bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Dysphagia and Speech and Language Delay in PHACE Syndrome
Authors: Martin Kari L. , Arvedson Joan C. , Bayer Michelle L. , Drolet Beth A. , Chun Robert , Siegel Dawn H.
Published: December 2014

PHACE (posterior fossa, hemangioma, arterial lesions, cardiac, and eye) syndrome consists of infantile hemangiomas of the head and neck along with a spectrum of noncutaneous anomalies. Neurodevelopmental abnormalities have also been noted. Here we describe the association between PHACE syndrome and abnormalities in oropharyngeal development and coordination manifesting as dysphagia or speech and language delay. A retrospective chart review was conducted of 34 patients with PHACE syndrome. Data were collected from prior clinical notes and radiographic studies and the results of a comprehensive questionnaire that those who attended the July 2012 PHACE Syndrome Family Conference completed. Seventeen of 34 patients with PHACE syndrome and signs or symptoms of dysphagia or speech or language problems were included for analysis. Nine had dysphagia, seven had a history of cardiac surgery, four had a posterior fossa malformation, and seven had lip or oropharynx hemangiomas. Speech or language delay was noted in 16; posterior fossa abnormalities and lip or oropharynx hemangiomas were the most commonly seen associated finding in this group. There was considerable overlap between subset populations with dysphagia, speech delay, and language delay. A subset of individuals with PHACE syndrome experience dysphagia, speech delay, or language delay. This risk seems to be greater in certain subsets of patients, including those with posterior fossa malformations or lip or oropharynx hemangiomas and those with a history of cardiac surgery. Although this descriptive study was not comprehensive enough to examine prevalence, the high incidence of dysphagia and speech and language delay seen in our cohort warrants future prospective studies to further investigate the association.
Intraventricular hemorrhage as a comorbid factor for intestinal obstruction in very low‐birthweight infants
Authors: Hisamatsu Chieko , Morioka Ichiro , Matsuo Kiyomi , Iijima Kazumoto , Nishijima Eiji
Published: December 2014

Background

In very low‐birthweight infants (VLBWI), intestinal obstruction (IO) tends to increase in severity due to the immaturity of the intestine and perinatal events. We examined the clinical comorbid factors related to IO in VLBWI.

Methods

Clinical data of 160 VLBWI admitted to the neonatal intensive care unit in 2006–2011 were retrospectively reviewed. Patients were divided into two groups: IO group (n = 62) and non‐IO group (n = 98). IO was defined as bile excretion via the mouth or nasogastric tube within 30 days after birth. The relationship between clinical factors and the incidence of IO was analyzed.

Results

On univariate analysis, gestational age, birthweight, and the incidence of chronic lung disease, patent ductus arteriosus, intraventricular hemorrhage (IVH), retinopathy of prematurity, and the postnatal use of mechanical ventilation, catecholamines, steroids, and sedatives were associated with IO. On multivariate analysis, only IVH was strongly associated with IO (OR, 4.74; P < 0.01).

Conclusions

IVH is a significant comorbid factor of IO in VLBWI.
Long‐Term Learning in a Short‐Term Study Abroad Program: “Are We Really Truly Helping the Community?”
Authors: Caldwell Penelope , Purtzer Mary Anne
Published: December 2014

Objective

To discover long‐term learning outcomes in a short‐term study abroad program. Students worked directly with community members to identify health issues, implement educational workshops addressing those issues, and evaluate health outcomes.

Design and Sample

This is a qualitative, descriptive study. Thematic analysis was conducted using a written questionnaire completed one or more years postimmersion. The sample was 41 nursing students who participated in a 10‐day immersion experience in remote Honduras.

Results

Four themes emerged revealing evidence of long‐term learning. Three of these themes, Embracing Other, Gaining Cultural Competencies, and Experiencing an Ethnocentric Shift, are supported in the literature. The fourth theme, Negotiating Ethical Dilemmas, offers a new finding.

Conclusion

Although educators have questioned ethical consequences of study abroad programs, there is a paucity of literature indicating that students are the ones doing the questioning. Implications for educators and community members alike include facilitating dialog about collective worldviews related to global health ethics when designing study abroad programs.
An Evaluation of the Treatment of Risk and Uncertainties in the IPCC Reports on Climate Change
Authors: Aven Terje , Renn Ortwin
Published: December 2014

Few global threats rival global climate change in scale and potential consequence. The principal international authority assessing climate risk is the Intergovernmental Panel on Climate Change (IPCC). Through repeated assessments the IPCC has devoted considerable effort and interdisciplinary competence to articulating a common characterization of climate risk and uncertainties. We have reviewed the assessment and its foundation for the Fifth Assessment Reports published in 2013 and 2014, in particular the guidance note for lead authors of the fifth IPCC assessment report on consistent treatment of uncertainties. Our analysis shows that the work carried out by the ICPP is short of providing a theoretically and conceptually convincing foundation on the treatment of risk and uncertainties. The main reasons for our assessment are: (i) the concept of risk is given a too narrow definition (a function of consequences and probability/likelihood); and (ii) the reports lack precision in delineating their concepts and methods. The goal of this article is to contribute to improving the handling of uncertainty and risk in future IPCC studies, thereby obtaining a more theoretically substantiated characterization as well as enhanced scientific quality for risk analysis in this area. Several suggestions for how to improve the risk and uncertainty treatment are provided.
Cognitive and Emotion‐Regulatory Mediators of the Relationship Between Behavioral Approach System Sensitivity and Nonsuicidal Self‐Injury Frequency
Authors: Burke Taylor A. , Stange Jonathan P. , Hamilton Jessica L. , Cohen Jonah N. , O'Garro‐Moore Jared , Daryanani Issar , Abramson Lyn Y. , Alloy Lauren B.
Published: December 2014

