bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of religion and spirituality in coping with kidney disease and haemodialysis in Thailand
Authors: Yodchai Kantaporn , Dunning Trisha , Savage Sally , Hutchinson Alison M. 
Published: June 2016

BackgroundPeople with chronic kidney disease (CKD) face various problems including psychological, socioeconomic and physical effects associated with CKD and its treatment. They need to develop strategies to help them cope with CKD and life challenges. Religion and spirituality are important coping strategies, but their role in helping people cope with CKD and haemodialysis (HD) in Thailand is relatively unknown.AimsTo investigate the role of religion and spirituality in coping with CKD and its treatment in Thailand.DesignAn exploratory, qualitative approach was undertaken using semistructured individual interviews.MethodPurposive sampling was used to recruit participants. Face‐to‐face, in‐depth individual interviews using open questions were conducted during January and February 2012. Interviews were audio‐recorded and transcribed verbatim. Data were analysed using the framework method of qualitative data analysis.FindingsTwenty people receiving HD participated: age range 23–77 years, mean 53.7 (±16.38 SD). Ten were women. Participants reported use of religious and spiritual practices to cope with CKD and its treatment, including religious and spiritual explanations for developing CKD, karmic disease, making merit, reading Dharma books, praying and chanting to save life and making a vow to Pran‐Boon.ConclusionReligion and spirituality provide powerful coping strategies that can help Thai people with CKD overcome the associated distress and difficulties. Religion and spirituality cannot be separated in Thai culture because Thai people are both religious and spiritual.
Differential impact of acute and prolonged cAMP agonist exposure on protein kinase A activation and human myometrium contractile activity
Authors: Lai Pei F. , Tribe Rachel M. , Johnson Mark R. 
Published: June 2016

Key points
Over 15 million babies are born prematurely each year with approximately 1 million of these babies dying as a direct result of preterm delivery.
β2‐Adrenoreceptor agonists that act via cAMP can reduce uterine contractions to delay preterm labour, but their ability to repress uterine contractions lasts ≤ 48 h and their use does not improve neonatal outcomes.
Previous research has suggested that cAMP inhibits myometrial contractions via protein kinase A (PKA) activation, but this has yet to be demonstrated with PKA‐specific agonists.
We investigated the role of PKA in mediating cAMP‐induced human myometrial relaxation, and the impact of prolonged cAMP elevation on myometrial contractility.
Our findings suggest that PKA is not the sole mediator of cAMP‐induced myometrial relaxation and that prolonged prophylactic elevation of cAMP alone is unlikely to prevent preterm labour (PTL).
AbstractAcute cAMP elevation inhibits myometrial contractility, but the mechanisms responsible are not fully elucidated and the long‐term effects are uncertain. Both need to be defined in pregnant human myometrium before the therapeutic potential of cAMP‐elevating agents in the prevention of preterm labour can be realised. In the present study, we tested the hypotheses that PKA activity is necessary for cAMP‐induced myometrial relaxation, and that prolonged cAMP elevation can prevent myometrial contractions. Myometrial tissues obtained from term, pre‐labour elective Caesarean sections were exposed to receptor‐independent cAMP agonists to determine the relationship between myometrial contractility (spontaneous and oxytocin‐induced), PKA activity, HSP20 phosphorylation and expression of contraction‐associated and cAMP signalling proteins. Acute (1 h) application of cAMP agonists promoted myometrial relaxation, but this was weakly related to PKA activation. A PKA‐specific activator, 6‐Bnz‐cAMP, increased PKA activity (6.8 ± 2.0 mean fold versus vehicle; P = 0.0313) without inducing myometrial relaxation. Spontaneous myometrial contractility declined after 24 h but was less marked when tissues were constantly exposed to cAMP agonists, especially for 8‐bromo‐cAMP (4.3 ± 1.2 mean fold versus vehicle; P = 0.0043); this was associated with changes to calponin, cofilin and HSP20 phosphorylated/total protein levels. Oxytocin‐induced contractions were unaffected by pre‐incubation with cAMP agonists despite treatments being able to enhance PKA activity and HSP20 phosphorylation. These data suggest that cAMP‐induced myometrial relaxation is not solely dependent on PKA activity and the ability of cAMP agonists to repress myometrial contractility is lost with prolonged exposure. We conclude that cAMP agonist treatment alone may not prevent preterm labour.
2D radially compensating excitation pulse in combination with an internal transceiver antenna for 3D MRI of the rectum at 7 T
Authors: van Kalleveen I. M. L. , Kroeze H. , Sbrizzi A. , Boer V. O. , Reerink O. , Philippens M. E. P. , van de Berg C. A. T. , Luijten P. R. , Klomp D. W. J. 
Published: June 2016

