bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential impact of propofol immediately after motor vehicle accident on later symptoms of posttraumatic stress disorder at 6-month follow up: a retrospective cohort study
Authors: Usuki Masato , Matsuoka Yutaka , Nishi Daisuke , Yonemoto Naohiro , Matsumura Kenta , Otomo Yasuhiro , Kim Yoshiharu , Kanba Shigenobu 
Published: October 2012

Abstract
Introduction
Critically injured patients are at risk of developing posttraumatic stress disorder (PTSD). Propofol was recently reported to enhance fear memory consolidation retrospectively. Thus, we investigated here whether administration of propofol within 72 h of a motor vehicle accident (MVA) affects the subsequent development of PTSD symptoms.

Methods
We examined data obtained from a prospective cohort study of MVA-related injured patients, admitted to the intensive care unit of a general hospital. We investigated the effect of propofol administration within 72 h of MVA on outcome. Primary outcome was diagnosis of full or partial PTSD as determined by the Clinician-Administered PTSD Scale (CAPS) at 6 months. Secondary outcomes were diagnosis of full or partial PTSD at 1 month and CAPS score indicating PTSD at 1 and 6 months. Multivariate analysis was conducted adjusting for being female, age, injury severity score (ISS), and administration of ketamine or midazolam within 72 h of MVA.

Results
Among 300 patients recruited (mean ISS, 8.0; median Glasgow Coma Scale (GCS) score, 15.0; age, 18 to 69 years), propofol administration showed a higher risk for full or partial PTSD as determined by CAPS at 6 months (odds ratio = 6.13, 95% confidence interval (CI): 1.57 to 23.85, P = 0.009) and at 1 month (odds ratio = 1.31, 95% CI: 0.41 to 4.23, P = 0.647) in the multivariate logistic regression. Multivariate regression analysis showed a trend toward adverse effects of propofol on PTSD symptom development at 6 months after MVA (β = 4.08, 95% CI: -0.49 to 8.64, P = 0.080), but not at 1 month after MVA (β = -0.42, 95% CI: -6.34 to 5.51, P = 0.890).

Conclusions
These findings suggest that using propofol in the acute phase after MVA might be associated with the development of PTSD symptoms 6 months later. However, since the design of this study was retrospective, these findings should be interpreted cautiously and further study is warranted.
Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study
Authors: Vaara Suvi T , Korhonen Anna-Maija , Kaukonen Kirsi-Maija , Nisula Sara , Inkinen Outi , Hoppu Sanna , Laurila Jouko J , Mildh Leena , Reinikainen Matti , Lund Vesa , Parviainen Ilkka , Pettilä Ville ,   The FINNAKI study group
Published: October 2012

Abstract
Introduction
Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.

Methods
We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.

Results
We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.

Conclusions
Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.
Differential DNA methylation in discrete developmental stages of the parasitic nematode Trichinella spiralis
Authors: Gao Fei , Liu Xiaolei , Wu Xiu-Ping , Wang Xue-Lin , Gong Desheng , Lu Hanlin , Xia Yudong , Song Yanxia , Wang Junwen , Du Jing , Liu Siyang , Han Xu , Tang Yizhi , Yang Huanming , Jin Qi , Zhang Xiuqing , Liu Mingyuan 
Published: October 2012

Abstract
Background
DNA methylation plays an essential role in regulating gene expression under a variety of conditions and it has therefore been hypothesized to underlie the transitions between life cycle stages in parasitic nematodes. So far, however, 5'-cytosine methylation has not been detected during any developmental stage of the nematode Caenorhabditis elegans. Given the new availability of high-resolution methylation detection methods, an investigation of life cycle methylation in a parasitic nematode can now be carried out.

Results
Here, using MethylC-seq, we present the first study to confirm the existence of DNA methylation in the parasitic nematode Trichinella spiralis, and we characterize the methylomes of the three life-cycle stages of this food-borne infectious human pathogen. We observe a drastic increase in DNA methylation during the transition from the new born to mature stage, and we further identify parasitism-related genes that show changes in DNA methylation status between life cycle stages.