Nonsuicidal self‐injury (NSSI) is highly prevalent among late adolescents and predicts the onset of suicidal ideation and behavior. Although research has established an association between the behavioral approach system (BAS) and NSSI, less research has explored mechanisms underlying this relationship. The authors examined negative and positive emotion regulation patterns, as well as the BAS‐relevant cognitive style of self‐criticism, as potential mechanisms through which a hypersensitive BAS might be related to NSSI frequency. Late adolescents (N = 177) with high and moderate BAS levels completed measures of self‐criticism, positive emotion regulation, brooding, and both lifetime and last‐year frequency of NSSI. Results indicated that self‐criticism and positive emotion dampening independently mediated the relationship between BAS and last‐year frequency of NSSI. Self‐criticism also mediated the relationship between BAS and lifetime frequency of NSSI. Results suggest that cognitive and emotion‐regulatory styles may help to explain why high BAS individuals are likely to engage in NSSI.
The NLstart2run study: Incidence and risk factors of running‐related injuries in novice runners
Authors: Kluitenberg B. , van Middelkoop M. , Smits D.W. , Verhagen E. , Hartgens F. , Diercks R. , van der Worp H.
Published: December 2014

Running is a popular form of physical activity, despite of the high incidence of running‐related injuries (RRIs). Because of methodological issues, the etiology of RRIs remains unclear. Therefore, the purposes of the study were to assess the incidence of RRIs and to identify risk factors for RRIs in a large group of novice runners. In total, 1696 runners of a 6‐week supervised “Start to Run” program were included in the NLstart2run study. All participants were aged between 18 and 65, completed a baseline questionnaire that covered potential risk factors, and completed at least one running diary. RRIs were registered during the program with a weekly running log. An RRI was defined as a musculo‐skeletal complaint of the lower extremity or back attributed to running and hampering running ability for three consecutive training sessions. During the running program, 10.9% of the runners sustained an RRI. The multivariable Cox regression analysis showed that a higher age, higher BMI, previous musculo‐skeletal complaints not attributed to sports and no previous running experience were related to RRI. These findings indicate that many novice runners participating in a short‐term running program suffer from RRIs. Therefore, the identified risk factors should be considered for screening and prevention purposes.
Ultra‐endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function
Authors: Stelzer I. , Kröpfl J. M. , Fuchs R. , Pekovits K. , Mangge H. , Raggam R. B. , Gruber H.‐J. , Prüller F. , Hofmann P. , Truschnig‐Wilders M. , Obermayer‐Pietsch B. , Haushofer A. C. , Kessler H. H. , Mächler P.
Published: December 2014

Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra‐endurance exercise‐induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra‐endurance exercise, there were significant increases in leukocytes, platelets, interleukin‐6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase‐9. Ultra‐endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein‐Barr virus was seen to be reactivated in one of seven athletes. The link between exercise‐induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra‐endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration.
Characteristics of the Social Support Networks of Maltreated Youth: Exploring the Effects of Maltreatment Experience and Foster Placement
Authors: Negriff Sonya , James Adam , Trickett Penelope K.
Published: December 2014

Little is known about the social support networks of maltreated youth or how youth in foster care may compare with those who remain with their parent(s). Social network characteristics and perceived social support were examined between (1) maltreated and comparison youth, (2) maltreated youth who remained with their biological parent, those with a foster parent, or a those with a kin caregiver, and (3) youth in stable placements and those who have changed placements. Data came from a sample of 454 adolescents (241 boys, 9–13 years old at enrollment) who took part in a longitudinal study of child maltreatment. Participants completed three assessments approximately 1 year apart. Results showed that on average, maltreated adolescents named significantly fewer people in their network than comparison adolescents. At Time 2, comparison adolescents reported more same‐aged friends. In the maltreatment group, youth with a foster parent reported significantly more older friends than maltreated youth with a kin caregiver. Fewer maltreated youth named a biological parent on the social support questionnaire at all three time points. More youth in kinship care described their caregiver as supportive than those in foster care. These findings indicate that despite heterogeneous placement histories, social support networks among maltreated youth were very similar.
Classroom Response Systems: Effects on the Critical Analysis Skills of Students in Introductory Science Courses
Authors: Adams Cindy Chesworth , Columba Lynn
Published: December 2014

College instructors often teach scientific thinking by asking students to review and analyze a primary research article. The main purpose of this study was to explore how classroom response systems (CRS) could help impact the quality of written analysis papers submitted for this assignment by students taking 100‐level biology courses at a medium‐sized suburban, two‐year college in the northeastern United States. Students in all participating course sections received written instructions on five key elements of critical analysis (CA) to include in scientific study analysis papers. Classroom instruction on recognizing these key elements in primary research papers was provided either via CRS or via an instructor‐facilitated classroom discussion enhanced by the same PowerPoint presentation. A rubric, designed specifically for this assignment, was validated prior to its use in this study. Fifty students participated in the study, and those who received the CRS intervention achieved significantly higher CA scores for identifying implications of study findings, while the group that received only written instructions achieved significantly higher CA scores for discussing the credibility of the references used by the authors in planning the critiqued study. The implications of this study are discussed along with ideas for future research.
Students' Concepts‐ and Theorems‐in‐Action on a Novel Task About Similarity
Authors: DeJarnette Anna Fricano , Walczak Marissa , González Gloriana
Published: December 2014

