bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Long‐run Relationship Between Trade and Population Health: Evidence from Five Decades
Authors: Herzer Dierk 
Published: June 2016

AbstractIn recent years, the increase in international trade has sparked a debate about the impact of international trade on population health. To date, however, there has been very little econometric research on the relationship between these two variables. This paper examines the long‐run relationship between trade openness and population health for a sample of 74 countries over five decades, from 1960 to 2010. Using panel time‐series techniques, it is shown that international trade in general has a robust positive long‐run effect on health, as measured by life expectancy and infant mortality. This effect tends to be greater in countries with lower development levels, higher taxes on income, profits, and capital gains, and less restrictive business and labour market regulations.
Properties of the feline tumour suppressor reduced expression in immortalized cells (REIC/Dkk‐3)
Authors: Ochiai K. , Oda H. , Shono S. , Kato Y. , Sugihara S. , Nakazawa S. , Azakami D. , Michishita M. , Onozawa E. , Bonkobara M. , Sako T. , Shun‐Ai L. , Ueki H. , Watanabe M. , Omi T. 
Published: June 2016

AbstractReduced expression in immortalized cells (REIC/Dkk‐3), a member of the human Dickkopf (Dkk) family, is a growth suppressor in human and canine mammary tumours. Mammary gland tumours are common neoplasms with high malignancy in female cats. The purpose of this study was to clone the feline REIC/Dkk‐3 homolog, investigate its expression in cell lines established from feline mammary gland tumours, and test its tumour suppressor function. Western blot analysis revealed that expression of the REIC/Dkk‐3 protein was reduced in feline mammary carcinoma cell lines. Forced expression of REIC/Dkk‐3 induced apoptosis in feline mammary tumour cell lines. These results demonstrate that REIC/Dkk‐3 expression, which is downregulated in feline mammary tumour cell lines, results in the induction of apoptosis in these cells. Our findings suggest that feline REIC/Dkk‐3 represents a potential molecular target for the development of therapies against feline mammary cancers.
Infectious crystalline keratopathy in dogs and cats: clinical, in vivo confocal microscopic, histopathologic, and microbiologic features of eight cases
Authors: Ledbetter Eric C. , McDonough Patrick L. , Kim Kay 
Published: June 2016

AbstractObjectiveTo describe clinical, in vivo confocal microscopic, histopathologic, and microbiologic features of canine and feline cases of infectious crystalline keratopathy (ICK).Animals studiedSix dogs and two cats with naturally acquired ICK.ProceduresMedical records of dogs and cats with a clinical diagnosis of ICK were reviewed. Signalment, medical history, clinical findings, and diagnostic evaluations were retrieved, including corneal cytology, histopathology, in vivo confocal microscopy, and microbiology results.ResultsAll animals presented with fine, needle‐like, and branching white crystalline anterior stromal opacities emanating from corneal facets or corneal epithelial defects. Mild conjunctival hyperemia and anterior uveitis were frequently present. Concurrent ocular and systemic diseases were common, including keratoconjunctivitis sicca, corneal sequestrum, diabetes mellitus, hyperadrenocorticism, and malignant neoplasia. Bacteria, with minimal or absent leukocytes, were identified by cytology and histopathology. Histopathologically, the crystalline corneal opacities corresponded with dense accumulations of bacteria present in the interlamellar stromal spaces and forming cord‐like projections within the stroma. In vivo confocal microscopy demonstrated deposits of reflective crystalline or amorphous structures within the stroma with a paucity of associated inflammatory changes. The most frequently cultured bacteria were alpha‐hemolytic Streptococcus and Staphylococcus species. Resolution of clinical lesions was achieved in most cases with long‐term medical or surgical therapy; however, the initiation of medical treatment was associated with an acute, dramatic onset of severe keratitis and anterior uveitis in some animals.ConclusionsInfectious crystalline keratopathy in dogs and cats shares many features with this condition in human patients. Prolonged medical therapy, or surgical intervention, is required for resolution.
New strategies for bacterial contaminations
Authors: Schmidt M. , Seifried E. 
Published: June 2016

