bluuebunny/crossref_metadata_2025 huggingface dataset:
Justice and Confucianism
Authors: Cline Erin M.
Published: March 2014

This article surveys contemporary scholarship on justice and early Confucianism and builds upon recent work on justice in the Analects by examining the relationship between justice and moral self‐cultivation in the Mengzi (Mencius) and the Xunzi. It is argued that focusing on early Confucian accounts of how a sense of justice is cultivated offers insights into Confucian views of justice because it shows how remarks on justice in the Analects, Mengzi, and Xunzi are not tangential, but rather are an important part of their accounts of Confucian moral self‐cultivation.
Idealization
Authors: Elliott‐Graves Alkistis , Weisberg Michael
Published: March 2014

This article reviews the recent literature on idealization, specifically idealization in the course of scientific modeling. We argue that idealization is not a unified concept and that there are three different types of idealization: Galilean, minimalist, and multiple models, each with its own justification. We explore the extent to which idealization is a permanent feature of scientific representation and discuss its implications for debates about scientific realism.
Medical Paternalism – Part 1
Authors: Groll Daniel
Published: March 2014

Medical clinicians – doctors, nurses, nurse practitioners etc. – are charged to act for the good of their patients. But not all ways of acting for a patient's good are on par: some are paternalistic; others are not. What does it mean to act paternalistically, both in general and specifically in a medical context? And when, if ever, is it permissible for a clinician to act paternalistically?

This paper deals with the first question, with a special focus on paternalism in medicine. While it is easy to give a rough characterization of paternalism (i.e. acting for another's good against that person's will), it is surprisingly difficult to provide a unified account of the myriad of actions that seem to count as paternalistic. After surveying four accounts of paternalism, I argue that two – what I call the authority and beneficence accounts – are the strongest on offer. According to the authority account, a clinician acts paternalistically when, for her patient's good, she usurps his decision‐making authority. According to the beneficence account, a clinician acts paternalistically when, for her patient's good, she acts only or overrindingly out of concern for his good. I show how the difference between these accounts matters (in part) for how we should think about the nature of surrogate decision making in medicine. I argue that there are reasons – albeit hardly decisive – to prefer the beneficence account to the authority account. I conclude by considering whether attempts by clinicians to rationally persuade their patients to pursue a particular course of action should be thought of as paternalistic.
Relationships between stomatal behavior, xylem vulnerability to cavitation and leaf water relations in two cultivars of Vitis vinifera
Authors: Tombesi Sergio , Nardini Andrea , Farinelli Daniela , Palliotti Alberto
Published: March 2014

Current understanding of physiological mechanisms governing stomatal behavior under water stress conditions is still incomplete and controversial. It has been proposed that coordination of stomatal kinetics with xylem vulnerability to cavitation [vulnerability curve (VC)] leads to different levels of isohydry/anisohydry in different plant species/cultivars. In this study, this hypothesis is tested in Vitis vinifera cultivars displaying contrasting stomatal behavior under drought stress. The cv Montepulciano (MP, near‐isohydric) and Sangiovese (SG, anisohydric) were compared in terms of stomatal response to leaf and stem water potential, as possibly correlated to different petiole hydraulic conductivity (kpetiole) and VC, as well as to leaf water relations parameters. MP leaves showed almost complete stomatal closure at higher leaf and stem water potentials than SG leaves. Moreover, MP petioles had higher maximum kpetiole and were more vulnerable to cavitation than SG. Water potential at the turgor loss point was higher in MP than in SG. In SG, the percentage reduction of stomatal conductance (PLgs) under water stress was almost linearly correlated with corresponding percentage loss of kpetiole (PLC), while in MP PLgs was less influenced by PLC. Our results suggest that V. vinifera near‐isohydric and anisohydric genotypes differ in terms of xylem vulnerability to cavitation as well as in terms of kpetiole, and that the coordination of these traits leads to their different stomatal responses under water stress conditions.
Effect of Bovine Follicular Fluid on Reactive Oxygen Species and Glutathione in Oocytes, Apoptosis and Apoptosis‐related Gene Expression ofIn vitro‐Produced Blastocysts
Authors: Park S‐H , Cho H‐S , Yu I‐J
Published: March 2014