Similarity is a fundamental concept in the middle grades. In this study, we applied Vergnaud's theory of conceptual fields to answer the following questions: What concepts‐in‐action and theorems‐in‐action about similarity surfaced when students worked in a novel task that required them to enlarge a puzzle piece? How did students use geometric and multiplicative reasoning at the same time in order to construct similar figures? We found that students used concepts of scaling and proportional reasoning, as well as the concept of circle and theorems about similar triangles, in their work on the problem. Students relied not only on visual perception, but also on numeric reasoning. Moreover, students' use of multiplicative and proportional concepts supported their geometric constructions. Knowledge of the concepts and ideas that students have available when working on a task about similarity can inform instruction by helping to ground formal introduction of new concepts in students' informal prior experiences and knowledge.
MIC gene polymorphism and haplotype diversity in Li nationality of Southern China
Authors: Lin L. , Yang W. , Chen E. , Gong Z. , Luo Q. Z. , Wei X. B. , Yu P.
Published: December 2014

Here, we report for the first time the polymorphisms of MICA and MICB in a healthy Li population of 344 unrelated individuals. By using polymerase chain reaction‐sequence specific priming (PCR‐SSP) and sequence‐based typing (PCR‐SBT), 17 MICA‐sequence alleles and 5 MICA‐STR (short tandem repeats, STR) alleles, as well as 17 MICB alleles were detected, among which MICA*010, MICA*A4 and MICB*005:02 were the most frequent alleles. In addition, linkage disequilibrium was investigated and the most common two‐locus haplotypes were MICB*005:02‐MICA*010 and MICB*008‐MICA*002:01. These results present informative genetic markers for the investigation of possible origins and the evolution of MHC class I haplotypes in the Li population.
TOND1confers tolerance to nitrogen deficiency in rice
Authors: Zhang Yangjun , Tan Lubin , Zhu Zuofeng , Yuan Lixing , Xie Daoxin , Sun Chuanqing
Published: December 2014

Nitrogen (N), the most important mineral nutrient for plants, is critical to agricultural production systems. N deficiency severely affects rice growth and decreases rice yields. However, excessive use of N fertilizer has caused severe pollution to agricultural and ecological environments. The necessity of breeding of crops that require lower input of N fertilizer has been recognized. Here we identified a major quantitative trait locus on chromosome 12,Tolerance Of Nitrogen Deficiency 1(TOND1), that confers tolerance to N deficiency in theindicacultivar Teqing. Sequence verification of 75indicaand 75japonicacultivars from 18 countries and regions demonstrated that only 27.3% of cultivars (41indicacultivars) containTOND1, whereas 72.7% of cultivars, including the remaining 34indicacultivars and all 75japonicacultivars, do not harbor theTOND1allele. Over‐expression ofTOND1increased the tolerance to N deficiency in theTOND1‐deficient rice cultivars. The identification ofTOND1provides a molecular basis for breeding rice varieties with improved grain yield despite decreased input of N fertilizers.
Reactive oxygen species‐provoked mitochondria‐dependent cell death during ageing of elm (Ulmus pumila L.) seeds
Authors: Wang Yu , Li Ying , Xue Hua , Pritchard Hugh W. , Wang Xiaofeng
Published: December 2014

Previous studies have shown that controlled deterioration treatment (CDT) induces programmed cell death in elm (Ulmus pumila L.) seeds, which undergo certain fundamental processes that are comparable to apoptosis in animals. In this study, the essential characteristics of mitochondrial physiology in elm seeds during CDT were identified by cellular ultrastructural analysis, whole‐body optical imaging, Western blotting and semi‐quantitative RT–PCR. The alteration in mitochondrial morphology was an early event during CDT, as indicated by progressive dynamic mitochondrial changes and rupture of the mitochondrial outer membrane; loss of mitochondrial transmembrane potential (Δψm) ensued, and mitochondrial ATP levels decreased. The mitochondrial permeability transition pore inhibitor cyclosporine A effectively suppressed these changes during ageing. The in situ localization of production of reactive oxygen species (ROS), and evaluation of the expression of voltage‐dependent anion‐selective channel and cyclophilin D indicated that the levels of mitochondrial permeability transition pore components were positively correlated with ROS production, leading to an imbalance of the cellular redox potential and ultimately to programmed cell death. Pre‐incubation with ascorbic acid slowed loss of mitochondrial Δψm, and decreased the effect of CDT on seed viability. However, there were no significant changes in multiple antioxidant elements or chaperones in the mitochondria during early stages of ageing. Our results indicate that CDT induces dynamic changes in mitochondrial physiology via increased ROS production, ultimately resulting in an irreversible loss of seed viability.
Liquid chromatography high‐resolution mass spectrometry for fatty acid profiling
Authors: Bromke Mariusz A. , Hochmuth Anton , Tohge Takayuki , Fernie Alisdair R. , Giavalisco Patrick , Burgos Asdrubal , Willmitzer Lothar , Brotman Yariv
Published: December 2014