BackgroundThe detection of bacterial contaminations in blood components can be classified in culture methods, rapid detection methods and experimental new technologies.Culture methodsCulture methods have shown their benefit through easy handling and high analytic sensitivity. The challenge with culture methods, with the negative‐to‐date release concept, is a risk for false negative screening results due to sample failures and a reduced clinical efficiency.Rapid detection methodsWithin the last decade, rapid bacterial detection systems (RBDS) were developed as an alternative option to culture systems. In RBDS, testing time is reduced to 2–3 h. Therefore, a negative‐to‐date release concept is not necessary using these systems.New technologiesIn addition, new technologies are currently in development to detect bacterial strains in blood components. Electrochemical biosensors were developed for many different analytes, which range in size from individual ions and small molecules to nucleic acids and proteins up to whole viruses and bacteria.ConclusionsBacterial detection in blood components, especially in platelets, is implemented in many blood donor services. New approaches are promising to come to a next level to be implemented into routine screening, but the analytical sensitivity has to be improved for some of the new test systems in the coming years. Due to the fact that a risk for bacterial contamination still occurs in all blood components, the focus in transfusion medicine in the next decade will be the development of general principles and strategies to detect or inactivate bacteria in all blood components. Therefore, new developments are gladly welcome.
Overcoming resource limitations of blood services in Indonesia
Authors: Soedarmono Y. S. M. 
Published: June 2016

BackgroundIndonesia suffers from high maternal mortality numbers; therefore, the blood service is an important part of the health service. A strong government commitment and good strategies have recently improved blood services significantly (e.g. supply, quality and access).AimsThe aim of this study was to describe the strategies needed to improve the blood services in Indonesia.MethodIndonesia has a diverse geography as well as unique infrastructure. Since 1950, the blood services have been run by the Indonesian Red Cross (IRC). There were three main problems identified: (1) inadequate organization of blood services; (2) limited access of blood; and (3) variable quality of blood products. To cope with these problems, the Ministry of Health (MOH) has made some new strategies.ResultsTo improve the organization of blood services, a National Committee of Blood Services was established to formulate policy and design new strategies. This was followed by establishing government and MOH regulations. These regulations emphasized 100% of voluntary donors with ensured quality. The National Agency for Food and Drugs Control (NAFDC) was appointed to control the quality of all blood products.ConclusionBlood services should be well organized, maintained and controlled. Organization of blood services run by IRC as well as hospitals might therefore be the best choice for Indonesia. However, strong commitment of both government and IRC remains the key to achieve an adequate and qualified blood service in Indonesia.
Charged particle transport in magnetic fields in EGSnrc
Authors: Malkov V. N. , Rogers D. W. O. 
Published: June 2016

Purpose:To accurately and efficiently implement charged particle transport in a magnetic field in EGSnrc and validate the code for the use in phantom and ion chamber simulations.Methods:The effect of the magnetic field on the particle motion and position is determined using one‐ and three‐point numerical integrations of the Lorentz force on the charged particle and is added to the condensed history calculation performed by the EGSnrc PRESTA‐II algorithm. The code is tested with a Fano test adapted for the presence of magnetic fields. The code is compatible with all EGSnrc based applications, including egs++. Ion chamber calculations are compared to experimental measurements and the effect of the code on the efficiency and timing is determined.Results:Agreement with the Fano test's theoretical value is obtained at the 0.1% level for large step‐sizes and in magnetic fields as strong as 5 T. The NE2571 dose calculations achieve agreement with the experiment within 0.5% up to 1 T beyond which deviations up to 1.2% are observed. Uniform air gaps of 0.5 and 1 mm and a misalignment of the incoming photon beam with the magnetic field are found to produce variations in the normalized dose on the order of 1%. These findings necessitate a clear definition of all experimental conditions to allow for accurate Monte Carlo simulations. It is found that ion chamber simulation times are increased by only 38%, and a 10 × 10 × 6 cm3 water phantom with (3 mm)3 voxels experiences a 48% increase in simulation time as compared to the default EGSnrc with no magnetic field.Conclusions:The incorporation of the effect of the magnetic fields in EGSnrc provides the capability to calculate high accuracy ion chamber and phantom doses for the use in MRI‐radiation systems. Further, the effect of apparently insignificant experimental details is found to be accentuated by the presence of the magnetic field.
Eravacycline Pharmacokinetics and Challenges in Defining Humanized Exposure
In Vivo
Authors: Thabit Abrar K. , Monogue Marguerite L. , Nicolau David P. 
Published: June 2016

