bluuebunny/crossref_metadata_2025 huggingface dataset:
Proximal patellar tendon pathology can develop during adolescence in young ballet dancers—A 2‐year longitudinal study
Authors: Rudavsky A. , Cook J. L. , Docking S.
Published: April 2018

Patellar tendinopathy (tendon pain and dysfunction), or jumper's knee, is prevalent in adult jumping athletes. Pathology in the proximal patellar tendon is a key risk factor for developing patellar tendinopathy. When pathology develops in the proximal patellar tendon is not known, although it is reported to exist in adolescent athletes. The aim of this study was to follow young jumping athletes (ballet dancers) through adolescence to identify whether pathology develops and its relation to the adolescent growth spurt. Fifty‐seven elite ballet students between ages 11 and 18 were monitored for 2 years. Data were collected every 6 months, including an ultrasound scan on their left tendons using ultrasound tissue characterization (UTC) to quantify intratendinous changes, anthropometric data to calculate peak height velocity (adolescent growth spurt), participant reports of any injuries or dance modifications, and a VISA‐P and single leg decline squat for patellar tendon pain. Nine percentage of adolescent dancers developed pathology during this study, and development was not associated with growth spurt. Peak height velocity and dance participation/volume both at the start and throughout the study were similar in those who did develop pathology and those who did not. Only 2 of 5 participants who developed pathology reported pain associated with their tendon. Pathology in the proximal patellar tendon can develop during adolescence.
Networked audiences and cultural globalization
Authors: Li Hongmei , Jung Sookeung
Published: April 2018

Most research approaches globalization from a top‐down perspective that looks at how past economic, political, and cultural arrangements influence non‐Western cultures. This essay instead uses the concept of the networked audience as an entry point to understand the dynamics of cultural globalization. We first discuss the mass audience in relation to cultural imperialism/homogenization. We then examine the recent shift to the networked audience in the context of digital globalization, computer networking, and social media. Afterwards, we investigate how the conceptualization of global networked audiences contributes to new understandings of global cultures and exchanges. The network perspective suggests that the traditional conceptualization of globalization via the center‐periphery model no longer works, but rather that cultural flows through networks enable individuals to have some, but limited, agency and power to resist corporate and elite controls.
Framing Black women: The utility of knowledge
Authors: Slatton Brittany C.
Published: April 2018

This article reviews the literature on the socially constructed knowledge or myths about Black women by placing it within a cultural context. I identify three domains of research within this field. The first is the cultural production of socially constructed mythologies of Black women throughout various historical epochs, which includes an analysis of books, journals, scientific/medical documents, images, and other cultural products. I focus on two primary categories of stereotypes found in the literature: 1.) the myth of pathology and primitiveness and 2.) the myth of antithetical womanhood. The second is the utility of cultural knowledge—which is to control and regulate culture and to justify and establish particular types of norms, preferences, laws, policies, and practices within society. Lastly, I will discuss the resistance culture of Black women, which developed in response to stereotypical perceptions created about them.
Assessing online misogyny: Perspectives from sociology and feminist media studies
Authors: Moloney Mairead Eastin , Love Tony P.
Published: April 2018

Scholarly and lay publications have highlighted increasing online misogyny. We review the dominant, cross‐disciplinary analyses and conceptualizations of cisnormative, heterosexist, misogynistic discourses. From feminist media scholarship, we highlight four terms intended to describe acts of online misogyny: online sexual harassment, gendertrolling, e‐bile, and disciplinary rhetoric. We then review the nascent sociological concept of virtual manhood acts (VMA) and situate it within the broader context of critical gender theory. VMA use the tools of technologically facilitated misogyny; they occur in online social spaces and, using textual and visual cues to signal a masculine self, enforce hegemonic gender norms, oppress women, and keep men “in the box.” VMA align with the interactionist view of gender as action and emphasize that a physical body is not needed to signal manhood. The concept of virtual manhood acts acknowledges that women are the primary victims of online oppression without obscuring the problematic practices of men that are central to this subjugation.
Allowing for the Projective Dimension of Agency in Analysing Alternative Food Networks
Authors: Le Velly Ronan
Published: April 2018

This article argues for including the projective dimension of agency in research into alternative food networks. Starting from a review of the literature, I show that referring to the notion of project is useful to answer the questions raised by the use of the term “alternative” and to reinforce analyses of hybridisation and conventionalisation processes. I argue that alternative food networks are characterised by a “promise of difference” in the projects of the actors who promote them. To clarify this notion of project, I rely on the work of French sociologists concerning the creation of “organised action”. I posit that taking account of the project amounts to recognising human beings' abilities to imagine and to construct new collectives such as those that are studied in research into alternative food networks. I also underscore the need to envision the project not as a clear determinant of action, but rather as a fuzzy landmark, meaning that negotiation and arbitration are required to set the rules involved in its implementation.
Another look at impulsivity: Could impulsive behavior be strategic?
Authors: Kopetz Catalina E. , Woerner Jacqueline I. , Briskin Julia L.
Published: April 2018

