bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Salmonella enterica Biofilm Formation Using Small-Molecule Adenosine Mimetics
Authors: Koopman Jacob A. , Marshall Joanna M. , Bhatiya Aditi , Eguale Tadesse , Kwiek Jesse J. , Gunn John S. 
Published: October 2014

ABSTRACT

Biofilms have been widely implicated in chronic infections and environmental persistence of
Salmonella enterica
, facilitating enhanced colonization of surfaces and increasing the ability of the bacteria to be transmitted to new hosts.
Salmonella enterica
serovar Typhi biofilm formation on gallstones from humans and mice enhances gallbladder colonization and bacterial shedding, while
Salmonella enterica
serovar Typhimurium biofilms facilitate long-term persistence in a number of environments important to food, medical, and farming industries.
Salmonella
regulates expression of many virulence- and biofilm-related processes using kinase-driven pathways. Kinases play pivotal roles in phosphorylation and energy transfer in cellular processes and possess an ATP-binding pocket required for their functions. Many other cellular proteins also require ATP for their activity. Here we test the hypothesis that pharmacological interference with ATP-requiring enzymes utilizing adenosine mimetic compounds would decrease or inhibit bacterial biofilm formation. Through the screening of a 3,000-member ATP mimetic library, we identified a single compound (compound 7955004) capable of significantly reducing biofilm formation by
S
. Typhimurium and
S
. Typhi. The compound was not bactericidal or bacteriostatic toward
S
. Typhimurium or cytotoxic to mammalian cells. An ATP-Sepharose affinity matrix technique was used to discover potential protein-binding targets of the compound and identified GroEL and DeoD. Compound 7955004 was screened against other known biofilm-forming bacterial species and was found to potently inhibit biofilms of
Acinetobacter baumannii
as well. The identification of a lead compound with biofilm-inhibiting capabilities toward
Salmonella
provides a potential new avenue of therapeutic intervention against
Salmonella
biofilm formation, with applicability to biofilms of other bacterial pathogens.
Seasonal Variation in Penicillin Use in Mexico and Brazil: Analysis of the Impact of Over-the-Counter Restrictions
Authors: Santa-Ana-Tellez Yared , Mantel-Teeuwisse Aukje K. , Leufkens Hubert G. M. , Wirtz Veronika J. 
Published: October 2014

ABSTRACT
During 2010, Mexico and Brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. We determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. We used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (DDD/TID) from IMS Health from the private sector in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. This database contains information on volume of antibiotics sold in retail pharmacies using information from wholesalers. We used interrupted time-series models controlling for external factors with the use of antihypertensives with interaction terms to assess changes in trend, level, and variation in use between quarters for total penicillin use and by active substance. The most used penicillin was amoxicillin, followed by amoxicillin-clavulanic acid and ampicillin (minimal use in Brazil). Before the restrictions, the seasonal variation in penicillin use was 1.1 DDD/TID in Mexico and 0.8 DDD/TID in Brazil. In Mexico, we estimated a significant decrease in the seasonal variation of 0.4 DDD/TID after the restriction, mainly due to changes in seasonal variation of amoxicillin and ampicillin. In Brazil, the seasonal variation did not change significantly, overall and in the breakdown by individual active substances. For Mexico, inappropriate penicillin use may have diminished after the restrictions were enforced. For Brazil, increasing use and no change in seasonal variation suggest that further efforts are needed to reduce inappropriate penicillin use.
Antibiotic-Loaded Synthetic Calcium Sulfate Beads for Prevention of Bacterial Colonization and Biofilm Formation in Periprosthetic Infections
Authors: Howlin R. P. , Brayford M. J. , Webb J. S. , Cooper J. J. , Aiken S. S. , Stoodley P. 
Published: October 2014

