bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct oral provocation tests in non‐immediate mild cutaneous reactions related to beta‐lactam antibiotics
Authors: Vezir Emine , Dibek Misirlioglu Emine , Civelek Ersoy , Capanoglu Murat , Guvenir Hakan , Ginis Tayfur , Toyran Muge , Kocabas Can N. 
Published: September 2015

BackgroundSkin testing has a limited role in the diagnosis of non‐immediate beta‐lactam hypersensitivity in children. The aim of this study was to report the results of oral provocation tests performed without skin tests in children with non‐immediate mild cutaneous reactions without systemic symptoms caused by beta‐lactam antibiotics.MethodsOral provocation tests with suspected antibiotics were performed to patients with non‐immediate mild cutaneous reactions without systemic symptoms caused by beta‐lactam antibiotics. Skin tests were not performed before provocation tests. A total of five doses were administered with half‐an‐hour intervals in increasing doses. Provocation was continued for 5 days.ResultsA total of 119 patients with a median age of 4.3 (IQR: 2–7.5) years, of whom 58% were males, were included in the study. Amoxicillin–clavulanic acid was the most frequently responsible agent in 87 (73.1%) patients, and most common type of rash was maculopapular in 74 (62.2%) patients. Four patients (3.4%) had an urticarial reaction during the provocation test.ConclusionWe did not experience any severe reactions during oral provocation test without previous skin tests performed to children with non‐immediate mild cutaneous reactions without systemic symptoms. Omitting skin tests before oral provocation test in this group of children can help decreasing the burden of allergy clinics and alleviating the discomfort of children.
Heart rate response to a caudal block in children anesthetized with sevoflurane after ultrasound confirmation of placement
Authors: Adler Adam C. , Schwartz Donald A. , Begley Annemarie , Friderici Jennifer , Connelly Neil Roy 
Published: September 2015

SummaryIntroductionPrevious studies identified decreasing heart rate (HR) as a predictor of successful caudal placement in children using halothane and isoflurane. No changes were found in HR in the one study using sevoflurane. We documented HR changes in children following a caudal block during sevoflurane anesthesia utilizing ultrasound to confirm successful caudal placement.MethodsSeventy‐one children (1–82 months) were anesthetized with sevoflurane. A caudal block was placed with confirmation by ultrasound. Four aliquots of bupivacaine 0.2% with epinephrine 5 μg·cc−1 were administered for a total volume of 1 cc·kg−1 with HR recorded for 4 min. The outcomes measured were HR changes from the initial baseline and during each 1‐min interval. The age‐related differences in HR were also analyzed.ResultsHeart rate change from the initial baseline after placing the caudal needle and allowing for equilibration ranged from −10.2% to +8.9% and the HR change from the baseline at the start of each aliquot injection ranged from −9.5% to +8.9%. Most participants (n = 60, 84.5%) experienced at least one HR reduction over the observation period. For patients <36 months, the HR change ranged from −11 to +12 b·min−1 (mean −0.3); for patients aged ≥36 months, the HR change ranged from −10 to +6 b·min−1 (mean −1.1).ConclusionsHeart rate changes following a caudal block in children ≤82 months of age anesthetized with sevoflurane is not a reliable indicator of a successful block. Despite 100% caudal success, many children had no decrease in HR, and in those that did, the decline was of a magnitude indeterminate from beat‐to‐beat variability.
An Ethnographic Meta‐Synthesis of Three Southwestern Rural Studies
Authors: Averill Jennifer B. 
Published: September 2015

AbstractObjectiveThe objectives were to synthesize cumulative findings across three critical ethnographic, community‐partnered studies in the southwestern United States and to describe the process of meta‐ethnography for that analysis.Design and SampleThe meta‐ethnography followed the design of Noblit and Hare for constructing an analysis of composite data, informed by community‐based participatory research and Stringer's ethnographic strategies of Look‐Think‐Act. The three studies occurred in rural settings of Colorado and New Mexico, engaging 129 total participants, along with community organizations and agencies as partners.MethodsMethods consisted of detailed review of each original study, mapping of major concepts and themes, and general analysis, interpretation, and synthesis across the studies.ResultsOverall themes were: health is the capacity to care for oneself and do work, meaningful relationships are key in health care interactions, patterns of discrimination persist in rural settings, poor literacy and health literacy are barriers, and food insecurity is a growing concern for older rural adults.ConclusionsResolutions involve practice, policy, and research and must incorporate all stakeholder groups in rural settings; a participatory approach is critical to prioritize and impact existing inequities; and work is needed to extend education and understanding of multiple cultures, groups, customs, and rural contexts.
Metabolite profiling reveals temperature effects on the VOCs and flavonoids of different plant populations
Authors: Goh H.‐H. , Khairudin K. , Sukiran N. A. , Normah M.N. , Baharum S.N. 
Published: September 2015