Quantification of fatty acids has been crucial to elucidate lipid biosynthesis pathways in plants. To date, fatty acid identification and quantification has relied mainly on gas chromatography (GC) coupled to flame ionization detection (FID) or mass spectrometry (MS), which requires the derivatization of samples and the use of chemical standards for annotation. Here we present an alternative method based on a simple procedure for the hydrolysis of lipids, so that fatty acids can be quantified by liquid chromatography mass spectrometry (LC‐MS) analysis. Proper peak annotation of the fatty acids in the LC‐MS‐based methods has been achieved by LC‐MS measurements of authentic standard compounds and elemental formula annotation supported by 13C isotope‐labeled Arabidopsis. As a proof of concept, we have compared the analysis by LC‐MS and GC‐FID of two previously characterized Arabidopsis thaliana knock‐out mutants for FAD6 and FAD7 desaturase genes. These results are discussed in light of lipidomic profiles obtained from the same samples. In addition, we performed untargeted LC‐MS analysis to determine the fatty acid content of two diatom species. Our results indicate that both LC‐MS and GC‐FID analyses are comparable, but that because of higher sensitivity and selectivity the LC‐MS‐based method allows for a broader coverage and determination of novel fatty acids.
A morphological phylogeny of Agrotis Ochsenheimer (Lepidoptera, Noctuidae), with emphasis on the South American species
Authors: San Blas Germán
Published: December 2014

The monophyly of Agrotis Ochsenheimer in addition to the relationships among the South American species of the genus and the relationship between Agrotis and Feltia Walker are examined. A cladistic analysis was performed based on 45 terminals, with 28 ingroup and 17 outgroup taxa, and 126 characters (two continuous and 124 discrete) from adult morphology, including male and female genitalia. Parsimony analyses were performed under equal and implied weighting. Results support Agrotis as a monophyletic group, sister to the South American species of Feltia (Feltia tent.), and the latter being more closely related to Agrotis than to the ‘true’ Feltia. Species of Agrotis that branched off first (including the type species) have characters shared with both Feltia and Agrotis. South American species of Agrotis (with some proviso) form a clade that branched off later, with some weakly supported species groups that had been proposed in previous works. Biogeographical aspects of the group are discussed after optimizing species distributions on the tree. Trees obtained after analyses using implied weights show similar relationships to those under equal weights, particularly regarding Feltia tent., showing Feltia tent. plus Agrotis forming a monophyletic group, sister to the ‘true’ Feltia.
Micro-Emulsion Phase Behavior of a Cationic Surfactant at Intermediate Interfacial Tension in Sandstone and Carbonate Rocks
Authors: Yassin Mahmood Reza , Ayatollahi Shahab , Rostami Behzad , Hassani Kamran , Taghikhani Vahid
Published: December 2014

Based on the conventional approach, the trapped oil in rock pores can be easily displaced when a Winsor type (III) micro-emulsion is formed in the reservoir during surfactant flooding. On the other hand, the Winsor type (III) involves three phase flow of water, oil, and micro-emulsion that causes considerable oil phase trapping and surfactant retention. This work presents an experimental study on the effect of micro-emulsion phase behavior during surfactant flooding in sandstone and carbonate core samples. In this study, after accomplishing salinity scan of a cationic surfactant (C16–N(CH3)3Br), the effects of Winsor (I), Winsor (III) and Winsor (II) on oil recovery factor, differential pressure drop, relative permeability, and relative permeability ratio were investigated extensively. To carry out a comparative study, homogeneous and similar sandstone and carbonate rocks were selected and the effects of wettability alteration and dynamic surfactant adsorption were studied on them. The results of oil recovery factor in both rock types showed that Winsor (I) and Winsor (III) are preferred compared to Winsor (II) phase behavior. In addition, comparison of normalized relative permeability ratio at high water saturations revealed that Winsor (I) has more appropriate oil and water relative permeability than Winsor (II). The results presented in this paper demonstrate that optimum salinity which results in higher recovery factor and better oil displacement may occur at salinities out of Winsor (III) range. Therefore, the best way to specify optimum salinity is to perform core flood experiments at several salinities, which cover all phase behaviors of Winsor (I), Winsor (III), and Winsor (II).
Thermal Conduction Performance of Fiber-Enhanced Polyalcohol Binary Systems
Authors: Wang Xiaowu , Li Yaochao , Wan Zhenpin
Published: December 2014

Polyalcohol has poor heat conduction performance. A fiber-enhanced polyalcohol binary system combines polyalcohol with a copper fiber net to improve its heat conduction performance. In a binary system without fibers, more heat input increases the wall temperature near the container than when the fiber is present. Compared to a polyalcohol binary system, pentaerythritol/Tris hydroxymethyl aminomethane (PE/TRIS) without fibers, fiber-enhanced polyalcohol system PE/TRIS shows quicker response to energy input from the exterior region. The phase change temperature in a fiber-enhanced polyalcohol binary system is much lower than that in a polyalcohol system without fibers. This is because of the metastate plastic state that presents a nonfaceted phase interface with a larger radius of curvature in a polyalcohol system without fibers. The porous structure of the fiber is smaller than the size of the phase interface in a polyalcohol system without fibers and can increase the equilibrium pressure and make the phase change easier.
Electrodeposition of p-type cuprous oxide layers on n-type zinc oxide layers with different electrical resistivities
Authors: Baek Seung Ki , Shin Jae Hui , Cho Sung Woon , Cho Hyung Koun
Published: December 2014