In the present article, we propose that impulsive behavior may be a response to certain needs or goals that people have in the moment and could therefore be strategic. We review briefly the dominant approaches and findings in the impulsivity literature. We then examine different behaviors that are typically considered impulsive such as delay discounting, risky sexual behavior, risk taking in the context of emotion dysregulation, and adolescent risk behavior and present evidence suggesting that they follow the general principles of goal pursuit. Specifically, they are (a) enacted when perceived as relevant to the individual's motivation; (b) less likely when alternative means to fulfill these goals are available; and (c) supported rather than reduced by sufficient executive control, a hallmark of goal pursuit. We do not argue that there is no impulsive behavior. Rather, we suggest that such behavior may represent individuals' attempts to fulfill current motivations or needs. This approach emphasizes the functionality and dynamism of the behavior, it provides a framework to explain the inconsistencies in the literature, it helps us to move away from pathologizing or moralizing the behavior, and it provides insights about potential strategies to mitigate the negative consequences of acting impulsively.
Race, debt and empire: Racialising the Newfoundland financial crisis of 1933
Authors: Cullen Declan
Published: April 2018

The recent global financial crisis and related sovereign debt crises in Ireland, Greece, Iceland, Puerto Rico and beyond have highlighted the pressing task of understanding how such crises reshape the spaces we live in. Geographers, most notably David Harvey, have traced the historical roots of the current crisis to the transformation of global financial capitalism since the 1970s. There has, however, been less work on understanding the nature and management of financial crises embedded in different historical geographies. This paper seeks to contribute to that task by investigating Newfoundland's sovereign debt crisis during the Great Depression and its management by the British Empire. Newfoundland, then an independent British Dominion, uniquely relinquished self‐government in return for financial aid. Managing the crisis required difficult ideological work. I argue that to reinforce an imperial geography underpinned by racial distinctions, and to preclude the possibility of default, Newfoundland was scripted as a racially degenerate place in need of metropolitan intervention. The financial crisis produced new racialised geographies that had significant effects on Newfoundland's future.
Top income shares inOECDcountries: The role of government ideology and globalisation
Authors: Dorn Florian , Schinke Christoph
Published: April 2018

This paper investigates how government ideology and globalisation are associated with top income shares in 17OECDcountries over the period 1970 to 2014. We use top income shares of the World Wealth and Income Database (WID). Globalisation is measured by theKOFindex of globalisation. Static and dynamic panel model results show that the top income shares increased more under right wing governments than under left wing governments. The ideology‐induced effect was stronger when globalisation proceeded more rapidly. Globalisation was positively correlated with income shares of the upper‐middle class (P99–P90), but negatively with income shares of the rich (top 1%) in the overall sample. We show that the relationship differs between Anglo‐Saxon countries and otherOECDcountries. Globalisation was more pro‐rich in Anglo‐Saxon countries than in otherOECDcountries. Government ideology does not turn out to have a statistically significant effect on top income shares in Anglo‐Saxon countries after the 1980s, whereas ideology‐induced differences in the distributional outcomes continued in otherOECDcountries.
Evaluation of the relationship between peripheral pulse palpation and Doppler systolic blood pressure in dogs presenting to an emergency service
Authors: Ateca Laura B. , Reineke Erica L. , Drobatz Kenneth J.
Published: April 2018

Objective

To assess the association between peripheral pulse palpation and Doppler‐derived systolic blood pressure (SBP) measurement in dogs presenting to an emergency service.

Design

Prospective observational study.

Setting

University veterinary teaching hospital.

Animals

Ninety‐three dogs that were presented to the emergency service. Dogs were eligible for inclusion in the study if a physical examination and a SBP measurement were performed prior to any interventions.

Interventions

None.

Measurements and Main Results

Both the femoral pulse quality and dorsal metatarsal pulse quality were digitally palpated and assessed as either strong, weak, or absent. The mean SBP in all dogs was 139 mm Hg (± 39 mm Hg). Seventeen (17/93; 18%) dogs were hypotensive with a SBP < 90 mm Hg (range, 40–88 mm Hg). The median SBP was not significantly different between dogs in the absent and present femoral pulse groups (P = 0.120) but the median SBP was significantly different between absent and present metatarsal pulse groups (P = 0.002). Dogs with absent metatarsal pulses were 7.6 times more likely to be hypotensive with a SBP < 90 mm Hg (OR, 7.6; 95% CI, 1.8–32) as compared to dogs with palpable metatarsal pulses. The sensitivity of absent metatarsal pulses to diagnose hypotension (SBP < 90 mm Hg) was 33% (95% CI, 10–65%) and the specificity was 94% (95% CI, 86–98%).

