bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substrate Inhibition of VanA byd-Alanine Reduces Vancomycin Resistance in a VanX-Dependent Manner
Authors: van der Aart Lizah T. , Lemmens Nicole , van Wamel Willem J. , van Wezel Gilles P. 
Published: June 2016

ABSTRACTThe increasing resistance of clinical pathogens against the glycopeptide antibiotic vancomycin, a last-resort drug against infections with Gram-positive pathogens, is a major problem in the nosocomial environment. Vancomycin inhibits peptidoglycan synthesis by binding to thed-Ala–d-Ala terminal dipeptide moiety of the cell wall precursor lipid II. Plasmid-transferable resistance is conferred by modification of the terminal dipeptide into the vancomycin-insensitive variantd-Ala–d-Lac, which is produced by VanA. Here we show that exogenousd-Ala competes withd-Lac as a substrate for VanA, increasing the ratio of wild-type to mutant dipeptide, an effect that was augmented by several orders of magnitude in the absence of thed-Ala–d-Ala peptidase VanX. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that high concentrations ofd-Ala led to the production of a significant amount of wild-type cell wall precursors, whilevanX-null mutants produced primarily wild-type precursors. This enhanced the efficacy of vancomycin in the vancomycin-resistant model organismStreptomyces coelicolor, and the susceptibility of vancomycin-resistant clinical isolates ofEnterococcus faecium(VRE) increased by up to 100-fold. The enhanced vancomycin sensitivity ofS. coelicolorcells correlated directly to increased binding of the antibiotic to the cell wall. Our work offers new perspectives for the treatment of diseases associated with vancomycin-resistant pathogens and for the development of drugs that target vancomycin resistance.
Development and Evaluation of a Gentamicin Pharmacokinetic Model That Facilitates Opportunistic Gentamicin Therapeutic Drug Monitoring in Neonates and Infants
Authors: Germovsek Eva , Kent Alison , Metsvaht Tuuli , Lutsar Irja , Klein Nigel , Turner Mark A. , Sharland Mike , Nielsen Elisabet I. , Heath Paul T. , Standing Joseph F. 
Published: June 2016

ABSTRACTTrough gentamicin therapeutic drug monitoring (TDM) is time-consuming, disruptive to neonatal clinical care, and a patient safety issue. Bayesian models could allow TDM to be performed opportunistically at the time of routine blood tests. This study aimed to develop and prospectively evaluate a new gentamicin model and a novel Bayesian computer tool (neoGent) for TDM use in neonatal intensive care. We also evaluated model performance for predicting peak concentrations and the area under the concentration-time curve from time 0 h to timeth (AUC0–t). A pharmacokinetic meta-analysis was performed on pooled data from three studies (1,325 concentrations from 205 patients). A 3-compartment model was used with the following covariates: allometric weight scaling, postmenstrual and postnatal age, and serum creatinine concentration. Final parameter estimates (standard errors) were as follows: clearance, 6.2 (0.3) liters/h/70 kg of body weight; central volume (V), 26.5 (0.6) liters/70 kg; intercompartmental disposition (Q), 2.2 (0.3) liters/h/70 kg; peripheral volume V2, 21.2 (1.5) liters/70 kg; intercompartmental disposition (Q2), 0.3 (0.05) liters/h/70 kg; peripheral volume V3, 148 (52.0) liters/70 kg. The model's ability to predict trough concentrations from an opportunistic sample was evaluated in a prospective observational cohort study that included data from 163 patients and 483 concentrations collected in five hospitals. Unbiased trough predictions were obtained; the median (95% confidence interval [CI]) prediction error was 0.0004 (−1.07, 0.84) mg/liter. Results also showed that peaks and AUC0–tvalues could be predicted (from one randomly selected sample) with little bias but relative imprecision, with median (95% CI) prediction errors being 0.16 (−4.76, 5.01) mg/liter and 10.8 (−24.9, 62.2) mg · h/liter, respectively. neoGent was implemented in R/NONMEM and in the freely available TDMx software.
Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection
Authors: Minandri Fabrizia , Imperi Francesco , Frangipani Emanuela , Bonchi Carlo , Visaggio Daniela , Facchini Marcella , Pasquali Paolo , Bragonzi Alessandra , Visca Paolo 
Published: June 2016