ABSTRACT
We assessed the pharmacokinetic profile of eravacycline, a novel antibiotic of the tetracycline class, and determined the dose in an immunocompetent murine thigh infection model that would provide free-drug exposure similar to that observed in humans after the administration of 1 mg/kg intravenously (i.v.) every 12 h (q12h). Eravacycline demonstrated a nonlinear protein-binding profile. The 2.5-mg/kg i.v. q12h dose in mice resulted in an area under the concentration-time curve for the free, unbound fraction of the drug of 1.64 mg · h/liter, which closely resembles the human exposure level.
Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens
In Vitro
and
In Vivo
Authors: Čipčić Paljetak Hana , Verbanac Donatella , Padovan Jasna , Dominis-Kramarić Miroslava , Kelnerić Željko , Perić Mihaela , Banjanac Mihailo , Ergović Gabrijela , Simon Nerrisa , Broskey John , Holmes David J. , Eraković Haber Vesna 
Published: June 2016

ABSTRACT

As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated
in vitro
and
in vivo
. MIC values against
Streptococcus pneumoniae
,
Streptococcus pyogenes
,
Staphylococcus aureus
, and
Haemophilus influenzae
strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible
erm
genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds.
In vivo
efficacy was assessed in a murine model of
S. pneumoniae
-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The
in vitro
antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible
erm
genes. They acted as typical protein synthesis inhibitors in an
Escherichia coli
transcription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an
S. pneumoniae
strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good
in vivo
efficacy.
Population Pharmacokinetics of Tenofovir in HIV-1-Uninfected Members of Serodiscordant Couples and Effect of Dose Reporting Methods
Authors: Lu Yanhui , Goti Vineet , Chaturvedula Ayyappa , Haberer Jessica E. , Fossler Michael J. , Sale Mark E. , Bangsberg David , Baeten Jared M. , Celum Connie L. , Hendrix Craig W. 
Published: June 2016

ABSTRACT
Antiretroviral preexposure prophylaxis (PrEP) with once-daily dosing of tenofovir and tenofovir-emtricitabine was shown to be effective for preventing HIV-1 infection in individuals who had HIV-1-seropositive partners (the Partners PrEP Study). We developed a population pharmacokinetic model for tenofovir and investigated the impacts of different dose reporting methods. Dosing information was collected as patient-reported dosing information (PRDI) from 404 subjects (corresponding to 1,280 drug concentration records) from the main trial and electronic monitoring-based adherence data collected from 211 subjects (corresponding to 327 drug concentration records) in an ancillary adherence study. Model development was conducted with NONMEM (7.2), using PRDI with a steady-state assumption or using PRDI replaced with electronic monitoring records where available. A two-compartment model with first-order absorption was the best model in both modeling approaches, with the need for an absorption lag time when electronic monitoring-based dosing records were included in the analysis. Age, body weight, and creatinine clearance were significant covariates on clearance, but only creatinine clearance was retained in the final models per stepwise selection. Sex was not a significant covariate on clearance. Tenofovir population pharmacokinetic parameter estimates and the precisions of the parameters from the two final models were comparable with the point estimates of the parameters, differing from 0% to 35%, and bootstrap confidence intervals widely overlapped. These findings indicate that PRDI was sufficient for population pharmacokinetic model development in this study, with a high level of adherence per multiple measures.
Activities of Tedizolid and Linezolid Determined by the Reference Broth Microdilution Method against 3,032 Gram-Positive Bacterial Isolates Collected in Asia-Pacific, Eastern Europe, and Latin American Countries in 2014
Authors: Pfaller Michael A. , Flamm Robert K. , Jones Ronald N. , Farrell David J. , Mendes Rodrigo E. 
Published: June 2016

