bluuebunny/crossref_metadata_2025 huggingface dataset:
Lived experience of blood glucose self‐monitoring among pregnant women with gestational diabetes mellitus: a phenomenological research
Authors: Youngwanichsetha Sununta , Phumdoung Sasitorn
Published: September 2016

Aims and objectives

To explore and describe lived experience of blood glucose self‐monitoring among pregnant Thai women with gestational diabetes mellitus.

Background

Self‐monitoring of blood glucose is an essential practice among pregnant women with diabetes to prevent complications in pregnancy and the newborn infant.

Design

Phenomenological research was employed to understand lived experiences in glycemic control.

Methods

Thirty participants were approached and interviewed using a semistructured interview guides. Qualitative data were analysed following Colaizzi's method.

Results

The findings revealed three themes: being worried about diabetes and blood testing, trying to control it and being patient for the child. Their worry comprised three dimensions: (1) wondering about the impacts of diabetes on the child, (2) concern about maternal health and (3) being worried about doing blood test. Trying to control diabetes was composed of three dimensions: (1) learning to test blood glucose, (2) being afraid of elevated blood sugar and (3) being aware of what to eat. Being patient for the child was composed of three dimensions: (1) overcoming food desires, (2) tolerating the fingerprick pain and (3) satisfaction with the outcomes.

Conclusions

Women with gestational diabetes experienced being worried and afraid regarding blood glucose self‐monitoring; however, they could overcome and tolerate this with some difficulties.

Relevance to clinical practice

These findings can be used to guide nursing practice in assessment of perception and response towards blood glucose self‐monitoring in order to improve achievement of a good glycaemic control among pregnant women with gestational diabetes mellitus.
Cultural and religious beliefs and values, and their impact on preferences for end‐of‐life care among four ethnic groups of community‐dwelling older persons
Authors: Ohr Seok , Jeong Sarah , Saul Peter
Published: September 2016

Aims and objectives

To explore specific cultural and religious beliefs and values concerning death and dying, truth telling, and advance care planning, and the preferences for end‐of‐life care among older persons from culturally and linguistically diverse backgrounds.

Background

Whilst literature indicates that culture impacts on end‐of‐life decision‐making significantly, there is limited evidence on the topic.

Design

A cross‐sectional survey.

Methods

A total of 171 community older persons who make regular visits to 17 day care centres expressed in a questionnaire their; (1) beliefs about death and dying, truth telling, and advance care planning, and (2) preferences for end‐of‐life care.

Results

More than 92% of respondents believed that dying is a normal part of life, and more than 70% felt comfortable talking about death. Whilst respondents accepted dying as a normal part of life, 64% of Eastern Europeans and 53% of Asia/Pacific groups believed that death should be avoided at all costs. People from the Asia/Pacific group reported the most consensual view against all of the life‐prolonging measures.

Conclusion

Cultural and religious beliefs and values may have an impact on preferences for treatment at end‐of‐life. The study offers nurses empirical data to help shape conversations about end‐of‐life care, and thus to enhance their commitment to help people ‘die well’.

Relevance to clinical practice

Information acquisition to extend understanding of each individual before proceeding with documentation of advance care planning is essential and should include retrieval of individuals’ cultural and religious beliefs and values, and preferences for care. An institutional system and/or protocol that promote conversations about these among nurses and other healthcare professionals are warranted.
Job Satisfaction of People With Intellectual Disabilities in Integrated and Sheltered Employment: An Exploration of the Literature
Authors: Akkerman Alma , Janssen Cees G. C. , Kef Sabina , Meininger Herman P.
Published: September 2016

Paying attention to job satisfaction of people with intellectual disabilities, in either integrated or sheltered employment, is important, to increase individual as well as organizational functioning and well‐being. Nevertheless, little is known about job satisfaction of employees with intellectual disabilities and the factors increasing or hindering this. The aim of this study was to explore existing research evidence regarding job satisfaction of people with intellectual disabilities in integrated and sheltered employment settings, and its associated factors. A systematic and comprehensive literature search revealed 13 relevant studies that were examined. Results indicated that people with intellectual disabilities in integrated employment and sheltered employment generally report satisfaction with their jobs. Satisfaction levels appear to be higher in integrated employment. Furthermore it was found that characteristics of the employee and of the employment setting were associated with job satisfaction, as well as social relations, support, and the fit between the employees’ needs and the work environment. Advancements can be made with respect to policy and practice of employment of people with intellectual disabilities. To improve their job satisfaction we suggest an integrative approach, taking into account that job satisfaction is an interplay between personal, situational, and social‐cognitive characteristics. This is reflected in current theoretical frameworks in general job satisfaction literature. Future research on job satisfaction of people with intellectual disabilities could profit from developments in general job satisfaction literature and in addition take account of factors particularly relevant to people with intellectual disabilities, the possible impact of comparison processes, and the development of sound measurement methods. Finally, we advocate for greater insight and involvement of people with intellectual disabilities in career related matters, to enhance their self‐determination and motivation and increase satisfaction.
Oral and dental diseases in a population of domestic ferrets (Mustela putorius furo)
Authors: Nemec A. , Zadravec M. , Račnik J.
Published: September 2016

Objective

Domestic ferrets have been used for many purposes, but recently their popularity as companion animals has increased greatly. However, data on their oral and dental diseases are rare. The objective of this study was therefore to describe oral and dental diseases in a population of client‐owned domestic ferrets.