Purpose:The high precession frequency in ultrahigh field MRI coincides with reduced RF penetration, increased RF power deposition and consequently can lead to reduced scan efficiency. However, the shorter wavelength enables the use of efficient antennas rather than loop coils. In fact, ultrathin monopole antennas have been demonstrated at 7 T, which fit in natural cavities like the rectum in the human body. As the RF field generated by the antenna provides an extremely nonuniform B1 field, the use of conventional RF pulses will lead to severe image distortions and highly nonuniform contrast. However, using the two predominant dimensions (orthogonal to the antenna), 2D RF pulses can be designed that counteract the nonuniform B1 into uniform flip angles. In this study the authors investigate the use of an ultrathin antenna not only for reception, but also for transmission in 7 T MRI of the rectum.Methods:The 2D radially compensating excitation (2D RACE) pulse was designed in matlab. SAR calculations between the 2D RACE pulse and an adiabatic RF pulse (BIR‐4) have been obtained, to visualize the gain in decreasing the SAR when using the 2D RACE pulse instead of an adiabatic RF pulse. The authors used the 7 T whole body MR system in combination with an internally placed monopole antenna used for transceiving and obtained 3D gradient echo images with a conventional sinc pulse and with the 2D RACE pulse. For extra clarity, they also reconstructed an image where the receive field of the antenna was removed.Results:Comparing the results of the SAR simulations of the 2D RACE pulse with a BIR‐4 pulse shows that for low flip angles (θ < 41°) the SAR can be decreased with a factor of 4.8 or even more, when using the 2D RACE pulse. Relative to a conventional sinc excitation, the 2D RACE pulse achieves more uniform flip angle distributions than a BIR‐4 pulse with a smaller SAR increase (16 × versus 64 ×).Conclusions:The authors have shown that the 2D RACE pulse provides more homogeneous flip angles for gradient echo sequences when compared to a conventional sinc pulse albeit at increased SAR. However, when compared to adiabatic RF pulses, as shown by simulations, the SAR of the 2D RACE pulse can be an order of magnitude less. Phantom and in vivo human rectum images are obtained to demonstrate that the 2D RACE pulse can provide a uniform excitation while transmitting with a single ultrathin endorectal antenna at 7 T. The combination of thin rectal antennas with efficient uniform transmit can open up new possibilities in high resolution imaging of rectal cancer.
Young Children’s Energy Expenditure and Moderate-to-vigorous Physical Activity on Weekdays and Weekends
Authors: Lee Jung Eun , Stodden David F. , Gao Zan 
Published: June 2016

Background:Few studies have examined young children’s leisure- and school-based energy expenditure (EE) and moderateto-vigorous physical activity (MVPA). The purpose of this study was to explore children’s estimated EE rates and time spent in MVPA in 3 time segments: at-school, after-school, and weekends.Methods:A total of 187 second and third grade children from 2 elementary schools participated in the study. Accelerometers were used to assess children’s 5-day EE and MVPA. Multiple 2 (Grade) × 2 (Gender) ANOVAs with repeated measures (Time) were conducted to examine the differences in the outcome variables.Results:Significant time effects on EE and MVPA were revealed. Children’s EE rate and minutes in MVPA per day were higher during after school and weekends than at school.Conclusions:Although children were more active outside of school, their MVPA during weekdays and weekends still fell far short of the recommended level of 60 minutes/day.
Is There Potential for Repurposing Statins as Novel Antimicrobials?
Authors: Hennessy Emma , Adams Claire , Reen F. Jerry , O'Gara Fergal 
Published: June 2016

ABSTRACT

Statins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called “pleiotropic effects,” which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth and
in vitro
and
in vivo
virulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents.
Isavuconazole Is Effective for the Treatment of Experimental Cryptococcal Meningitis
Authors: Wiederhold Nathan P. , Kovanda Laura , Najvar Laura K. , Bocanegra Rosie , Olivo Marcos , Kirkpatrick William R. , Patterson Thomas F. 
Published: June 2016