AbstractTemperature is one of the key factors in limiting the distribution of plants and controlling major metabolic processes. A series of simulated reciprocal transplant experiments were performed to investigate the effect of temperature on plant chemical composition. Polygonum minus of different lowland and highland origin were grown under a controlled environment with different temperature regimes to study the effects on secondary metabolites. We applied gas chromatography–mass spectrometry and liquid chromatography time‐of‐flight mass spectrometry to identify the chemical compounds. A total of 37 volatile organic compounds and 85 flavonoids were detected, with the largest response observed in the compositional changes of aldehydes and terpenes in highland plants under higher temperature treatment. Significantly less anthocyanidin compounds and larger amounts of flavonols were detected under higher temperature treatment. We also studied natural variation in the different plant populations growing under the same environment and identified compounds unique to each population through metabolite fingerprinting. This study shows that the origin of different plant populations influences the effects of temperature on chemical composition.
Novel retinopathy in related Gordon setters: a clinical, behavioral, electrophysiological, and genetic investigation
Authors: Good Kathryn L. , Komáromy András M. , Kass Philip H. , Ofri Ron 
Published: September 2015

AbstractPurposeTo conduct ophthalmic, behavioral, electrophysiological, and genetic testing on two related Gordon setters presented for day blindness and compare findings with those of nine related and unrelated Gordon setters.MethodsAll dogs underwent comprehensive ophthalmic examination. Maze testing was conducted under different light intensities. Rod and cone function was assessed electroretinographically. DNA samples were screened for five canine retinal disease gene mutations.ResultsOphthalmic examination was unremarkable in all dogs. There was no notable difference between day blind dogs and the reference population in scotopic and mesopic maze tests. Day blind dogs performed worse in the photopic maze with slower course completion time and more obstacle collisions. Electroretinography revealed extinguished cone function in day blind dogs and depressed rod responses in all but two reference dogs. One reference population dog presented with day blindness 1 year after initial examination. Mutations that cause achromatopsia (in CNGB3) and cone‐rod dystrophies (in ADAM9 and IQCB1) were not detected in any dog tested, although five reference dogs were carriers of the mutation in C2orf71 that causes rod–cone degeneration 4 (rcd4) in Gordon setters and in polski owczarek nizinny dogs.ConclusionsThis report describes a novel retinopathy in related Gordon setters that has clinical signs and vision testing results consistent with achromatopsia but electroretinographic results suggestive of cone‐rod dystrophy. The majority of Gordon setters in this study had low rod responses on electroretinography but it is unclear whether this was indicative of rod dysfunction or normal for the breed. Longer‐term observation of affected individuals is warranted.
Dysferlin deficiency blunts β‐adrenergic‐dependent lusitropic function of mouse heart
Authors: Wei Bin , Wei Hongguang , Jin J.‐P. 
Published: September 2015