Methods

In this cross‐sectional clinical study, detailed oral and dental examination and full‐mouth dental radiographs were performed in 57 client‐owned ferrets.

Results

Variations in occlusion and number of roots per tooth were noted in comparison with previously published literature on ferrets. Periodontal disease, attrition/abrasion and dental fractures, especially of the canine teeth, were commonly observed. Periapical disease associated with dental fractures, malocclusion, tooth resorption and neoplasia was uncommon.

Conclusion and Clinical Relevance

This study indicates that thorough oral and dental examination supported by dental radiography under general anaesthesia should be performed in domestic ferrets as a part of regular veterinary care.
Associations of human leucocyte antigen class II‐DQB1 alleles with hepatitis C virus infection in Egyptian population: a multicentre family‐based study
Authors: El‐Bendary M. , Neamatallah M. , Esmat G. , Kamel E. , Elalfy H. , Besheer T. , Eldeib D. , Eladl A.‐H. , El‐Setouhy M. , El‐Gilany A.‐H. , El‐Waseef A.
Published: September 2016

Hepatitis C infection is a global pandemic. HLA‐DQB1 alleles are believed to have an effective role in immune response against HCV including susceptibility to or protection from this infection. The aim of this study was to investigate the contribution of HLA‐DQB1 alleles in the outcome of HCV genotype‐4 infection through a family‐based association study. Egyptian families with HCV (324) were recruited for this study (324 index positive for RNA‐HCV, 225 positive relatives representing chronic hepatitis C cases and 582 family members negative for HCV‐RNA [control], 63 of whom spontaneously cleared the virus. All subjects were genotyped for HLA‐DQB1 alleles by sequence‐specific primers (SSP‐PCR) and sequence‐based typing (SBT) methods. The frequency of DQB1*02:01:01 carriage was significantly higher in infected patients when compared to controls and those who spontaneously cleared virus (OR=5.47, P<.0001 and OR= 6.5234, P<.0001, respectively), and the carriage of the DQB1*03:01:01:01 allele was significantly higher in those who cleared and controls when compared to the infected patients (OR=0.2889, P<.0001 and OR=0.3016, P<.0001, respectively). On the other hand, the frequency of DQB1*06:01:01 and QB1*05:01:01:01 alleles was not associated with infection (comparison of infected and cleared patients showed OR of 2.1598 [P<.01]), but it becomes nonsignificant after adjustments with the Bonferroni formula (PC>0.05) and OR= 1.3523, P>.05, respectively. This study shows that clearance of HCV is associated with DQB1*03:01:01:01 allele and chronicity of HCV infection associated with the risk allele: DQB1*02:01:01.
Magnetite in the unequilibrated CK chondrites: Implications for metamorphism and new insights into the relationship between the CV and CK chondrites
Authors: Dunn Tasha L. , Gross Juliane , Ivanova Marina A. , Runyon Simone E. , Bruck Andrea M.
Published: September 2016

Bulk isotopic and elemental compositions of CV and CK chondrites have led to the suggestion that both originate from the same asteroid. It has been argued that magnetite compositions also support this model; however, magnetite has been studied almost exclusively in the equilibrated (type 4‐6) CKs. Magnetite in seven unequilibrated CKs analyzed here is enriched in MgO, TiO2, and Al2O3 relative to the equilibrated CKs, suggesting that magnetite compositions are affected by metamorphism. Magnetite in CKs is compositionally distinct from CVs, particularly in abundances of Cr2O3, NiO, and TiO2. Although there are minor similarities between CV and equilibrated CK chondrite magnetite, this is contrary to what we would expect if the CVs and CKs represent a single metamorphic sequence. CV magnetite should resemble CK3 magnetite, as both were metamorphosed to type 3 conditions. Oxygen fugacities and temperatures of CVox and CK chondrites are also difficult to reconcile using existing CV‐CK parent body models. Mineral chemistries, which eliminate issues of bulk sample heterogeneity, provide a reliable alternative to techniques that involve a small amount of sample material. CV and CK chondrite magnetite has distinct compositional differences that cannot be explained by metamorphism.
Water undersaturated mantle plume volcanism on present‐day Mars
Authors: Kiefer Walter S. , Li Qingsong
Published: September 2016

Based on meteorite evidence, the present‐day Martian mantle has a combined abundance of up to a few hundred ppm of H2O, Cl, and F, which lowers the solidus and enhances the magma production rate. Adiabatic decompression melting in upwelling mantle plumes is the best explanation for young (last 200 Myr) volcanism on Mars. We explore water undersaturated mantle plume volcanism using a finite element mantle convection model coupled to a model of hydrous peridotite melting. Relative to a dry mantle, the reduction in solidus temperature due to water increases the magma production rate by a factor of 1.3–1.7 at 50 ppm water and by a factor of 1.9–3.2 at 200 ppm water. Mantle water also decreases the viscosity and increases the vigor of convection, which indirectly increases the magma production rate by thinning the thermal boundary layer and increasing the flow velocity. At conditions relevant to Mars, these indirect effects can cause an order of magnitude increase in the magma production rate. Using geologic and geophysical observations of the Late Amazonian magma production rate and geochemical observations of melt fractions in shergottite meteorites, present‐day Mars is constrained to have a core–mantle boundary temperature of ~1750 to 1800 °C and a volume‐averaged thermal Rayleigh number of 2 × 106 to 107, indicating that moderately vigorous mantle convection has persisted to the present day. Melting occurs at depths of 2.5–6 GPa and is controlled by the Rayleigh number at the low pressure end and by the mantle water concentration at high pressure.
Heterogeneous histories of Ni‐bearing pyrrhotite and pentlandite grains in the CI chondrites Orgueil and Alais
Authors: Berger Eve L. , Lauretta Dante S. , Zega Thomas J. , Keller Lindsay P.
Published: September 2016