ABSTRACT

Pseudomonas aeruginosa
is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients. Iron is essential for bacterial growth, and
P. aeruginosa
expresses multiple iron uptake systems, whose role in lung infection deserves further investigation.
P. aeruginosa
Fe
3+
uptake systems include the pyoverdine and pyochelin siderophores and two systems for heme uptake, all of which are dependent on the TonB energy transducer.
P. aeruginosa
also has the FeoB transporter for Fe
2+
acquisition. To assess the roles of individual iron uptake systems in
P. aeruginosa
lung infection, single and double deletion mutants were generated in
P. aeruginosa
PAO1 and characterized
in vitro
, using iron-poor media and human serum, and
in vivo
, using a mouse model of lung infection. The iron uptake-null mutant (
tonB1 feoB
) and the Fe
3+
transport mutant (
tonB1
) did not grow aerobically under low-iron conditions and were avirulent in the mouse model. Conversely, the wild type and the
feoB
,
hasR phuR
(heme uptake), and
pchD
(pyochelin) mutants grew
in vitro
and caused 60 to 90% mortality in mice. The pyoverdine mutant (
pvdA
) and the siderophore-null mutant (
pvdA pchD
) grew aerobically in iron-poor media but not in human serum, and they caused low mortality in mice (10 to 20%). To differentiate the roles of pyoverdine in iron uptake and virulence regulation, a
pvdA fpvR
double mutant defective in pyoverdine production but expressing wild-type levels of pyoverdine-regulated virulence factors was generated. Deletion of
fpvR
in the
pvdA
background partially restored the lethal phenotype, indicating that pyoverdine contributes to the pathogenesis of
P. aeruginosa
lung infection by combining iron transport and virulence-inducing capabilities.
Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders
Authors: Hatcher Christopher L. , Mott Tiffany M. , Muruato Laura A. , Sbrana Elena , Torres Alfredo G. 
Published: June 2016

ABSTRACT

Burkholderia mallei
is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for
Burkholderia
, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded
B. mallei
Δ
tonB
Δ
hcp1
(CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal
B. mallei
challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the
B. mallei
lux
(CSM001) wild-type strain.
Transcription of Sialic Acid Catabolism Genes in Corynebacterium glutamicum Is Subject to Catabolite Repression and Control by the Transcriptional Repressor NanR
Authors: Uhde Andreas , Brühl Natalie , Goldbeck Oliver , Matano Christian , Gurow Oksana , Rückert Christian , Marin Kay , Wendisch Volker F. , Krämer Reinhard , Seibold Gerd M. 
Published: June 2016

ABSTRACT

Corynebacterium glutamicum
metabolizes sialic acid (Neu5Ac) to fructose-6-phosphate (fructose-6P) via the consecutive activity of the sialic acid importer SiaEFGI,
N
-acetylneuraminic acid lyase (NanA),
N
-acetylmannosamine kinase (NanK),
N
-acetylmannosamine-6P epimerase (NanE),
N
-acetylglucosamine-6P deacetylase (NagA), and glucosamine-6P deaminase (NagB). Within the cluster of the three operons
nagAB
,
nanAKE
, and
siaEFGI
for Neu5Ac utilization a fourth operon is present, which comprises
cg2936
, encoding a GntR-type transcriptional regulator, here named NanR. Microarray studies and reporter gene assays showed that
nagAB
,
nanAKE
,
siaEFGI
, and
nanR
are repressed in wild-type (WT)
C. glutamicum
but highly induced in a Δ
nanR C. glutamicum
mutant. Purified NanR was found to specifically bind to the nucleotide motifs A[AC]G[CT][AC]TGATGTC[AT][TG]ATGT[AC]TA located within the
nagA-nanA
and
nanR-sialA
intergenic regions. Binding of NanR to promoter regions was abolished in the presence of the Neu5Ac metabolism intermediates GlcNAc-6P and
N
-acetylmannosamine-6-phosphate (ManNAc-6P). We observed consecutive utilization of glucose and Neu5Ac as well as fructose and Neu5Ac by WT
C. glutamicum
, whereas the deletion mutant
C. glutamicum
Δ
nanR
simultaneously consumed these sugars. Increased reporter gene activities for
nagAB
,
nanAKE
, and
nanR
were observed in cultivations of WT
C. glutamicum
with Neu5Ac as the sole substrate compared to cultivations when fructose was present. Taken together, our findings show that Neu5Ac metabolism in
C. glutamicum
is subject to catabolite repression, which involves control by the repressor NanR.