Conclusions
Our data contribute to the understanding of the developmental changes that occur in an important human parasite, and raises the possibility that targeting DNA methylation processes may be a useful strategy in developing therapeutics to impede infection. In addition, our conclusion that DNA methylation is a mechanism for life cycle transition in T. spiralis prompts the question of whether this may also be the case in any other metazoans. Finally, our work constitutes the first report, to our knowledge, of DNA methylation in a nematode, prompting a re-evaluation of phyla in which this epigenetic mark was thought to be absent.
Cytosine methylation and hydroxymethylation mark DNA for elimination in Oxytricha trifallax
Authors: Bracht John R , Perlman David H , Landweber Laura F 
Published: October 2012

Abstract
Background
Cytosine methylation of DNA is conserved across eukaryotes and plays important functional roles regulating gene expression during differentiation and development in animals, plants and fungi. Hydroxymethylation was recently identified as another epigenetic modification marking genes important for pluripotency in embryonic stem cells.

Results
Here we describe de novo cytosine methylation and hydroxymethylation in the ciliate Oxytricha trifallax. These DNA modifications occur only during nuclear development and programmed genome rearrangement. We detect methylcytosine and hydroxymethylcytosine directly by high-resolution nano-flow UPLC mass spectrometry, and indirectly by immunofluorescence, methyl-DNA immunoprecipitation and bisulfite sequencing. We describe these modifications in three classes of eliminated DNA: germline-limited transposons and satellite repeats, aberrant DNA rearrangements, and DNA from the parental genome undergoing degradation. Methylation and hydroxymethylation generally occur on the same sequence elements, modifying cytosines in all sequence contexts. We show that the DNA methyltransferase-inhibiting drugs azacitidine and decitabine induce demethylation of both somatic and germline sequence elements during genome rearrangements, with consequent elevated levels of germline-limited repetitive elements in exconjugant cells.

Conclusions
These data strongly support a functional link between cytosine DNA methylation/hydroxymethylation and DNA elimination. We identify a motif strongly enriched in methylated/hydroxymethylated regions, and we propose that this motif recruits DNA modification machinery to specific chromosomes in the parental macronucleus. No recognizable methyltransferase enzyme has yet been described in O. trifallax, raising the possibility that it might employ a novel cytosine methylation machinery to mark DNA sequences for elimination during genome rearrangements.
Fasting-Induced FGF21 Is Repressed by LXR Activation via Recruitment of an HDAC3 Corepressor Complex in Mice
Authors: Archer Amena , Venteclef Nicolas , Mode Agneta , Pedrelli Matteo , Gabbi Chiara , Clément Karine , Parini Paolo , Gustafsson Jan-Åke , Korach-André Marion 
Published: October 2012

AbstractThe liver plays a pivotal role in the physiological adaptation to fasting and a better understanding of the metabolic adaptive responses may give hints on new therapeutic strategies to control the metabolic diseases. The liver X receptors (LXRs) are well-established regulators of lipid and glucose metabolism. More recently fibroblast growth factor 21 (FGF21) has emerged as an important regulator of energy homeostasis. We hypothesized that the LXR transcription factors could influence Fgf21 expression, which is induced in response to fasting. Wild-type, LXRα−/−, and LXRβ−/− mice were treated for 3 d with vehicle or the LXR agonist GW3965 and fasted for 12 h prior to the killing of the animals. Interestingly, serum FGF21 levels were induced after fasting, but this increase was blunted when the mice were treated with GW3965 independently of genotypes. Compared with wild-type mice, GW3965-treated LXRα−/− and LXRβ−/− mice showed improved insulin sensitivity and enhanced ketogenic response at fasting. Of note is that during fasting, GW3965 treatment tended to reduce liver triglycerides as opposed to the effect of the agonist in the fed state. The LXR-dependent repression of Fgf21 seems to be mainly mediated by the recruitment of LXRβ onto the Fgf21 promoter upon GW3965 treatment. This repression by LXRβ occurs through the recruitment and stabilization of the repressor complex composed of retinoid-related orphan receptor-α/Rev-Erbα/histone deacetylase 3 onto the Fgf21 promoter. Our data clearly demonstrate that there is a cross talk between the LXR and FGF21 signaling pathways in the adaptive response to fasting.
Dual Antiplatelet Agent—Induced Spontaneous Liver Hematoma
Authors: Darwish Omar S , Iqbal Erum 
Published: October 2012