Compositional and structural analyses of CI chondrite iron–nickel sulfide grains reveal heterogeneity both across and within the Orgueil and Alais meteorites. Orgueil grains with the 4C monoclinic pyrrhotite structure have variable metal‐to‐sulfur ratios and nickel contents. These range from the nominal ratio of 0.875 for Fe7S8 with <1 atom% nickel to a high metal‐to‐sulfur ratio of 0.97 with 15 atom% nickel. These data reveal a previously unrecognized low‐temperature solid solution between Fe7S8 and Fe5Ni3S8. We have also identified 6C monoclinic pyrrhotite among the Orgueil iron–nickel sulfides. The occurrence of pentlandite in Orgueil is confirmed for the first time crystallographically. In contrast, sulfide grains in Alais do not show the same spread in composition and structure; rather they represent the endmembers: low‐Ni 4C monoclinic pyrrhotite and pentlandite. We investigate possible formation/alteration scenarios: crystallization from a melt, solid‐state diffusion and/or exsolution, oxidation of pre‐existing sulfides, and precipitation from a fluid. Sulfide grains are sensitive to alteration conditions; these data suggest that the structures and compositions of the sulfide assemblages in Orgueil and Alais were established by late‐stage parent body aqueous alteration, followed in some cases by low‐temperature solid‐state processes. The samples record different alteration histories, with Orgueil experiencing lower equilibration temperatures (25 °C) than Alais (100–135 °C). We conclude that millimeter‐scale heterogeneity existed in alteration conditions (e.g., temperature, pH, oxygen fugacity, sulfur fugacity, duration of alteration) on the parent body. This variability is evidenced by the diversity among sulfide grains located within millimeters of one another.
A vision for collaborative training infrastructure for bioinformatics
Authors: Williams Jason J. , Teal Tracy K.
Published: September 2016

In biology, a missing link connecting data generation and data‐driven discovery is the training that prepares researchers to effectively manage and analyze data. National and international cyberinfrastructure along with evolving private sector resources place biologists and students within reach of the tools needed for data‐intensive biology, but training is still required to make effective use of them. In this concept paper, we review a number of opportunities and challenges that can inform the creation of a national bioinformatics training infrastructure capable of servicing the large number of emerging and existing life scientists. While college curricula are slower to adapt, grassroots startup‐spirited organizations, such as Software and Data Carpentry, have made impressive inroads in training on the best practices of software use, development, and data analysis. Given the transformative potential of biology and medicine as full‐fledged data sciences, more support is needed to organize, amplify, and assess these efforts and their impacts.
Critical Diamond–Blackfan anemia due to ribosomal protein S19 missense mutation
Authors: Ozono Shuichi , Mitsuo Miho , Noguchi Maiko , Nakagawa Shin‐ichiro , Ueda Koichiro , Inada Hiroko , Ohga Shouichi , Ito Etsuro
Published: September 2016

Diamond–Blackfan anemia (DBA) is a rare congenital disorder characterized by pure erythrocyte aplasia, and approximately 70% of patients carry mutations in the genes encoding ribosomal proteins (RP). Here, we report the case of a male infant with DBA who presented with anemic crisis (hemoglobin [Hb] concentration 1.5 g/dL) at 58 days after birth. On admission, the infant was pale and had tachypnea, but recovered with intensive care, including red blood cell transfusions, and prednisolone. Based on the clinical diagnosis of DBA, the father of the infant had cyclosporine‐A‐dependent anemia. On analysis of RP genes when the infant was 6 months old, both the infant and the father, but not the mother, were found to harbor a mutation of RPS19 (c.167G > C, p. R56P). Therefore, genetic background search and early neonatal health check‐ups are recommended for families with a history of inherited bone marrow failure syndromes.
Cardiac catheterization in children with pulmonary arterial hypertension
Authors: Matsuura Hiroyuki
Published: September 2016