Conclusions

Absent metatarsal pulses are highly specific in the diagnosis of hypotension. However, dogs with palpable metatarsal pulses can still be hypotensive. Dorsal metatarsal pulse palpation is useful during triage assessment of dogs presenting to an emergency service, though it should not be used as the only indicator of a dog's cardiovascular stability and should not replace an actual blood pressure measurement.
Detection of intra‐cardiac thrombi and congestive heart failure in cats using computed tomographic angiography
Authors: Vititoe Kyle P. , Fries Ryan C. , Joslyn Stephen , Selmic Laura E. , Howes Mark , Vitt Jordan P. , O'Brien Robert T.
Published: April 2018

Arterial thromboembolism is a life‐threatening condition in cats most commonly secondary to cardiac disease. Echocardiography is the reference standard to evaluate for presence of a thrombus. In humans, computed tomographic (CT) angiography is becoming widely used to detect left atrial thrombi precluding the use of sedation. The purpose of this prospective, controlled, methods comparison pilot study was threefold: (1) describe new CT angiography protocol used in awake cats with cardiac disease and congestive heart failure; (2) determine accuracy of continuous and dynamic acquisition CT angiography to identify and characterize cardiac thrombi from spontaneous echocardiographic contrast using transthoracic echocardiography as our reference standard; (3) identify known negative prognostic factors and comorbidities of the thorax that CT angiography may provide that complement or supersede echocardiographic examination. Fourteen cats with heart disease were recruited; 7 with thrombi and 7 with spontaneous echocardiographic contrast. Echocardiography and awake CT angiography were performed using a microdose of contrast. Six of 7 thrombi were identified on CT angiography as filling defects by at least one reviewer within the left auricle (n = 6) and right heart (n = 1). Highest sensitivity (71.4%) was in continuous phase and highest specificity (85.7%) was in dynamic studies with fair to moderate interobserver agreement (0.38 and 0.44). CT angiography identified prognostic cardiac information (left atrial enlargement, congestive heart failure, arterial thromboembolism) and comorbidities (suspected idiopathic pulmonary fibrosis, asthma). This study indicates CT angiography can readily identify cardiac thrombi, important prognostic information and comorbidities, and can be safely performed in cats with cardiac disease and congestive heart failure.
Influence of fitness and age on the endothelial response to acute inflammation
Authors: Schroeder Elizabeth C. , Lane‐Cordova Abbi D. , Ranadive Sushant M. , Baynard Tracy , Fernhall Bo
Published: April 2018

New Findings

What is the central question of the study?

What are the effects of age and fitness on the vascular response to acute inflammation in younger and older adults?

What is the main finding and its importance?

In older adults, cardiorespiratory fitness level has a differential impact on endothelial function after acute inflammation. Compared with older adults with low fitness, older, moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications in support of the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors.

Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with ageing. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to induce acute inflammation. Blood pressure, flow‐mediated dilatation (FMD), augmentation index, carotid elastic modulus and inflammatory markers were measured before and 24 h after vaccination. Peak oxygen uptake was measured via a treadmill test. ‘Fit’ was defined as a peak oxygen uptake greater than the age‐ and sex‐determined 50th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (P < 0.05). The YA (low fit, from 11.5 ± 1.8 to 9.2 ± 1.3%; moderately fit, from 11.9 ± 0.8 to 9.0 ± 0.8%) and moderately fit OA (from 7.5 ± 1.0 to 3.9 ± 0.8%) had similar reductions in FMD at 24 h (P < 0.05). Low‐fit OA did not reduce FMD at 24 h (from 5.5 ± 0.4 to 5.2 ± 0.5%, P > 0.05). The reduction in FMD in YA was similar between fitness groups (P > 0.05). All groups had similar reductions in mean arterial pressure and increases in inflammatory markers. The augmentation index and carotid elastic modulus did not change during acute inflammation. In conclusion, in OA, higher fitness is associated with a greater decrease in endothelial function during acute inflammation, and this response is similar to that of young adults. This suggests that moderately fit OA may maintain vascular reactivity in response to stress, indicating preserved vascular function in moderately fit versus low‐fit OA.
Carbonic anhydrase is not a relevant nitrite reductase or nitrous anhydrase in the lung
Authors: Pickerodt Philipp A. , Kronfeldt Sebastian , Russ Martin , Gonzalez‐Lopez Adrian , Lother Philipp , Steiner Elvira , Vorbrodt Katja , Busch Thilo , Boemke Willehad , Francis Roland C. E. , Swenson Erik R.
Published: April 2018

Key points

Carbonic anhydrase (CA) inhibitors such as acetazolamide inhibit hypoxic pulmonary vasoconstriction (HPV) in humans and other mammals, but the mechanism of this action remains unknown.

It has been postulated that carbonic anhydrase may act as a nitrous anhydrase in vivo to generate nitric oxide (NO) from nitrite and that this formation is increased in the presence of acetazolamide.

Acetazolamide reduces HPV in pigs without evidence of any NO generation, whereas nebulized sodium nitrite reduces HPV by NO formation; however; combined infusion of acetazolamide with sodium nitrite inhalation did not further increase exhaled NO concentration over inhaled nitrite alone in pigs exposed to alveolar hypoxia.