OBJECTIVE: To report a case of a spontaneous liver hematoma in a patient receiving dual antiplatelet therapy for 5 years after coronary stent implantation. CASE SUMMARY: A 76-year-old man with coronary artery disease presented to the hospital with acute right upper quadrant pain. He had been taking clopidogrel 75 mg/day, a P2Y12 inhibitor, and aspirin 81 mg/day for 5 years after having a drug-eluting stent (DES) placed. Given a drop in hemoglobin (from 13.0 g/dL to 8.6 g/dL) and elevated liver enzymes, subsequent studies were performed and revealed a large liver hematoma. Clopidogrel and aspirin were discontinued. Aspirin was restarted 1 month later; there was no recurrence of bleeding. DISCUSSION: Current guidelines recommend that a P2Y12 inhibitor and aspirin after DES implantation be given for at least 12 months. However, because of concern for late stent thrombosis, some clinicians encourage patients to continue taking dual antiplatelet therapy beyond this period as long as the risk of bleeding is low. An objective causality assessment suggested that the liver hematoma was possibly related to the combination of clopidogrel and aspirin. To our knowledge, this is the first report of a patient who developed a liver hematoma while on aspirin and clopidogrel. Some recent studies have shown that the use of dual antiplatelet therapy for longer than 12 months does not reduce the rate of myocardial infarction or death from cardiac cause compared with aspirin monotherapy. CONCLUSIONS: It may be safer to maintain dual antiplatelet therapy for no more than 12 months after DES placement.
Pseudo-Adversarialism: A Theoretical Comparison Between the U.S. and Japanese Criminal Procedures
Authors: Nakao Keisuke , Tsumagari Masatoshi 
Published: October 2012

Abstract
This article offers a unified theoretical framework to address two distinctive forms of adversarial procedure: the bona fide adversarial system and the pseudo-adversarial system. In the former, a harsh contest between the prosecution and the defense is promoted, and an acquittal is rendered with substantial likelihood. In the latter, the prosecution overpowers the defense so that defendants are almost always convicted. We explain this procedural dichotomy as a result of optimal incentive designs institutionalized through controlling a judge's standard of proof beyond a reasonable doubt, a prosecutor's discretionary rule for indictment, and a defendant's right to counsel. Our theory suggests that the bona fide adversarial system performs suitably with jury trials, publicly-elected prosecutors, and government-based defense systems, while the pseudo-adversarial system is shaped by bench trials, career prosecutors, and court-appointed defense counsels. The Japanese pseudo-adversarial system might still be influenced by the defunct inquisitorial system initiated during the Meiji Restoration.
Identification and quantification of hemoglobins in whole blood: the analytical and organizational aspects of Capillarys 2 Flex Piercing compared with agarose electrophoresis and HPLC methods
Authors: Altinier Sara , Varagnolo Mariacristina , Zaninotto Martina , Plebani Mario 
Published: October 2012

Abstract

Background: The present study was conducted to evaluate the analytical performance and the organizational aspects of Capillarys 2 Flex Piercing system (CFP) respect to agarose electrophoresis and HPLC methods in hemoglobinopathies screening.

