bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic/Pharmacodynamic Determinants of Vancomycin Efficacy in Enterococcal Bacteremia
Authors: Jumah Muhammed Taufiq Bin , Vasoo Shawn , Menon Sanjay R. , De Partha Pratim , Neely Michael , Teng Christine B. 
Published: December 2017

ABSTRACT

While pharmacokinetic-pharmacodynamic targets for vancomycin therapy are recognized for invasive methicillin-resistant
Staphylococcus aureus
infections, scant data are available to guide therapy for other Gram-positive infections. A retrospective single-center cohort of patients with
Enterococcus
bacteremia hospitalized between 1 January 2009 and 31 May 2015 were studied. The average vancomycin AUC
0–24
was computed using a Bayesian approach. The MIC was determined by gradient diffusion (Etest; bioMérieux), and the average AUC
0–24
/MIC value over the initial 72 h of therapy was calculated. We assessed 30-day all-cause mortality as the primary outcome. Classification and regression tree analysis (CART) was used to identify the vancomycin AUC
0–24
/MIC value associated with 30-day mortality. Fifty-seven patients with enterococcal bacteremia (32
E. faecium
, 21
E. faecalis
, and 4 other
Enterococcus
spp.) were studied. The median vancomycin MIC was 0.75 mg/liter (range, 0.38 to 3 mg/liter). All-cause 30-day mortality occurred in 10 of 57 patients (17.5%). A CART-derived vancomycin AUC/MIC
Etest
value of ≥389 was associated with reduced mortality (
P
= 0.017); failure to achieve this independently predicted 30-day mortality (odds ratio, 6.83 [95% confidence interval = 1.51 to 30.84];
P
= 0.01). We found that a vancomycin AUC/MIC
Etest
value of ≥389 achieved within 72 h was associated with reduced mortality. Larger, prospective studies are warranted to verify the vancomycin pharmacodynamic targets associated with maximal clinical outcomes and acceptable safety.
The cGAS/STING Pathway Detects Streptococcus pneumoniae but Appears Dispensable for Antipneumococcal Defense in Mice and Humans
Authors: Ruiz-Moreno Juan Sebastian , Hamann Lutz , Jin Lei , Sander Leif E. , Puzianowska-Kuznicka Monika , Cambier John , Witzenrath Martin , Schumann Ralf R. , Suttorp Norbert , Opitz Bastian 
Published: December 2017

ABSTRACT

Streptococcus pneumoniae
is a frequent colonizer of the upper respiratory tract and a leading cause of bacterial pneumonia. The innate immune system senses pneumococcal cell wall components, toxin, and nucleic acids, which leads to production of inflammatory mediators to initiate and control antibacterial defense. Here, we show that the cGAS (cyclic GMP-AMP [cGAMP] synthase)-STING pathway mediates detection of pneumococcal DNA in mouse macrophages to primarily stimulate type I interferon (IFN) responses. Cells of human individuals carrying
HAQ TMEM173
, which encodes a common hypomorphic variant of STING, were largely or partly defective in inducing type I IFNs and proinflammatory cytokines upon infection. Subsequent analyses, however, revealed that STING was dispensable for restricting
S. pneumoniae
during acute pneumonia in mice. Moreover, explorative analyses did not find differences in the allele frequency of
HAQ TMEM173
in nonvaccinated pneumococcal pneumonia patients and healthy controls or an association of
HAQ TMEM173
carriage with disease severity. Together, our results indicate that the cGAS/STING pathway senses
S. pneumoniae
but plays no major role in antipneumococcal immunity in mice and humans.
Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction
Authors: McMurray John J V , Trueman David , Hancock Elizabeth , Cowie Martin R , Briggs Andrew , Taylor Matthew , Mumby-Croft Juliet , Woodcock Fionn , Lacey Michael , Haroun Rola , Deschaseaux Celine 
Published: December 2017

ObjectiveChronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia.MethodsA cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER).ResultsIn the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%–94% in the UK, 84% in Denmark and 95% in Colombia.ConclusionsOur analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF.
Measurement of glycerol turnover by infusion of nonisotopic glycerol in normal and injured subjects
Authors: Carpentier Yvon A. , Jeevanandam Malayappa , Robin Arnold P. , Nordenström Jorgen , Burr Robert E. , Leibel Rudolph L. , Hirsch Jules , Elwyn David H. , Kinney John M. 
Published: December 2017