Cardiac catheterization of childhood pulmonary arterial hypertension (PAH) is used to assess the severity of the disease as well as prognosis, selection of the most adequate pulmonary vasodilators, and evaluation of effectiveness. Sudden deterioration of cardiovascular hemodynamics, however, can be easily induced by pain, patient agitation, catheter manipulation, and by vasodilator provocation tests; these could trigger a pulmonary hypertension crisis, vagotony, respiratory distress, and hemoptysis resulting in critical complications, including death. Those patients with New York Heart Association functional class IV are at an especially high risk. It is noteworthy that pulmonary arteriography is a contraindication in patients with PAH. In a review of 7218 adult patients, 76 (1.1%) serious complications, including four deaths, were reported; with regard to the pediatric patients, 29 (10.7%) out of 270 patients with complications, including one with cardiogenic shock requiring cardiopulmonary resuscitation in addition to minor complications, were reported. To prevent serious complications, basic and routine precautions, such as oxygen and concomitant transcutaneous oxygen saturation and electrocardiogram monitoring during transportation to and from the catheter laboratory, are mandatory. Furthermore, the cooperation of experienced physicians and well informed medical staff in addition to meticulous preparation, for example, calculation of prior doses of catecholamine and confirmation of the presence of emergency equipment, is required.
Vested Interests, Venue Shopping, and Policy Stability: The Long Road to Improving Air Quality in Oregon's Willamette Valley
Authors: Ley Aaron J.
Published: September 2016

A lot of scholarly attention has focused on why groups choose to pursue their policy goals in one venue over another. This manuscript adds to the literature by testing a new theory of venue shopping, the Adaptive Venue Shopping Framework. This manuscript finds empirical support that groups choose venues by strategically assessing the institutional context which involves three primary elements: the group's mix of resources, their opponent's resource strengths, and the degree of venue accessibility, which is a combination of opponents' degree of control over a venue and a venue's image amiability or receptivity. In addition to confirming these findings, this case study links the literature on venue shopping with recent scholarship about “vested interests” by demonstrating how a powerful agricultural group came to dominate in a legislative venue, how it protected its policy victories from reversal, and how it kept policy making from shifting into alternative venues, thus leading to long‐term policy stability. Furthermore, it demonstrates how newly emerged groups can achieve policy success against stronger opponents by threatening to seek their policy goals in alternative institutions.
Supererogation, Sacrifice, and the Limits of Duty
Authors: Archer Alfred
Published: September 2016

It is often claimed that all acts of supererogation involve sacrifice. This claim is made because it is thought that it is the level of sacrifice involved that prevents these acts from being morally required. In this paper, I will argue against this claim. I will start by making a distinction between two ways of understanding the claim that all acts of supererogation involve sacrifice. I will then examine some purported counterexamples to the view that supererogation always involves sacrifice and examine their limitations. Next, I will examine how this view might be defended, building on comments by Dale Dorsey and Henry Sidgwick. I will then argue that the view and the argument in favor of it should be rejected. I will finish by showing how an alternative explanation for the limits of moral obligation avoids the problems facing The Sacrifice View.
Getting Expression‐Based Semantics Right: Its Proper Objects of Evaluation and Limits
Authors: Spewak Jr David C.
Published: September 2016

Often those attempting to resolve the answering machine paradox appeal to Kaplan's claim that the objects of semantic evaluation are expression‐types evaluated with respect to indices, instead of utterances, as part of their solution. This article argues that Dylan Dodd and Paula Sweeney exemplify the kind of mistakes theorists make in applying such expression‐based semantic theories in that (1) they conflate what is asserted with semantic content, and (2) they take their approach to utterance interpretation as having semantic significance. In light of these mistakes, we learn two things. First, we learn how expression‐based semantic theorists can avoid making these kinds of mistakes. Second, we learn how the limits of expression‐based semantics can contribute to what we should expect a semantic theory to explain regarding how semantics fits into a more general theory of linguistic communication and linguistic understanding.
Meaning in Life: In Defense of the Hybrid View
Authors: Evers Daan , van Smeden Gerlinde Emma
Published: September 2016

According to Susan Wolf's hybrid view about meaning in life, a life is meaningful in virtue of subjective attraction to objectively valuable pursuits. Recently, several philosophers have presented counterexamples to the subjective element in Wolf's view. We argue that these examples are not clearly successful and present a modified version which is even stronger in the face of them. Finally, we offer some positive reasons for accepting a subjective condition on a meaningful life.
Vulnerability in Intimate Relationships
Authors: Tsai George
Published: September 2016

Intimate relationships such as love and friendship involve familiar patterns of vulnerability. Loving someone renders one susceptible to distress and sorrow when the beloved is harmed and when the loving relationship is impaired. The distinctive kind of vulnerability bound up with intimate relationships also presents an opportunity for wrongful exploitation: for one participant to unfairly use, take advantage of, the other. In the case of commercial exploitation (e.g., exploitation of sweatshop workers), the remedy typically involves either preventing those in the relevant positions of power from taking advantage of the vulnerability of the powerless or removing the vulnerabilities of those in the relevant positions of powerlessness. I argue there are there limits to the application of these two strategies in the intimate relationship context, and I consider what (if anything) might guard against the possibility of exploitation in intimate relationships.
Unjust Exploitation
Authors: Wood Allen
Published: September 2016

Is exploitation always unjust? Is it by definition unjust? If we answer both these questions negatively, as I do, then we need to ask: when is exploitation unjust and when is it not? Exploitation is the use of a vulnerability for the exploiter's ends. This is sometimes morally wrong, even when it is not unjust. But it is unjust when it violates the exploited person's rightful freedom. When is labor for hire exploitative? Whenever the terms of the labor contract permit either the employer or the employee to make use of the vulnerability of the other. But when is such exploitation unjust? When it involves the ownership by either of the conditions of life of the other, because then one is in a position of control over the other and deprives the other of a free mode of life. In capitalist wage labor, this is often the case—the employer, or a class to which the employer belongs, owns the conditions of life for the employed. When this is so, the employed do not have the free life which is basic to human rights.
Exploitation and Consequentialism
Authors: Sample Ruth
Published: September 2016

