bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of oral care solutions on mucous membrane integrity and bacterial colonization
Authors: Özden Dilek , Türk Gülengün , Düger Cevdet , Güler Elem K , Tok Fatma , Gülsoy Zuhal
Published: December 2013

Aim

This research was conducted with the aim of determining the influence of three different oral care solutions on oral mucous membrane integrity in critically ill patients.

Background

Oral care is a basic part of nursing care in intensive care units.

Design

A randomized controlled trial was conducted.

Method

A total of 60 patients (20 patients in each group) comprised the study sample of the research. Patients were randomly allocated to three groups. Patients in groups 1, 2 and 3 were administered mouth care three times a day using 5% sodium bicarbonate, 0·2% chlorhexidine and saline solution, respectively. Data were collected by means of a ‘Descriptive characteristics form’ and an ‘oral assessment tool’.

Results

Mean scores of oral assessment tool increased according to days in all groups, however, this increase was found to be statistically insignificant (p > 0·05). Mean scores of the patients in saline solution group were seen to be lower than those of the other groups. When inter‐group comparison of days was done, the difference between oral assessment scores was found to be statistically significant (p = 0·000).

Conclusion

It was found that there was no difference between patient groups receiving saline solution, sodium bicarbonate and 0·2% chlorhexidine for mouth care in terms of oral mucous membrane integrity; oral mucosa of all patients was found to be mildly dysfunctioning.

Relevance to clinical practice

It is thought that standardized protocols for oral hygiene developed in the light of the findings of randomized controlled trials may improve the oral health in critically ill patients.
The emergence of cardiometabolic disease risk in Chinese children and adults: consequences of changes in diet, physical activity and obesity
Authors: Adair L. S. , Gordon‐Larsen P. , Du S. F. , Zhang B. , Popkin B. M.
Published: December 2013

Strong secular declines in physical activity, increased fat and salt intake, and increased obesity, especially abdominal obesity, mark China's recent nutrition transition. The China Health and Nutrition 2009 Survey collected anthropometry, blood pressure and fasting blood samples from more than 9,000 individuals ≥7 years of age. We focus on elevated blood pressure and plasma markers of diabetes, inflammation and dyslipidemia. We used international definitions of cardiometabolic risk and estimated age‐ and sex‐specific prevalence ratios for each outcome for high waist circumference or overweight. We used logistic regression to assess each risk factor's association with diet, physical activity, overweight and abdominal obesity. Cardiometabolic risk prevalence was high in all age groups Prevalence ratios for most risk factors were nearly doubled for overweight or high waist circumference groups. Prevalence ratios were higher in younger than older adults. Low physical activity consistently predicted higher cardiometabolic risk across most outcomes and age‐sex groups. The co‐occurrence of overweight and high waist circumference was highly predictive of dyslipidemia, elevated glycated haemoglobin and diabetes. High prevalence of cardiometabolic risk factors and their strong association with weight status and abdominal obesity in young adults portend increases in cardiometabolic morbidity and mortality. Early interventions will be required to reverse trends.
The physical activity transition among adults in China: 1991–2011
Authors: Ng S. W. , Howard A.‐G. , Wang H. J. , Su C. , Zhang B.
Published: December 2013

Previous studies have linked work, home production, travel activities and inactivity with weight and health outcomes. However, these focused on average physical activity (PA) over time rather than changes in PA and associated sociodemographic and economic factors and urbanicity. Using the 1991–2011 China Health and Nutrition Survey data, we estimated the metabolic equivalent of task hours per week for individuals in occupational, domestic, travel and active leisure domains and sedentary hours per week. We present the distributions among adult men and women (aged 18–60), and use quantile regression models to explore factors associated with these trends. Trend analyses on the distribution of PA show declines along the whole distribution of occupational PA for men and women and domestic PA for women in China. These patterns remain consistent after adjusting for individual‐ and household‐level factors. Controlling for urbanicity mitigated the decrease in occupational PA, particularly for men, but not the decrease in domestic PA. Given China's rapid urbanization and its association with occupational PA declines and the strong time trend in domestic PA, there is a need to invest in interventions and policies that promote PA during leisure and travel times.
Progress in understanding oral health and HIV/AIDS
Authors: Patton LL
Published: December 2013

Over the last 30 years, there have been significant advances in our scientific knowledge of HIV disease, including prevention, detection, medical management, and attempts at cure. Investigations and observations of the oral cavity in individuals with HIV disease have contributed substantially to scientific discovery and innovation. Challenges remain for managing existing and emerging oral diseases associated with HIV and understanding the contribution of latent oral mucosal reservoirs to HIV eradication.
N‐Alkoxyheterocycles As Irreversible Photooxidants
Authors: Wosinska Zofia M. , Stump Faye L. , Ranjan Rajeev , Lorance Edward D. , Finley GeNita N. , Patel Priya P. , Khawaja Muzamil A. , Odom Katie L. , Kramer Wolfgang H. , Gould Ian R.
Published: December 2013