We conclude that acetazolamide does not function as either a nitrous anhydrase or a nitrite reductase in the lungs of pigs, and probably other mammals, to explain its vasodilating actions in the pulmonary or systemic circulations.

The carbonic anhydrase (CA) inhibitors acetazolamide and its structurally similar analogue methazolamide prevent or reduce hypoxic pulmonary vasoconstriction (HPV) in dogs and humans in vivo, by a mechanism unrelated to CA inhibition. In rodent blood and isolated blood vessels, it has been reported that inhibition of CA leads to increased generation of nitric oxide (NO) from nitrite and vascular relaxation in vitro. We tested the physiological relevance of augmented NO generation by CA from nitrite with acetazolamide in anaesthetized pigs during alveolar hypoxia in vivo. We found that acetazolamide prevents HPV in anaesthetized pigs, as in other mammalian species. A single nebulization of sodium nitrite reduces HPV, but this action wanes in the succeeding 3 h of hypoxia as nitrite is metabolized and excreted. Pulmonary artery pressure reduction and NO formation as measured by exhaled gas concentration from inhaled sodium nitrite were not increased by acetazolamide during alveolar hypoxia. Thus, our data argue against a physiological role of carbonic anhydrase as a nitrous anhydrase or nitrite reductase as a mechanism for its inhibition of HPV in the lung and blood in vivo.
β1 subunit stabilises sodium channel Nav1.7 against mechanical stress
Authors: Körner Jannis , Meents Jannis , Machtens Jan‐Philipp , Lampert Angelika
Published: April 2018

Key points

The voltage‐gated sodium channel Nav1.7 is a key player in neuronal excitability and pain signalling. In addition to voltage sensing, the channel is also modulated by mechanical stress.

Using whole‐cell patch‐clamp experiments, we discovered that the sodium channel subunit β1 is able to prevent the impact of mechanical stress on Nav1.7.

An intramolecular disulfide bond of β1 was identified to be essential for stabilisation of inactivation, but not activation, against mechanical stress using molecular dynamics simulations, homology modelling and site‐directed mutagenesis.

Our results highlight the role of segment 6 of domain IV in fast inactivation.

We present a candidate mechanism for sodium channel stabilisation against mechanical stress, ensuring reliable channel functionality in living systems.

Voltage‐gated sodium channels are key players in neuronal excitability and pain signalling. Precise gating of these channels is crucial as even small functional alterations can lead to pathological phenotypes such as pain or heart failure. Mechanical stress has been shown to affect sodium channel activation and inactivation. This suggests that stabilising components are necessary to ensure precise channel gating in living organisms. Here, we show that mechanical shear stress affects voltage dependence of activation and fast inactivation of the Nav1.7 channel. Co‐expression of the β1 subunit, however, protects both gating modes of Nav1.7 against mechanical shear stress. Using molecular dynamics simulation, homology modelling and site‐directed mutagenesis, we identify an intramolecular disulfide bond of β1 (Cys21‐Cys43) which is partially involved in this process: the β1‐C43A mutant prevents mechanical modulation of voltage dependence of activation, but not of fast inactivation. Our data emphasise the unique role of segment 6 of domain IV for sodium channel fast inactivation and confirm previous reports that the intracellular process of fast inactivation can be modified by interfering with the extracellular end of segment 6 of domain IV. Thus, our data suggest that physiological gating of Nav1.7 may be protected against mechanical stress in a living organism by assembly with the β1 subunit.
Competencia social y ciudadana en las pruebas de diagnóstico general
Authors: Mayorga-Fernández María José , Gallardo-Gil Monsalud , Pérez-Gómez Ángel Ignacio
Published: April 2018

Ofrecemos un análisis de las pruebas de Evaluación General de Diagnóstico del Ministerio de Educación de España respecto a la competencia social y ciudadana. Es la primera vez que esta competencia se contempla en un programa de evaluación educativa. Nuestro objetivo es valorar si estas pruebas pueden ser consideradas herramientas útiles para evaluar el desarrollo de las capacidades cognitivas de segundo orden. Para este análisis se ha realizado un estudio cualitativo, fundamentado en el análisis de contenido interjueces y contraste con juicio de expertos. Los resultados muestran que las capacidades predominantes en estas pruebas son reproducción y comprensión-aplicación.
La percepción del conflicto escolar en tres comunidades de aprendizaje
Authors: Vizcarra-Morales María Teresa , Rekalde-Rodríguez Itziar , Macazaga-López Ana María
Published: April 2018

Esta investigación analiza la percepción del conflicto en tres comunidades de aprendizaje para explorar el significado que atribuyen al término conflicto y averiguar con qué escenarios asocian su aparición. La metodología reside en la perspectiva comunicativa crítica y las técnicas han sido los relatos y las entrevistas. Los resultados indican que el conflicto se considera un hecho natural que en ocasiones deriva en comportamientos agresivos y que hay espacios que facilitan su aparición. Las conclusiones reflejan la necesidad de contemplar la dinámica procesual del conflicto y ofrecer contextos educativos en los que experimentar y aprender a gestionar las emociones.
Characterization of Refractive Errors in a Population of Children from 2 to 14 Years of Age in Bogotá, Colombia*
Authors: Lince-Rivera Isabella , Camacho Flórez Gabriel Eduardo , Kunzel Gallo Alexa
Published: April 2018