Contents

The reactive oxygen species (ROS) generated during thein vitromaturation of oocytes affect oocyte maturation and subsequent embryonic development. Bovine follicular fluid (bFF) has an effective antioxidant capacity. This study was conducted to investigate the effects of supplementing oocyte maturation media withbFFfrom different size classes (3–8 and 9–13 mm) on the glutathione (GSH) and ROS levels of oocytes. Embryonic development and apoptosis, as well as the relative abundance of INFτ, BAX, BCL2 and HSP70 transcripts in blastocysts, were also monitored. Oocytes collected from ovaries were matured in TCM‐199 with FBS (control) and 10% 3–8 mm (M), 9–13 mm (L) or a mixture of 3–8 mm and 9–13 mm (M + L)bFF. Glutathione and ROS levels in oocytes after 24 h were assessed by Cell Tracker Blue CMF2HC and DCHFDA staining, respectively. Apoptosis in day‐8 blastocysts was assessed by TUNEL staining. The relative abundance of BAX, BCL2, HSP70 and INFτtranscripts was assessed using quantitative real‐time polymerase chain reaction (PCR). The GSH level was significantly higher in the L group compared to the other groups (p < 0.05), while the ROS levels in the M group were significantly higher than in the other groups (p < 0.05). The apoptosis levels of blastocysts in the FBS group were significantly higher than those in the M + L group (p < 0.05), although the embryonic development did not differ between the groups. The HSP70 and INFτexpression levels in group M were significantly greater than in the controls (p < 0.05). There was no significant difference in BAX expression between the groups. Supplementation withbFFfrom various sizes of follicles into the maturation medium was capable of supporting oocyte cytoplasmic maturation by decreasing the ROS. Moreover,bFFsubsequently affected antioxidative gene expression, increasing HSP70 and INFτexpressions.
Addition of Cholesterol‐Loaded Cyclodextrins to the Thawing Extender: Effects on Boar Sperm Quality
Authors: Tomás C , Gómez‐Fernández J , Gómez‐Izquierdo E , Mocé E , de Mercado E
Published: March 2014

Contents

The aim of the present study was to evaluate the effect that the addition of cholesterol‐loaded cyclodextrins (CLC) to the thawing extender has on the quality of frozen‐thawed boar sperm. Pooled semen (n = 5) from three boars was used for the experiments. The semen was cryopreserved with an egg‐yolk‐based extender, it was diluted after thawing in Beltsville thawing solution (BTS) supplemented with different concentrations ofCLC(0, 12.5, 25, 50 or 100 mg/500 × 106sperm), and these samples were incubated at 37°C for 150 min. The following parameters of sperm quality were evaluated 30 and 150 min after incubation: sperm with intact plasma membrane (SIPM; %), sperm with normal acrosomal ridge (NAR; %), total motile sperm (TMS; %), progressively motile sperm (PMS; %) and kinetic parameters. BothSIPMandNARincreased (p < 0.05) when the thawing extender was supplemented with 12.5, 25 and 50 mgCLC/500 × 106sperm. Nevertheless, motility decreased (p < 0.05) when the concentration ofCLCexceeded 12.5 mgCLC/500 × 106sperm. In conclusion, our results suggest that the supplementation of thawing extenders withCLCimproves sperm viability and reduces acrosome damage after freezing/thawing.
An Enduring Somatic Threat Model of Posttraumatic Stress Disorder Due to Acute Life‐Threatening Medical Events
Authors: Edmondson Donald
Published: March 2014

Posttraumatic stress disorder (PTSD) occurs in 12–25% of survivors of acute life‐threatening medical events such as heart attack, stroke, and cancer, and is associated with recurrence of cardiac events and mortality in heart attack survivors. This article reviews the current state of knowledge about PTSD after such events, and proposes an Enduring Somatic Threat (EST) model of PTSD due to acute life‐threatening medical events to address underappreciated differences between PTSD due to past, discrete/external traumatic events (such as combat) and PTSD due to acute manifestations of chronic disease that are enduring/internal in nature (such as heart attack and stroke). The differences include the external versus internal/somatic source of the threat, the past versus present/future temporal focus of threatening cognitions, the different types and consequences of avoidance behavior, and the different character and consequences of hyperarousal. Although important differences between the two types of PTSD exist, the EST model proposes that the underlying fear of mortality maintains PTSD symptoms due to both discrete/external and ongoing/somatic events. Finally, this article offers a research agenda for testing the EST model, with a particular focus on areas that may improve cardiovascular prognosis and health behaviors in survivors of heart attack and stroke.
Implicit Consistency Processes in Social Cognition: Explicit‐Implicit Discrepancies Across Systems of Evaluation
Authors: Shoda Tonya M. , McConnell Allen R. , Rydell Robert J.
Published: March 2014

What happens when our automatic evaluations conflict with our attitudes that we can reflect on and articulate? In this paper, we review some processes by which explicit implicit evaluative discrepancies (EIEDs) arise and can impact our thoughts, feelings, and behavior, using a dual‐systems perspective on attitudes to explain the psychological processes underlying these evaluative inconsistencies. EIEDs emerge when differential positive and negative evaluations toward attitude objects reside in systems of knowledge governed by language and reasoning (i.e., explicit evaluations) and systems of knowledge that are association‐based (i.e., implicit evaluations). We discuss factors that produce EIEDs, including the influence of extrapersonal associations on attitudes, temporal, and qualitative differences in encountering attitude‐relevant information, and the differential influence of processing goals. Finally, we discuss consequences of holding EIEDs, including their impact on behaviors toward attitude objects, enhanced elaboration and scrutiny of social information, motivated reasoning, errant affective forecasting, and self‐regulatory success and failure.
Positive Emotion Differentiation: A Functional Approach
Authors: Shiota Michelle N. , Neufeld Samantha L. , Danvers Alexander F. , Osborne Elizabeth A. , Sng Oliver , Yee Claire I.
Published: March 2014