IMPORTANCE
Neu5Ac utilization is currently regarded as a common trait of both pathogenic and commensal bacteria. Interestingly, the nonpathogenic soil bacterium
C. glutamicum
efficiently utilizes Neu5Ac as a substrate for growth. Expression of genes for Neu5Ac utilization in
C. glutamicum
is here shown to depend on the transcriptional regulator NanR, which is the first GntR-type regulator of Neu5Ac metabolism not to use Neu5Ac as effector but relies instead on the inducers GlcNAc-6P and ManNAc-6P. The identification of conserved NanR-binding sites in intergenic regions within the operons for Neu5Ac utilization in pathogenic
Corynebacterium
species indicates that the mechanism for the control of Neu5Ac catabolism in
C. glutamicum
by NanR as described in this work is probably conserved within this genus.
Comparing cognitive-behavioural psychotherapy and psychoeducation for non-specific symptoms associated with indoor air: a randomised control trial protocol
Authors: Selinheimo Sanna , Vuokko Aki , Sainio Markku , Karvala Kirsi , Suojalehto Hille , Järnefelt Heli , Paunio Tiina 
Published: June 2016

IntroductionIndoor air-related conditions share similarities with other conditions that are characterised by medically unexplained symptoms (MUS)-a combination of non-specific symptoms that cannot be fully explained by structural bodily pathology. In cases of indoor air-related conditions, these symptoms are not fully explained by either medical conditions or the immunological–toxicological effects of environmental factors. The condition may be disabling, including a non-adaptive health behaviour. In this multifaceted phenomenon, psychosocial factors influence the experienced symptoms. Currently, there is no evidence of clinical management of symptoms, which are associated with the indoor environment and cannot be resolved by removing the triggering environmental factors. The aim of this study is to compare the effect of treatment-as-usual (TAU) and two psychosocial interventions on the quality of life, and the work ability of employees with non-specific indoor air-related symptomatology.Methods and analysesThe aim of this ongoing randomised controlled trial is to recruit 60 participants, in collaboration with 5 occupational health service units. The main inclusion criterion is the presence of indoor air-related recurrent symptoms in ≥2 organ systems, which have no pathophysiological explanation. After baseline clinical investigations, participants are randomised into interventions, which all include TAU: cognitive-behavioural psychotherapy, psychoeducation and TAU (control condition). Health-related quality of life, measured using the 15D-scale, is the primary outcome. Secondary outcomes include somatic and psychiatric symptoms, occupational factors, and related underlying mechanisms (ie, cognitive functioning). Questionnaires are completed at baseline, at 3, 6 and 12-month follow-ups. Data collection will continue until 2017. The study will provide new information on the individual factors related to indoor air-associated symptoms, and on ways in which to support work ability.Ethics and disseminationThe Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, has granted approval for the study. The results will be published in peer-reviewed journals.Trial registration numberNCT02069002; Pre-results.
Improving physical health for people taking antipsychotic medication in the Community Learning Disabilities Service
Authors: Thomson Helen , Hall Ian , Shah Amar 
Published: June 2016

Adherence with antipsychotic monitoring guidelines is notoriously low nationally. Without active monitoring and measures to improve metabolic abnormalities, more patients may develop related morbidity and mortality. An audit highlighted antipsychotic monitoring in this learning disability service in London did not match guideline recommendations. People with intellectual disability also experience health inequalities. Psychiatrists are well placed to provide advice and assistance that is suitable for those with complex communication, behaviour, and social needs.The QI team tested ideas to increase rates of antipsychotic reviews. The focus was the follow up monitoring of all universal measures recommended by NICE 2014, collected at 2-weekly intervals. We trialled interventions in four broad categories; Intervention 1: to make monitoring more structured and planned; Intervention 2: to increase staff and patient awareness of healthy eating and exercise programs; Intervention 3: to increase the collection of diet and exercise histories from patients; Intervention 4: to improve the uptake of blood tests.The interventions created an improvement in monitoring. There are lessons in the methodology for others carrying out similar projects.
Succeeding in Sustained Reduction in the use of Restraint using the Improvement Model
Authors: Bell Alyssa , Gallacher Neil 
Published: June 2016