Key points
Deficiency of dysferlin causes limb‐girdle muscular dystrophy 2B and Miyoshi myopathy with cardiac involvement that leads to dilated cardiomyopathy and heart failure. The pathogenesis and pathophysiology of dysferlin cardiomyopathy are not fully understood.
We studied cardiac phenotypes of young dysferlin gene knockout mice to investigate the primary pathological and pathophysiological changes.
In comparison with wild‐type controls, dysferlin‐deficient cardiomyocytes showed slower Ca2+ re‐sequestration, and dysferlin deficiency blunted the β‐adrenergic effect on relaxation and pumping function of ex vivo working hearts.
Dysferlin deficiency increased phosphorylation of ventricular myosin light chain 2, suggesting a compensatory response to the impaired cardiac lusitropic function.
The data suggest that delayed calcium re‐sequestration and post‐translational modification of myofilament proteins may provide potential targets to develop new treatments for dysferlin cardiomyopathy.
AbstractDysferlin is a cell membrane bound protein with a role in the repair of skeletal and cardiac muscle cells. Deficiency of dysferlin leads to limb‐girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy. In cardiac muscle, dysferlin is located at the intercalated disc and transverse tubule membranes. Loss of dysferlin causes death of cardiomyocytes, notably in ageing hearts, leading to dilated cardiomyopathy and heart failure in LGM2B patients. To understand the primary pathogenesis and pathophysiology of dysferlin cardiomyopathy, we studied cardiac phenotypes of young adult dysferlin knockout mice and found early myocardial hypertrophy with largely compensated baseline cardiac function. Cardiomyocytes isolated from dysferlin‐deficient mice showed normal shortening and re‐lengthening velocities in the absence of external load with normal peak systolic Ca2+ but slower Ca2+ re‐sequestration than wild‐type controls. The effects of isoproterenol on relaxation velocity, left ventricular systolic pressure and stroke volume were blunted in dysferlin‐deficient mouse hearts compared with that in wild‐type hearts. Young dysferlin‐deficient mouse hearts expressed normal isoforms of myofilament proteins whereas the phosphorylation of ventricular myosin light chain 2 was significantly increased, implying a molecular response to the impaired lusitropic function. These early phenotypes of diastolic cardiac dysfunction and blunted lusitropic response of cardiac muscle to β‐adrenergic stimulation indicate a novel pathogenic mechanism of dysferlin cardiomyopathy.
Las “Constituciones” de los Estados democráticos; ¿Armas eficaces en el marco de la lucha contra el terrorismo internacional?
Authors: Zamorano Guzmán Cristian 
Published: September 2015

Este artículo propone una presentación noexhaustiva de las diferentes maneras de cómoes abordado el fenómeno terrorista por las disposicionesde las Cartas Magnas, esencialmenteeuropeas y americanas, de diferentes ordenamientosjurídicos mencionando igualmente elcaso chileno. Frente a la (re)aparición de unterrorismo internacional, la problemática quese trata de plantear y resolver acá es de saberhasta dónde se puede prevalecer el principio deseguridad pública sobre el respeto y la defensade los derechos y libertades individuales, esteconjunto de principios siendo por esencia inherentesal contenido de una Constitución de un Estado que se reivindica democrático. En elmarco de esta correlación de fuerza, se trataráigualmente de responder a la pregunta, si unaConstitución “democrática” es un arma eficaz delucha contra el terrorismo internacional o si setrata de alejarse del espíritu de esta para podercombatirlo eficientemente.
Consideraciones para la Optimización de la Estrategia Nacional de Prevención y Erradicación de las Peores Formas de Trabajo Infantil y Protección al Joven Trabajador 2008 – 2015
Authors: Fábregas Peña Julio José 
Published: September 2015

Llama profundamente la atención que aunqueen Colombia existe una Estrategia nacionalpara prevenir y erradicar las peores formas detrabajo infantil, las cifras relacionadas con losniños, niñas y adolescentes que son explotadoslaborablemente son altas. Por esta razón, surge lanecesidad de revisar esta situación proponiendorecomendaciones para la optimización de dicha estrategia; de acuerdo con las reformas laboralesrealizadas por el gobierno tanto a fines del sigloXX como a principios del siglo XXI, y en el contextode la desigualdad social que caracteriza alpaís, es que se han vinculado estas realidadescomo principales causas del trabajo infantil y delmantenimiento de sus altas cifras en Colombia.Con ello, además surge la propuesta de conectarestos aspectos a la promoción y aplicación delconcepto de trabajo decente para así tambiéneliminar la pauperización de la fuerza laboraladulta, proteger a la población menor de 18 añosde edad de las peores formas de trabajo infantily, en consecuencia, disminuir los altos índices de este problema.
Involucramiento, participación política y tipología del consumo de medios en Colombia
Authors: Ortiz Ayala Alejandra , Orozco Margarita María 
Published: September 2015

<p>En los últimos diez años, la relación entre la política y los ciudadanos se ha visto atravesada por el surgimiento de las redes sociales e Internet, herramientas potencialmente democratizadoras que pueden brindar información y espacios de participación política más accesibles.</p><p>Este estudio se propone analizar dos dimensiones del uso de Internet y redes sociales: entretenimiento y active political Internet uses (APIU), para identificar su impacto sobre el involucramiento político y la participación política de los colombianos.</p><p>Los resultados sugieren que los usos activos políticos de Internet no tienen efectos significativos en el involucramiento político, ni en la participación política electoral. </p><p> </p>
Efficacy of Humanized High-Dose Meropenem, Cefepime, and Levofloxacin against Enterobacteriaceae Isolates Producing Verona Integron-Encoded Metallo-β-Lactamase (VIM) in a Murine Thigh Infection Model
Authors: Ghazi Islam M. , Crandon Jared L. , Lesho Emil P. , McGann Patrick , Nicolau David P. 
Published: September 2015