While positive emotion can be conceptualized broadly as a response to the potential for reward, the environment offers different kinds of rewards, and these are best approached in somewhat different ways. A functional approach to positive emotion differentiation distinguishes among several different types of rewards with strong implications for adaptive fitness and posits the existence of “discrete” positive emotions that promote an adaptive response to each reward. A taxonomy of eight positive emotions, dubbed the “PANACEAS” taxonomy based on an acronym of the first letter of each of the eight constructs, is presented as an example of this approach. Positive emotion constructs defined through functional analyses are useful for guiding empirical research, especially for identifying prototypical eliciting stimuli, and generating hypotheses about the implications of different positive emotions for a variety of outcomes. Research findings are reviewed that support the importance of positive emotion differentiation in understanding the effects of positive emotions on cognition, physiology, and behavior. Advantages of the functional approach are discussed, as well as implications of the approach for evaluating major theories of the structure of emotion.
Decreased immunoglobulin G levels after living‐donor liver transplantation is a risk factor for bacterial infection and sepsis
Authors: Yoshizumi T. , Shirabe K. , Ikegami T. , Yamashita N. , Mano Y. , Yoshiya S. , Matono R. , Harimoto N. , Uchiyama H. , Toshima T. , Maehara Y.
Published: March 2014

Background

Several studies have suggested an association between post‐transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living‐donor liver transplantation (LDLT).

Methods

Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post‐transplant bacterial infection and sepsis within 3 months after LDLT were analyzed.

Results

Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty‐four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27–10.7, respectively. Twenty‐four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end‐stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38–12.0, respectively.

Conclusions

Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post‐transplant bacterial infection and sepsis.
Comparison of long‐term and short‐term administration of itraconazole for primary antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation: a multicenter, randomized, open‐label trial
Authors: Lin R. , Xu X. , Li Y. , Sun J. , Fan Z. , Jiang Q. , Huang F. , Zhou H. , Nie D. , Guo Z. , Mao Y. , Xiao Y. , Liu Q.
Published: March 2014

Background

The optimal agents and duration of primary antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remain a matter of discussion.

Objective

Our objective was to compare the efficacy and safety of long‐term and short‐term administration of itraconazole (ITCZ) for primary antifungal prophylaxis in allo‐HSCT recipients.

Methods

This multicenter, randomized, open‐label pilot study was performed in 4 transplant centers in China. Recipients of allo‐HSCT without a history of invasive fungal disease (IFD) were randomly assigned to the long‐term or the short‐term arm. Randomization was carried out by a center computer system. Intravenous ITCZ was given to the patients in both study arms with a loading dose of 400 mg/day for 2 days followed by 200 mg/day until day +14 or when the white blood cell count was >1.0 × 109/L, and then switched to oral ITCZ solution; prophylaxis was continued until day +30 post transplantation in the short‐term arm or until day +90 in the long‐term arm. The trough serum concentrations of ITCZ also were measured. The primary study endpoint was the incidence of IFD (proven, probable, and possible) within day +90 post transplantation.

Results

A total of 128 recipients were enrolled in this study; 59 of them were randomized to the long‐term arm and 62 were randomized to the short‐term arm, forming the modified intent‐to‐treat (mITT) set. The incidence of IFD within day +90, the primary endpoint, was not significantly different between the 2 arms for the mITT set (6.78% in the long‐term arm vs. 6.45% in the short‐term arm, P = 0.94), or for the per‐protocol set (6.90% in the long‐term arm vs. 6.67% in the short‐term arm, P = 0.96). From day +30 to day +90, the incidence of IFD was 0% and 6.45%, respectively, in the patients with long‐term and short‐term prophylaxis for the mITT set (P = 0.11). The mean trough serum concentrations of ITCZ was maintained at >500 ng/mL throughout administration. The incidences of withdrawal because of drug‐related adverse events in patients with long‐term and short‐term prophylaxis were 6.78% and 0%, respectively (P = 0.05).

Conclusions

Long‐term and short‐term administration of ITCZ both seemed effective in preventing IFD in recipients of allo‐HSCT. Further study with large sample size should be performed to evaluate this result. ITCZ shows the same pharmacokinetics in recipients of allo‐HSCT as in non‐recipients.
Nonvolatile memory devices with AlOx embedded Zr-doped HfO2 high-k gate dielectric stack
Authors: Lin Chi-Chou , Kuo Yue , Zhang Shumao
Published: March 2014

MOS capacitors with the ZrHfO-AlOx-ZrHfO gate dielectric structure have been fabricated and studied for memory functions. Without the embedded AlOx film, the capacitor traps negligible amount of charges. With the embedded AlOx layer, the sample traps a large amount of holes or negligible amount of electrons depending on the polarity of the applied gate voltage. The charge retention and frequency dispersion measurements show that some of the holes are loosely retained at the tunnel ZrHfO/AlOx interface and some are deeply retained to the AlOx related sites. The leakage current–voltage curve further confirms the charge trapping capability of the AlOx embedded sample. Nearly half of the originally trapped holes can be retained in the memory device for more than 10 years. The AlOx embedded ZrHfO high-k stack is a good gate dielectric for the nonvolatile memory device.
Patterning of silicon nitride for CMOS gate spacer technology. III. Investigation of synchronously pulsed CH3F/O2/He plasmas
Authors: Blanc Romuald , Leverd François , Darnon Maxime , Cunge Gilles , David Sylvain , Joubert Olivier
Published: March 2014