Irreversible photooxidation based on N–O bond fragmentation is demonstrated for N‐methoxyheterocycles in both the singlet and triplet excited state manifolds. The energetic requirements for bond fragmentation are studied in detail. Bond fragmentation in the excited singlet manifold is possible for ππ* singlet states with energies significantly larger than the N–O bond dissociation energy of ca 55 kcal mol−1. For the nπ* triplet states, N–O bond fragmentation does not occur in the excited state for orbital overlap and energetic reasons. Irreversible photooxidation occurs in the singlet states by bond fragmentation followed by electron transfer. Irreversible photooxidation occurs in the triplet states via bimolecular electron transfer to the donor followed by bond fragmentation. Using these two sensitization schemes, donors can be irreversibly oxidized with oxidation potentials ranging from ca 1.6–2.2 V vs SCE. The corresponding N‐ethylheterocycles are characterized as conventional reversible photooxidants in their triplet states. The utility of these sensitizers is demonstrated by irreversibly generating the guanosine radical cation in buffered aqueous solution.
Comparative Analysis of Cellular Phenotypes Within the Neointima From Vein Segments Collected Prior to Vascular Access Surgery and Stenotic Arteriovenous Dialysis Accesses
Authors: Lee Timmy , Wang Yang , Arend Lois , Cornea Virgilius , Campos Begona , Munda Rino , Roy‐Chaudhury Prabir
Published: December 2013

Venous stenosis, secondary to venous neointimal hyperplasia (VNH), at the arteriovenous anastomosis (AV) is a major etiology of vascular access failure in AV fistulas (AVF) and AV grafts (AVG). Recently, our group has reported that severe VNH also occurs prior to vascular access placement. The objective of this study was to perform a comparison of the cellular phenotypes within the neointima from veins collected from subjects at the time of new vascular access creation and stenotic veins from subjects with failed AVGs and AVFs. Vein samples, collected at the time of new access surgery, and stenotic vein segments, collected at access revision, were evaluated for expression of α‐smooth muscle actin (SMA), vimentin, and desmin within the neointima, and quantified using semiquantitative scoring. Within the neointima, the majority of cells from vein samples collected at the time of new access surgery were contractile smooth muscle cells, and veins from stenotic AVF and AVG were predominately myofibroblasts. Our results suggest the possibility of different mechanistic pathways in response to vascular injury that occurs prior to vascular access creation vs. after access creation, and that divergent therapeutic approaches may be needed for treating vascular injury in these two settings.
Identity Politics in the Educational System in South Tyrol: Balancing between Minority Protection and the Need to Manage Diversity
Authors: Wisthaler Verena
Published: December 2013

This article focuses on the educational system in South Tyrol as one of the pillars of language and identity politics used for minority protection and elaborates on possible future developments triggered by immigration. After a historical overview of the coexistence of the three linguistic groups in South Tyrol, the article will explore, from the perspective of the educational system, the institutional framework guaranteeing the protection of the German‐speaking and Ladin minority and in particular their languages as the most important markers of the particular local identities. The article then examines how the educational system in South Tyrol deals with increasing immigration, assessing the strengths and weaknesses in relation to whether the educational system facilitates, on the one hand, the development of a multilingual society and, on the other, individual language competences and thus individual multilingualism.
Liturgy of Nation‐Formation: Patrick Pearse and the Theological Background of the Easter Rising of 1916
Authors: Ruczaj Maciej
Published: December 2013

The Dublin 1916 Easter Rising is most often analysed in terms of the ‘blood sacrifice’ concept and its ‘theatrical’ aspect with both rhetorical devices being ascribed to Patrick (Padraic) Pearse – poet, dramatist, and a crucial figure in the development of the discourse of Irish nationalism. This article proposes a reading of Pearse's literary and political texts centred on the relation between the religious and the political. Starting with the delineation of the complex ‘translation of the sacred’ from the religious to the secular context, the article then examines the two above‐mentioned key dimensions of the Rising, its sacrificial and ‘theatrical’ aspects, demonstrating their theological affinities. The two are interconnected through the thomistic theory of the liturgical sign, suggesting that the Easter Rising, as a crucial event in the construction of Irish nationhood, was devised and carried out per analogiam to the liturgical symbolism of the Catholic Mass.
Pedagogy, Provocation and Paradox:Denmark'sKunstnernesStudieskole
Authors: Greaves Kerry
Published: December 2013

The last two decades of the nineteenth century witnessed an apparent revolution in art education inDenmark with the establishment of the ‘Free Schools’, a group of alternative schools that provided students with a choice other than theRoyalAcademy. The most important of these schools, theKunstnernesStudieskole(Artists'StudySchool, established in 1882), was subsidised by the government and headed by Laurits Tuxen,P.S. Krøyer, and Kristian Zahrtmann,Academy‐trained artists who modeled the school's education on the French atelier system. The debate that formed theStudySchool was at its core one of democratization, which was perceived to be synonymous with international modernism. Yet its artists functioned within a network of fluid roles designed to openly augment the existing pedagogical structure from within – a specificallyDanish phenomenon. This article proposes an alternative framework for late‐nineteenth‐centuryDanish art education systems that situates theStudySchool within the context ofDanish culture and as an extension of the social democratic tendencies proliferating at this time, which were significantly influenced by the preacherN.F.S. Grundtvig.Danish artists' actual situation had more to do with assimilating a myriad of local and international impulses into a specificallyDanish version of modernism.
Cognitive Distance and Obstacles to Subsidiary Business Success‐The Experience of Chinese Companies in Germany
Authors: Si Yuefang , Liefner Ingo
Published: December 2013