ABSTRACT

Periprosthetic infection (PI) causes significant morbidity and mortality after fixation and joint arthroplasty and has been extensively linked to the formation of bacterial biofilms. Poly(methyl methacrylate) (PMMA), as a cement or as beads, is commonly used for antibiotic release to the site of infection but displays variable elution kinetics and also represents a potential nidus for infection, therefore requiring surgical removal once antibiotics have eluted. Absorbable cements have shown improved elution of a wider range of antibiotics and, crucially, complete biodegradation, but limited data exist as to their antimicrobial and antibiofilm efficacy. Synthetic calcium sulfate beads loaded with tobramycin, vancomycin, or vancomycin-tobramycin dual treatment (in a 1:0.24 [wt/wt] ratio) were assessed for their abilities to eradicate planktonic methicillin-resistant
Staphylococcus aureus
(MRSA) and
Staphylococcus epidermidis
relative to that of PMMA beads. The ability of the calcium sulfate beads to prevent biofilm formation over multiple days and to eradicate preformed biofilms was studied using a combination of viable cell counts, confocal microscopy, and scanning electron microscopy of the bead surface. Biofilm bacteria displayed a greater tolerance to the antibiotics than their planktonic counterparts. Antibiotic-loaded beads were able to kill planktonic cultures of 10
6
CFU/ml, prevent bacterial colonization, and significantly reduce biofilm formation over multiple days. However, established biofilms were harder to eradicate. These data further demonstrate the difficulty in clearing established biofilms; therefore, early preventive measures are key to reducing the risk of PI. Synthetic calcium sulfate loaded with antibiotics has the potential to reduce or eliminate biofilm formation on adjacent periprosthetic tissue and prosthesis material and, thus, to reduce the rates of periprosthetic infection.
Impact of Nonlinear Interactions of Pharmacokinetics and MICs on Sputum Bacillary Kill Rates as a Marker of Sterilizing Effect in Tuberculosis
Authors: Chigutsa Emmanuel , Pasipanodya Jotam G. , Visser Marianne E. , van Helden Paul D. , Smith Peter J. , Sirgel Frederick A. , Gumbo Tawanda , McIlleron Helen 
Published: October 2014

ABSTRACT

The relationships between antituberculosis drug exposure and treatment effects on humans receiving multidrug therapy are complex and nonlinear. In patients on treatment, an analysis of the rate of decline in the sputum bacillary burden reveals two slopes. The first is the α-slope, which is thought to reflect bactericidal effect, followed by a β-slope, which is thought to reflect sterilizing activity. We sought to characterize the effects of standard first-line treatment on sterilizing activity. Fifty-four patients receiving combination therapy for pulmonary tuberculosis in a clinical trial had drug concentrations measured and
Mycobacterium tuberculosis
isolates available for MIC identification. Sputum sample cultures were performed at baseline and weekly for 8 weeks. A time-to-event model based on the days to positivity in the liquid cultures was used to estimate the β-slope. The pharmacokinetic parameters of rifampin, isoniazid, ethambutol, and pyrazinamide were determined for each patient. Multivariate adaptive regression splines analyses, which simultaneously perform linear and nonlinear analyses, were used to identify the relationships between the predictors and the β-slope. The potential predictors examined included HIV status, lung cavitation, 24-h area under the concentration-time curve (AUC), peak drug concentration (
C
max
), AUC/MIC ratio,
C
max
/MIC ratio, and the time that that concentration persisted above MIC. A rifampin
C
max
of >8.2 mg/liter and a pyrazinamide AUC/MIC of >11.3 were key predictors of the β-slope and interacted positively to increase the β-slope. In patients with a rifampin AUC of <35.4 mg · h/liter, an increase in the pyrazinamide AUC/MIC and/or ethambutol
C
max
/MIC increased the β-slope, while increasing isoniazid
C
max
decreased it, suggesting isoniazid antagonism. Antibiotic concentrations and MICs interact in a nonlinear fashion as the main drivers of a sterilizing effect. The results suggest that faster speeds of sterilizing effect might be achieved by omitting isoniazid and by increasing rifampin, pyrazinamide, and ethambutol exposures. However, isoniazid and ethambutol exposures may only be of importance when rifampin exposure is low. These findings need confirmation in larger studies. (This study has been registered at
controlled-trials.com
under registration no. ISRCTN80852505.)
Effect of Rifampin and Rifabutin on Serum Itraconazole Levels in Patients with Chronic Pulmonary Aspergillosis and Coexisting Nontuberculous Mycobacterial Infection
Authors: Moon Seong Mi , Park Hye Yun , Jeong Byeong-Ho , Jeon Kyeongman , Lee Soo-Youn , Koh Won-Jung 
Published: October 2014