Si3N4 spacer etching processes are one of the most critical steps of transistor fabrication technologies since they must be at the same time very anisotropic to generate straight spacer profiles and extremely selective to silicon in order to minimize the silicon consumption in source/drain regions. Minimizing the silicon recess and ion-induced damages to silicon surfaces are key criterions for fully depleted silicon on insulator technologies in order to ensure a high surface quality for the subsequent step of silicon epitaxy. In this work, the authors investigate synchronously pulsed CH3F/O2/He plasmas for the etching of Si3N4 spacers selectively toward Si (the selectivity typically relies on the oxidation of the silicon layer). First, they compare the Si3N4 and silicon etch rates measured in continuous wave (CW) plasmas, while varying the [CH3F]/[O2] ratio, to the etch rates measured using pulsed plasmas. Using angle resolved x-ray photoelectron spectroscopy and scanning transmission electron microscopy (STEM) cross sections, they show that the silicon thickness oxidized during the Si3N4 etching decreases from 1.5 nm in CW to 0.5 using a plasma pulsed at 1 kHz and 10% duty cycle, and the percentage of carbon implanted into the silicon substrate is reduced by a factor 2 using pulsed plasma conditions. Moreover, STEM cross sections show an improvement of the spacer profile when the plasma is pulsed at 1 kHz and low duty cycles, with a rounded spacer top leading to a better gate encapsulation, instead of the faceted spacer obtained using CW plasma conditions.
Offensive and Defensive Agility: A Sex Comparison of Lower Body Kinematics and Ground Reaction Forces
Authors: Spiteri Tania , Hart Nicolas H. , Nimphius Sophia
Published: March 2014

The aim of this study was to compare biomechanical and perceptual-cognitive variables between sexes during an offensive and defensive agility protocol. Twelve male and female (n = 24) recreational team sport athletes participated in this study, each performing 12 offensive and defensive agility trials (6 left, 6 right) changing direction in response to movements of a human stimulus. Three-dimensional motion, ground reaction force (GRF), and impulse data were recorded across plant phase for dominant leg change of direction (COD) movements, while timing gates and high-speed video captured decision time, total running time, and post COD stride velocity. Subjects also performed a unilateral isometric squat to determine lower body strength and limb dominance. Group (sex) by condition (2 × 2) MANOVAs with follow-up ANOVAs were conducted to examine differences between groups (P ≤ .05). Male athletes demonstrated significantly greater lower body strength, vertical braking force and impulse application, knee and spine flexion, and hip abduction, as well as faster decision time and post COD stride velocity during both agility conditions compared with females. Differences between offensive and defensive movements appear to be attributed to differences in decision time between sexes. This study demonstrates that biomechanical and perceptual-cognitive differences exist between sexes and within offensive and defensive agility movements.
Is Health One Future for Kinesiology?
Authors: Booth Frank W.
Published: March 2014

Exercise physiology is an old profession that dates back to 1500 B.C.E., having rises and falls in intervening years. The author provides comments from firsthand observations he has experienced in the past six decades. Events in the 1950s and 1960s caused a rise in exercise physiology in the next decades, with a decline being initiated in the late 1990s by the Center for Scientific Review's decision to treat exercise by individual organs or individual diseases rather than as a preexisting vibrant translational science for human health. In the opinion of this author and of some National Institutes of Health (NIH) program officials, the decline of qualified individuals to wisely spend taxpayer's monies on exercise research has resulted in the December 13, 2013 publication of the NIH's “Request for Information (RFI): Identifying Gaps in Understanding the Mechanisms of Physical Activity-Induced Health Benefits.”
Interdisciplinary-Integration-Interface: The Past, Present, and Future of Biomechanics
Authors: Gregor Robert J. , Childers W. Lee , Lyle Mark A. , Fetters Linda
Published: March 2014

Biomechanics is a diverse field of study founded in a vertically integrated body of knowledge, from cells to behavior, with the goal of understanding the function of biological systems using methods in mechanics. Historically, the field lies in the general domain of science, not to be isolated but well integrated with others focused on the study of movement. Using advances in technology as a conduit, specific examples of collaborative research involving biomechanics, motor development, and neuromuscular control are discussed. Challenges in the study of interface control (i.e., hypotheses focused on the neural control of movement, performance enhancement, and injury prevention) are presented in the context of the intellectual interface required among scientists to gain a new understanding of the function of biological systems.
Youth Development: An Approach for Physical Activity Behavioral Science
Authors: Dzewaltowski David A. , Rosenkranz Richard R.
Published: March 2014