The development of metal oxide semiconductor-based absorber layers consisting of earth abundant elements is currently in the early stages of research. Cuprous oxide (Cu2O) is a representative p-type oxide material with an appropriate band gap for this application. To produce all-oxide photovoltaic cells, the authors grew Cu2O films on top of n-type Zinc oxide (ZnO) layers by electrodeposition. Prior to the electrodeposition of Cu2O, the underlying ZnO layers were deposited by atomic layer deposition at different temperatures. The resulting films had different electrical conductivities. For the low conductivity ZnO grown at 100 °C, the Cu2O layer was coated with a highly (111) preferred orientation leading to low electrical resistivity. Consequently, these Cu2O/ZnO heterojunction solar cells showed relatively high conversion efficiencies despite the low conductivity of the ZnO. Conversely, the Cu2O deposited on the highly conductive ZnO film (grown at 150 °C) exhibited extremely low photocurrent, which was attributed to low crystallinity and poor electrical properties.
Exercise Increases the Dynamics of Diurnal Cortisol Secretion and Executive Function in People With Amnestic Mild Cognitive Impairment
Authors: Tortosa-Martínez Juan , Clow Angela , Caus-Pertegaz Nuria , González-Caballero Gloria , Abellán-Miralles Immaculada , Saenz María José
Published: December 2014

Regular physical activity is protective against, and beneficial for, mild cognitive impairment (MCI), dementia, and Alzheimer’s disease. The mechanisms underlying these benefits remain unknown although it has been suggested that exercise-induced changes in the circadian pattern of cortisol secretion may be implicated. Fitness, salivary cortisol levels (0 and 30 min postawakening, midday, 5 p.m., and 9 p.m.), and cognitive function were determined in a group of amnestic MCI patients (n = 39) before and after a three-month exercise program (n = 19) or usual care (n = 20). At baseline, fitness measures were positively correlated with peak levels of cortisol and a greater fall in cortisol concentration from peak levels to midday. The exercise intervention successfully increased fitness and resulted in a greater fall in cortisol concentration from peak to midday, compared with the control group. The exercise intervention enhanced indices of executive function, although memory, mood, and functionality were not affected.
E-cadherin interactome complexity and robustness resolved by quantitative proteomics
Authors: Guo Zhenhuan , Neilson Lisa J. , Zhong Hang , Murray Paul S. , Zanivan Sara , Zaidel-Bar Ronen
Published: December 2014

The protein interaction network associated with E-cadherin is robust to changes in cell-cell adhesion.
Identification of Capsular Types in Carbapenem-Resistant Klebsiella pneumoniae Strains by
wzc
Sequencing and Implications for Capsule Depolymerase Treatment
Authors: Pan Yi-Jiun , Lin Tzu-Lung , Lin Yi-Tsung , Su Po-An , Chen Chun-Tang , Hsieh Pei-Fang , Hsu Chun-Ru , Chen Ching-Ching , Hsieh Yu-Chia , Wang Jin-Town
Published: December 2014

Klebsiella pneumoniae
is an important human pathogen associated with a variety of diseases, and the prevalence of multidrug-resistant
K. pneumoniae
(MDRKP) is rapidly increasing. Here we determined the capsular types of 85 carbapenem-resistant
K. pneumoniae
(CRKP) strains by
wzc
sequencing and investigated the presence of carbapenemases and integrons among CRKP strains. Ten CRKP strains (12%) were positive for carbapenemase (imipenemase, 6/85 strains;
K. pneumoniae
carbapenemase, 3/85 strains; Verona integron-encoded metallo-β-lactamase, 1/85 strains). Capsular type K64 accounted for 32 CRKP strains (38%), followed by K62 (13%), K24 (8%), KN2 (7%), and K28 (6%). Sequence types (STs) were determined by multilocus sequence typing (MLST), and the results indicated that ST11, which accounted for 47% of these CRKP strains (40/85 strains), was the major ST. We further isolated a K64-specific capsule depolymerase (K64dep), which could enhance serum and neutrophil killing
in vitro
and increase survival rates for K64
K. pneumoniae
-inoculated mice. The toxicity study demonstrated that mice treated with K64dep showed normal biochemical parameters and no significant histopathological changes of liver, kidney, and spleen, indicating that enzyme treatment did not cause toxicity in mice. Therefore, the findings of capsular type clustering among CRKP strains and effective treatment with capsule depolymerase for MDRKP infections are important for capsule-based vaccine development and therapy.
In Vitro
and
In Vivo
Antiviral Activity and Resistance Profile of Ombitasvir, an Inhibitor of Hepatitis C Virus NS5A
Authors: Krishnan Preethi , Beyer Jill , Mistry Neeta , Koev Gennadiy , Reisch Thomas , DeGoey David , Kati Warren , Campbell Andrew , Williams Laura , Xie Wangang , Setze Carolyn , Molla Akhteruzzaman , Collins Christine , Pilot-Matias Tami
Published: December 2014