ABSTRACT

We investigated the effects of rifampin and rifabutin on serum itraconazole levels in patients with chronic pulmonary aspergillosis. Serum itraconazole concentrations were significantly lower in patients who received itraconazole with rifampin (median, 0.1 μg/ml;
P
< 0.001) or rifabutin (median, 0.34 μg/ml;
P
< 0.001) than those receiving itraconazole alone (median, 5.92 μg/ml). Concomitant use of rifampin or rifabutin and itraconazole should be avoided in patients with chronic pulmonary aspergillosis and coexisting mycobacterial infections.
The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication
Authors: Carocci Margot , Hinshaw Stephen M. , Rodgers Mary A. , Villareal Valerie A. , Burri Dominique J. , Pilankatta Rajendra , Maharaj Natalya P. , Gack Michaela U. , Stavale Eric J. , Warfield Kelly L. , Yang Priscilla L. 
Published: October 2014

ABSTRACT

Dengue virus (DENV), a member of the
Flaviviridae
family, is a mosquito-borne pathogen and the cause of dengue fever. The increasing prevalence of DENV worldwide heightens the need for an effective vaccine and specific antivirals. Due to the dependence of DENV upon the lipid biosynthetic machinery of the host cell, lipid signaling and metabolism present unique opportunities for inhibiting viral replication. We screened a library of bioactive lipids and modulators of lipid metabolism and identified 4-hydroxyphenyl retinamide (4-HPR) (fenretinide) as an inhibitor of DENV in cell culture. 4-HPR inhibits the steady-state accumulation of viral genomic RNA and reduces viremia when orally administered in a murine model of DENV infection. The molecular target responsible for this antiviral activity is distinct from other known inhibitors of DENV but appears to affect other members of the
Flaviviridae
, including the West Nile, Modoc, and hepatitis C viruses. Although long-chain ceramides have been implicated in DENV replication, we demonstrate that DENV is insensitive to the perturbation of long-chain ceramides in mammalian cell culture and that the effect of 4-HPR on dihydroceramide homeostasis is separable from its antiviral activity. Likewise, the induction of reactive oxygen species by 4-HPR is not required for the inhibition of DENV. The inhibition of DENV
in vivo
by 4-HPR, combined with its well-established safety and tolerability in humans, suggests that it may be repurposed as a pan-
Flaviviridae
antiviral agent. This work also illustrates the utility of bioactive lipid screens for identifying critical interactions of DENV and other viral pathogens with host lipid biosynthesis, metabolism, and signal transduction.
Macrophages Are the Determinant of Resistance to and Outcome of Nonlethal Babesia microti Infection in Mice
Authors: Terkawi Mohamad Alaa , Cao Shinuo , Herbas Maria S. , Nishimura Maki , Li Yan , Moumouni Paul Franck Adjou , Pyarokhil Asadullah Hamid , Kondoh Daisuke , Kitamura Nobuo , Nishikawa Yoshifumi , Kato Kentaro , Yokoyama Naoaki , Zhou Jinlin , Suzuki Hiroshi , Igarashi Ikuo , Xuan Xuenan 
Published: October 2014