A new technique for measuring glycerol turnover in human subjects is presented using a staged infusion of unlabeled glycerol. A total of 105 measurements was made in normal subjects and postoperative or acutely ill patients. The relation between glycerol turnover rate (Rt) and concentration (C) (Rt = 31 + 2.07C) from 80 staged infusion measurements in 21 normal subjects did not differ significantly from observations of others made by isotope dilution. In 11 patients, glycerol turnover was also measured by dilution of isotopic glycerol. Mean values did not differ significantly between the two methods. The average difference, regardless of sign, for individual values was 17%. This agreement tends to validate the assumptions of both methods. Advantages of the staged infusion method are that it is quicker and easier to perform and does not entail a risk due to administration of radioactive materials. Evidence obtained in this study from a three-stage procedure indicates that satisfactory information may be obtained from a two-stage infusion at successive rates of 250 and 600 μmol/min for 70 min each, with a prime of 2 mmol given as a bolus at the start of each stage. isotope dilution; glycerol clearance; glycerol concentration; lipolysis; futile cycle Submitted on December 27, 1983 Accepted on April 18, 1984
The mutual interaction of vasoconstriction and endothelial damage in stenotic arteries
Authors: Tulenko T. N. , Constantinescu D. , Kikuchi T. , Cox R. H. , Santamore W. P. 
Published: December 2017

Page H885: T. N. Tulenko, D. Constantinescu, T. Kikuchi, R. H. Cox, and W. P. Santamore. “The mutual interaction of vasoconstriction and endothelial damage in stenotic arteries.” Figure 5 should appear as the following. (See PDF)
Expression of vascular escape: conductance or resistance?
Authors: D'Almeida Mark S. , Lautt W. Wayne 
Published: December 2017

Vascular escape is that phenomenon whereby a tachyphylaxis occurs in the vasoconstriction of an arteriole to a constant sympathetic stimulation. Vascular escape, in vivo, is primarily a blood flow event. Calculated resistance, as an index of vascular tone, does not consistently describe the responses of the arterioles undergoing vascular escape. Conductance, which is the inverse of resistance, obviates several of the errors produced by the use of resistance. In this study, we illustrate this issue using hypothetical and experimental data. Escape responses were calculated in terms of resistance and conductance and plotted against blood flow escape responses. Resistance escape responses were nonlinearly related to blood flow escapes and overestimated vascular escape with both hypothetical and experimental data. Conductance escape responses were linearly related to flow escape responses and consistently described vascular escape. We therefore conclude that conductance is a better index of vascular tone to express vascular escape. arterial vascular tone; vasoconstriction; autoregulatory escape; blood flow; blood pressure Submitted on July 18, 1991 Accepted on November 11, 1991
Microvascular pressure profile of serosal vessels of rat trachea
Authors: Ballard S. T. , Nations R. H. , Taylor A. E. 
Published: December 2017

Pages H1303–H1304: S. T. Ballard, R. H. Nations, and A. E. Taylor. “Microvascular pressure profile of serosal vessels of rat trachea.” Measurements of microvessel diameter were overestimated because of a calibration error. The corrected vessel diameters are 0.56 times those originally reported. The corrected diameter ranges for arterioles, venules, and venular sinuses should be 6–53, 11–42, and 67–236 μm, respectively. When it is assumed that capillaries fall between 10-μm arterioles and venules, capillary pressures predicted by a four-parameter logistical function range from 34.5 and 12.7% of mean arterial pressure. Therefore, when the average large venular pressure was 5% of mean arterial pressure, fractional precapillary (systemic to 10-μm-diam arterioles), capillary (10-μm-diam arterioles to 10-μm-diam venules), and postcapillary (10-μm-diam venules to large venules) resistances would represent 69, 23, and 8%, respectively, of the total microvascular resistance. A revised Fig. 1 comparing experimental data with those of Nordin et al. (3), who measured microvascular pressure in rabbit tracheal mucosa, follows. (See PDF)
LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker
Authors: Bressy Christian , Lac Sophie , Nigri Jérémy , Leca Julie , Roques Julie , Lavaut Marie-Nöelle , Secq Véronique , Guillaumond Fabienne , Bui Thi-Thien , Pietrasz Daniel , Granjeaud Samuel , Bachet Jean-Baptiste , Ouaissi Mehdi , Iovanna Juan , Vasseur Sophie , Tomasini Richard 
Published: December 2017