ABSTRACT

We evaluated the efficacy of isavuconazole against cryptococcal meningitis. Treatment with either oral isavuconazole (120 mg/kg and 240 mg/kg twice a day [BID]) or fluconazole as the positive control significantly improved survival in mice infected intracranially with either
Cryptococcus neoformans
USC1597 or H99 and significantly reduced brain fungal burdens for both isolates. Concentrations of isavuconazole in plasma and brain tissue also demonstrated that the greatest improvements in survival and fungal burden were associated with elevated exposures.
Isolation and Characterization of NDM-Positive Escherichia coli from Municipal Wastewater in Jeddah, Saudi Arabia
Authors: Mantilla-Calderon David , Jumat Muhammad Raihan , Wang Tiannyu , Ganesan Pugalenthi , Al-Jassim Nada , Hong Pei-Ying 
Published: June 2016

ABSTRACT

The emergence of resistance to last-resort antibiotics is a public health concern of global scale. Besides direct person-to-person propagation, environmental pathways might contribute to the dissemination of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Here, we describe the incidence of
bla
NDM-1
, a gene conferring resistance to carbapenems, in the wastewater of the city of Jeddah, Saudi Arabia, over a 1-year period.
bla
NDM-1
was detected at concentrations ranging from 10
4
to 10
5
copies/m
3
of untreated wastewater during the entire monitoring period. These results indicate the ubiquity and high incidence of
bla
NDM-1
in the local wastewater. To track the bacteria carrying
bla
NDM-1
, we isolated
Escherichia coli
PI7, a strain of sequence type 101 (ST101), from wastewater around the Hajj event in October 2013. Genome sequencing of this strain revealed an extensive repertoire of ARGs as well as virulence and invasive traits. These traits were further confirmed by antibiotic resistance profiling and
in vitro
cell internalization in HeLa cell cultures. Given that this strain remains viable even after a certain duration in the sewerage, and that Jeddah lacks a robust sanitary infrastructure to fully capture all generated sewage, the presence of this bacterium in the untreated wastewater represents a potential hazard to the local public health. To the best of our knowledge, this is the first report of a
bla
NDM-1
-positive
E. coli
strain isolated from a nonnosocomial environment in Saudi Arabia and may set a priority concern for the need to establish improved surveillance for carbapenem-resistant
E. coli
in the country and nearby regions.
In Vitro
and
In Vivo
Assessments of Cardiovascular Effects with Omadacycline
Authors: Tanaka S. Ken , Villano Stephen 
Published: June 2016

ABSTRACT

Omadacycline is a first-in-class aminomethylcycline antibiotic with a broad spectrum of activity against Gram-positive and Gram-negative aerobes and anaerobes and atypical bacterial pathogens. A series of nonclinical studies, including mammalian pharmacologic receptor binding studies, human ether-a-go-go-related gene (hERG) channel binding studies, studies of the effects on
ex vivo
sinoatrial (SA) node activity, and studies of
in vivo
effects on cardiovascular function in the cynomolgus monkey, was undertaken to assess the cardiovascular risk potential. Omadacycline was found to bind almost exclusively to the muscarinic subtype 2 acetylcholine receptor (M
2
), and in the SA node model it antagonized the effect of a pan-muscarinic agonist (carbamylcholine) in a concentration-dependent manner. Omadacycline exhibited no effect on hERG channel activity at 100 μg/ml (179.5 μM), with a 25% inhibitory concentration of 166 μg/ml (298.0 μM). Omadacycline had no effect on QTc in conscious monkeys at doses up to 40 mg/kg of body weight. Overall, omadacycline appears to attenuate the parasympathetic influence on the heart rate but has a low potential to induce cardiac arrhythmia or to have clinically significant cardiovascular toxicity.
Predictors of Inadequate Linezolid Concentrations after Standard Dosing in Critically Ill Patients
Authors: Taubert Max , Zoller Michael , Maier Barbara , Frechen Sebastian , Scharf Christina , Holdt Lesca-Miriam , Frey Lorenz , Vogeser Michael , Fuhr Uwe , Zander Johannes 
Published: June 2016