Introduction: Refractive errors can have important repercussions in the performance of an individual, especially in the pediatric community. Objective: To determine the prevalence of refractive errors within a sample of 112 children between the ages of 2 and 14 from the Colegio La Candelaria in the city of Bogotá. Methods: Cross-sectional study that evaluated through visual acuity, ocular motility, ophthalmoscopy, retinoscopy, and subjective exam, the visual capacity of the children in question. Results: We found a prevalence of refractive errors of 18.8% where 13.4% represented astigmatism, 3.6% hypermetropia and 1.8% myopia. Discussion: These results were compared with those exposed on a thesis performed in 1973 by which patients with similar conditions were tested. In this study, the refractive errors were of 30.48%, a difference that can be explained by variations in population characteristics. Lastly, it arises the need of screening in other communities.
Terapia de remplazo nicotínico asociada con reducción gradual del consumo de cigarrillos como estrategia de cesación de tabaco. Reporte de caso
Authors: Becerra Martínez Nelci Astrid , García Padilla Pilar
Published: April 2018

El habitual proyecto de definir una fecha para dejar de fumar abruptamente ha sido refutado por muchos pacientes que han mostrado interés por reducir su consumo de modo gradual. La reducción progresiva utilizando terapia sustitutiva con nicotina previa a la cesación permitiría tratar a un mayor número de fumadores. El artículo presenta el caso de un paciente con alta dependencia a la nicotina, interesado en dejar de fumar, pero no de manera abrupta.
Gold nanoparticles functionalized with angiogenin-mimicking peptides modulate cell membrane interactions
Authors: Cucci Lorena M. , Munzone Alessia , Naletova Irina , Magrì Antonio , La Mendola Diego , Satriano Cristina
Published: April 2018

Angiogenin is a protein crucial in angiogenesis, and it is overexpressed in many cancers and downregulated in neurodegenerative diseases, respectively. The protein interaction with actin, through the loop encompassing the 60–68 residues, is an essential step in the cellular cytoskeleton reorganization. This, in turn, influences the cell proliferation and migration processes. In this work, hybrid nanoassemblies of gold nanoparticles with angiogenin fragments containing the 60–68 sequence were prepared and characterized in their interaction with both model membranes of supported lipid bilayers (SLBs) and cellular membranes of cancer (neuroblastoma) and normal (fibroblasts) cell lines. The comparison between physisorption and chemisorption mechanisms was performed by the parallel investigation of the 60–68 sequence and the peptide analogous containing an extra cysteine residue. Moreover, steric hindrance and charge effects were considered with a third analogous peptide sequence, conjugated with a fluorescent carboxyfluorescein (Fam) moiety. The hybrid nanobiointerface was characterized by means of ultraviolet-visible, atomic force microscopy and circular dichroism, to scrutinize plasmonic changes, nanoparticles coverage and conformational features, respectively. Lateral diffusion measurements on SLBs “perturbed” by the interaction with the gold nanoparticles-peptides point to a stronger membrane interaction in comparison with the uncoated nanoparticles. Cell viability and proliferation assays indicate a slight nanotoxicity in neuroblastoma cells and a proliferative activity in fibroblasts. The actin staining confirms different levels of interaction between the hybrid assemblies and the cell membranes.
Numerical analyses of nonlinear behavior of microbubble contrast agents in ultrasound field and effective parameters
Authors: Khalili Saber , Mahdi Miralam
Published: April 2018

This research aims to investigate the effects of some parameters on the nonlinear dynamics of an encapsulated microbubble. In the present study, the radial behavior of an encapsulated microbubble with modified Rayleigh-Plesset equation presented by Marmottant, van der Meer, Emmer, Versluis, de Jong, Hilgenfeldt, and Lohse [J. Acoust. Soc. Am. 118(6), 3499–3505 (2005)] is solved with matlab programming software. Radial dynamics of an individual microbubble for a free and coated state and effects of the added shell are also investigated. Results show that dilatational interfacial viscosity (ks) of the shell and changes of surface tension have significant effects on the amplitude of oscillations, bubble dynamics, and bubble surface velocity. Regarding the fact that the velocity of the bubble surface has a significant role in stability and collapse of the bubble, it can be noted that this velocity is reduced considerably by adding the shell. Because of extensive usage of nonlinear microbubble oscillations in medical imaging techniques, the nonlinear response of a lipid-coated contrast agent called “compression-only” behavior is studied and effective parameters on this behavior are investigated. The results of bubble radius excursion reveal the fact that excitation frequency, pressure, and dilatational interfacial viscosity of the bubble affect the compression-only behavior.
Genetic Diversity among Staphylococcus aureus Isolates Showing Oxacillin and/or Cefoxitin Resistance Not Linked to the Presence of
mec
Genes
Authors: Argudín M. Angeles , Roisin S. , Nienhaus L. , Dodémont M. , de Mendonça R. , Nonhoff C. , Deplano A. , Denis O.
Published: April 2018