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL6-related stem cell–promoting factor LIF supports PDAC-associated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared with healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral nerves. Cancer cells and stromal cells in PDAC tissues both expressed LIF, but only stromal cells could secrete it. Biological investigations showed that LIF promoted the differentiation of glial nerve sheath Schwann cells and induced their migration by activating JAK/STAT3/AKT signaling. LIF also induced neuronal plasticity in dorsal root ganglia neurons by increasing the number of neurites and the soma area. Notably, injection of LIF-blocking antibody into PDAC-bearing mice reduced intratumoral nerve density, supporting a critical role for LIF function in PANR. In serum from human PDAC patients and mouse models of PDAC, we found that LIF titers positively correlated with intratumoral nerve density. Taken together, our findings suggest LIF as a candidate serum biomarker and diagnostic tool and a possible therapeutic target for limiting the impact of PANR in PDAC pathophysiology and metastatic progression.
Significance: This study suggests a target to limit neural remodeling in pancreatic cancer, which contributes to poorer quality of life and heightened metastatic progression in patients. Cancer Res; 78(4); 909–21. ©2017 AACR.
Molecular Predicators of Duodenal Familial Adenomatous Polyposis Chemoprevention: Do Chemopreventive Drugs Hit Their Presumed Molecular Targets?
Authors: Shureiqi Imad 
Published: December 2017

Abstract
Patients with familial adenomatous polyposis (FAP) have an increased risk of developing duodenal adenomas and adenocarcinomas. In previous trials, sulindac (a cyclooxygenase inhibitor) alone failed to significantly suppress duodenal tumorigenesis in FAP patients, but sulindac plus the tyrosine kinase inhibitor erlotinib significantly reduced duodenal polyp burden. Delker and colleagues report in this issue (beginning on page 4) on transcriptome analyses that aimed to identify the molecular targets mediating the response to sulindac–erlotinib. Their exploratory transcriptome analyses suggested that sulindac–erlotinib suppressed duodenal polyposis via inhibiting Wnt/β-catenin, EGFR, and cyclooxygenase pathways. This perspective discusses the significance and limitations of the study. Cancer Prev Res; 11(1); 1–3. ©2017 AACR.
See related article by Delker et al., p. 4
Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures and Malignancy Risk in Adults With Congenital Heart Disease
Authors: Cohen Sarah , Liu Aihua , Gurvitz Michelle , Guo Liming , Therrien Judith , Laprise Claudie , Kaufman Jay S. , Abrahamowicz Michal , Marelli Ariane J. 
Published: December 2017

Background:
Adults with congenital heart disease (CHD) are exposed to increasing amounts of low-dose ionizing radiation (LDIR) from cardiac procedures. Cancer prevalence in this population is higher than in the general population. This study estimates the association between LDIR exposure from cardiac procedures and incident cancer in adult patients with CHD.

Methods:
The study population derived from the Quebec Congenital Heart Disease Database. We measured cumulative numbers of LDIR-related cardiac procedures for each patient until 1 year before the time of cancer diagnosis or administrative censoring. To assess the association between LDIR exposure and cancer risk, we conducted a nested case-control study and matched cancer cases with controls on sex, CHD severity, birth year, and age.