As part of the Scottish Patient Safety Programme – Mental Health one of the main drivers was the reduction of harm to patients caused by restraint. The aim of this project was to reduce the number of restraints on our Acute Admissions ward.Through use the of the Improvement Model (PDSA), frontline staff were empowered to implement small tests of change at a grassroots level. This approach has led to frontline staff having ownership of driving the changes on a daily basis within the Clinical area.The use of a restraint data collection tool has been adapted and developed with frontline staff to ensure that the staff have ownership of data collected and is used to facilitate improvement. This data is used to inform the development of our Physical Interventions training. Most recently, following analysis, were able to introduce changes to promote the increased use of de-escalation and a shift from prone restraint to the safer seated restraint position.Patient involvement has been paramount with their inclusion in the debrief process. The information gleaned from the patients is used for staff and patient reflection. This has created a learning environment not only for staff but also patients and carers. Everyone involved is able to identify reasons and triggers and generate ideas to reduce the possibility of another restraint.The use of staff and patient safety climate surveys has ensured that we are constantly monitoring improvements in the feeling of safety amongst staff and patients.Our approach has resulted in a change in the culture of restraint resulting in a sustained reduction of 50% in restraint.
Mobile phones and seizures: drug-resistant epilepsy is less common in mobile-phone-using patients
Authors: Nagarjunakonda Sundarachary , Amalakanti Sridhar , Uppala Veeramma , Gajula Rama Krishna , Tata Ramya Sree , Bolla Hima Bindu , Rajanala Lalitha , Athina Srinivasulu , Daggumati Rajeswari , Lavu Harish , Devanaboina Anil Kumar 
Published: June 2016

ABSTRACTBackgroundEpilepsy is a condition where patients have seizures due to abnormal nerve impulses in the brain. The effect of mobile phone radiation on patients with seizures is not known.ObjectiveTo compare the seizure profile of patients not using mobile phones with that of their peers using mobile phones.MethodsIn a retrospective cohort study performed at the neurology outpatient department of Guntur Medical College Hospital, Guntur, India from September 2014 to September 2015, we included 178 consecutive epileptic patients aged 16–65 years, who had had seizure disorder for 1 year or more. On the basis of their possession and usage of mobile phones, patients were divided into three groups: no mobile group (NMG), home mobile group (HMG) and personal mobile group (PMG). We obtained data on seizure frequency and recorded details of mobile phone usage and their antiepileptic drug (AED) treatment.Results107 NMG, 3 HMG and 68 PMG patients were finalised for the analysis. There was no significant difference in the number of seizures in the past year between the three groups. The PMG (3.7%) contained a clinically significant lower proportion of patients with drug-resistant epilepsy than the NMG (28.2%). Patients with drug-responsive epilepsy were 7.4 (95% CI 1.4 to 39.9) (p=0.01) times more likely to be found in the PMG than in the NMG after adjustment for differences in sex and occupation.ConclusionsAlthough the experimental data remain inconclusive, our clinical study suggests that patients who use mobile phones are less likely to have drug-resistant epilepsy.
Analysis of Distributed Power Flow Controller in Power System Network for Improving Power Flow Control
Authors: Saini Kuldeep , Saxena Aakash , Farooqi M.R. 
Published: June 2016

<p>In this paper, a new power flow controlling device called Distributed Power Flow Controller (DPFC) is presented that offers the same control capability as the unified power-flow controller (UPFC) but with much lower cost and high reliability. The DPFC eliminates the common DC link within the UPFC, to enable the independent operation of the shunt and the series converter. The D-FACTS concept is employed to the series converter to increase the reliability. Multiple low-rating single-phase converters replace the high-rating three-phase series converter, which significantly reduces the cost and increases the reliability. The active power that is exchanged through the common DC link in the UPFC is now transferred through the transmission line at the 3rd harmonic frequency. The DPFC is modeled in a rotating dq-frame. The modeling and analysis of DPFC in a two area two bus interconnected system is done in MATLAB/Simulink environment and comparison between the DPFC and UPFC considering the power flow and cost are also shown.</p><p> </p>
« Quand on parlait le berbère à la cour de Grenade » : quelques réflexions sur la berbérité de la taifa ziride (al-Andalus, xie siècle)
Authors: Sarr Bilal 
Published: June 2016