ABSTRACT

We aimed to describe the
in vivo
activity of humanized pharmacokinetic exposures of meropenem and comparators against Verona integron-encoded metallo-β-lactamase (MBL) (VIM)-producing
Enterobacteriaceae
in a murine model. Levofloxacin activity was predicted by its MIC, and cefepime activity displayed variability, whereas meropenem produced a >1 log CFU reduction against all isolates despite high MICs indicative of resistance. Our results suggest that despite
in vitro
resistance, high-dose meropenem may be a possible option against infections caused by
Enterobacteriaceae
producing MBL-type carbapenemases.
Fluoroquinolone Impact on Nasal Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Colonization Durations in Neurologic Long-Term-Care Facilities
Authors: Couderc Clotilde , Thiébaut Anne C. M. , Lawrence Christine , Bouchiat Coralie , Herrmann Jean-Louis , Salomon Jérôme , Guillemot Didier 
Published: September 2015

ABSTRACTStaphylococcus aureusnasal carriage is a risk factor for subsequent infection. Estimates of colonization duration vary widely among studies, and factors influencing the time to loss of colonization, especially the impact of antibiotics, remain unclear. We conducted a prospective study on patients naive forS. aureuscolonization in 4 French long-term-care facilities. Data on nasal colonization status and potential factors for loss of colonization were collected weekly. We estimated methicillin-resistantS. aureus(MRSA) and methicillin-sensitiveS. aureus(MSSA) colonization durations using the Kaplan-Meier method and investigated factors for loss of colonization using shared-frailty Cox proportional hazards models. A total of 285S. aureuscolonization episodes were identified in 149 patients. The median time to loss of MRSA or MSSA colonization was 3 weeks (95% confidence interval, 2 to 8 weeks) or 2 weeks (95% confidence interval, 2 to 3 weeks), respectively. In multivariable analyses, the methicillin resistance phenotype was not associated withS. aureuscolonization duration (P= 0.21); the use of fluoroquinolones (hazard ratio, 3.37; 95% confidence interval, 1.31 to 8.71) and having a wound positive for a nonnasal strain (hazard ratio, 2.17; 95% confidence interval, 1.15 to 4.07) were associated with earlier loss of MSSA colonization, while no factor was associated with loss of MRSA colonization. These results suggest that the methicillin resistance phenotype does not influence theS. aureuscolonization duration and that fluoroquinolones are associated with loss of MSSA colonization but not with loss of MRSA colonization.
High Efficacy of Finafloxacin on Helicobacter pylori Isolates at pH 5.0 Compared with That of Other Fluoroquinolones
Authors: Lee Jung Won , Kim Nayoung , Nam Ryoung Hee , Kim Jung Mogg , Park Jong Youn , Lee Sun Min , Kim Joo Sung , Lee Dong Ho , Jung Hyun Chae 
Published: September 2015

ABSTRACT

Finafloxacin is a novel fluoroquinolone with improved antimicrobial efficacy, especially in an acidic environment. The efficacy of finafloxacin for the inhibition of
Helicobacter pylori
infection was compared with the efficacies of levofloxacin and moxifloxacin at neutral and acidic pH. The impacts of
gyrA
point mutation on the efficacy of those three fluoroquinolones were also investigated. A total of 128 clinical
H. pylori
strains were utilized. MICs of levofloxacin, moxifloxacin, and finafloxacin were determined at pH 5.0 and pH 7.0 by the agar dilution method. The impact of
gyrA
point mutations that are responsible for fluoroquinolone resistance was analyzed; the results showed 50 strains with an Asn-87 point mutation, 48 strains with an Asp-91 point mutation, and the remaining 30 strains with no
gyrA
mutations. The use of finafloxacin led to MIC values at pH 5.0 that were lower than the values seen at pH 7.0 for 112 strains (112/128, 87.5%), and this proportion was higher than that seen with moxifloxacin (21/128, 16.4%,
P
< 0.001). Finafloxacin also demonstrated a rate of susceptibility (MIC, <1 μg/ml) (37.5%, 48/128) at pH 5.0 that was higher than that seen with moxifloxacin (2.3%, 3/128) (
P
< 0.001). The trends were similar regardless of which of the Asn-87, Asp-91, and A2143 point mutations were present. In conclusion, the superior antimicrobial efficacy of finafloxacin against
H. pylori
in an acidic environment suggests the possible use of finafloxacin for treatment of
H. pylori
infection, as has been proposed by its developer, Merlion Pharma.
Validation and Application of a Liquid Chromatography-Tandem Mass Spectrometry Method To Determine the Concentrations of Sofosbuvir Anabolites in Cells
Authors: Rower Joseph E. , Jimmerson Leah C. , Chen Xinhui , Zheng Jia-Hua , Hodara Ariel , Bushman Lane R. , Anderson Peter L. , Kiser Jennifer J. 
Published: September 2015