Results:

The study included 24 833 adult patients with CHD aged 18 to 64 years from 1995 to 2009. In >250 791 person-years of follow-up, 602 cancer cases were observed (median age, 55.4 years). The cumulative incidence of cancer estimated up to 64 years of age was 15.3% (95% confidence interval [CI], 14.2–16.5). Cases had more LDIR-related cardiac procedures than controls (1410 versus 921 per 1000 adult patients with CHD,
P
<0.0001). Cumulative LDIR exposure was independently associated with cancer (odds ratio [OR], 1.08 per procedure; 95% CI, 1.04–1.13). Similar results were obtained by using dose estimates for LDIR exposure (OR, 1.10 per 10 mSv; 95% CI, 1.05–1.15) with a possible dose-related response. The effect measure was in the same direction, and the association was persistent for exposure from ≥6 procedures in all sensitivity analyses: after excluding most smoking-related cancer cases (OR, 1.10 per procedure; 95% CI, 1.05–1.16 and OR when exposure from ≥6 procedures, 3.08; 95% CI, 1.77–5.37), and after applying a 3-year lag period (OR, 1.09 per procedure; 95% CI, 1.03–1.14 and OR when exposure from ≥6 procedures: 2.58; 95% CI, 1.43–4.69).

Conclusions:
To our knowledge, this is the first large population-based study to analyze and document the association between LDIR-related cardiac procedures and incident cancer in the population of adults with CHD. Confirmations of these findings by prospective studies are needed to reinforce policy recommendations for radiation surveillance in patients with CHD where no regulation currently exists. Physicians ordering and performing cardiac imaging should ensure that exposure is as low as reasonably achievable without sacrificing quality of care.
Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure
Authors: Long Qing‐Qing , Wang Hao , Gao Wei , Fan Yi , Li Ya‐Fei , Ma Yao , Yang Yang , Shi Hao‐Jie , Chen Bing‐Rui , Meng Hao‐Yu , Wang Qi‐Ming , Wang Fang , Wang Ze‐Mu , Wang Lian‐Sheng 
Published: December 2017

Background

Congestive heart failure (
CHF
) is a common cardiovascular disease that is often accompanied by ventricular arrhythmias. The decrease of the slow component of the delayed rectifier potassium current (

I
K

s
) in
CHF
leads to action potential (
AP
) prolongation, and the

I
K

s
is an important contributor to the development of ventricular arrhythmias. However, the molecular mechanisms underlying ventricular arrhythmias are still unknown.

Methods and Results

Kcna2 and Kcna2 antisense RNA (Kcna2
AS)
transcript expression was measured in rat cardiac tissues using quantitative real‐time reverse transcription–polymerase chain reaction and Western blotting. There was a 43% reduction in Kcna2
mRNA
in the left ventricular myocardium of rats with
CHF
. Kcna2 knockdown in the heart decreased the I
Ks
and prolonged
AP
s in cardiomyocytes, consistent with the changes observed in heart failure. Conversely, Kcna2 overexpression in the heart significantly attenuated the
CHF
‐induced decreases in the I
Ks
,
AP
prolongation, and ventricular arrhythmias. Kcna2
AS
was upregulated ≈1.7‐fold in rats with
CHF
and with phenylephrine‐induced cardiomyocyte hypertrophy. Kcna2
AS
inhibition increased the
CHF
‐induced downregulation of Kcna2. Consequently, Kcna2 AS mitigated the decrease in the I
Ks
and the prolongation of
AP
s in vivo and in vitro and reduced ventricular arrhythmias, as detected using electrocardiography.

Conclusions

Ventricular Kcna2
AS
expression increases in rats with
CHF
and contributes to reduced

I
K

s
, prolonged
AP
s, and the occurrence of ventricular arrhythmias by silencing Kcna2. Thus, Kcna2
AS
may be a new target for the prevention and treatment of ventricular arrhythmias in patients with
CHF
.
Gene transfer into hematopoietic stem cells reduces HLH manifestations in a murine model of Munc13-4 deficiency
Authors: Soheili Tayebeh , Durand Amandine , Sepulveda Fernando E. , Rivière Julie , Lagresle-Peyrou Chantal , Sadek Hanem , de Saint Basile Geneviève , Martin Samia , Mavilio Fulvio , Cavazzana Marina , André-Schmutz Isabelle 
Published: December 2017

Key Points
UNC13D gene transfer into HSCs corrects all clinical and biological signs of HLH in a mouse model. Munc13-4 is expressed in mature CD8+ T cells allowing the correction of cytotoxic activity and consequently efficient viral restriction.
A construção da identidade institucional da regulação bancária brasileira: uma análise à luz da teoria do path dependence
Authors: Jantalia Fabiano 
Published: December 2017

