pharmacokinetic Drug-Drug Interaction of Antimalarial Drugs α/β-Arteether and Sulfadoxine-Pyrimethamine
Authors: Chhonker Y. S. , Bhosale V. V. , Sonkar S. K. , Chandasana H. , Kumar D. , Vaish S. , Choudhary S. C. , Bhadhuria S. , Sharma S. , Singh R. K. , Jain G. K. , Vaish A. K. , Gaur S. P. S. , Bhatta R. S. 
Published: July 2017

ABSTRACT

Antimalarial drug combination therapy is now being widely used for the treatment of uncomplicated malaria. The objective of the present study was to investigate the effects of coadministration of intramuscular α/β-arteether (α/β-AE) and oral sulfadoxine-pyrimethamine (SP) on the pharmacokinetic properties of each drug as a drug-drug interaction study to support the development of a fixed-dose combination therapy. A single-dose, open-label, crossover clinical trial was conducted in healthy adult Indian male volunteers (18 to 45 years,
n
= 13) who received a single dose of AE or SP or a combination dose of AE and SP. Blood samples were collected up to 21 days postadministration, and concentrations of α-AE, β-AE, sulfadoxine, and pyrimethamine were determined by using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and statistically analyzed to calculate the geometric mean ratio and confidence interval. Following single-dose coadministration of intramuscular AE and oral SP, the pharmacokinetic properties of α/β-AE were not significantly affected, and α/β-AE had no significant effect on the pharmacokinetic properties of SP in these selected groups of healthy volunteers. However, more investigations are needed to explore this further. (This study has been registered in the clinical trial registry of India under approval no. CTRI/2011/11/002155.)
AtlA Mediates Extracellular DNA Release, Which Contributes to Streptococcus mutans Biofilm Formation in an Experimental Rat Model of Infective Endocarditis
Authors: Jung Chiau-Jing , Hsu Ron-Bin , Shun Chia-Tung , Hsu Chih-Chieh , Chia Jean-San 
Published: July 2017

ABSTRACT

Host factors, such as platelets, have been shown to enhance biofilm formation by oral commensal streptococci, inducing infective endocarditis (IE), but how bacterial components contribute to biofilm formation
in vivo
is still not clear. We demonstrated previously that an isogenic mutant strain of
Streptococcus mutans
deficient in autolysin AtlA (Δ
atlA
) showed a reduced ability to cause vegetation in a rat model of bacterial endocarditis. However, the role of AtlA in bacterial biofilm formation is unclear. In this study, confocal laser scanning microscopy analysis showed that extracellular DNA (eDNA) was embedded in
S. mutans
GS5 floes during biofilm formation on damaged heart valves, but an Δ
atlA
strain could not form bacterial aggregates. Semiquantification of eDNA by PCR with bacterial 16S rRNA primers demonstrated that the Δ
atlA
mutant strain produced dramatically less eDNA than the wild type. Similar results were observed with
in vitro
biofilm models. The addition of polyanethol sulfonate, a chemical lysis inhibitor, revealed that eDNA release mediated by bacterial cell lysis is required for biofilm initiation and maturation in the wild-type strain. Supplementation of cultures with calcium ions reduced wild-type growth but increased eDNA release and biofilm mass. The effect of calcium ions on biofilm formation was abolished in Δ
atlA
cultures and by the addition of polyanethol sulfonate. The VicK sensor, but not CiaH, was found to be required for the induction of eDNA release or the stimulation of biofilm formation by calcium ions. These data suggest that calcium ion-regulated AtlA maturation mediates the release of eDNA by
S. mutans
, which contributes to biofilm formation in infective endocarditis.
Effectiveness of a targeted lifestyle intervention in primary care on diet and physical activity among South Asians at risk for diabetes: 2-year results of a randomised controlled trial in the Netherlands
Authors: Vlaar Everlina M A , Nierkens Vera , Nicolaou Mary , Middelkoop Barend J C , Busschers Wim B , Stronks Karien , van Valkengoed Irene G M 
Published: July 2017

ObjectivesIn South Asian populations, little is known about the effects of intensive interventions to reduce the risk of type 2 diabetes on health behaviour. We examined the effectiveness at 2 years of a culturally targeted lifestyle intervention on diet, physical activity and determinants of behaviour change among South Asians at risk for diabetes.DesignRandomised controlled trial with de facto masking.SettingPrimary care.ParticipantsA total of 536 18- to 60-year-old South Asians at risk for diabetes (ie, with impaired glucose tolerance, impaired fasting glucose or relatively high insulin resistance) were randomised to the intervention (n=283) or a control (n=253) group. Data of 314 participants (n=165 intervention, n=149 control) were analysed.InterventionsThe culturally targeted intervention consisted of individual counselling using motivational interviewing (six to eight sessions in the first 6 months plus three to four booster sessions), a family session, cooking classes and a supervised physical activity programme. The control group received generic lifestyle advice.Outcome measuresWe compared changes in physical activity, diet and social-cognitive underlying determinants between the two groups at 2-year follow-up with independent-sample t-tests, chi-square tests and Fisher’s exact tests.ResultsAt the 2-year follow-up, participants in the intervention group were more moderately to vigorously active than at baseline, but compared with changes in the control group, the difference was not significant (change min/week 142.9 vs 0.5, p=0.672). Also, no significant difference was found between the two groups in changes on any of the components of the diet or the social-cognitive determinants of diet and physical activity.ConclusionsThe culturally targeted lifestyle intervention led to high drop-out and was not effective in promoting healthy behaviour among South Asians at risk for diabetes. Given the high a priori risk, we recommend to develop new strategies, preferably more acceptable, to promote healthy behaviour.Trial registrationNTR1499; Results.www.trialregister.nl/trialreg/admin/rctview.asp?TC=1499
Non-Hermitian interaction of a discrete state with a continuum
Authors: Longhi Stefano 
Published: July 2017