The success of foreign direct investment (FDI) from developing countries to developed countries is critically dependent on managing the differences in the knowledge bodies of the regions and players involved. The theories that at least partly explain successful FDI of this kind use the terms cognitive distance and embeddedness. Most of the empirical research takes the perspective of regions and has addressed the problem of becoming embedded in the host regions. This paper takes the firm perspective and examines cognitive distance regarding not only the host region, but also the knowledge of the firms involved. It uses qualitative information from an extensive study of Chinese affiliates in Germany. In contrast to many other studies, this paper shows that a fast and successful process of becoming embedded in the host region can hamper the subsidiary's success, as it may cause conflict with the parent firm.
Mapping the Green Building Industry: How Local are Architects and General Contractors?
Authors: Cidell Julie
Published: December 2013

This paper is an empirical analysis of the geography of the green building economy within the United States, based on the location of the architects and contractors involved in producing green buildings in a selection of metropolitan areas. An overwhelming percentage of both architects and contractors are locally‐based, suggesting that rather than green building expertise clustering in a few cities, it has diffused nationwide. This has positive implications for the spread of knowledge about how to build more sustainably and also suggests that economic geographers need to broaden their study of the architecture industry beyond iconic buildings in world cities.
Dengue epidemics and adverse obstetrical outcomes in French Guiana: a semi‐ecological study
Authors: Hanf Matthieu , Friedman Eleanor , Basurko Celia , Roger Amaury , Bruncher Pascal , Dussart Philippe , Flamand Claude , Carles Gabriel , Buekens Pierre , Breart Gerard , Carme Bernard , Nacher Mathieu
Published: December 2013

Objective

To determine whether dengue epidemics are associated with an increase in adverse obstetrical outcomes.

Methods

Semi‐ecological study combining individual data on obstetrical events from the perinatal registry and aggregated exposure data from the epidemiologic surveillance of dengue in Cayenne, French Guiana between 2004 and 2007.

Results

After adjustment for individual risk factors, analysis showed that an epidemic level of dengue transmission during the first trimester was associated with an increased risk of post‐partum haemorrhage and preterm birth. The associated risks seemed to depend on the epidemic level.

Conclusions

Despite its limitations, this study suggests that dengue in the first trimester may be related to preterm birth and to post‐partum bleeding, thus leading to specific hypotheses that should be tested in prospective studies.
The non‐linear elasticity of the muscle sarcomere and the compliance of myosin motors
Authors: Fusi Luca , Brunello Elisabetta , Reconditi Massimo , Piazzesi Gabriella , Lombardi Vincenzo
Published: December 2013

Key points

The force in the half‐sarcomere (hs), the functional unit of muscle, is due to the contributions of individual myosin motors arranged in parallel in the half‐myosin filament and pulling on the opposing actin filament.

According to a linear hs model, during an isometric contraction the force rises to its maximal steady value (T0) in proportion to the number of actin‐attached motors, while the hs strain rises with a slope that depends on the compliance of the myofilaments.

We measured the hs stiffness, superimposing small 4 kHz length oscillations on the development of isometric contraction, and found an elastic element in parallel to the myosin motors with a constant stiffness ∼1/20th that of the motor array at T0.

The results support a structural model in which myosin motors are distributed in multiple substates, of which only the first ones are occupied during isometric force generation, causing a motor strain of ∼1.7 nm.

Force in striated muscle is due to attachment of the heads of the myosin, the molecular motors extending from the myosin filament, to the actin filament in each half‐sarcomere, the functional unit where myosin motors act in parallel. Mechanical and X‐ray structural evidence indicates that at the plateau of isometric contraction (force T0), less than half of the elastic strain of the half‐sarcomere is due to the strain in the array of myosin motors (s), with the remainder being accounted for by the compliance of filaments acting as linear elastic elements in series with the motor array. Early during the development of isometric force, however, the half‐sarcomere compliance has been found to be less than that expected from the linear elastic model assumed above, and this non‐linearity may affect the estimate of s. This question is investigated here by applying nanometre–microsecond‐resolution mechanics to single intact fibres from frog skeletal muscle at 4°C, to record the mechanical properties of the half‐sarcomere throughout the development of force in isometric contraction. The results are interpreted with mechanical models to estimate the compliance of the myosin motors. Our conclusions are as follows: (i) early during the development of an isometric tetanus, an elastic element is present in parallel with the myosin motors, with a compliance of ∼200 nm MPa−1 (∼20 times larger than the compliance of the motor array at T0); and (ii) during isometric contraction, s is 1.66 ± 0.05 nm, which is not significantly different from the value estimated with the linear elastic model.
Activity‐dependent regulation of NMDA receptors in substantia nigra dopaminergic neurones
Authors: Wild Angela R. , Jones Susan , Gibb Alasdair J.
Published: December 2013

Key points

Calcium ion influx through N‐methyl‐d‐aspartate receptors (NMDARs) may contribute to substantia nigra pars compacta (SNc) dopaminergic neurone dysfunction in Parkinson's disease.