ABSTRACT

Sofosbuvir (SOF) is a highly efficacious and well-tolerated uridine nucleotide analog that inhibits the hepatitis C virus (HCV) NS5B polymerase enzyme. SOF is administered as a prodrug, which undergoes intracellular phosphorylation by host enzymes to a monophosphate, diphosphate, and finally a pharmacologically active triphosphate. In order to fully understand the clinical pharmacology of SOF, there is a great need to determine the intracellular phosphate concentrations of the drug. We describe the validation and utilization of a method to characterize SOF's disposition into various
in vivo
cell types, including hepatocytes, peripheral blood mononuclear cells (PBMC), and red blood cells (RBC). Standard bioanalytical validation criteria were applied to lysed cellular matrices, with a validated linear range of 50 to 50,000 fmol/sample for each phosphate moiety. The assay was utilized to collect the first data demonstrating concentrations of phosphorylated anabolites formed in PBMC, hepatocytes, and RBC
in vivo
during SOF therapy. Median concentrations in PBMC were 220 (range, 51.5 to 846), 70.2 (range, 25.8 to 275), and 859 (range, 54.5 to 6,756) fmol/10
6
cells in the monophosphate, diphosphate, and triphosphate fractions, respectively. In contrast, RBC triphosphate concentrations were much lower than those of PBMC, as the median concentration was 2.91 (range, 1.14 to 10.4) fmol/10
6
cells. The PBMC triphosphate half-life was estimated at 26 h using noncompartmental approaches, while nonlinear mixed-effect modeling was used to estimate a 69 h half-life for this moiety in RBC. The validated method and the data it generates provide novel insight into the cellular disposition of SOF and its phosphorylated anabolites
in vivo
.
Isolation Site Influences Virulence Phenotype of Serotype 14 Streptococcus pneumoniae Strains Belonging to Multilocus Sequence Type 15
Authors: Amin Zarina , Harvey Richard M. , Wang Hui , Hughes Catherine E. , Paton Adrienne W. , Paton James C. , Trappetti Claudia 
Published: September 2015

ABSTRACT

Streptococcus pneumoniae
is a diverse species causing invasive as well as localized infections that result in massive global morbidity and mortality. Strains vary markedly in pathogenic potential, but the molecular basis is obscured by the diversity and plasticity of the pneumococcal genome. We have previously reported that
S. pneumoniae
serotype 3 isolates belonging to the same multilocus sequence type (MLST) differed markedly in
in vitro
and
in vivo
phenotypes, in accordance with the clinical site of isolation, suggesting stable niche adaptation within a clonal lineage. In the present study, we have extended our analysis to serotype 14 clinical isolates from cases of sepsis or otitis media that belong to the same MLST (ST15). In a murine intranasal challenge model, five ST15 isolates (three from blood and two from ears) colonized the nasopharynx to similar extents. However, blood and ear isolates exhibited significant differences in bacterial loads in other host niches (lungs, ear, and brain) at both 24 and 72 h postchallenge. In spite of these differences, blood and ear isolates were present in the lungs at similar levels at 6 h postchallenge, suggesting that early immune responses may underpin the distinct virulence phenotypes. Transcriptional analysis of lung tissue from mice infected for 6 h with blood isolates versus ear isolates revealed 8 differentially expressed genes. Two of these were exclusively expressed in response to infection with the ear isolate. These results suggest a link between the differential capacities to elicit early innate immune responses and the distinct virulence phenotypes of clonally related
S. pneumoniae
strains.