The interaction of a discrete state coupled to a continuum is a longstanding problem of major interest in different areas of quantum and classical physics. In Hermitian models, several dynamical decoupling schemes have been suggested, in which the discrete-continuum interaction can be substantially reduced and even suppressed. In this work, we consider a discrete state interacting with a continuum via a time-dependent non-Hermitian coupling with finite (albeit arbitrarily long) duration, and show rather generally that for a wide class of coupling temporal shapes, in which the real and imaginary parts of the coupling are related each other by a Hilbert transform, the discrete state returns to its initial condition after the interaction with the continuum, while the continuum keeps trace of the interaction. Such a behavior, which does not have any counterpart in Hermitian dynamics, can be referred to as non-Hermitian pseudo decoupling. Non-Hermitian pseudo decoupling is illustrated by considering a non-Hermitian extension of the Fano–Anderson model in a one-dimensional tight-binding lattice. Such a non-Hermitian model can describe, for example, photonic hopping dynamics in a tight-binding chain of optical microrings or resonators, in which non-Hermitian coupling can be realized by fast modulation of the real and imaginary (gain/loss) parts of the refractive index of the edge microring.
Utility of 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines in HIV-Infected Adults With Carotid Atherosclerosis
Authors: Phan Binh An P. , Weigel Bernard , Ma Yifei , Scherzer Rebecca , Li Danny , Hur Sophia , Kalapus S.C. , Deeks Steven , Hsue Priscilla 
Published: July 2017

Background—
Although HIV is associated with increased atherosclerotic cardiovascular disease (CVD) risk, it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. We compared the 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III recommendations in HIV-infected adults and evaluated associations with carotid artery intima-media thickness and plaque.

Methods and Results—

Carotid artery intima-media thickness was measured at baseline and 3 years later in 352 HIV-infected adults without clinical atherosclerotic CVD and not on statins. Plaque was defined as IMT >1.5 mm in any segment. At baseline, the median age was 43 (interquartile range, 39–49), 85% were men, 74% were on antiretroviral medication, and 50% had plaque. The American College of Cardiology/American Heart Association guidelines were more likely to recommend statins compared with the Adult Treatment Panel III guidelines, both overall (26% versus 14%;
P
<0.001), in those with plaque (32% versus 17%;
P
=0.0002), and in those without plaque (16% versus 7%;
P
=0.025). In multivariable analysis, older age, higher low-density lipoprotein cholesterol, pack per year of smoking, and history of opportunistic infection were associated with baseline plaque. Baseline IMT (hazard ratio, 1.18 per 10% increment; 95% confidence interval, 1.05–1.33;
P
=0.005) and plaque (hazard ratio, 2.06; 95% confidence interval, 1.02–4.08;
P
=0.037) were each associated with all-cause mortality, independent of traditional CVD risk factors.

Conclusions—
Although the American College of Cardiology/American Heart Association guidelines recommended statins to a greater number of HIV-infected adults compared with the Adult Treatment Panel III guidelines, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Baseline carotid atherosclerosis but not atherosclerotic CVD risk scores was an independent predictor of mortality. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased atherosclerotic CVD risk and may be considered for statins.
Vitamin or Supplement Use among Adults, Behavioral Risk Factor Surveillance System, 13 States, 2001
Authors: Balluz Lina S. , Okoro Catherine A. , Bowman Barbara A. , Serdula Mary K. , Mokdad Ali H. 
Published: July 2017

Objective. The authors examined vitamin/supplement (V/S) use and its relationship to sociodemographics, health behaviors, and health conditions among adults in 13 states. Methods. This investigation used 2001 data from a cross-sectional study of non-institutionalized adults aged ⩾18 years, the Behavioral Risk Factor Surveillance System. Results. Of 45,415 respondents with complete data (18,723 males and 26,692 females), 56.5% ( n=5,652) reported current V/S use. After adjusting for age, sex, race/ethnicity, and education, the authors found a statistically significant association between V/S use and positive health risk behavior (adjusted odds ratio [OR] = 1.46; p<0.001). Also, V/S use was found to increase with age ( p<0.001). No association was found between V/S use and the absence of specific chronic disease conditions (adjusted OR=0.93; p=0.052). Conclusions. People who used V/S in the states surveyed were more likely to demonstrate positive health risk behaviors than those who did not report V/S use. Thus it appears that individuals who are most likely to use V/S are least likely to need V/S. It is crucial that individuals report quantity and frequency of V/S use when providing medical or diet histories to health care providers.
Illegal Alcohol Sales and Use of Alcohol Control Policies at Community Festivals
Authors: Toomey Traci L. , Erickson Darin J. , Patrek William , Fletcher Linda A. , Wagenaar Alexander C. 
Published: July 2017