The construction of Brazil´s banking regulation institutional identity: an analysis in the light of the path dependence theory O artigo tem por objetivo analisar o processo de construção dos arranjos institucionais da regulação bancária à luz da teoria da dependência de trajetórias (path dependence theory). O autor sustenta que a estrutura institucional vigente, baseada na repartição de competência entre o Conselho Monetário Nacional e o Banco Central do Brasil, é desnecessariamente burocrática e complexa. A partir de uma análise histórico-evolutiva do setor, argumenta-se que fatos antecedentes da história da regulação bancária brasileira acabaram por erigir grandes entraves, restrições e limitações ao processo de definição do aparato institucional de regulação e supervisão bancárias. Aplicando a teoria da dependência de trajetórias, o autor conclui que o modelo institucional vigente de regulação bancária brasileira sofreu, na verdade, um travamento por questões históricas, de modo que sua trajetória de construção acabou marcada pela autorreprodução ou autorreforço das estruturas, o que dificultou a concepção de um arcabouço regulatório mais racional. The article aims to analyze the process of construction of the institutional arrangements of banking regulation in Brazil in the light of path dependence theory. The author argues that the institutional structure in place in Brazil, based on the division of powers between the National Monetary Council and the Central Bank of Brazil, is unnecessarily bureaucratic and complex. From an analysis of history and evolution of the sector, it is argued that facts history of the history of banking regulation in Brazil came to erect high barriers, restrictions and limitations of the process of defining the institutional arrangements for regulating and supervising banks. Applying the theory of dependence of trajectories, the author concludes that the institutional framework of banking regulation in Brazil suffered, in fact, a lock-in by historical events, so that its trajectory of construction was marked by self-reinforcement of structures, making it difficult to design a more rational regulatory framework.
Effects of a telescopic intramedullary rod for treating patients with osteogenesis imperfecta of the femur
Authors: Rosemberg D. L. , Goiano E. O. , Akkari M. , Santili C. 
Published: December 2017

Purpose To introduce a new model of telescopic intramedullary rod (TIR), evaluate its effects on treating patients presenting with moderate and severe osteogenesis imperfecta (OI) and to compare the findings with those of other telescopic rods. Methods A total of 21 patients (nine girls and 12 boys; mean age at first operation, 6.6 years, 1.52 to 13.18) who underwent 52 femoral operations were monitored during a mean of 9.96 years (3.39 to 14.54). Patient characteristics, telescoping rod capability and its complications were examined. Results According to the Sillence classification, we investigated one patient with type I, nine with type III and 11 with type IV OI. Revision rates at up to five years (36%) were inferior to those found for the Fassier-Duval rod (46%). The main cause of revision was fracture (15 patients), followed by rod migration (nine), and infection (two). The rod exhibited higher telescopic capacity in boys than girls. Type III most commonly required an operation; the age group with the highest number of procedures was five to ten years. Male migration was the main cause of rod migration. Conclusion The TIR has a satisfactory cost-benefit ratio with less complication rates and low production costs. The TIR is a feasible alternative to the commonly used Fassier-Duval rod. Level of Evidence IV
Subtalar coalition resection utilizing live navigation: A technique tip
Authors: Stokman J. J. , Mitchell J. , Noonan K. 
Published: December 2017

Purpose Describe the surgical technique of talocalcaneal coalition resection using live CT navigation. Methods A ten-year-old female with left talocalcaneal coalition hindfoot pain refractory to conservative management underwent surgical coalition resection using live CT navigation. The procedure and discussion of this technique is described in detail. Results With minimal radiation exposure to the patient, CT navigation for this complex talocalcaneal coalition was both helpful and potentially timesaving by allowing immediate localization and guided resection of the coalition. Conclusion In the case of a complex subtalar coalition resection, CT navigation poses minimal patient radiation exposure and allows immediate localization and guided resection of the coalition. Level of Evidence Level V
A High Efficiency Optical Power Splitter in a Y-Branch Photonic Crystal for DWDM Optical Communication Systems
Authors: Taleb Hesami Azar Milad , Alipour-Banaei Hamed , Zavvari Mahdi 
Published: December 2017

AbstractIn this paper a high efficiency optical power splitter based on two-dimensional photonic crystals is proposed. The photonic crystal cavity is assumed to be constructed by TiO