Positive youth development (PYD) is an emerging area of study and practice that targets fostering the assets of young people to avoid problem behaviors and excel in meeting diverse life challenges. This paper describes how PYD evolved from treating problem behaviors to preventing problem behaviors in at-risk youth, to more recently helping all youth thrive and excel in numerous domains. Although evidence to inform community policy and practice has emerged, there is a lack of consensus on how to define PYD, and this lack of consensus has impacted progress in PYD physical activity behavioral science. This paper recommends PYD physical activity behavioral science reject disciplinary boundaries and (a) examine the nature of person-environment interaction in the context of physical activity as the primary outcome, (b) target big-picture physical activity outcome questions, and (c) come to a consensus on the domains of physical activity behavioral science research competencies.
Neglected Diseases, Delinquent Diagnostics
Authors: Kessel Mark
Published: March 2014

Modest investments in diagnostic technologies for neglected diseases can drive dramatic health-outcome improvements in resource-poor settings.
Efficacy of the Novel Topical Antimicrobial Agent PXL150 in a Mouse Model of Surgical Site Infections
Authors: Håkansson Joakim , Björn Camilla , Lindgren Kerstin , Sjöström Emma , Sjöstrand Veronika , Mahlapuu Margit
Published: March 2014

Antimicrobial peptides have recently emerged as a promising new group to be evaluated in the therapeutic intervention of infectious diseases. This study evaluated the anti-infectious effect of the short, synthetic, broad-spectrum antimicrobial peptide PXL150 in a mouse model of staphylococcal surgical site infections. We found that administration of PXL150, formulated in an aqueous solution or in a hydroxypropyl cellulose gel, significantly reduced the bacterial counts in the wound compared with placebo treatment, warranting further investigations of the potential of this peptide as a novel local treatment of microbial infections.
Effectiveness of Primary Anti-Aspergillus Prophylaxis during Remission Induction Chemotherapy of Acute Myeloid Leukemia
Authors: Gomes Marisa Z. R. , Jiang Ying , Mulanovich Victor E. , Lewis Russell E. , Kontoyiannis Dimitrios P.
Published: March 2014

Although antifungal prophylaxis is frequently administered to patients with acute myeloid leukemia (AML) during remission-induction chemotherapy (RIC), its impact on reducing invasive fungal infections (IFIs) outside clinical trials is rarely reported. We performed a retrospective observational study to identify risk factors for development of IFIs (definite or probable, using revised European Organization for Research and Treatment of Cancer [EORTC] criteria) and all-cause mortality in a cohort of 152 AML patients receiving RIC (2009 to 2011). We also compared rates of IFI and mortality in patients who received echinocandin versus anti-
Aspergillus
azole (voriconazole or posaconazole) prophylaxis during the first 120 days of RIC. In multivariate analysis, clofarabine-based RIC (hazard ratio [HR], 3.5; 95% confidence interval [CI], 1.5 to 8.3;
P
= 0.004) and echinocandin prophylaxis (HR, 4.6; 95% CI, 1.8 to 11.9;
P
= 0.002) were independently associated with higher rates of IFI rates during RIC. Subsequent analysis failed to identify any malignancy- or chemotherapy-related covariates linked to echinocandin prophylaxis that accounted for the higher rates of breakthrough IFI. Although the possibility of other confounding variables cannot be excluded, our findings suggest that echinocandin-based prophylaxis during RIC for AML may be associated with a higher risk of breakthrough IFI.
Expression of the Effector Protein IncD in Chlamydia trachomatis Mediates Recruitment of the Lipid Transfer Protein CERT and the Endoplasmic Reticulum-Resident Protein VAPB to the Inclusion Membrane
Authors: Agaisse Hervé , Derré Isabelle
Published: March 2014

Chlamydia trachomatis
is an obligate intracellular human pathogen responsible for ocular and genital infections. To establish its membrane-bound intracellular niche, the inclusion,
C. trachomatis
relies on a set of effector proteins that are injected into the host cells or inserted into the inclusion membrane. We previously proposed that insertion of the
C. trachomatis
effector protein IncD into the inclusion membrane contributes to the recruitment of the lipid transfer protein CERT to the inclusion. Due to the genetically intractable status of
C. trachomatis
at that time, this model of IncD-CERT interaction was inferred from ectopic expression of IncD and CERT in the host cell. In the present study, we investigated the impact of conditionally expressing a FLAG-tagged version of IncD in
C. trachomatis
. This genetic approach allowed us to establish that IncD-3×FLAG localized to the inclusion membrane and caused a massive recruitment of the lipid transfer protein CERT that relied on the PH domain of CERT. In addition, we showed that the massive IncD-dependent association of CERT with the inclusion led to an increased recruitment of the endoplasmic reticulum (ER)-resident protein VAPB, and we determined that, at the inclusion, CERT-VAPB interaction relied on the FFAT domain of CERT. Altogether, the data presented here show that expression of the
C. trachomatis
effector protein IncD mediates the recruitment of the lipid transfer protein CERT and the ER-resident protein VAPB to the inclusion.
Catheter-Associated Urinary Tract Infection by Pseudomonas aeruginosa Is Mediated by Exopolysaccharide-Independent Biofilms
Authors: Cole Stephanie J. , Records Angela R. , Orr Mona W. , Linden Sara B. , Lee Vincent T.
Published: March 2014