Responses of NMDARs in dopaminergic neurones showed use‐dependent run‐down that was not readily reversible and was partly dependent on Ca2+ influx and partly dependent on clathrin‐mediated endocytosis.

Thus, we report regulation of NMDARs in SNc dopaminergic neurones by intracellular Ca2+ at both synaptic and extrasynaptic sites and provide evidence for activity‐dependent changes in receptor trafficking.

N‐Methyl‐d‐aspartate receptors (NMDARs) are Ca2+‐permeable glutamate receptors that play a critical role in synaptic plasticity and promoting cell survival. However, overactive NMDARs can trigger cell death signalling pathways and have been implicated in substantia nigra pars compacta (SNc) pathology in Parkinson's disease. Calcium ion influx through NMDARs recruits Ca2+‐dependent proteins that can regulate NMDAR activity. The surface density of NMDARs can also be regulated dynamically in response to receptor activity via Ca2+‐independent mechanisms. We have investigated the activity‐dependent regulation of NMDARs in SNc dopaminergic neurones. Repeated whole‐cell agonist applications resulted in a decline in the amplitude of NMDAR currents (current run‐down) that was use dependent and not readily reversible. Run‐down was reduced by increasing intracellular Ca2+ buffering or by reducing Ca2+ influx but did not appear to be mediated by the same regulatory proteins that cause Ca2+‐dependent run‐down in hippocampal neurones. The NMDAR current run‐down may be mediated in part by a Ca2+‐independent mechanism, because intracellular dialysis with a dynamin‐inhibitory peptide reduced run‐down, suggesting a role for clathrin‐mediated endocytosis in the regulation of the surface density of receptors. Synaptic NMDARs were also subject to current run‐down during repeated low‐frequency synaptic stimulation in a Ca2+‐dependent but dynamin‐independent manner. Thus, we report, for the first time, regulation of NMDARs in SNc dopaminergic neurones by changes in intracellular Ca2+ at both synaptic and extrasynaptic sites and provide evidence for activity‐dependent changes in receptor trafficking. These mechanisms may contribute to intracellular Ca2+ homeostasis in dopaminergic neurones by limiting Ca2+ influx through the NMDAR.
Sarcomere‐length dependence of myosin filament structure in skeletal muscle fibres of the frog
Authors: Reconditi Massimo , Brunello Elisabetta , Fusi Luca , Linari Marco , Martinez Manuel Fernandez , Lombardi Vincenzo , Irving Malcolm , Piazzesi Gabriella
Published: December 2013

Key points

Contraction of skeletal muscle is thought to be regulated by a structural change in the actin‐containing thin filaments of the sarcomere, but recent results have suggested that a structural change in the myosin‐containing thick filaments may also be involved.

We show that thick filament structure in resting muscle depends on the overlap with the thin filaments of the region of the thick filament containing myosin binding protein C (MyBP‐C).

During isometric contraction, the regions of the thick filaments that do not overlap with thin filaments are highly disordered, in contrast to their helical order in resting muscle.

The results provide strong support for the role of a structural transition in the thick filaments, mediated by an interaction between MyBP‐C and the thin filaments, in the physiological regulation of contraction in skeletal muscle.

X‐ray diffraction patterns were recorded at beamline ID02 of the European Synchrotron Radiation Facility from small bundles of skeletal muscle fibres from Rana esculenta at sarcomere lengths between 2.1 and 3.5 μm at 4°C. The intensities of the X‐ray reflections from resting fibres associated with the quasi‐helical order of the myosin heads and myosin binding protein C (MyBP‐C) decreased in the sarcomere length range 2.6–3.0 μm but were constant outside it, suggesting that an OFF conformation of the thick filament is maintained by an interaction between MyBP‐C and the thin filaments. During active isometric contraction the intensity of the M3 reflection from the regular repeat of the myosin heads along the filaments decreased in proportion to the overlap between thick and thin filaments, with no change in its interference fine structure. Thus, myosin heads in the regions of the thick filaments that do not overlap with thin filaments are highly disordered during isometric contraction, in contrast to their quasi‐helical order at rest. Heads in the overlap region that belong to two‐headed myosin molecules that are fully detached from actin are also highly disordered, in contrast to the detached partners of actin‐attached heads. These results provide strong support for the concept of a regulatory structural transition in the thick filament involving changes in both the organisation of the myosin heads on its surface and the axial periodicity of the myosin tails in its backbone, mediated by an interaction between MyBP‐C and the thin filaments.
Integration of Protein Abundance and Structure Data Reveals Competition in the ErbB Signaling Network
Authors: Kiel Christina , Verschueren Erik , Yang Jae-Seong , Serrano Luis
Published: December 2013

Competition among mutually exclusive binding partners contributes to context-dependent differences in signaling responses.
New Dosing Strategies for an Old Antibiotic: Pharmacodynamics of Front-Loaded Regimens of Colistin at Simulated Pharmacokinetics in Patients with Kidney or Liver Disease
Authors: Rao Gauri G. , Ly Neang S. , Haas Curtis E. , Garonzik Samira , Forrest Alan , Bulitta Jurgen B. , Kelchlin Pamela A. , Holden Patricia N. , Nation Roger L. , Li Jian , Tsuji Brian T.
Published: December 2013