In Exploitation: What It Is and Why It's Wrong (2003), I argued that the major non‐Marxist “ethically thick” approaches to exploitation were not successful in capturing what we find morally objectionable in paradigmatic cases of exploitation. My argument there focused on the consequentialist account of exploitation defended by Robert Goodin. Here I revisit the question of whether the recent multi‐level act consequentialist account of exploitation defended by Richard Arneson is successful. I raise questions about the nature of the account, and conclude that it is a possibly coherent and ultimately inadequate account of the wrongness of exploitation.
Enacting immanent potentialities:Tcheb‐tchibstrategies at the centre of the urban fringe in Nouakchott, Mauritania
Authors: Vium Christian
Published: September 2016

The urban fringe areas of Nouakchott, the capital city of the Islamic Republic of Mauritania, have become virtual epicentres of informal property speculation, as the state‐owned land that people illegally inhabit becomes an increasingly valuable commodity in the wake of urban redevelopment plans and vast infrastructural development projects. By applying ingenious ‘poaching’ strategies based on anticipation, the marginalized, impoverished people inhabiting these areas appropriate and manipulate space in order to survive. In their attempt to counter the state's technologies of governance through what is commonly known astcheb‐tchib, a form of creative improvisation, they become a driving force in the dynamic and contested reconfigurations of the urban landscape. Based on extended ethnographic fieldwork focusing on the strategies of former nomads who are now sedentarized on the urban fringe, this article conceives large‐scale urban renewal as a dynamic process that generates an emergent space of immanent potentiality that the urban poor attempt to strategically appropriate and enact to make the most of a potentially destructive process.
Adverse effects of red blood cell transfusions in neonates: a systematic review and meta‐analysis
Authors: Keir Amy , Pal Sanchita , Trivella Marialena , Lieberman Lani , Callum Jeannie , Shehata Nadine , Stanworth Simon J.
Published: September 2016

BACKGROUND

Controversy exists regarding the contribution of blood transfusions to a range of adverse clinical outcomes in neonates. The aim of our systematic review was to identify the broader literature on harmful effects and associations potentially attributable to red blood cell (RBC) transfusions.

STUDY DESIGN AND METHODS

A comprehensive search of MEDLINE (PubMed) and EMBASE was undertaken. Eligible studies included both randomized controlled trials (RCTs) and nonrandomized studies examining the effects of small volume (10‐20 mL/kg) RBC transfusions on neonates. Primary outcomes of interest were mortality, chronic lung disease, retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. Two independent authors conducted a review of abstracts and then of full‐text article reviews as well as data extraction and quality assessments.

RESULTS

Sixty‐one studies were eligible for inclusion, including 16 (26%) randomized studies. The majority of studies were nonrandomized (n = 45; 74%), which included 32 observational studies with and 13 studies without a comparator group. There was no evidence that rates of mortality differed between restrictive and liberal strategies for transfusion (eight RCTs: risk ratio, 1.24; 95% confidence interval, 0.89‐1.672, heterogeneity = 0%) or for necrotizing enterocolitis (five RCTs: risk ratio, 1.45; 95% confidence interval, 0.91‐2.33; heterogeneity = 0%). A liberal strategy also was not superior to restrictive transfusion practice in the pooled randomized studies for rates of retinopathy of prematurity, chronic lung disease, or intraventricular hemorrhage.

CONCLUSIONS

Statistically significant differences in a range of harmful outcomes between neonates exposed to restrictive and liberal RBC transfusion practice were not found. However, the risks of bias identified in many studies and the lack of consistent reporting and definitions of events limits our conclusions.
Chlorhexidine-induced elastic and adhesive changes of Escherichia coli cells within a biofilm
Authors: Rodgers Nicole , Murdaugh Anne
Published: September 2016

Chlorhexidine is a widely used, commercially available cationic antiseptic. Although its mechanism of action on planktonic bacteria has been well explored, far fewer studies have examined its interaction with an established biofilm. The physical effects of chlorhexidine on a biofilm are particularly unknown. Here, the authors report the first observations of chlorhexidine-induced elastic and adhesive changes to single cells within a biofilm. The elastic changes are consistent with the proposed mechanism of action of chlorhexidine. Atomic force microscopy and force spectroscopy techniques were used to determine spring constants and adhesion energy of the individual bacteria within an Escherichia coli biofilm. Medically relevant concentrations of chlorhexidine were tested, and cells exposed to 1% (w/v) and 0.1% more than doubled in stiffness, while those exposed to 0.01% showed no change in elasticity. Adhesion to the biofilm also increased with exposure to 1% chlorhexidine, but not for the lower concentrations tested. Given the prevalence of chlorhexidine in clinical and commercial applications, these results have important ramifications on biofilm removal techniques.
High frequency imaging and elastic effects for a solid cylinder with axis oblique relative to a nearby horizontal surface
Authors: Plotnick Daniel S. , Marston Philip L.
Published: September 2016