ABSTRACT

In the present study, we examined the contributions of macrophages to the outcome of infection with
Babesia microti
, the etiological agent of human and rodent babesiosis, in BALB/c mice. Mice were treated with clodronate liposome at different times during the course of
B. microti
infection in order to deplete the macrophages. Notably, a depletion of host macrophages at the early and acute phases of infection caused a significant elevation of parasitemia associated with remarkable mortality in the mice. The depletion of macrophages at the resolving and latent phases of infection resulted in an immediate and temporal exacerbation of parasitemia coupled with mortality in mice. Reconstituting clodronate liposome-treated mice at the acute phase of infection with macrophages from naive mice resulted in a slight reduction in parasitemia with improved survival compared to that of mice that received the drug alone. These results indicate that macrophages play a crucial role in the control of and resistance to
B. microti
infection in mice. Moreover, analyses of host immune responses revealed that macrophage-depleted mice diminished their production of Th1 cell cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Furthermore, depletion of macrophages at different times exaggerated the pathogenesis of the infection in deficient IFN-γ
−/−
and severe combined immunodeficiency (SCID) mice. Collectively, our data provide important clues about the role of macrophages in the resistance and control of
B. microti
and imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function.
Leishmania major Telomerase TERT Protein Has a Nuclear/Mitochondrial Eclipsed Distribution That Is Affected by Oxidative Stress
Authors: Campelo Riward , Díaz Lozano Isabel , Figarella Katherine , Osuna Antonio , Ramírez José Luis 
Published: October 2014

ABSTRACT

In its canonical role the reverse transcriptase telomerase recovers the telomeric repeats that are lost during DNA replication. Other locations and activities have been recently described for the telomerase protein subunit TERT in mammalian cells. In the present work, using biochemistry, molecular biology, and electron microscopy techniques, we found that in the human parasite
Leishmania major
, TERT (and telomerase activity) shared locations between the nuclear, mitochondrial, and cytoplasmic compartments. Also, some telomerase activity and TERT protein could be found in ∼100-nm nanovesicles. In the mitochondrial compartment, TERT appears to be mainly associated with the kinetoplast DNA. When
Leishmania
cells were exposed to H
2
O
2
, TERT changed its relative abundance and activity between the nuclear and mitochondrial compartments, with the majority of activity residing in the mitochondrion. Finally, overexpression of TERT in
Leishmania
transfected cells not only increased the parasitic cell growth rate but also increased their resistance to oxidative stress.
MifM Monitors Total YidC Activities of Bacillus subtilis, Including That of YidC2, the Target of Regulation
Authors: Chiba Shinobu , Ito Koreaki 
Published: October 2014

ABSTRACT

The YidC/Oxa1/Alb3 family proteins are involved in membrane protein biogenesis in bacteria, mitochondria, and chloroplasts. Recent studies show that YidC uses a channel-independent mechanism to insert a class of membrane proteins into the membrane.
Bacillus subtilis
has two YidC homologs, SpoIIIJ (YidC1) and YidC2 (YqjG); the former is expressed constitutively, while the latter is induced when the SpoIIIJ activity is compromised. MifM is a substrate of SpoIIIJ, and its failure in membrane insertion is accompanied by stable ribosome stalling on the
mifM-yidC2
mRNA, which ultimately facilitates
yidC2
translation. While mutational inactivation of SpoIIIJ has been known to induce
yidC2
expression, here, we show that the level of this induction is lower than that observed when the membrane insertion signal of MifM is defective. Moreover, this partial induction of YidC2 translation is lowered further when YidC2 is overexpressed in
trans
. These results suggest that YidC2 is able to insert MifM into the membrane and to release its translation arrest. Thus, under SpoIIIJ-deficient conditions, YidC2 expression is subject to MifM-mediated autogenous feedback repression. Our results show that YidC2 uses a mechanism that is virtually identical to that used by SpoIIIJ; Arg75 of YidC2 in its intramembrane yet hydrophilic cavity is functionally indispensable and requires negatively charged residues of MifM as an insertion substrate. From these results, we conclude that MifM monitors the total activities of the SpoIIIJ and the YidC2 pathways to control the synthesis of YidC2 and to maintain the cellular capability of the YidC mode of membrane protein biogenesis.
Quorum Sensing Regulates the Osmotic Stress Response in Vibrio harveyi
Authors: van Kessel Julia C. , Rutherford Steven T. , Cong Jian-Ping , Quinodoz Sofia , Healy James , Bassler Bonnie L. 
Published: October 2014