ABSTRACT

Tedizolid and linezolid
in vitro
activities against 3,032 Gram-positive pathogens collected in Asia-Pacific, Eastern European, and Latin American medical centers during 2014 were assessed. The isolates were tested for susceptibility by the current reference broth microdilution methods. Due to concern over the effect of MIC endpoint criteria on the results of testing the oxazolidinones tedizolid and linezolid, MIC endpoint values were read by two methods: (i) reading the MIC at the first well where the trailing began without regard for pinpoint trailing, according to CLSI M07-A10 and M100-S26 document instructions for reading linezolid (i.e., 80% inhibition of growth; these reads were designated tedizolid 80 and linezolid 80), and (ii) at 100% inhibition of growth (designated tedizolid 100 and linezolid 100). All
Staphylococcus aureus
,
Streptococcus pyogenes
,
Streptococcus agalactiae
,
Streptococcus anginosus
group, and
Enterococcus faecalis
isolates were inhibited at tedizolid 80 and 100 MIC values of 0.25 and 0.5, 0.25 and 0.25, 0.25 and 0.5, 0.12 and 0.25, and 0.5 and 1 μg/ml, respectively. Generally, MIC
50
and MIC
90
results for tedizolid 80 and linezolid 80 were one doubling dilution lower than those read at 100% inhibition. Tedizolid was 4- to 8-fold more potent than linezolid against all the isolates tested regardless of the MIC endpoint criterion used. Despite the differences in potency, >99.9% of isolates tested in this survey were susceptible to both linezolid and tedizolid using CLSI and EUCAST interpretive criteria. In conclusion, tedizolid demonstrated greater
in vitro
potency than linezolid against Gram-positive pathogens isolated from patients in medical centers across the Asia-Pacific region, Eastern Europe, and Latin America.
In Vitro
and
In Vivo
Effectiveness of an Innovative Silver-Copper Nanoparticle Coating of Catheters To Prevent Methicillin-Resistant Staphylococcus aureus Infection
Authors: Ballo Myriam K. S. , Rtimi Sami , Pulgarin César , Hopf Nancy , Berthet Aurélie , Kiwi John , Moreillon Philippe , Entenza José M. , Bizzini Alain 
Published: June 2016

ABSTRACT

In this study, silver/copper (Ag/Cu)-coated catheters were investigated for their efficacy in preventing methicillin-resistant
Staphylococcus aureus
(MRSA) infection
in vitro
and
in vivo
. Ag and Cu were sputtered (67/33% atomic ratio) on polyurethane catheters by direct-current magnetron sputtering.
In vitro
, Ag/Cu-coated and uncoated catheters were immersed in phosphate-buffered saline (PBS) or rat plasma and exposed to MRSA ATCC 43300 at 10
4
to 10
8
CFU/ml.
In vivo
, Ag/Cu-coated and uncoated catheters were placed in the jugular vein of rats. Directly after, MRSA (10
7
CFU/ml) was inoculated in the tail vein. Catheters were removed 48 h later and cultured.
In vitro
, Ag/Cu-coated catheters preincubated in PBS and exposed to 10
4
to 10
7
CFU/ml prevented the adherence of MRSA (0 to 12% colonization) compared to uncoated catheters (50 to 100% colonization;
P
< 0.005) and Ag/Cu-coated catheters retained their activity (0 to 20% colonization) when preincubated in rat plasma, whereas colonization of uncoated catheters increased (83 to 100%;
P
< 0.005). Ag/Cu-coating protection diminished with 10
8
CFU/ml in both PBS and plasma (50 to 100% colonization).
In vivo
, Ag/Cu-coated catheters reduced the incidence of catheter infection compared to uncoated catheters (57% versus 79%, respectively;
P
= 0.16) and bacteremia (31% versus 68%, respectively;
P
< 0.05). Scanning electron microscopy of explanted catheters suggests that the suboptimal activity of Ag/Cu catheters
in vivo
was due to the formation of a dense fibrin sheath over their surface. Ag/Cu-coated catheters thus may be able to prevent MRSA infections. Their activity might be improved by limiting plasma protein adsorption on their surfaces.
Impact of
sarA
and Phenol-Soluble Modulins on the Pathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus
Authors: Loughran Allister J. , Gaddy Dana , Beenken Karen E. , Meeker Daniel G. , Morello Roy , Zhao Haibo , Byrum Stephanie D. , Tackett Alan J. , Cassat James E. , Smeltzer Mark S. 
Published: June 2016