Methicillin-resistant
Staphylococcus aureus
isolates lacking
mec
genes (
n
= 32), collected from Belgian hospitals, were characterized for their β-lactamase production and the presence of mutations in
pbp
genes, the
pbp4
promoter, and genes involved in penicillin-binding protein 4 overproduction (
gdpP
and
yjbH
). Twelve isolates were β-lactamase hyperproducers (BHPs), while 12 non-BHP isolates might produce an incomplete GdpP protein. Most isolates showed nucleotide missense mutations in
pbp
genes. A few isolates also showed mutations in the
pbp4
promoter.
Incomplete Downregulation of CD4 Expression Affects HIV-1 Env Conformation and Antibody-Dependent Cellular Cytotoxicity Responses
Authors: Prévost Jérémie , Richard Jonathan , Medjahed Halima , Alexander Audrey , Jones Jennifer , Kappes John C. , Ochsenbauer Christina , Finzi Andrés
Published: April 2018

HIV-1-infected cells expressing envelope glycoproteins (Env) in the CD4-bound conformation on their surfaces are targeted by antibody-dependent cellular cytotoxicity (ADCC) mediated by CD4-induced (CD4i) antibodies and sera from HIV-1-infected individuals (HIV+sera). By downregulating the surface expression of CD4, Nef prevents Env-CD4 interaction, thus protecting HIV-1-infected cells from ADCC. HIV-1 infectious molecular clones (IMCs) are widely used to measure ADCC. In order to facilitate the identification of infected cells and high-throughput ADCC analysis, reporter genes (e.g., theRenillaluciferase [LucR] gene) are often introduced into IMC constructs. We evaluated the susceptibility of HIV-1-infected CD4+T lymphocytes to ADCC using a panel of parental IMCs and derivatives that expressed the LucR reporter gene, utilizing different molecular strategies, including one specifically designed to retain Nef expression. We found that in some of these constructs, Nef expression in CD4+T cells was suboptimal, and consequently, CD4 downregulation was incomplete. CD4 molecules remaining on the cell surface resulted in the exposure of ADCC-mediating CD4i epitopes on Env and a dramatic increase in the susceptibility of the infected cells to ADCC. Strikingly, protection from ADCC was observed when cells were infected with the parental IMC, which exhibited strong CD4 downregulation. This discrepancy between the parental and Nef-impaired viruses was independent of the strains of Env expressed, but rather, it was correlated with the levels of CD4 surface expression. Overall, our results indicate that caution should be taken when selecting IMCs for ADCC measurements and that CD4 downregulation needs to be carefully monitored when drawing conclusions about the nature and magnitude of ADCC.

IMPORTANCEIn-depth understanding of the susceptibility of HIV-1-infected cells to ADCC might help establish correlates of vaccine protection and guide the development of HIV-1 vaccine strategies. Different ADCC assays have been developed, including those using infectious molecular clones (IMCs) carrying a LucR reporter gene that greatly facilitates large-scale quantitative analysis. We previously reported different molecular strategies for introducing LucR while maintaining Nef expression and function and, consequently, CD4 surface downregulation. Here, we demonstrate that utilizing IMCs that exhibit impaired Nef expression can have undesirable consequences due to incomplete CD4 downregulation. CD4 molecules remaining on the cell surface resulted in the exposure of ADCC-mediating CD4i epitopes on Env and a dramatic increase in the susceptibility of the infected cells to ADCC. Overall, our results indicate that CD4 downregulation needs to be carefully monitored when drawing conclusions about the nature and magnitude of ADCC.
Listeria monocytogenes Source Distribution Analysis Indicates Regional Heterogeneity and Ecological Niche Preference among Serotype 4b Clones
Authors: Lee Sangmi , Chen Yi , Gorski Lisa , Ward Todd J. , Osborne Jason , Kathariou Sophia
Published: April 2018

Biodiversity analysis of the foodborne pathogen
Listeria monocytogenes
recently revealed four serotype 4b major hypervirulent clonal complexes (CCs), i.e., CC1, CC2, CC4, and CC6. Hypervirulence was indicated by overrepresentation of these clones, and serotype 4b as a whole, among human clinical isolates in comparison to food. However, data on potential source-dependent partitioning among serotype 4b clones in diverse regions are sparse. We analyzed a panel of 347 serotype 4b isolates, primarily from North America, to determine the distribution of clones in humans, other animals, food, and water. CC1, CC2, CC4, and CC6 predominated, but surprisingly, only three clones, i.e., CC2 and the singleton sequence types (STs) ST382 and ST639, exhibited significant source-dependent associations, with higher propensity for food (CC2) or water (ST382 and ST639) than other sources. Pairwise comparisons between human and food isolates identified CC4 as the only serotype 4b clone significantly overrepresented among human isolates. Our analysis also revealed several serotype 4b clones emerging in North America. Two such emerging clones, ST382 (implicated in several outbreaks since 2014) and ST639, were primarily encountered among human and water isolates. Findings suggest that in spite of the ubiquity of CC1, CC2, CC4, and CC6, regional heterogeneity in serotype 4b is substantially larger than previously surmised. Analysis of even large strain panels from one region may not adequately predict clones unique to, and emerging in, other areas. Serotype 4b clonal complexes may differ in ecological niche preference, suggesting the need to further elucidate reservoirs and vehicles, especially for emerging clones.