ABSTRACT

Bacteria use a chemical communication process called quorum sensing to monitor cell density and to alter behavior in response to fluctuations in population numbers. Previous studies with
Vibrio harveyi
have shown that LuxR, the master quorum-sensing regulator, activates and represses >600 genes. These include six genes that encode homologs of the
Escherichia coli
Bet and ProU systems for synthesis and transport, respectively, of glycine betaine, an osmoprotectant used during osmotic stress. Here we show that LuxR activates expression of the glycine betaine operon
betIBA-proXWV
, which enhances growth recovery under osmotic stress conditions. BetI, an autorepressor of the
V. harveyi
betIBA-proXWV
operon, activates the expression of genes encoding regulatory small RNAs that control quorum-sensing transitions. Connecting quorum-sensing and glycine betaine pathways presumably enables
V. harveyi
to tune its execution of collective behaviors to its tolerance to stress.
Effect of vitamin D3supplementation on glycated hemoglobin (HbA1c), fructosamine, serum lipids, and body mass index: a randomized, double-blinded, placebo-controlled trial among healthy immigrants living in Norway
Authors: Madar Ahmed A , Knutsen Kirsten V , Stene Lars C , Brekke Mette , Meyer Haakon E , Lagerløv Per 
Published: October 2014

ObjectiveDespite the suggested role of vitamin D in the prevention of diabetes and cardiovascular disease or its risk factors, the evidence is not consistent and there is a paucity of randomized controlled trials in this field. We aimed to investigate the effect of 16-week daily vitamin D3supplementation on glycated hemoglobin (HbA1c), fructosamine, body mass index (BMI), and serum lipids.DesignDouble-blind, randomized, placebo-controlled trial.SettingImmigrant community centers in Oslo, Norway.Participants251 healthy adults aged 18–50 years with a non-Western immigrant background. All participants performed the baseline test and 215 (86%) returned to the follow-up test.Intervention16 weeks of daily oral supplementation with either 10 μg vitamin D3, 25 μg vitamin D3,or placebo.Main outcome measuresDifference in absolute change during the 16-week intervention between the intervention groups combined (10 or 25 μg of vitamin D3/day) and placebo, in HbA1c, fructosamine, serum lipids (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), and BMI.ResultsA total of 215 (86%) participants completed the study. Serum 25-hydroxyvitamin D increased from 29 nmol/L at baseline to 49 nmol/L after intervention, with little change in the placebo group. However, there was no difference in change of HbA1c between those receiving vitamin D3compared with placebo (mean difference: 0.01% (95% CI −0.04 to 0.06, p=0.7)). Neither did the vitamin D3supplementation have any effect on the other end points: fructosamine, serum lipids, and BMI.Conclusions16-week vitamin D3supplementation to healthy immigrants from South Asia, the Middle East, or Africa and now living in Norway with low vitamin D status did not improve HbA1c, fructosamine, lipid profiles, or BMI. An updated meta-analysis of similar published trials showed that our results were generally consistent with those of other studies.Trial registration numberNCT01263288.
A cross-sectional study on health-related knowledge and its predictors among Chinese vocational college students
Authors: Wang Weina , Hou Yanli , Hu Nan , Zhang Dongxian , Tao Junliang , Man Yonghong , Wang Aimei , Li Ling , Bi Yongyi 
Published: October 2014

ObjectivesThis study sought to examine the level of health-related knowledge and its predictors among vocational college students in China.Study designA cross-sectional study.MethodsA survey was performed to collect data on heath-related knowledge and potential risk factors among 708 students in four higher vocational colleges at Nanyang, Henan, China. Linear regression models were conducted to identify the predictors of the level of health-related knowledge.ResultsThe level of health-related knowledge among Chinese vocational college students is extremely low (only 1.4% students have an adequate level of health-related knowledge). According to the multivariate analysis, major, year of class, place of origin and a mother's education level are significantly associated with health-related knowledge in Chinese vocational college students.ConclusionsHealth education and health promotion efforts are encouraged to improve the level of health-related knowledge in this population. Attention and efforts to improve health-related knowledge of Chinese vocational college students who come from rural areas, whose mothers have a lower level of education, who are in non-medicine majors and during the first few years of vocational college is warranted.