Pseudomonas aeruginosais an opportunistic human pathogen that is especially adept at forming surface-associated biofilms.P. aeruginosacauses catheter-associated urinary tract infections (CAUTIs) through biofilm formation on the surface of indwelling catheters.P. aeruginosaencodes three extracellular polysaccharides, PEL, PSL, and alginate, and utilizes the PEL and PSL polysaccharides to form biofilmsin vitro; however, the requirement of these polysaccharides duringin vivoinfections is not well understood. Here we show in a murine model of CAUTI that PAO1, a strain harboringpel,psl, andalggenes, and PA14, a strain harboringpelandalggenes, form biofilms on the implanted catheters. To determine the requirement of exopolysaccharide duringin vivobiofilm infections, we tested isogenic mutants lacking thepel,psl, andalgoperons and showed that PA14 mutants lacking these operons can successfully form biofilms on catheters in the CAUTI model. To determine the host factor(s) that induces the ΔpelDmutant to form biofilm, we tested mouse, human, and artificial urine and show that urine can induce biofilm formation by the PA14 ΔpelDmutant. By testing the major constituents of urine, we show that urea can induce apel-,psl-, andalg-independent biofilm. Thesepel-,psl-, andalg-independent biofilms are mediated by the release of extracellular DNA. Treatment of biofilms formed in urea with DNase I reduced the biofilm, indicating that extracellular DNA supports biofilm formation. Our results indicate that the opportunistic pathogenP. aeruginosautilizes a distinct program to form biofilms that are independent of exopolysaccharides during CAUTI.
Development of an Aotus nancymaae Model for Shigella Vaccine Immunogenicity and Efficacy Studies
Authors: Gregory Michael , Kaminski Robert W. , Lugo-Roman Luis A. , Galvez Carrillo Hugo , Tilley Drake Hamilton , Baldeviano Christian , Simons Mark P. , Reynolds Nathanael D. , Ranallo Ryan T. , Suvarnapunya Akamol E. , Venkatesan Malabi M. , Oaks Edwin V.
Published: March 2014

Several animal models exist to evaluate the immunogenicity and protective efficacy of candidate
Shigella
vaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenic
Escherichia coli
(ETEC) and
Campylobacter
spp. have been successfully developed with
Aotus nancymaae
, and the addition of a
Shigella-Aotus
challenge model would facilitate the testing of combination vaccines. A series of experiments were designed to identify the dose of
Shigella flexneri
2a strain 2457T that induces an attack rate of 75% in the
Aotus
monkey. After primary challenge, the dose required to induce an attack rate of 75% was calculated to be 1 × 10
11
CFU.
Shigella
-specific immune responses were low after primary challenge and subsequently boosted upon rechallenge. However, preexisting immunity derived from the primary challenge was insufficient to protect against the homologous
Shigella
serotype. A successive study in
A. nancymaae
evaluated the ability of multiple oral immunizations with live-attenuated
Shigella
vaccine strain SC602 to protect against challenge. After three oral immunizations, animals were challenged with
S. flexneri
2a 2457T. A 70% attack rate was demonstrated in control animals, whereas animals immunized with vaccine strain SC602 were protected from challenge (efficacy of 80%;
P
= 0.05). The overall study results indicate that the
Shigella-Aotus nancymaae
challenge model may be a valuable tool for evaluating vaccine efficacy and investigating immune correlates of protection.
Bacterial Genome Instability
Authors: Darmon Elise , Leach David R. F.
Published: March 2014

Bacterial genomes are remarkably stable from one generation to the next but are plastic on an evolutionary time scale, substantially shaped by horizontal gene transfer, genome rearrangement, and the activities of mobile DNA elements. This implies the existence of a delicate balance between the maintenance of genome stability and the tolerance of genome instability. In this review, we describe the specialized genetic elements and the endogenous processes that contribute to genome instability. We then discuss the consequences of genome instability at the physiological level, where cells have harnessed instability to mediate phase and antigenic variation, and at the evolutionary level, where horizontal gene transfer has played an important role. Indeed, this ability to share DNA sequences has played a major part in the evolution of life on Earth. The evolutionary plasticity of bacterial genomes, coupled with the vast numbers of bacteria on the planet, substantially limits our ability to control disease.
Utilization of Glyphosate as Phosphate Source: Biochemistry and Genetics of Bacterial Carbon-Phosphorus Lyase
Authors: Hove-Jensen Bjarne , Zechel David L. , Jochimsen Bjarne
Published: March 2014