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an
in vitro
pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10
8
CFU/ml) of
Pseudomonas aeruginosa
. The pharmacokinetics were simulated for patients with hepatic (half-life [
t
1/2
] of 3.2 h) or renal (
t
1/2
of 14.8 h) disease. Front-loaded regimens (
n
= 5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (
f
AUC) compared to those with traditional dosing regimens (
n
= 14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (
f
AUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (
f
AUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log
10
within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of
P. aeruginosa
. The current study, which utilizes an
in vitro
pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.
Genomic Analyses of DNA Transformation and Penicillin Resistance in Streptococcus pneumoniae Clinical Isolates
Authors: Fani Fereshteh , Leprohon Philippe , Zhanel George G. , Bergeron Michel G. , Ouellette Marc
Published: December 2013

Alterations in penicillin-binding proteins, the target enzymes for β-lactam antibiotics, are recognized as primary penicillin resistance mechanisms in
Streptococcus pneumoniae
. Few studies have analyzed penicillin resistance at the genome scale, however, and we report the sequencing of
S. pneumoniae
R6 transformants generated while reconstructing the penicillin resistance phenotypes from three penicillin-resistant clinical isolates by serial genome transformation. The genome sequences of the three last-level transformants T2-18209, T5-1983, and T3-55938 revealed that 16.2 kb, 82.7kb, and 137.2 kb of their genomes had been replaced with 5, 20, and 37 recombinant sequence segments derived from their respective parental clinical isolates, documenting the extent of DNA transformation between strains. A role in penicillin resistance was confirmed for some of the mutations identified in the transformants. Several multiple recombination events were also found to have happened at single loci coding for penicillin-binding proteins (PBPs) that increase resistance. Sequencing of the transformants with MICs for penicillin similar to those of the parent clinical strains confirmed the importance of mosaic PBP2x, -2b, and -1a as a driving force in penicillin resistance. A role in resistance for mosaic PBP2a was also observed for two of the resistant clinical isolates.
Validation of a Novel Murine Wound Model of Acinetobacter baumannii Infection
Authors: Thompson Mitchell G. , Black Chad C. , Pavlicek Rebecca L. , Honnold Cary L. , Wise Matthew C. , Alamneh Yonas A. , Moon Jay K. , Kessler Jennifer L. , Si Yuanzheng , Williams Robert , Yildirim Suleyman , Kirkup Benjamin C. , Green Romanza K. , Hall Eric R. , Palys Thomas J. , Zurawski Daniel V.
Published: December 2013

Patients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which includeA. baumannii(the ESKAPE pathogens areEnterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies). As new therapies are being developed to counterA. baumanniiinfections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine wound model in which a diminutive inoculum of a clinically relevant, multidrug-resistantA. baumanniiisolate can proliferate, form biofilms, and be effectively treated with antibiotics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and qualitative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA community profiling, histopathology, peptide nucleic acid-fluorescencein situhybridization, and scanning electron microscopy assessment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treated animals provides a clear window within which novel antimicrobial therapies can be assessed. The model can be used to evaluate antimicrobials for their ability to reduce specific pathogen loads in wounded tissues and clear biofilms. Ultimately, the mouse model approach allows for highly powered studies and serves as an initial multifacetedin vivoassessment prior to testing in larger animals.
Retrospective Analysis of the Efficacies of Two Different Regimens of Aqueous Penicillin G Administered to Children with Pneumonia
Authors: Brandão Alyson , Simbalista Raquel , Borges Igor C. , Andrade Dafne C. , Araújo Marcelo , Nascimento-Carvalho Cristiana M.
Published: December 2013

Community-acquired pneumonia (CAP) is an important childhood health problem. Penicillin remains appropriate for treating children with CAP. Clinical data are lacking on disease evolution in children treated with different posologic schemes of aqueous penicillin G. To assess if there were differences in disease evolution between children with CAP treated with 6 or 4 daily doses of aqueous penicillin G, we reviewed the medical charts of hospitalized patients 2 months to 11.5 years of age. Pneumonia was radiologically confirmed based on the detection of pulmonary infiltrate or pleural effusion on the chest radiograph taken on admission and read by a pediatric radiologist blinded to the clinical data. The total daily dose of aqueous penicillin G was 200,000 IU/kg of body weight. Data were recorded on admission, during disease evolution up to the 7th day of treatment, and at the final outcome. The results of hospitalization and the daily frequency of physical signs suggestive of pneumonia were assessed. The subgroups comprised 120 and 144 children who received aqueous penicillin G in 6 or 4 daily doses, respectively. Children ≥5 years of age were more frequent in the 4-daily-doses subgroup (16.0% versus 4.2%; respectively,
P
= 0.02). There were no differences between the compared subgroups in terms of final outcomes, lengths of hospitalization, durations of aqueous penicillin G use, frequencies of aqueous penicillin G substitution, or daily frequencies of tachypnea, fever, chest retraction, lower chest recession, nasal flaring, and cyanosis up to the 7th day of treatment. The studied posologic regimens were similarly effective in treating children hospitalized with a radiologically confirmed CAP diagnosis. Aqueous penicillin G (200,000 IU/kg/day) may be given in 4 daily doses to children with CAP.
Antibiotic Utilization for Acute Respiratory Tract Infections in U.S. Emergency Departments
Authors: Donnelly John P. , Baddley John W. , Wang Henry E.
Published: December 2013