Ombitasvir (ABT-267) is a hepatitis C virus (HCV) NS5A inhibitor with picomolar potency, pan-genotypic activity, and 50% effective concentrations (EC
50
s) of 0.82 to 19.3 pM against HCV genotypes 1 to 5 and 366 pM against genotype 6a. Ombitasvir retained these levels of potency against a panel of 69 genotype 1 to 6 chimeric replicons containing the NS5A gene derived from HCV-infected patients, despite the existence of natural sequence diversity within NS5A.
In vitro
resistance selection identified variants that conferred resistance to ombitasvir in the HCV NS5A gene at amino acid positions 28, 30, 31, 58, and 93 in genotypes 1 to 6. Ombitasvir was evaluated
in vivo
in a 3-day monotherapy study in 12 HCV genotype 1-infected patients at 5, 25, 50, or 200 mg dosed once daily. All patients in the study were HCV genotype 1a infected and were without preexisting resistant variants at baseline as determined by clonal sequencing. Decreases in HCV RNA up to 3.1 log
10
IU/ml were observed. Resistance-associated variants at position 28, 30, or 93 in NS5A were detected in patient samples 48 hours after the first dose. Clonal sequencing analysis indicated that wild-type virus was largely suppressed by ombitasvir during 3-day monotherapy, and at doses higher than 5 mg, resistant variant M28V was also suppressed. Ombitasvir was well tolerated at all doses, and there were no serious or severe adverse events. These data support clinical development of ombitasvir in combination with inhibitors targeting HCV NS3/4A protease (ABT-450 with ritonavir) and HCV NS5B polymerase (ABT-333, dasabuvir) for the treatment of chronic HCV genotype 1 infection. (Study M12-116 is registered at ClinicalTrials.gov under registration no. NCT01181427.)
Macrolide-Resistant Mycoplasma pneumoniae in Adults in Zhejiang, China
Authors: Zhou Zibo , Li Xiangzhi , Chen Xiaojian , Luo Fangjun , Pan Changwang , Zheng Xiaoping , Tan Feng
Published: December 2014

Mycoplasma pneumoniae
is a major pathogen causing community-acquired pneumoniae (CAP), which is generally treated with macrolides. In recent years, however, although macrolide-resistant
M. pneumoniae
has been reported frequently, particularly in China, very little is known about the prevalence of macrolide-resistant
M. pneumoniae
infection in adults. In this study, we survey the macrolide-resistant
M. pneumoniae
in adults in Zhejiang province and characterize the mechanisms of resistance to macrolide. Six hundred fifty throat swab samples were collected from adult patients with CAP from January 2012 to August 2014. These samples were assayed by nested PCR and then cultivated for
M. pneumoniae
. All isolates were sequenced to determine the mutation in domain V of the 23S rRNA gene. The activities of 10 antibiotics against macrolide-resistant
M. pneumoniae
isolates were also investigated
in vitro
. Moreover, restriction fragment length polymorphism (RFLP) analysis of the amplified P1 gene was used to type 50 resistant strains. One hundred percent (71/71) of
M. pneumoniae
strains isolated from adults with CAP were resistant to erythromycin (MIC = 128 to >256 μg/ml), clarithromycin (MIC = 128 to >256 μg/ml), and azithromycin (MIC = 32 to >64 μg/ml). Furthermore, all macrolide-resistant
M. pneumoniae
strains identified had an A2063G mutation in domain V of the 23S rRNA gene. Forty-six resistant strains (92.0%) were classified into type I strain on the basis of P1 gene PCR-RFLP analysis. According to these findings, it is suggested that macrolide-resistant
M. pneumoniae
infection is very prevalence among adults in Zhejiang province. Thus, there is necessary to perform the epidemiological monitoring of macrolide-resistant
M. pneumoniae
in the future.
Broad Coverage of Genetically Diverse Strains of Clostridium difficile by Actoxumab and Bezlotoxumab Predicted by
In Vitro
Neutralization and Epitope Modeling
Authors: Hernandez Lorraine D. , Racine Fred , Xiao Li , DiNunzio Edward , Hairston Nichelle , Sheth Payal R. , Murgolo Nicholas J. , Therien Alex G.
Published: December 2014

Clostridium difficile
infections (CDIs) are the leading cause of hospital-acquired infectious diarrhea and primarily involve two exotoxins, TcdA and TcdB. Actoxumab and bezlotoxumab are human monoclonal antibodies that neutralize the cytotoxic/cytopathic effects of TcdA and TcdB, respectively. In a phase II clinical study, the actoxumab-bezlotoxumab combination reduced the rate of CDI recurrence in patients who were also treated with standard-of-care antibiotics. However, it is not known whether the antibody combination will be effective against a broad range of
C. difficile
strains. As a first step toward addressing this, we tested the ability of actoxumab and bezlotoxumab to neutralize the activities of toxins from a number of clinically relevant and geographically diverse strains of
C. difficile
. Neutralization potencies, as measured in a cell growth/survival assay with purified toxins from various
C. difficile
strains, correlated well with antibody/toxin binding affinities. Actoxumab and bezlotoxumab neutralized toxins from culture supernatants of all clinical isolates tested, including multiple isolates of the BI/NAP1/027 and BK/NAP7/078 strains, at antibody concentrations well below plasma levels observed in humans. We compared the bezlotoxumab epitopes in the TcdB receptor binding domain across known TcdB sequences and found that key substitutions within the bezlotoxumab epitopes correlated with the relative differences in potencies of bezlotoxumab against TcdB of some strains, including ribotypes 027 and 078. Combined with
in vitro
neutralization data, epitope modeling will enhance our ability to predict the coverage of new and emerging strains by actoxumab-bezlotoxumab in the clinic.
Inactivation of Murine Norovirus on a Range of Copper Alloy Surfaces Is Accompanied by Loss of Capsid Integrity
Authors: Warnes Sarah L. , Summersgill Emma N. , Keevil C. William
Published: December 2014