IMPORTANCE
In
Listeria monocytogenes
, serotype 4b strains are leading contributors to human disease, but intraserotype distributions among different sources and regions remain poorly elucidated. Analysis of 347 serotype 4b isolates from four different sources, mostly from North America, confirmed the overall predominance of the major clones CC1, CC2, CC4, and CC6 but found that only CC4 was significantly associated with human disease, while CC2 was significantly associated with food. Remarkably, several emerging clones were identified among human isolates from North America, with some of these also exhibiting a propensity for surface water. The latter included the singleton clones ST382, implicated in several outbreaks in the United States since 2014, and ST639. These clones were noticeably underrepresented among much larger panels from other regions. Though associated with North America for the time being, they may eventually become globally disseminated through the food trade or other venues.
Determining the Specificity of Cascade Binding, Interference, and Primed Adaptation
In Vivo
in the
Escherichia coli
Type I-E CRISPR-Cas System
Authors: Cooper Lauren A. , Stringer Anne M. , Wade Joseph T.
Published: April 2018

In clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) immunity systems, short CRISPR RNAs (crRNAs) are bound by Cas proteins, and these complexes target invading nucleic acid molecules for degradation in a process known as interference. In type I CRISPR-Cas systems, the Cas protein complex that binds DNA is known as Cascade. Association of Cascade with target DNA can also lead to acquisition of new immunity elements in a process known as primed adaptation. Here, we assess the specificity determinants for Cascade-DNA interaction, interference, and primed adaptation
in vivo
, for the type I-E system of
Escherichia coli
. Remarkably, as few as 5 bp of crRNA-DNA are sufficient for association of Cascade with a DNA target. Consequently, a single crRNA promotes Cascade association with numerous off-target sites, and the endogenous
E. coli
crRNAs direct Cascade binding to >100 chromosomal sites. In contrast to the low specificity of Cascade-DNA interactions, >18 bp are required for both interference and primed adaptation. Hence, Cascade binding to suboptimal, off-target sites is inert. Our data support a model in which the initial Cascade association with DNA targets requires only limited sequence complementarity at the crRNA 5′ end whereas recruitment and/or activation of the Cas3 nuclease, a prerequisite for interference and primed adaptation, requires extensive base pairing.

IMPORTANCE
Many bacterial and archaeal species encode CRISPR-Cas immunity systems that protect against invasion by foreign DNA. In the
Escherichia coli
CRISPR-Cas system, a protein complex, Cascade, binds 61-nucleotide (nt) CRISPR RNAs (crRNAs). The Cascade complex is directed to invading DNA molecules through base pairing between the crRNA and target DNA. This leads to recruitment of the Cas3 nuclease, which destroys the invading DNA molecule and promotes acquisition of new immunity elements. We made the first
in vivo
measurements of Cascade binding to DNA targets. Thus, we show that Cascade binding to DNA is highly promiscuous; endogenous
E. coli
crRNAs can direct Cascade binding to >100 chromosomal locations. In contrast, we show that targeted degradation and acquisition of new immunity elements require highly specific association of Cascade with DNA, limiting CRISPR-Cas function to the appropriate targets.
Gender and survival from out-of-hospital cardiac arrest: a New Zealand registry study
Authors: Dicker Bridget , Conaglen Kate , Howie Graham
Published: April 2018

Objective

To determine the relationships between survival from all-cause out-of-hospital cardiac arrest (OHCA) and gender in New Zealand.

Methods

A retrospective observational study was conducted using data compliant with the Utstein guidelines from the St John New Zealand OHCA Registry for adult patients who were treated for an OHCA between 1 October 2013 and 30 September 2015. Univariate logistic regression was used to investigate factors associated with return of spontaneous circulation sustained to handover at hospital and survival to 30 days. Multivariate logistic regression models were used to investigate outcome differences in survival according to gender at 30 days postevent.

Results

Women survived to hospital handover in 29% of cases, which was not significantly different from men (31%). When adjusted for age, location, aetiology, initial rhythm and witnessed status, there was no significant difference in 30-day survival between men (16%) and women (13%) (adjusted OR 1.22, 95% CI (0.96 to 1.55), p=0.11).