The calibrated acoustic backscattering spectrum versus aspect angle, also called the “acoustic color” or “acoustic template,” of solid cylinders located near a flat interface was previously studied for the case where the cylinder axis was vertically oblique relative to the interface and was insonified by a beam at a non-zero grazing angle. The presence of the interface allows for multiple paths by which sound is backscattered. These multipaths are highly dependent on the relative orientations of the target, the interface, and the source/receiver. In this work, the effects of vertical obliquity on the reconstructed synthetic aperture acoustic images is presented. Several robust orientation dependent features are considered and the physical mechanisms responsible identified through geometric arguments. Information about a target's three-dimensional orientation and size may be gleaned from these images, aiding the interpretation of features within the target's acoustic template. Specific features observed in the reconstructed image are associated with features in the acoustic color. The coupling conditions for surface elastic waves are also considered.
Frequency based noise coherence-function extension and application to passive bottom-loss estimation
Authors: Muzi Lanfranco , Siderius Martin , Nielsen Peter L.
Published: September 2016

Accurate modeling of acoustic propagation in the ocean waveguide is important to SONAR-performance prediction. Particularly in shallow waters, a crucial contribution to the total transmission loss is the bottom refection loss, which can be estimated passively by beamforming the natural surface-noise acoustic field recorded by a vertical line array of hydrophones. However, the performance in this task of arrays below 2 m of length is problematic for frequencies below 10 kHz It is shown in this paper that, when the data are free of interference from sources other than wind and wave surface noise, data from a shorter array can be used to approximate the coherence function of a longer array. This improves the angular resolution of the estimated bottom loss, often making use of data at frequencies above the array design frequency. Application to simulated and experimental data shows that the technique, rigorously justified for a halfspace bottom, is effective also on more complex bottom types. Dispensing with active sources, small autonomous underwater vehicles equipped with short arrays can be envisioned as compact, efficient seabed-characterization systems. The proposed technique is shown to improve significantly the reflection-loss estimate of an array that would be a candidate for such application.
Combined targeting of BCL-2 and BCR-ABL tyrosine kinase eradicates chronic myeloid leukemia stem cells
Authors: Carter Bing Z. , Mak Po Yee , Mu Hong , Zhou Hongsheng , Mak Duncan H. , Schober Wendy , Leverson Joel D. , Zhang Bin , Bhatia Ravi , Huang Xuelin , Cortes Jorge , Kantarjian Hagop , Konopleva Marina , Andreeff Michael
Published: September 2016

Inhibition of BCL-2, MCL-1, and BCL-X
L
eradicates CML stem cells in a mouse model and primary blast crisis samples.
Inhibition of Cytochrome P450 2B6 Activity by Voriconazole Profiled Using Efavirenz Disposition in Healthy Volunteers
Authors: Desta Zeruesenay , Metzger Ingrid F. , Thong Nancy , Lu Jessica B. L. , Callaghan John T. , Skaar Todd C. , Flockhart David A. , Galinsky Raymond E.
Published: September 2016

Cytochrome P450 2B6 (CYP2B6) metabolizes clinically important drugs and other compounds. Its expression and activity vary widely among individuals, but quantitative estimation is hampered by the lack of safe and selective
in vivo
probes of CYP2B6 activity. Efavirenz, a nonnucleoside HIV-1 reverse transcriptase inhibitor, is mainly cleared by CYP2B6, an enzyme strongly inhibited
in vitro
by voriconazole. To test efavirenz metabolism as an
in vivo
probe of CYP2B6 activity, we quantified the inhibition of CYP2B6 activity by voriconazole in 61 healthy volunteers administered a single 100-mg oral dose of efavirenz with and without voriconazole administration. The kinetics of efavirenz metabolites demonstrated formation rate-limited elimination. Compared to control, voriconazole prolonged the elimination half-life (
t
1/2
) and increased both the maximum concentration of drug in serum (
C
max
) and the area under the concentration-time curve from 0 h to
t
(AUC
0–

t

) of efavirenz (mean change of 51%, 36%, and 89%, respectively) (
P
< 0.0001) with marked intersubject variability (e.g., the percent change in efavirenz AUC
0–

t

ranged from 0.4% to ∼224%). Voriconazole decreased efavirenz 8-hydroxylation by greater than 60% (
P
< 0.0001), whereas its effect on 7-hydroxylation was marginal. The plasma concentration ratio of efavirenz to 8-hydroxyefavirenz, determined 1 to 6 h after dosing, was significantly increased by voriconazole and correlated with the efavirenz AUC
0–

t

(Pearson
r
= >0.8;
P
< 0.0001). This study demonstrates the mechanisms of voriconazole-efavirenz interaction, establishes the use of a low dose of efavirenz as a safe and selective
in vivo
probe for phenotyping CYP2B6 activity, and identifies several easy-to-use indices that should enhance understanding of the mechanisms of CYP2B6 interindividual variability. (This study is registered at ClinicalTrials.gov under identifier NCT01104376.)
Complete Sequencing of Plasmids Containing
bla
OXA-163
and
bla
OXA-48
in Escherichia coli Sequence Type 131
Authors: Stoesser Nicole , Sheppard Anna E. , Peirano Gisele , Sebra Robert , Lynch Tarah , Anson Luke , Kasarskis Andrew , Motyl Mary R. , Crook Derrick W. , Pitout Johann D.
Published: September 2016