ABSTRACT

Adequate linezolid blood concentrations have been shown to be associated with an improved clinical outcome. Our goal was to assess new predictors of inadequate linezolid concentrations often observed in critically ill patients. Fifty-two critically ill patients with severe infections receiving standard dosing of linezolid participated in this prospective observational study. Serum samples (median, 32 per patient) were taken on four consecutive days, and total linezolid concentrations were quantified. Covariates influencing linezolid pharmacokinetics were identified by multivariate analysis and a population pharmacokinetic model. Target attainment (area under the concentration-time curve over 12 h [AUC
12
]/MIC ratio of >50; MIC = 2 mg/liter) was calculated for both the study patients and a simulated independent patient group (
n
= 67,000). Target attainment was observed for only 36% of the population on both days 1 and 4. Independent covariates related to significant decreases of linezolid concentrations included higher weight, creatinine clearance rates, and fibrinogen and antithrombin concentrations, lower concentrations of lactate, and the presence of acute respiratory distress syndrome (ARDS). Linezolid clearance was increased in ARDS patients (by 82%) and in patients with elevated fibrinogen or decreased lactate concentrations. In simulated patients, most covariates, including fibrinogen and lactate concentrations and weight, showed quantitatively minor effects on target attainment (difference of ≤9% between the first and fourth quartiles of the respective parameters). In contrast, the presence of ARDS had the strongest influence, with only ≤6% of simulated patients reaching this target. In conclusion, the presence of ARDS was identified as a new and strong predictor of insufficient linezolid concentrations, which might cause treatment failure. Insufficient concentrations might also be a major problem in patients with combined alterations of other covariate parameters. (This study has been registered at ClinicalTrials.gov under registration number NCT01793012.)
Wild-Type and Non-Wild-Type Mycobacterium tuberculosis MIC Distributions for the Novel Fluoroquinolone Antofloxacin Compared with Those for Ofloxacin, Levofloxacin, and Moxifloxacin
Authors: Yu Xia , Wang Guirong , Chen Suting , Wei Guomei , Shang Yuanyuan , Dong Lingling , Schön Thomas , Moradigaravand Danesh , Parkhill Julian , Peacock Sharon J. , Köser Claudio U. , Huang Hairong 
Published: June 2016

ABSTRACT

Antofloxacin (AFX) is a novel fluoroquinolone that has been approved in China for the treatment of infections caused by a variety of bacterial species. We investigated whether it could be repurposed for the treatment of tuberculosis by studying its
in vitro
activity. We determined the wild-type and non-wild-type MIC ranges for AFX as well as ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), using the microplate alamarBlue assay, of 126 clinical
Mycobacterium tuberculosis
strains from Beijing, China, of which 48 were OFX resistant on the basis of drug susceptibility testing on Löwenstein-Jensen medium. The MIC distributions were correlated with mutations in the quinolone resistance-determining regions of
gyrA
(
Rv0006
) and
gyrB
(
Rv0005
). Pharmacokinetic/pharmacodynamic (PK/PD) data for AFX were retrieved from the literature. AFX showed lower MIC levels than OFX but higher MIC levels than LFX and MFX on the basis of the tentative epidemiological cutoff values (ECOFFs) determined in this study. All strains with non-wild-type MICs for AFX harbored known resistance mutations that also resulted in non-wild-type MICs for LFX and MFX. Moreover, our data suggested that the current critical concentration of OFX for Löwenstein-Jensen medium that was recently revised by the World Health Organization might be too high, resulting in the misclassification of phenotypically non-wild-type strains with known resistance mutations as wild type. On the basis of our exploratory PK/PD calculations, the current dose of AFX is unlikely to be optimal for the treatment of tuberculosis, but higher doses could be effective.
p53 Mediates Colistin-Induced Autophagy and Apoptosis in PC-12 Cells
Authors: Zhang Ling , Xie Daoyuan , Chen Xueping , Hughes Maria L. R. , Jiang Guozheng , Lu Ziyin , Xia Chunli , Li Li , Wang Jinli , Xu Wei , Sun Yuan , Li Rui , Wang Rui , Qian Feng , Li Jian , Li Jichang 
Published: June 2016