Using data provided by the written sources and the archaeology, this article aims at analysing the Zirid Taifa of Granada, studying its different elements (administration, organisation of the state, the succession to power and material culture) in order to discover its authentic Berber aspects. The Zirides, recently arrived in al-Andalus, offer us a unique opportunity to draw comparisons between the process of Islamisation in the Maghreb and in al-Andalus. The decisive power of the tribal ǧamāʿa, the important role of women, the persistence of a Berber onomastics and the use of Berber language are features of a group that maintains a North African identity. Other areas, such as the evolution of the city, the pottery and the administrative structure of the state are clearly borrowed from the Arab-Andalusian tradition.
À partir des données fournies par les sources écrites et l’archéologie, cet article se propose d’analyser la taifa ziride de Grenade, en étudiant ses différents éléments (l’organisation de l’État, la désignation des émirs et la culture matérielle) afin de révéler leurs aspects authentiquement berbères. Les Zirides, récemment arrivés en al-Andalus, nous offrent une occasion unique d’établir des parallèles entre le processus d’arabo-islamisation au Maghreb et celui d’al-Andalus. Le pouvoir de décision important de la ǧamāʿa tribale, le rôle de la femme, la persistance d’une onomastique berbère et l’utilisation de la langue berbère sont caractéristiques d’un groupe qui conserve une identité nord-africaine. D’autres domaines comme l’évolution de la ville, le mobilier céramique et la structure administrative de l’État ont en revanche nettement emprunté à la tradition arabo-andalouse.
This article is in French
Femmes des Mille et une nuits
Authors: Garcin Jean-Claude 
Published: June 2016

We can assume that we find for the first time in the 15th century the character of Šahrazād as a courageous woman who had taken upon herself to get the king away from his bias against the women after his wife deceived him. Šahrazād tells him stories in which women have not infrequently more fortitude and deserve more to be trusted than men who are sometimes immature. But there are also from the same century other stories in which ancient themes continue, for instance about crafty and lustful women. In the 16th century, “Dalila the wily” upgrade crafty women, but in the seventeeth century, the Ottoman’s connections with Protestant communities in Germany introduced to the Arabian Nights European witches and bird-women. Anyway men have to avoid to fall in love with women. During the 18th century, a solution to the problem of good relationship between men and women is sketched in the “Masrūr and Zayn al-Mawāṣif” story. The two characters, a christian man and a jewish woman, live happily after they had both converted to Islam. In the same way, the Arabian Nights end when the king gives up his bias against the women and marry Šahrazād, “a good wife [. . .] a pure, a chaste, a devout one”. But he has to keep faith with his wife and preserve responbility for her, according to Islamic Law.
Du ixe/xve siècle semble dater le personnage d’une Šahrazād qui s’est donné pour mission de faire revenir le roi de ses préventions sur les femmes, après qu’il ait découvert l’infidélité de son épouse. Šahrazād lui présente des contes où les femmes apparaissent souvent comme plus fortes et dignes de confiance que les personnages masculins, parfois immatures. Mais le recueil enregistre également pour cette époque, des contes où les vieux topoï de la femme rusée et lubrique persistent. Au xe/xvie siècle, le personnage de « Dalila la Rusée » revalorise la ruse des femmes, mais, au xie/xviie siècle, les contacts du pouvoir ottoman avec les protestants d’Allemagne introduisent dans les contes des Nuits, sorcières et femmes-oiseaux venues d’Europe, et les femmes à nouveau sont renvoyées à leur rôle de reproductrices dont il ne faut surtout pas s’éprendre. C’est au xiie/xviiie siècle, qu’une solution s’ébauche. Dans le conte de « Masrūr et Zayn al-Mawāṣif », les deux héros, un chrétien et une juive, trouvent leur bonheur dans une conversion à l’islam. De même à la fin des Nuits, lorsque le roi abandonne ses préventions à l’égard des femmes et épouse Šahrazād, la « bonne épouse [. . .] pure, chaste et pieuse », devient l’épouse du roi revenu de ses erreurs, et au roi s’imposent pour sa part les devoirs de fidélité et d’autorité sur sa femme, comme l’enseigne l’Islam.
This article is in French.