Objectives. The primary goals of this study were to assess the propensity for alcohol sales to underage customers and obviously intoxicated customers at community festivals, and to assess the prevalence of alcohol control policies at these events. A secondary goal was to identify server and festival characteristics and festival policies related to the likelihood of illegal alcohol sales. Methods. We conducted pseudo-underage purchase attempts at 43 festivals and pseudo-intoxicated purchase attempts at 50 festivals to assess the likelihood of illegal sales. Research staff made observations at festivals and contacted festival planners by telephone following each event to assess which alcohol policies were implemented. We conducted backwards stepwise multivariate analyses for each purchase attempt outcome to identify policies and characteristics related to likelihood of illegal alcohol sales. Results. Pseudo-intoxicated buyers purchased beer in 89% of 95 attempts (standard deviation [SD]=0.31) and pseudo-underage buyers were able to purchase beer in 50% of 82 attempts (SD=0.50). All festival planners reported having at least two of the 10 alcohol policies we assessed, but no festival had implemented all 10 policies. Server characteristics were not related to either purchase attempt outcome. In the multivariate analyses, having more alcohol control policies was related to a greater likelihood of illegal sales to intoxicated customers; however, having more alcohol control policies was associated with a lesser likelihood of alcohol sales to underage customers. Restricting the number of servings per person was also associated with a lesser likelihood of alcohol sales to underage customers. Conclusions. Propensity for illegal alcohol sales at festivals is very high. Research is needed to identify interventions to prevent illegal alcohol sales at these events.
Escherichia Coli O157:H7 Outbreak Associated with Consumption of Ground Beef, June–July 2002
Authors: Vogt Richard L. , Dippold Laura 
Published: July 2017

Objective. A case-control and environmental study tested the hypothesis that purchasing and eating ground beef from a specific source was the cause of a cluster of cases of hemolytic uremic syndrome (HUS) and Escherichia coli ( E. coli) O157:H7 gastroenteritis. Methods. A case-control study comparing risk factors was conducted over the telephone on nine case-patients with 23 selected controls. An environmental investigation was conducted that consisted of reviewing beef handling practices at a specific local supermarket and obtaining ground beef samples from the store and two households with case-patients. Results. The analysis of the case-control study showed that eight case-patients (89%) purchased ground beef at Grocery Chain A compared with four controls who did not develop illness (17%) (matched odds ratio=undefined; 95% confidence interval 2.8, ∞; p=0.006). The environmental investigation showed that Grocery Chain A received meat from Meatpacker A. Laboratory analysis of meat samples from Meatpacker A and Grocery Chain A and stool samples from some patients recovered an identical strain of E. coli O157:H7 according to pulse-field gel electrophoresis. Conclusions. Both the case-control and environmental studies showed that purchasing ground beef at Grocery Chain A, which received ground beef from Meatpacker A, was the major risk factor for illness in eight case-patients; the ninth case-patient was found to be unrelated to the outbreak. Furthermore, meat from Meatpacker A was associated with a nationwide outbreak of E. coli O157:H7 illness that resulted in the second largest recall of beef in U.S. history at the time.
Vaccine Beliefs of Parents Who Oppose Compulsory Vaccination
Authors: Kennedy Allison M. , Brown Cedric J. , Gust Deborah A. 
Published: July 2017

Objectives. Our objectives were the following: ( 1) to describe the sociodemographic factors, vaccine beliefs, and behaviors that are associated with parental opposition to compulsory vaccination, and ( 2) to determine if the availability of a philosophical exemption in a parent's state of residence is associated with parental opposition to compulsory vaccination. Methods. Data from the 2002 HealthStyles survey were analyzed. Chi-square analysis was used to identify significant associations between belief and behavior questions and opposition to compulsory vaccination for school entry. Multivariate logistic regression was conducted using significant variables from the bivariate analysis to identify independent predictors of opposition to compulsory vaccination among surveyed parents. Results. Of respondents with at least one child aged ⩽18 years living in the household ( n = 1,527), 12% were opposed to compulsory vaccination. Survey results indicate that a parent's belief regarding compulsory vaccination for school entry is significantly associated with beliefs in the safety and utility of vaccines, as well as intention to have the youngest child fully vaccinated. Residence in a state that permits philosophical exemption to vaccination also was significantly associated with a parent's opposition to compulsory vaccination for school entry. Conclusions. Providing basic information to parents regarding vaccines and vaccine-preventable diseases may help reduce opposition to compulsory vaccination by reinforcing the safety and importance of routine childhood vaccinations.