Methods: The measurement of imprecision in HbA2 and HbF quantification was verified on HbA2 CFP control and on three samples; 74 whole blood samples were used to evaluate migration time imprecision of hemoglobin variants S, C and E (HbS, HbC, and HbE); to compare methods, 451 samples were tested on CFP and HPLC; reference values were verified as value distribution in 160 blood donors and at ROC curve analysis on 449 samples from routine analysis.

Results: Imprecision: the analytical CV%s ranged from 1.25 to 3.9 at HbA2 quantification, the CV% was 3.78 at HbF quantification; the running time imprecision for HbS and HbC and HbE ranged from 0.20 to 0.69%. Method comparison: at regression analysis findings were HbA2: CFP=1.21×HPLC–0.64, HbF: CFP=1.31×HPLC-0.75, HbS: CFP=1.10×HPLC-3.24. Reference values: the HbA2 95th percentile range was 2.5–2.8; HbF was undetectable in 154 out 160 samples tested; at ROC curve analysis the best combination of sensitivity and diagnostic efficiency was obtained using 2.2 and 3.0, as reference values, for HbA2 and 1.1 as the upper reference limit for HbF. Organizational aspects: with respect to the procedures currently implemented in our laboratory CFP requires 2 h less time and obviates the need for some manual steps.

Conclusions: The quantification, reproducibility and diagnostic efficiency provided by CFP in identification and quantification of hemoglobins appear accurate. In addition, the use of primary tubes allows improved safety, and the avoidance of some manual steps, that prolong working time and are a source of possible errors.
Preanalytical quality improvement: in quality we trust
Authors: Lippi Giuseppe , Becan-McBride Kathleen , Behúlová Darina , Bowen Raffick A. , Church Stephen , Delanghe Joris , Grankvist Kjell , Kitchen Steve , Nybo Mads , Nauck Matthias , Nikolac Nora , Palicka Vladimir , Plebani Mario , Sandberg Sverre , Simundic Ana-Maria 
Published: October 2012

Abstract
Total quality in laboratory medicine should be defined as the guarantee that each activity throughout the total testing process is correctly performed, providing valuable medical decision-making and effective patient care. In the past decades, a 10-fold reduction in the analytical error rate has been achieved thanks to improvements in both reliability and standardization of analytical techniques, reagents, and instrumentation. Notable advances in information technology, quality control and quality assurance methods have also assured a valuable contribution for reducing diagnostic errors. Nevertheless, several lines of evidence still suggest that most errors in laboratory diagnostics fall outside the analytical phase, and the pre- and postanalytical steps have been found to be much more vulnerable. This collective paper, which is the logical continuum of the former already published in this journal 2 years ago, provides additional contribution to risk management in the preanalytical phase and is a synopsis of the lectures of the 2nd European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)-Becton Dickinson (BD) European Conference on Preanalytical Phase meeting entitled “Preanalytical quality improvement: in quality we trust” (Zagreb, Croatia, 1–2 March 2013). The leading topics that will be discussed include quality indicators for preanalytical phase, phlebotomy practices for collection of blood gas analysis and pediatric samples, lipemia and blood collection tube interferences, preanalytical requirements of urinalysis, molecular biology hemostasis and platelet testing, as well as indications on best practices for safe blood collection. Auditing of the preanalytical phase by ISO assessors and external quality assessment for preanalytical phase are also discussed.
Clinical applications of maternal plasma fetal DNA analysis: translating the fruits of 15 years of research
Authors: Kwun Chiu Rossa Wai , Dennis Lo Yuk Ming 
Published: October 2012