Conclusion

No statistical differences were found in 30-day survival between genders when adjustments for unfavourable Utstein variables were accounted for.
CM-Score: a validated scoring system to predict CDKN2A germline mutations in melanoma families from Northern Europe
Authors: Potjer Thomas P , Helgadottir Hildur , Leenheer Mirjam , van der Stoep Nienke , Gruis Nelleke A , Höiom Veronica , Olsson Håkan , van Doorn Remco , Vasen Hans F A , van Asperen Christi J , Dekkers Olaf M , Hes Frederik J
Published: April 2018

Background

Several factors have been reported that influence the probability of a germline CDKN2A mutation in a melanoma family. Our goal was to create a scoring system to estimate this probability, based on a set of clinical features present in the patient and his or her family.

Methods

Five clinical features and their association with CDKN2A mutations were investigated in a training cohort of 1227 Dutch melanoma families (13.7% with CDKN2A mutation) using multivariate logistic regression. Predefined features included number of family members with melanoma and with multiple primary melanomas, median age at diagnosis and presence of pancreatic cancer or upper airway cancer in a family member. Based on these five features, a scoring system (CDKN2A Mutation(CM)-Score) was developed and subsequently validated in a combined Swedish and Dutch familial melanoma cohort (n=421 families; 9.0% with CDKN2A mutation).

Results

All five features were significantly associated (p<0.05) with a CDKN2A mutation. At a CM-Score of 16 out of 49 possible points, the threshold of 10% mutation probability is approximated (9.9%; 95% CI 9.8 to 10.1). This probability further increased to >90% for families with ≥36 points. A CM-Score under 16 points was associated with a low mutation probability (≤4%). CM-Score performed well in both the training cohort (area under the curve (AUC) 0.89; 95% CI 0.86 to 0.92) and the external validation cohort (AUC 0.94; 95% CI 0.90 to 0.98).

Conclusion

We developed a practical scoring system to predict CDKN2A mutation status among melanoma-prone families. We suggest that CDKN2A analysis should be recommended to families with a CM-Score of ≥16 points.
Mutations in plasmalemma vesicle-associated protein cause severe syndromic protein-losing enteropathy
Authors: Broekaert Ilse Julia , Becker Kerstin , Gottschalk Ingo , Körber Friederike , Dötsch Jörg , Thiele Holger , Altmüller Janine , Nürnberg Peter , Hünseler Christoph , Cirak Sebahattin
Published: April 2018

Background

Protein-losing enteropathy (PLE) is characterised by gastrointestinal protein leakage due to loss of mucosal integrity or lymphatic abnormalities. PLE can manifest as congenital diarrhoea and should be differentiated from other congenital diarrhoeal disorders. Primary PLEs are genetically heterogeneous and the underlying genetic defects are currently emerging.

Objectives

We report an infant with fatal PLE for whom we aimed to uncover the underlying pathogenic mutation.

Methods

We performed whole exome sequencing (WES) for the index patient. Variants were classified based on the American College of Medical Genetics and Genomics guidelines. WES results and our detailed clinical description of the patient were compared with the literature.

Results

We discovered a novel homozygous stop mutation (c.988C>T, p.Q330*) in the Plasmalemma Vesicle-Associated Protein (PLVAP) gene in a newborn with fatal PLE, facial dysmorphism, and renal, ocular and cardiac anomalies. The Q330* mutation is predicted to result in complete loss of PLVAP protein expression leading to deletion of the diaphragms of endothelial fenestrae, resulting in plasma protein extravasation and PLE. Recently, another single homozygous stop mutation in PLVAP causing lethal PLE in an infant was reported.

Conclusions

Our findings validate PLVAP mutations as a cause of syndromic PLE. Prenatal anomalies, severe PLE and syndromic features may guide the diagnosis of this rare disease.
Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations
Authors: Kinney Michael O , Morrow James , Patterson Chris C , Campbell Ellen , Russell Aline , Smithson Henry W , Parsons Linda , Morrison Patrick J , Bromley Rebecca , Liggan Brenda , Delanty Norman , Irwin Beth , Hunt Stephen J , Craig John J
Published: April 2018

Objectives

After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time.

Methods

The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates.

Results

Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08).

Conclusion

Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes.
The Minimum Cost Flow Problem of Uncertain Random Network
Authors: Abdi Soheila , Baroughi Fahimeh , Alizadeh Behrooz
Published: April 2018

The aim of this paper is to present a novel method for solving the minimum cost flow problem on networks with uncertain-random capacities and costs. The objective function of this problem is an uncertain random variable and the constraints of the problem do not make a deterministic feasible set. Under the framework of uncertain random programming, a corresponding [Formula: see text]-minimum cost flow model with a prespecified confidence level [Formula: see text], is formulated and its main properties are analyzed. It is proven that there exists an equivalence relationship between this model and the classical deterministic minimum cost flow model. Then an algorithm is proposed to find the maximum amount of [Formula: see text] such that for it, the feasible set of [Formula: see text]-minimum cost flow model is nonempty. Finally, a numerical example is presented to illustrate the efficiency of our proposed method.