ABSTRACT

We used a murine model of acute, posttraumatic osteomyelitis to evaluate the virulence of two divergent
Staphylococcus aureus
clinical isolates (the USA300 strain LAC and the USA200 strain UAMS-1) and their isogenic
sarA
mutants. The results confirmed that both strains caused comparable degrees of osteolysis and reactive new bone formation in the acute phase of osteomyelitis. Conditioned medium (CM) from stationary-phase cultures of both strains was cytotoxic to cells of established cell lines (MC3TC-E1 and RAW 264.7 cells), primary murine calvarial osteoblasts, and bone marrow-derived osteoclasts. Both the cytotoxicity of CM and the reactive changes in bone were significantly reduced in the isogenic
sarA
mutants. These results confirm that
sarA
is required for the production and/or accumulation of extracellular virulence factors that limit osteoblast and osteoclast viability and that thereby promote bone destruction and reactive bone formation during the acute phase of
S. aureus
osteomyelitis. Proteomic analysis confirmed the reduced accumulation of multiple extracellular proteins in the LAC and UAMS-1
sarA
mutants. Included among these were the alpha class of phenol-soluble modulins (PSMs), which were previously implicated as important determinants of osteoblast cytotoxicity and bone destruction and repair processes in osteomyelitis. Mutation of the corresponding operon reduced the cytotoxicity of CM from both UAMS-1 and LAC cultures for osteoblasts and osteoclasts. It also significantly reduced both reactive bone formation and cortical bone destruction by CM from LAC cultures. However, this was not true for CM from cultures of a UAMS-1
psm
α
mutant, thereby suggesting the involvement of additional virulence factors in such strains that remain to be identified.
Porphyromonas gulae Has Virulence and Immunological Characteristics Similar to Those of the Human Periodontal Pathogen Porphyromonas gingivalis
Authors: Lenzo Jason C. , O'Brien-Simpson Neil M. , Orth Rebecca K. , Mitchell Helen L. , Dashper Stuart G. , Reynolds Eric C. 
Published: June 2016

ABSTRACT

Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogen
Porphyromonas gingivalis
is the lysyl- and arginyl-specific proteolytic activity of the gingipains. We screened several
Porphyromonas
species isolated from companion animals—
P. asaccharolytica
,
P. circumdentaria
,
P. endodontalis
,
P. levii
,
P. gulae
,
P. macacae
,
P. catoniae
, and
P. salivosa
—for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that of
Porphyromonas gingivalis
. Only
P. gulae
exhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in the
P. gulae
strain ATCC 51700 and all publicly available 12 draft genomes of
P. gulae
strains.
P. gulae
ATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those in
P. gingivalis
W50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytose
P. gulae
ATCC 51700 and the fimbriated
P. gingivalis
ATCC 33277 at similar levels. In response to
P. gulae
ATCC 51700, macrophages secreted higher levels of cytokines than those induced by
P. gingivalis
ATCC 33277 but lower than those induced by
P. gingivalis
W50, except for the interleukin-6 response. Our results indicate that
P. gulae
exhibits virulence characteristics similar to those of the human periodontal pathogen
P. gingivalis
and therefore may play a key role in the development of periodontitis in companion animals.