OXA-48-like enzymes have emerged as important extended-spectrum β-lactamases/carbapenemases in
Escherichia coli
sequence type 131 (ST131). We report the structures of the first fully sequenced
bla
OXA-163
plasmid and of two other
bla
OXA-48
plasmids in this lineage.
bla
OXA-163
was located on a 71-kb IncN plasmid with other resistance genes.
bla
OXA-48
was present on IncL/M plasmids, genetically similar to other
bla
OXA-48
plasmid sequences, and consistent with interspecies/interlineage spread. The presence of
bla
OXA-48-like
genes on epidemic plasmids in ST131 is of concern.
Review of Experimental Compounds Demonstrating Anti-Toxoplasma Activity
Authors: McFarland Madalyn M. , Zach Sydney J. , Wang Xiaofang , Potluri Lakshmi-Prasad , Neville Andrew J. , Vennerstrom Jonathan L. , Davis Paul H.
Published: September 2016

Toxoplasma gondii
is a ubiquitous apicomplexan parasite capable of infecting humans and other animals. Current treatment options for
T. gondii
infection are limited and most have drawbacks, including high toxicity and low tolerability. Additionally, no FDA-approved treatments are available for pregnant women, a high-risk population due to transplacental infection. Therefore, the development of novel treatment options is needed. To aid this effort, this review highlights experimental compounds that, at a minimum, demonstrate inhibition of
in vitro
growth of
T. gondii
. When available, host cell toxicity and
in vivo
data are also discussed. The purpose of this review is to facilitate additional development of anti-
Toxoplasma
compounds and potentially to extend our knowledge of the parasite.
Results from the Canadian Nosocomial Infection Surveillance Program on Carbapenemase-Producing
Enterobacteriaceae
, 2010 to 2014
Authors: Mataseje Laura F. , Abdesselam Kahina , Vachon Julie , Mitchel Robyn , Bryce Elizabeth , Roscoe Diane , Boyd David A. , Embree Joanne , Katz Kevin , Kibsey Pamela , Simor Andrew E. , Taylor Geoffrey , Turgeon Nathalie , Langley Joanne , Gravel Denise , Amaratunga Kanchana , Mulvey Michael R.
Published: September 2016

Carbapenemase-producing
Enterobacteriaceae
(CPE) are increasing globally; here we report on the investigation of CPE in Canada over a 5-year period. Participating acute care facilities across Canada submitted carbapenem-nonsusceptible
Enterobacteriaceae
from 1 January 2010 to 31 December 2014 to the National Microbiology Laboratory. All CPE were characterized by antimicrobial susceptibilities, pulsed-field gel electrophoresis, multilocus sequence typing, and plasmid restriction fragment length polymorphism analysis and had patient data collected using a standard questionnaire. The 5-year incidence rate of CPE was 0.09 per 10,000 patient days and 0.07 per 1,000 admissions. There were a total of 261 CPE isolated from 238 patients in 58 hospitals during the study period.
bla
KPC-3
(64.8%) and
bla
NDM-1
(17.6%) represented the highest proportion of carbapenemase genes detected in Canadian isolates. Patients who had a history of medical attention during international travel accounted for 21% of CPE cases. The hospital 30-day all-cause mortality rate for the 5-year surveillance period was 17.1 per 100 CPE cases. No significant increase in the occurrence of CPE was observed from 2010 to 2014. Nosocomial transmission of CPE, as well as international health care, is driving its persistence within Canada.
MicroRNAs Regulate Cytokine Responses in Gingival Epithelial Cells
Authors: Chen Steven C. Y. , Constantinides Christos , Kebschull Moritz , Papapanou Panos N.
Published: September 2016

MicroRNAs (miRNAs) have been established as key regulators of various biological processes with possible involvement in the pathobiology of periodontal disease. Expanding our earlier observations of substantial differential expression of specific miRNAs between clinically healthy and periodontitis-affected gingival tissues, we used miRNA inhibitors (sponges) in loss-of-function experiments to investigate the involvement of specific miRNAs in the response of pocket epithelium-derived, telomerase-immortalized human gingival keratinocytes (TIGKs) to microbial infection. We constructed stable knockdown (KD) cell lines for five epithelium-expressed miRNAs (miR-126, miR-141, miR-155, miR-210, and miR-1246) and assessed their response to infection with periodontal pathogens using microarray analysis, quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot assay. miR-126 KD cells showed lower expression of interleukin 8 (IL-8) and CXCL1, both on the mRNA and protein levels, than did controls upon stimulation by heat-killed wild-type
Porphyromonas gingivalis
, live
P. gingivalis
protease-deficient mutant KDP128, and live
Aggregatibacter actinomycetemcomitans
. In contrast, infection of miR-155 KD and miR-210 KD cells with the same organisms resulted in higher IL-8 and CXCL1 mRNA and protein expression. These effects appeared to be regulated by NF-κB, as suggested by altered transcription and/or phosphorylation status of components of the NF-κB system. Reduced neutrophil-like HL-60 cell chemotactic activity was observed in response to infection of miR-126 KD cells, indicating that miR-126 plays an important role in immune responses. Our findings indicate that specific miRNAs regulate the expression of inflammatory cytokines in human gingival epithelial cells in response to microbial infection.
Mapping the Regulatory Network for Salmonella enterica Serovar Typhimurium Invasion
Authors: Smith Carol , Stringer Anne M. , Mao Chunhong , Palumbo Michael J. , Wade Joseph T.
Published: September 2016