After several decades of use of glyphosate, the active ingredient in weed killers such as Roundup, in fields, forests, and gardens, the biochemical pathway of transformation of glyphosate phosphorus to a useful phosphorus source for microorganisms has been disclosed. Glyphosate is a member of a large group of chemicals, phosphonic acids or phosphonates, which are characterized by a carbon-phosphorus bond. This is in contrast to the general phosphorus compounds utilized and metabolized by microorganisms. Here phosphorus is found as phosphoric acid or phosphate ion, phosphoric acid esters, or phosphoric acid anhydrides. The latter compounds contain phosphorus that is bound only to oxygen. Hydrolytic, oxidative, and radical-based mechanisms for carbon-phosphorus bond cleavage have been described. This review deals with the radical-based mechanism employed by the carbon-phosphorus lyase of the carbon-phosphorus lyase pathway, which involves reactions for activation of phosphonate, carbon-phosphorus bond cleavage, and further chemical transformation before a useful phosphate ion is generated in a series of seven or eight enzyme-catalyzed reactions. The
phn
genes, encoding the enzymes for this pathway, are widespread among bacterial species. The processes are described with emphasis on glyphosate as a substrate. Additionally, the catabolism of glyphosate is intimately connected with that of aminomethylphosphonate, which is also treated in this review. Results of physiological and genetic analyses are combined with those of bioinformatics analyses.
Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation
Authors: Bräsen Christopher , Esser Dominik , Rauch Bernadette , Siebers Bettina
Published: March 2014

The metabolism ofArchaea, the third domain of life, resembles in its complexity those ofBacteriaand lowerEukarya. However, this metabolic complexity inArchaeais accompanied by the absence of many “classical” pathways, particularly in central carbohydrate metabolism. Instead,Archaeaare characterized by the presence of unique, modified variants of classical pathways such as the Embden-Meyerhof-Parnas (EMP) pathway and the Entner-Doudoroff (ED) pathway. The pentose phosphate pathway is only partly present (if at all), and pentose degradation also significantly differs from that known for bacterial model organisms. These modifications are accompanied by the invention of “new,” unusual enzymes which cause fundamental consequences for the underlying regulatory principles, and classical allosteric regulation sites well established inBacteriaandEukaryaare lost. The aim of this review is to present the current understanding of central carbohydrate metabolic pathways and their regulation inArchaea. In order to give an overview of their complexity, pathway modifications are discussed with respect to unusual archaeal biocatalysts, their structural and mechanistic characteristics, and their regulatory properties in comparison to their classic counterparts fromBacteriaandEukarya. Furthermore, an overview focusing on hexose metabolic, i.e., glycolytic as well as gluconeogenic, pathways identified in archaeal model organisms is given. Their energy gain is discussed, and new insights into different levels of regulation that have been observed so far, including the transcript and protein levels (e.g., gene regulation, known transcription regulators, and posttranslational modification via reversible protein phosphorylation), are presented.
Nitrofurantoin immune-mediated drug-induced liver injury: a serious complication of a commonly prescribed medication
Authors: Hydes Theresa , Wright Mark , Jaynes Eleanor , Nash Kathryn
Published: March 2014

Nitrofurantoin is recommended for first line prophylaxis of recurrent urinary tract infections. Despite a number of side effects it is increasingly prescribed due to its high efficacy, low cost and minimal antimicrobial resistance. Nitrofurantoin-induced immune-mediated liver injury is a particularly serious complication, resulting in both acute hepatic failure and cirrhosis with continued use. We describe the course of two patients who recently presented to our hospital in order to highlight this.
Severe vitamin B12deficiency with pancytopenia, hepatosplenomegaly and leukoerythroblastosis in two Syrian refugee infants: a challenge to differentiate from acute leukaemia
Authors: Belen Burcu , Hismi Burcu Ozturk , Kocak Ulker
Published: March 2014

Megaloblastic anaemia due to vitamin B12deficiency is rare in childhood. However, as most cases are due to maternal insufficiency, it is mainly seen in breastfed infants especially when the mother's socioeconomic status is low and the nutrition is not adequate. We present case of two Syrian refugee infants with severe vitamin B12deficiency with pancytopenia, hepatosplenomegaly and leukoerythroblastosis.
Longitudinal assessment of chlorpyrifos exposure and self-reported neurological symptoms in adolescent pesticide applicators
Authors: Khan Khalid , Ismail Ahmed A , Abdel Rasoul Gaafar , Bonner Matthew R , Lasarev Michael R , Hendy Olfat , Al-Batanony Manal , Crane Alice L , Singleton Steven T , Olson James R , Rohlman Diane S
Published: March 2014

Objectives

Occupational exposure of organophosphorus pesticides, such as chlorpyrifos (CPF), in adolescents is of particular concern because of the potential vulnerability of the developing neurological system. The objectives of this study were to examine how neurological symptoms reported over the application season vary across time, whether these effects are reversible postapplication and if there are associations between CPF biomarkers and neurological symptoms in an adolescent study population.

Setting

The longitudinal study was conducted in two agricultural districts of Menoufia Governorate, Egypt between April 2010 and January 2011.

Participants

Male adolescent participants, including CPF applicators (n=57) and non-applicators (n=38), were recruited.

Primary and secondary outcome measures

Self-reported data for 25 neurological symptoms were collected at 32 time points over the 8-month period before, during and after the application season. Additionally, urine and blood samples were collected to measure urine trichloro-2-pyridinol (TCPy), a CPF-specific biomarker and blood cholinesterase activity.