Norovirus is one of the most common causes of acute viral gastroenteritis. The virus is spread via the fecal-oral route, most commonly from infected food and water, but several outbreaks have originated from contamination of surfaces with infectious virus. In this study, a close surrogate of human norovirus causing gastrointestinal disease in mice, murine norovirus type 1 (MNV-1), retained infectivity for more than 2 weeks following contact with a range of surface materials, including Teflon (polytetrafluoroethylene [PTFE]), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. Persistence was slightly prolonged on ceramic surfaces. A previous study in our laboratory observed that dry copper and copper alloy surfaces rapidly inactivated MNV-1 and destroyed the viral genome. In this new study, we have observed that a relatively small change in the percentage of copper, between 70 and 80% in copper nickels and 60 and 70% in brasses, had a significant influence on the ability of the alloy to inactivate norovirus. Nickel alone did not affect virus, but zinc did have some antiviral effect, which was synergistic with copper and resulted in an increased efficacy of brasses with lower percentages of copper. Electron microscopy of purified MNV-1 that had been exposed to copper and stainless steel surfaces suggested that a massive breakdown of the viral capsid had occurred on copper. In addition, MNV-1 that had been exposed to copper and treated with RNase demonstrated a reduction in viral gene copy number. This suggests that capsid integrity is compromised upon contact with copper, allowing copper ion access to the viral genome.
Granzyme-Mediated Regulation of Host Defense in the Liver in Experimental Leishmania donovani Infection
Authors: Murray Henry W. , Mitchell-Flack Marisa , Zheng Hua , Ma Xiaojing
Published: December 2014

In the livers of susceptible C57BL/6 (B6) mice infected withLeishmania donovani, CD8+T cell mechanisms are required for granuloma assembly, macrophage activation, intracellular parasite killing, and self-cure. Since gene expression of perforin and granzymes A and B (GzmA and GzmB), cytolytic proteins linked to CD8+cell effector function, was enhanced in infected liver tissue, B6 mice deficient in these granular proteins were used to gauge host defense roles. Neither perforin nor GzmA was required; however, mice deficient in GzmB (GzmB−/−, GzmB cluster−/−, and GzmA×B cluster double knockout [DKO] mice) showed both delayed granuloma assembly and initially impaired control of parasite replication. Since these two defects in B6 mice were limited to early-stage infection, innately resistant 129/Sv mice were also tested. In this genetic setting, expression of both innate and subsequent T (Th1) cell-dependent acquired resistance, including the self-cure phenotype, was entirely derailed in GzmA×B cluster DKO mice. These results, in susceptible B6 mice for GzmB and in resistant 129/Sv mice for GzmA and/or the GzmB cluster, point to granzyme-mediated host defense regulation in the liver in experimental visceral leishmaniasis.
The Staphylococcus aureus NuoL-Like Protein MpsA Contributes to the Generation of Membrane Potential
Authors: Mayer Sonja , Steffen Wojtek , Steuber Julia , Götz Friedrich
Published: December 2014

In aerobic microorganisms, the entry point of respiratory electron transfer is represented by the NADH:quinone oxidoreductase. The enzyme couples the oxidation of NADH with the reduction of quinone. In the type 1 NADH:quinone oxidoreductase (Ndh1), this reaction is accompanied by the translocation of cations, such as H
+
or Na
+
. In
Escherichia coli
, cation translocation is accomplished by the subunit NuoL, thus generating membrane potential (Δψ). Some microorganisms achieve NADH oxidation by the alternative, nonelectrogenic type 2 NADH:quinone oxidoreductase (Ndh2), which is not cation translocating. Since these enzymes had not been described in
Staphylococcus aureus
, the goal of this study was to identify proteins operating in the NADH:quinone segment of its respiratory chain. We demonstrated that Ndh2 represents a NADH:quinone oxidoreductase in
S. aureus
. Additionally, we identified a hypothetical protein in
S. aureus
showing sequence similarity to the proton-translocating subunit NuoL of complex I in
E. coli
: the NuoL-like protein MpsA. Mutants with deletion of the
nuoL
-like gene
mpsA
and its corresponding operon,
mpsABC
(
mps
for membrane potential-generating system), exhibited a small-colony-variant-like phenotype and were severely affected in Δψ and oxygen consumption rates. The MpsABC proteins did not confer NADH oxidation activity. Using an Na
+
/H
+
antiporter-deficient
E. coli
strain, we could show that MpsABC constitute a cation-translocating system capable of Na
+
transport. Our study demonstrates that MpsABC represent an important functional system of the respiratory chain of
S. aureus
that acts as an electrogenic unit responsible for the generation of Δψ.
Evolution of Aromatic β-Glucoside Utilization by Successive Mutational Steps in Escherichia coli
Authors: Zangoui Parisa , Vashishtha Kartika , Mahadevan Subramony
Published: December 2014