Abstract
The collection of fetal genetic materials is required for the prenatal diagnosis of fetal genetic diseases. The conventional methods for sampling fetal genetic materials, such as amniocentesis and chorionic villus sampling, are invasive in nature and are associated with a risk of fetal miscarriage. For decades, scientists had been pursuing studies with goals to develop non-invasive methods for prenatal diagnosis. In 1997, the existence of fetal derived cell-free DNA molecules in plasma of pregnant women was first demonstrated. This finding provided a new source of fetal genetic material that could be obtained safely through the collection of a maternal blood sample and provided a new avenue for the development of non-invasive prenatal diagnostic tests. Now 15 years later, the diagnostic potential of circulating fetal DNA analysis has been realized. Fruitful research efforts have resulted in the clinical implementation of a number of non-invasive prenatal tests based on maternal plasma DNA analysis and included tests for fetal sex assessment, fetal rhesus D blood group genotyping and fetal chromosomal aneuploidy detection. Most recently, research groups have succeeded in decoding the entire fetal genome from maternal plasma DNA analysis which paved the way for the achievement of non-invasive prenatal diagnosis of many single gene diseases. A paradigm shift in the practice of prenatal diagnosis has begun.
Botulinum toxin for the treatment of achalasia in pregnancy
Authors: Fels Heather , Stohl Hindi E. , Lee Richard H. , Aghajanian Paola 
Published: October 2012

Abstract
There is a paucity of data on the perinatal management of achalasia, an esophageal dysmotility disorder involving an abnormal relaxation of the lower esophageal sphincter. Botulinum toxin A is a well-described treatment for achalasia in the non-pregnant state but has been infrequently used for treatment of this condition in pregnancy. We describe a case of a successful treatment of achalasia in the first trimester of pregnancy with botulinum toxin A, and a subsequently uncomplicated pregnancy course and pregnancy outcome.
Can Centralization of Cancer Surgery Improve Social Welfare?
Authors: Ho Vivian , Short Marah N. , Ku-Goto Meei-Hsiang 
Published: October 2012

Abstract
The empirical association between high hospital procedure volume and lower mortality rates has led to recommendations for the centralization of complex surgical procedures. Yet redirecting patients to a select number of high-volume hospitals creates potential negative consequences for market competition. We use patient-level data to estimate the association between hospital procedure volume and patient mortality and costs. We also estimate the association between hospital market concentration and mortality, cost, and prices. We use our estimates to simulate the change in social welfare resulting from redirecting patients at low-volume hospitals to high-volume facilities. We find that a higher procedure volume leads to significant reductions in mortality for patients undergoing surgery for pancreatic cancer, but not colon cancer. Procedure volume also influences costs for both surgeries, but in a nonlinear fashion. Increased market concentration is associated with higher costs and prices for colon cancer, but not pancreatic cancer patients. Simulations indicated that centralizing pancreatic cancer surgery is unambiguously welfare enhancing. In contrast, there is less evidence to suggest that centralizing colon cancer surgery would be welfare improving.
A Reexamination of the Costs of Medical R&D Regulation
Authors: Philipson Tomas J. , Sun Eric , Goldman Dana , Jena Anupam B. 
Published: October 2012

Abstract
Recent evidence suggests that the economic value of increased health has been enormous, with most of these gains being driven by medical R&D. The R&D process for pharmaceuticals is particularly expensive and time consuming, with well-known studies from the Tufts Center for the Study of Drug Development suggesting that developing a single successful drug costs around $1 billion and takes roughly 12 years. We argue that these estimates are incomplete because they do not incorporate the social costs imposed by the regulatory process, namely the costs to producers in terms of forgone profits and the costs to consumers in terms of delayed access to drugs. In this article, we develop a framework to estimate the social costs imposed by the regulatory process. Under this framework, delays in drug development are socially costly because of reduced consumer surplus (due to delayed access to beneficial therapies), reduced producer variable profits, and increased R&D expenditures. We apply this framework to the case of therapies aimed at treating AIDS, non-Hodgkin’s lymphoma, and breast cancer. In each case, we find that the effects of drug delays on consumer surplus and variable producer profits are far larger than the effects on R&D costs. These findings suggest that patients, not firms, would be the primary beneficiaries from any improvements in streamlining the drug development process.