Salmonella enterica
pathogenicity island 1 (SPI-1) encodes proteins required for invasion of gut epithelial cells. The timing of invasion is tightly controlled by a complex regulatory network. The transcription factor (TF) HilD is the master regulator of this process and senses environmental signals associated with invasion. HilD activates transcription of genes within and outside SPI-1, including six other TFs. Thus, the transcriptional program associated with host cell invasion is controlled by at least 7 TFs. However, very few of the regulatory targets are known for these TFs, and the extent of the regulatory network is unclear. In this study, we used complementary genomic approaches to map the direct regulatory targets of all 7 TFs. Our data reveal a highly complex and interconnected network that includes many previously undescribed regulatory targets. Moreover, the network extends well beyond the 7 TFs, due to the inclusion of many additional TFs and noncoding RNAs. By comparing gene expression profiles of regulatory targets for the 7 TFs, we identified many uncharacterized genes that are likely to play direct roles in invasion. We also uncovered cross talk between SPI-1 regulation and other regulatory pathways, which, in turn, identified gene clusters that likely share related functions. Our data are freely available through an intuitive online browser and represent a valuable resource for the bacterial research community.

IMPORTANCE
Invasion of epithelial cells is an early step during infection by
Salmonella enterica
and requires secretion of specific proteins into host cells via a type III secretion system (T3SS). Most T3SS-associated proteins required for invasion are encoded in a horizontally acquired genomic locus known as
Salmonella
pathogenicity island 1 (SPI-1). Multiple regulators respond to environmental signals to ensure appropriate timing of SPI-1 gene expression. In particular, there are seven transcription regulators that are known to be involved in coordinating expression of SPI-1 genes. We have used complementary genome-scale approaches to map the gene targets of these seven regulators. Our data reveal a highly complex and interconnected regulatory network that includes many previously undescribed target genes. Moreover, our data functionally implicate many uncharacterized genes in the invasion process and reveal cross talk between SPI-1 regulation and other regulatory pathways. All datasets are freely available through an intuitive online browser.
aroA
-Deficient Salmonella enterica Serovar Typhimurium Is More Than a Metabolically Attenuated Mutant
Authors: Felgner Sebastian , Frahm Michael , Kocijancic Dino , Rohde Manfred , Eckweiler Denitsa , Bielecka Agata , Bueno Emilio , Cava Felipe , Abraham Wolf-Rainer , Curtiss Roy , Häussler Susanne , Erhardt Marc , Weiss Siegfried
Published: September 2016

Recombinant attenuated
Salmonella enterica
serovar Typhimurium strains are believed to act as powerful live vaccine carriers that are able to elicit protection against various pathogens. Auxotrophic mutations, such as a deletion of
aroA
, are commonly introduced into such bacteria for attenuation without incapacitating immunostimulation. In this study, we describe the surprising finding that deletion of
aroA
dramatically increased the virulence of attenuated
Salmonella
in mouse models. Mutant bacteria lacking
aroA
elicited increased levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) after systemic application
.
A detailed genetic and phenotypic characterization in combination with transcriptomic and metabolic profiling demonstrated that Δ
aroA
mutants display pleiotropic alterations in cellular physiology and lipid and amino acid metabolism, as well as increased sensitivity to penicillin, complement, and phagocytic uptake. In concert with other immunomodulating mutations, deletion of
aroA
affected flagellin phase variation and gene expression of the virulence-associated genes
arnT
and
ansB
. Finally,
ΔaroA
strains displayed significantly improved tumor therapeutic activity. These results highlight the importance of a functional shikimate pathway to control homeostatic bacterial physiology. They further highlight the great potential of
ΔaroA
-attenuated
Salmonella
for the development of vaccines and cancer therapies with important implications for host-pathogen interactions and translational medicine.

IMPORTANCE
Recombinant attenuated bacterial vector systems based on genetically engineered
Salmonella
have been developed as highly potent vaccines. Due to the pathogenic properties of
Salmonella
, efficient attenuation is required for clinical applications. Since the hallmark study by Hoiseth and Stocker in 1981 (S. K. Hoiseth and B. A. D. Stocker, Nature 291:238–239, 1981, http://dx.doi.org/10.1038/291238a0), the auxotrophic Δ
aroA
mutation has been generally considered safe and universally used to attenuate bacterial strains. Here, we are presenting the remarkable finding that a deletion of
aroA
leads to pronounced alterations of gene expression, metabolism, and cellular physiology, which resulted in increased immunogenicity, virulence, and adjuvant potential of
Salmonella.
These results suggest that the enhanced immunogenicity of
aroA
-deficient
Salmonella
strains might be advantageous for optimizing bacterial vaccine carriers and immunotherapy. Accordingly, we demonstrate a superior performance of Δ
aroA Salmonella
in bacterium-mediated tumor therapy. In addition, the present study highlights the importance of a functional shikimate pathway to sustain bacterial physiology and metabolism.