Results

Applicators and non-applicators report the highest numbers of symptoms during the application season, followed by a reduction in symptoms after the application ended. Applicators reported a greater percentage of neurological symptoms, relative to baseline, than non-applicators after accounting for potential covariates. Among the applicators, cumulative TCPy was positively and significantly associated with the average percentage of symptoms (B=4.56, 95% CI 3.29 to 5.84; p<0.001). Significant associations (p=0.03–0.07) between the change in butyrylcholinesterase activity from the preapplication to the postapplication season and several domains of neurological symptoms were also found, even after adjusting for potential covariates.

Conclusions

These observations demonstrate changes in the reporting of symptoms across the application season, showing an increase in symptom reporting during application and recovery following the end of pesticide application. These findings reinforce the growing concern regarding the neurotoxic health effects of CPF in adolescent applicators in developing countries and the need for developing and implementing intervention programmes.
Management of urinary tract infections in elderly patients: Strategies for improvement
Authors: Lim Vee Han , Whitehurst Thomas , Usoro Emem , Ming Ng Sieu
Published: March 2014

Urinary tract infection (UTI) is one of the most common infections affecting the elderly. However, UTI is overdiagnosed and overtreated in this group. This project aimed to look into strategies for improving the management of UTI in elderly medical inpatients. A retrospective audit was performed on the case notes of medical inpatients in a district general hospital from December 2012 to April 2013. The target measures for improvement include increasing adherence to SIGN guidelines in the diagnosis of UTI, increasing the frequency and timeliness of urinary culture collection in suspected UTI, and increasing use of urine culture sensitivities to tailor antimicrobial treatments.

Initial baseline measurement revealed 16 patients treated for UTI. 31.3% of these fulfilled SIGN criteria for UTI. 68.5% had urine cultures performed. 60% of patients with positive urine cultures had correct antibiotic therapy after sensitivity results. The mean time from the diagnosis of UTI to urine collection for culture was 4 days.

Three further cycles were performed. Following each cycle, improvement measures were implemented to raise the awareness of medical staff about the management of UTI in the elderly. These comprised presentations to junior doctors at local teaching sessions; emails to ward managers with results of the previous audit cycle broken down by ward; and prominent display of guidelines on medical wards and ensuring availability of ‘Newcastle pads’ for taking sterile urine cultures from incontinent patients.

In the final cycle, 19 patients were diagnosed with UTI. 42.1% of these fulfilled SIGN criteria for diagnosis of UTI. 89.5% had urine cultures sent. 86.7% of patients with a positive urine culture were treated with appropriate antibiotics after sensitivities became available. Mean time from UTI diagnosis to culture collection improved to zero days.

In conclusion, continuous educational measures, performance feedback, and increased availability of specialist equipment are imperative for improving management of UTIs in the elderly.
The value of autopsies in the era of high-tech medicine: discrepant findings persist
Authors: Kuijpers Chantal C H J , Fronczek Judith , van de Goot Frank R W , Niessen Hans W M , van Diest Paul J , Jiwa Mehdi
Published: March 2014

Aims

Although the autopsy is still the gold standard for quality assessment of clinical diagnoses, autopsy rates have been declining over the last decades to <10%. The aim of this study was to investigate the value of autopsies in the high-tech medicine era by determining the frequency of discrepancies between clinical and autopsy diagnoses.

Methods

We classified all adult autopsy cases (n=460), performed at Symbiant, Pathology Expert Centre, in 2007 and 2012/2013, as having major, or minor discrepancy or total concordance. The roles of possible contributory factors were analysed. Finally, we assessed the role of microscopic examination in identifying cause of death.

Results

Major and minor discrepancies were found in 23.5% and 32.6% of the classifiable autopsies, respectively. Most commonly observed major discrepancies were myocardial infarction, pulmonary embolism and pneumonia. Improper imaging and discontinuation of active treatment were significantly associated with a higher and a lower frequency of major discrepancies, respectively. Comparing 2007 and 2012/2013, the frequency of minor discrepancies significantly increased from 26.8% to 39.3%. Final admission length of >2 days was significantly associated with a lower frequency of class III minor discrepancies. Microscopic examination contributed to establishing cause of death in 19.6% of the cases.

Conclusions

Discrepant findings persist at autopsy, even in the era of high-tech medicine. Therefore, autopsies still should serve as a very important part of quality control in clinical diagnosis and treatment. Learning from individual and system-related diagnostic errors can aid in improving patient safety.
Fasting increases serum bilirubin levels in clinically normal, healthy males but not females: a retrospective study from phase I clinical trial participants
Authors: Griffin Paul M , Elliott Suzanne L , Manton Kerry J
Published: March 2014

Aim

To examine if fasting affects serum bilirubin levels in clinically healthy males and females.

Methods

We used retrospective data from phase I clinical trials where blood was collected in either a fed or fasting state at screening and predosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n=105) or females (n=30) aged 18–48 inclusive who participated in a phase I clinical trial in 2012 or 2013.

Results

We found a statistically significant increase in total serum bilirubin levels in fasting males as compared with non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females.

Conclusions

The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.