The
bglA
gene of
Escherichia coli
encodes phospho-β-glucosidase A capable of hydrolyzing the plant-derived aromatic β-glucoside arbutin. We report that the sequential accumulation of mutations in
bglA
can confer the ability to hydrolyze the related aromatic β-glucosides esculin and salicin in two steps. In the first step, esculin hydrolysis is achieved through the acquisition of a four-nucleotide insertion within the promoter of the
bglA
gene, resulting in enhanced steady-state levels of the
bglA
transcript. In the second step, hydrolysis of salicin is achieved through the acquisition of a point mutation within the
bglA
structural gene close to the active site without the loss of the original catabolic activity against arbutin. These studies underscore the ability of microorganisms to evolve additional metabolic capabilities by mutational modification of preexisting genetic systems under selection pressure, thereby expanding their repertoire of utilizable substrates.
Specific exercise effects of preventive neuromuscular training intervention on anterior cruciate ligament injury risk reduction in young females: meta-analysis and subgroup analysis
Authors: Sugimoto Dai , Myer Gregory D , Barber Foss Kim D , Hewett Timothy E
Published: December 2014

Context

Clinical trials have demonstrated that preventive neuromuscular training (PNMT) can be effective to reduce ACL injuries in young females. However, the magnitude of the overall effect of PNMT for ACL injury reduction has not reached consensus. In addition, the effects of individual exercises in PNMT that optimise ACL injury reduction are unknown.

Objective

The purpose of this project was to systematically review previously published clinical trials and evaluate types of exercises that best support ACL injury reduction in young females.

Data sources

The key words ‘knee’, ‘anterior cruciate ligament’, ‘ACL’, ‘prospective’, ‘neuromuscular’, ‘training’, ‘female’, and ‘prevention’ were used for studies published from 1995 to May 2012 in PubMed and EBSCO host.

Study selection

Inclusion criteria for the current analysis were: (1) documented number of ACL injuries, (2) employed a PNMT intervention that aimed to reduce ACL injuries, (3) had a comparison group, (4) used a prospective controlled study design, (5) recruited female athletes and (6) recorded exercises implemented in the PNMT.

Data extraction

The number of ACL injuries and female athletes in each group (control and intervention) were extracted. In addition, exercises were categorised into four types and analysed for each investigation.

Data synthesis

A total of 14 clinical trials met the inclusion criteria. The subgroup analyses identified fewer ACL injuries in PNMT that focused on strengthening (OR 0.32, 95% CI 0.23 to 0.46, p=0.001), proximal control exercises (OR 0.33, 95% CI 0.23 to 0.47, p=0.001) and multiple exercise interventions (OR 0.32, CI 0.22 to 0.46, p=0.001).

Conclusions

The current subgroup analyses indicate strengthening, proximal control exercises and multi exercise genres increased efficacy in PNMT intervention designed to reduce ACL injury in young female athletes.
Cerebrovascular reactivity assessed by transcranial Doppler ultrasound in sport-related concussion: a systematic review
Authors: Gardner Andrew J , Tan Can Ozan , Ainslie Philip N , van Donkelaar Paul , Stanwell Peter , Levi Christopher R , Iverson Grant L
Published: December 2014

Background

Traumatic brain injury influences regulation of cerebral blood flow in animal models and in human studies. We reviewed the use of transcranial Doppler ultrasound (US) to monitor cerebrovascular reactivity following sport-related concussion.

Review method

A narrative and systematic review of articles published in the English language, from December 1982 to October 2013.

Data sources

Articles were retrieved via numerous databases using relevant key terms. Observational, cohort, correlational, cross-sectional and longitudinal studies were included.

Results

Three publications met the criteria for inclusion; these provided data from 42 athletes and 33 controls. All three studies reported reductions in cerebrovascular reactivity via transcranial Doppler US.

Conclusions

These initial results support the use of cerebrovascular reactivity as a research tool for identifying altered neurophysiology and monitoring recovery in adult athletes. Larger cross-sectional, prospective and longitudinal studies are required to understand the sensitivity and prognostic value of cerebrovascular reactivity in sport-related concussion.
A review of the effectiveness of psychological interventions used for anxiety and depression in chronic obstructive pulmonary disease
Authors: Smith Sheree M S , Sonego Sandra , Ketcheson Leah , Larson Janet L
Published: December 2014

Background

Anxiety and depression are recognised co-morbidities associated with COPD and have been related to poor health outcomes. Therapies to relieve anxiety and depression are currently not detailed in clinical guidelines.

Methods

A systematic review of psychological interventions for anxiety and depression in adults with COPD was conducted. Meta-analysis utilising the random effects model was undertaken for 4 studies that employed the same psychological intervention type, Cognitive Behavioural Therapy (CBT).

Results

Seven studies met the inclusion criteria. Four studies used CBT. Included studies utilised psychotherapy, uncertainty management and minimal psychological therapy. 70% of participants were male. Many studies had poor methodological quality. The meta-analysis showed a small decrease in symptoms for both anxiety (SMD −0.49, 95% CI −1.04, 0.06, P=0.08, n=193) and depression (SMD −0.37, 95% CI −0.86, 0.11, P=0.13, n=193). No change occurred when sensitivity analyses were conducted.

Conclusion

Anxiety and depression in COPD patients are known to impact on health outcomes. Effective psychological interventions such as CBT may assist people with COPD in reducing psychological burden. There remains a need for well-designed studies to provide substantive evidence for the use of psychological interventions in this patient population.