ABSTRACT

The mechanism of colistin-induced neurotoxicity is still unknown. Our recent study (L. Zhang, Y. H. Zhao, W. J. Ding, G. Z. Jiang, Z. Y. Lu, L. Li, J. L. Wang, J. Li, and J. C. Li, Antimicrob Agents Chemother 59:2189–2197, 2015,
http://dx.doi.org/10.1128/AAC.04092-14
; H. Jiang, J. C. Li, T. Zhou, C. H. Wang, H. Zhang, and H. Wang, Int J Mol Med 33:1298–1304, 2014,
http://dx.doi.org/10.3892/ijmm.2014.1684
) indicates that colistin induces autophagy and apoptosis in rat adrenal medulla PC-12 cells, and there is interplay between both cellular events. As an important cellular stress sensor, phosphoprotein p53 can trigger cell cycle arrest and apoptosis and regulate autophagy. The aim of the present study was to investigate the involvement of the p53 pathway in colistin-induced neurotoxicity in PC-12 cells. Specifically, cells were treated with colistin (125 μg/ml) in the absence and presence of a p53 inhibitor, pifithrin-α (PFT-α; 20 nM), for 12 h and 24 h, and the typical hallmarks of autophagy and apoptosis were examined by fluorescence/immunofluorescence microscopy and electron microscopy, real-time PCR, and Western blotting. The results indicate that colistin had a stimulatory effect on the expression levels of the target genes and proteins involved in autophagy and apoptosis, including LC3-II/I, p53, DRAM (damage-regulated autophagy modulator), PUMA (p53 upregulated modulator of apoptosis), Bax, p-AMPK (activated form of AMP-activated protein kinase), and caspase-3. In contrast, colistin appeared to have an inhibitory effect on the expression of p-mTOR (activated form of mammalian target of rapamycin), which is another target protein in autophagy. Importantly, analysis of the levels of p53 in the cells treated with colistin revealed an increase in nuclear p53 at 12 h and cytoplasmic p53 at 24 h. Pretreatment of colistin-treated cells with PFT-α inhibited autophagy and promoted colistin-induced apoptosis. This is the first study to demonstrate that colistin-induced autophagy and apoptosis are associated with the p53-mediated pathway.
Discovery of Antischistosomal Drug Leads Based on Tetraazamacrocyclic Derivatives and Their Metal Complexes
Authors: Khan M. O. Faruk , Keiser Jennifer , Amoyaw P. N. A. , Hossain Mohammad F. , Vargas Mireille , Le Justin G. , Simpson Natalie C. , Roewe Kimberly D. , Freeman TaRynn N. Carder , Hasley Travis R. , Maples Randall D. , Archibald Stephen J. , Hubin Timothy J. 
Published: June 2016

ABSTRACT

Praziquantel (PZQ) is the only drug available for the treatment of schistosomiasis, and since its large-scale use might be associated with the onset of resistance, new antischistosomal drugs should be developed. A series of 26 synthetic tetraazamacrocyclic derivatives and their metal complexes were synthesized, characterized, and screened for antischistosomal activity by application of a phased screening program. The compounds were first screened against newly transformed schistosomula (NTS) of harvested
Schistosoma mansoni
cercariae, then against adult worms, and finally,
in vivo
using the mouse model of
S. mansoni
infection. At a concentration of 33 μM, incubation with a total of 12 compounds resulted in the mortality of NTS at the 62% to 100% level. Five of these showing 100% inhibition of viability of NTS at 10 μM were selected for further screening for determination of the 50 inhibitory concentrations (IC
50
s) against both NTS and adult worms. Against NTS, all 5 compounds showed IC
50
s comparable to the IC
50
of the standard drug, PZQ (0.87 to 9.65 μM for the 5 compounds versus 2.20 μM for PZQ). Three of these, which are the bisquinoline derivative of cyclen and its Fe
2+
and Mn
2+
complexes, showed micromolar IC
50
s (1.62 μM, 1.34 μM, and 4.12 μM, respectively, versus 0.10 μM for PZQ) against adult worms.
In vivo
, the worm burden reductions were 12.3%, 88.4%, and 74.5%, respectively, at a single oral dose of 400 mg/kg of body weight. The Fe
2+
complex exhibited activity
in vivo
comparable to that of PZQ, pointing to the discovery of a novel drug lead for schistosomiasis.
Efficacy of a Novel Tricyclic Topoisomerase Inhibitor in a Murine Model of Neisseria gonorrhoeae Infection
Authors: Savage Victoria J. , Charrier Cédric , Salisbury Anne-Marie , Box Helen , Chaffer-Malam Nathan , Huxley Anthony , Kirk Ralph , Noonan Gary M. , Mohmed Sarfraz , Craighead Mark W. , Ratcliffe Andrew J. , Best Stuart A. , Stokes Neil R. 
Published: June 2016

ABSTRACT

There is an urgent need for new antibiotics to treat multidrug-resistant
Neisseria gonorrhoeae
. In this report, the microbiology,
in vivo
pharmacokinetics, and efficacy of REDX05931, a representative novel tricyclic topoisomerase inhibitor, were evaluated. REDX05931 demonstrated high oral bioavailability in mice and reduced
N. gonorrhoeae
infection after a single dose in a mouse model of gonorrhea. These data support the potential of this series of small molecules as a new treatment for drug-resistant gonorrheal infections.