Inappropriate use of antibiotics for acute respiratory tract infections (ARTIs) has decreased in many outpatient settings. For patients presenting to U.S. emergency departments (EDs) with ARTIs, antibiotic utilization patterns are unclear. We conducted a retrospective cohort study of ED patients from 2001 to 2010 using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). We identified patients presenting to U.S. EDs with ARTIs and calculated rates of antibiotic utilization. Diagnoses were classified as antibiotic appropriate (otitis media, sinusitis, pharyngitis, tonsillitis, and nonviral pneumonia) or antibiotic inappropriate (nasopharyngitis, unspecified upper respiratory tract infection, bronchitis or bronchiolitis, viral pneumonia, and influenza).There were 126 million ED visits with a diagnosis of ARTI, and antibiotics were prescribed in 61%. Between 2001 and 2010, antibiotic utilization decreased for patients aged <5 presenting with antibiotic-inappropriate ARTI (rate ratio [RR], 0.94; confidence interval [CI], 0.88 to 1.00). Utilization also decreased significantly for antibiotic-inappropriate ARTI patients aged 5 to 19 years (RR, 0.89; CI, 0.85 to 0.94). Utilization remained stable for antibiotic-inappropriate ARTI among adult patients aged 20 to 64 years (RR, 0.99; CI, 0.97 to 1.01). Among adults, rates of quinolone use for ARTI increased significantly from 83 per 1,000 visits in 2001 to 2002 to 105 per 1,000 in 2009 to 2010 (RR, 1.08; CI, 1.03 to 1.14). Although significant progress has been made toward reduction of antibiotic utilization for pediatric patients with ARTI, the proportion of adult ARTI patients receiving antibiotics in U.S. EDs is inappropriately high. Institution of measures to reduce inappropriate antibiotic use in the ED setting is warranted.
A Screen for and Validation of Prodrug Antimicrobials
Authors: Fleck Laura E. , North E. Jeffrey , Lee Richard E. , Mulcahy Lawrence R. , Casadei Gabriele , Lewis Kim
Published: December 2013

The rise of resistant pathogens and chronic infections tolerant to antibiotics presents an unmet need for novel antimicrobial compounds. Identifying broad-spectrum leads is challenging due to the effective penetration barrier of Gram-negative bacteria, formed by an outer membrane restricting amphipathic compounds, and multidrug resistance (MDR) pumps. In chronic infections, pathogens are shielded from the immune system by biofilms or host cells, and dormant persisters tolerant to antibiotics are responsible for recalcitrance to chemotherapy with conventional antibiotics. We reasoned that the dual need for broad-spectrum and sterilizing compounds could be met by developing prodrugs that are activated by bacterium-specific enzymes and that these generally reactive compounds could kill persisters and accumulate over time due to irreversible binding to targets. We report the development of a screen for prodrugs, based on identifying compounds that nonspecifically inhibit reduction of the viability dye alamarBlue, and then eliminate generally toxic compounds by testing for cytotoxicity. A large pilot of 55,000 compounds against
Escherichia coli
produced 20 hits, 3 of which were further examined. One compound, ADC111, is an analog of a known nitrofuran prodrug nitrofurantoin, and its activity depends on the presence of activating enzymes nitroreductases. ADC112 is an analog of another known antimicrobial tilbroquinol with unknown mechanism of action, and ADC113 does not belong to an approved class. All three compounds had a good spectrum and showed good to excellent activity against persister cells in biofilm and stationary cultures. These results suggest that screening for overlooked prodrugs may present a viable platform for antimicrobial discovery.
Population Analysis of Escherichia coli Isolates with Discordant Resistance Levels by Piperacillin-Tazobactam Broth Microdilution and Agar Dilution Testing
Authors: Shubert Carole , Slaughter Jen , Creely David , van Belkum Alex , Gayral Jean Pierre , Dunne William Michael , Zambardi Gilles , Shortridge Dee
Published: December 2013

Population analysis was performed for 42
Escherichia coli
isolates to determine whether heterogeneity of resistance was a factor in piperacillin-tazobactam category differences between agar dilution and broth microdilution. Of 20 isolates discordant between methods, 80% were heterogeneous. Of 22 isolates in agreement, 59% were homogeneous. Heterogeneity and homogeneity rates for those in agreement were significantly different from those that were discordant (
P
value, 0.010). Heterogeneity of resistance expression appears to be an important factor in category differences observed between broth microdilution and agar dilution for piperacillin-tazobactam.
Transcription Factor CCG-8 as a New Regulator in the Adaptation to Antifungal Azole Stress
Authors: Sun Xianyun , Wang Kangji , Yu Xinxu , Liu Jie , Zhang Hanxing , Zhou Fucai , Xie Baogui , Li Shaojie
Published: December 2013

Antifungal azoles are widely used for controlling fungal infections. Fungi are able to change the expression of many genes when they adapt to azole stress, and increased expression of some of these genes can elevate resistance to azoles. However, the regulatory mechanisms behind transcriptional adaption to azoles in filamentous fungi are poorly understood. In this study, we found that deletion of the transcription factor gene
ccg-8
, which is known to be a clock-controlled gene, made
Neurospora crassa
hypersensitive to azoles. A comparative genome-wide analysis of the responses to ketoconazole of the wild type and the
ccg-8
mutant revealed that the transcriptional responses to ketoconazole of 78 of the 488 transcriptionally ketoconazole-upregulated genes and the 427 transcriptionally ketoconazole-downregulated genes in the wild type were regulated by CCG-8. Ketoconazole sensitivity testing of all available knockout mutants for CCG-8-regulated genes revealed that CCG-8 contributed to azole adaption by regulating the ketoconazole responses of many genes, including the target gene (
erg11
), an azole transporter gene (
cdr4
), a hexose transporter gene (
hxt13
), a stress response gene (locus number NCU06317, named
kts-1
), two transcription factor genes (NCU01386 [named
kts-2
] and
fsd-1/ndt80
), four enzyme-encoding genes, and six unknown-function genes. CCG-8 also regulated phospholipid synthesis in
N. crassa
in a manner similar to that of its homolog in
Saccharomyces cerevisiae
, Opi1p. However, there was no cross talk between phospholipid synthesis and azole resistance in
N. crassa
. CCG-8 homologs are conserved and are common in filamentous fungi. Deletion of the CCG-8 homolog-encoding gene in
Fusarium verticillioides
(
Fvccg-8
) also made this fungus hypersensitive to antifungal azoles.
BsaB, a Novel Adherence Factor of Group B Streptococcus
Authors: Jiang Shengmei , Wessels Michael R.
Published: December 2013

Streptococcus agalactiae
(group B
Streptococcus
[GBS]) is a leading cause of neonatal sepsis and meningitis, peripartum infections in women, and invasive infections in chronically ill or elderly individuals. GBS can be isolated from the gastrointestinal or genital tracts of up to 30% of healthy adults, and infection is thought to arise from invasion from a colonized mucosal site. Accordingly, bacterial surface components that mediate attachment of GBS to host cells or the extracellular matrix represent key factors in the colonization and infection of the human host. We identified a conserved GBS gene of unknown function that was predicted to encode a cell wall-anchored surface protein. Deletion of the gene and a cotranscribed upstream open reading frame (ORF) in GBS strain 515 reduced bacterial adherence to VK2 vaginal epithelial cells
in vitro
and reduced GBS binding to fibronectin-coated microtiter wells. Expression of the gene product in
Lactococcus lactis
conferred the ability to adhere to VK2 cells, to fibronectin and laminin, and to fibronectin-coated ME-180 cervical epithelial cells. Expression of the recombinant protein in
L. lactis
also markedly increased biofilm formation. The adherence function of the protein, named
b
acterial
s
urface
a
dhesin of G
B
S (BsaB), depended both on a central BID1 domain found in bacterial intimin-like proteins and on the C-terminal portion of the BsaB protein. Expression of BsaB in GBS, like that of several other adhesins, was regulated by the CsrRS two-component system. We conclude that BsaB represents a newly identified adhesin that participates in GBS attachment to epithelial cells and the extracellular matrix.
Low-Dose Intradermal Infection with Trypanosoma congolense Leads to Expansion of Regulatory T Cells and Enhanced Susceptibility to Reinfection
Authors: Onyilagha Chukwunonso , Okwor Ifeoma , Kuriakose Shiby , Singh Rani , Uzonna Jude
Published: December 2013

BALB/c mice are highly susceptible to experimental intraperitonealTrypanosoma congolenseinfection. However, a recent report showed that these mice are relatively resistant to primary intradermal low-dose infection. Paradoxically, repeated low-dose intradermal infections predispose mice to enhanced susceptibility to an otherwise noninfectious dose challenge. Here, we explored the mechanisms responsible for this low-dose-induced susceptibility to subsequent low-dose challenge infection. We found that akin to intraperitoneal infection, low-dose intradermal infection led to production of interleukin-10 (IL-10), IL-6, IL-12, tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), and gamma interferon (IFN-γ) by spleen and draining lymph node cells. Interestingly, despite the absence of parasitemia, low-dose intradermal infection led to expansion of CD4+CD25+Foxp3+cells (T regulatory cells [Tregs]) in both the spleens and lymph nodes draining the infection site. Depletion of Tregs by anti-CD25 monoclonal antibody (MAb) treatment during primary infection or before challenge infection following repeated low-dose infection completely abolished the low-dose-induced enhanced susceptibility. In addition, Treg depletion was associated with dramatic reduction in serum levels of TGF-β and IL-10. Collectively, these findings show that low-dose intradermal infection leads to rapid expansion of Tregs, and these cells mediate enhanced susceptibility to subsequent infection.
Salmonella enterica Serovar Typhimurium Infection-Induced CD11b+Gr1+Cells Ameliorate Allergic Airway Inflammation
Authors: Ganesh Venkateswaran , Baru Abdul Mannan , Hesse Christina , Friedrich Christin , Glage Silke , Gohmert Melanie , Jänke Christine , Sparwasser Tim
Published: December 2013

Allergies are mainly characterized as an unrestrained Th2-biased immune response. Epidemiological data associate protection from allergic diseases with the exposure to certain infectious agents during early stages of life. Modulation of the immune response by pathogens has been considered to be a major factor influencing this protection. Recent evidence indicates that immunoregulatory mechanisms induced upon infection ameliorate allergic disorders. A longitudinal study has demonstrated reduced frequency and incidence of asthma in children who reported a prior infection withSalmonella. Experimental studies involvingSalmonella entericaserovar Typhimurium-infected murine models have confirmed protection from induced allergic airway inflammation; however, the underlying cause leading to this amelioration remains incompletely defined. In this study, we aimed to delineate the regulatory function ofSalmonellaTyphimurium infection in the amelioration of allergic airway inflammation in mice. We observed a significant increase in CD11b+Gr1+myeloid cell populations in mice after infection withS. Typhimurium. Usingin vitroandin vivostudies, we confirmed that these myeloid cells reduce airway inflammation by influencing Th2 cells. Further characterization showed that the CD11b+Gr1+myeloid cells exhibited their inhibitory effect by altering GATA-3 expression and interleukin-4 (IL-4) production by Th2 cells. These results indicate that the expansion of myeloid cells uponS. Typhimurium infection could potentially play a significant role in curtailing allergic airway inflammation. These findings signify the contribution of myeloid cells in preventing Th2-mediated diseases and suggest their possible application as therapeutics.
Chlamydia trachomatis-Infected Epithelial Cells and Fibroblasts Retain the Ability To Express Surface-Presented Major Histocompatibility Complex Class I Molecules
Authors: Kägebein Danny , Gutjahr Melanie , Große Christina , Vogel Annette B. , Rödel Jürgen , Knittler Michael R.
Published: December 2013

The obligate intracellular bacterial pathogenChlamydia trachomatisis the causative agent of a variety of infectious diseases such as trachoma and sexually transmitted diseases. In infected target cells,C. trachomatisreplicates within parasitophorous vacuoles and expresses the protease-like activity factor CPAF. Previous studies have suggested that CPAF degrades the host transcription factors RFX5 and NF-κB p65, which are involved in the regulation of constitutive and inducible expression of major histocompatibility complex class I (MHC I). It was speculated thatChlamydiasuppresses the surface presentation of MHC I in order to evade an effective immune response. Nevertheless, a recent study suggested that RFX5 and NF-κB p65 may not serve as target substrates for CPAF-mediated degradation, raising concerns about the proposed MHC I subversion byChlamydia. Hence, we investigated the direct influence ofChlamydiaon MHC I expression and surface presentation in infected host cells. By using nine different human cells and cell lines infected withC. trachomatis(serovar D or LGV2), we demonstrate that chlamydial infection does not interfere with expression, maturation, transport, and surface presentation of MHC I, suggesting functional antigen processing in bacterium-infected cells. Our findings provide novel insights into the interaction of chlamydiae with their host cells and should be taken into consideration for the design of future therapies and vaccines.
Doxycycline and suicidality
Authors: Atigari Onome Victor , Hogan Carys , Healy David
Published: December 2013

A case series outlining three young individuals with no history of mental disorder who were treated for skin conditions with doxycycline, but developed suicidal ideation with an outcome of suicide in two of the cases. One of these individuals had CYP2C19*2 heterozygote genotype associated with a diminished cytochrome p450 enzyme activity and two of his siblings had developed severe anxiety previously while on doxycycline. Another had previously developed mood difficulties on a lower dose of doxycycline which resolved after discontinuation. In the third individual, a discontinuation of doxycycline has led to the resolution of symptoms without the need for psychotropic medications.
Soil moisture monitoring at the field scale using neutron probe
Authors: Kodikara J. , Rajeev P. , Chan D. , Gallage C.
Published: December 2013

Measurement of the moisture variation in soils is required for geotechnical design and research because soil properties and behavior can vary as moisture content changes. The neutron probe, which was developed more than 40 years ago, is commonly used to monitor soil moisture variation in the field. This study reports a full-scale field monitoring of soil moisture using a neutron moisture probe for a period of more than 2 years in the Melbourne (Australia) region. On the basis of soil types available in the Melbourne region, 23 sites were chosen for moisture monitoring down to a depth of 1500 mm. The field calibration method was used to develop correlations relating the volumetric moisture content and neutron counts. Observed results showed that the deepest “wetting front” during the wet season was limited to the top 800 to 1000 mm of soil whilst the top soil layer down to about 550 mm responded almost immediately to the rainfall events. At greater depths (550 to 800 mm and below 800 mm), the moisture variations were relatively low and displayed predominantly periodic fluctuations. This periodic nature was captured with Fourier analysis to develop a cyclic moisture model on the basis of an analytical solution of a one-dimensional moisture flow equation for homogeneous soils. It is argued that the model developed can be used to predict the soil moisture variations as applicable to buried structures such as pipes.