bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of obesity and obesity‐related conditions with carotid extra‐medial thickness in children and adolescents
Authors: Bekdas M. , Kaya E. , Dagistan E. , Goksugur S. B. , Demircioglu F. , Erkocoglu M. , Dilek M.
Published: December 2015

Background

Carotid extra‐medial thickness (EMT) and carotid intima‐media thickness (cIMT) provide information concerning vascular changes.

Objectives

In this study, we aimed to evaluate the association between carotid EMT and obesity and its metabolic complications in children.

Methods

The study included 38 obese subjects and 30 age‐matched and sex‐matched healthy controls aged between 7 and 17 years. For all subjects, complete blood count, fasting blood glucose, serum insulin, aspartate aminotransferase, alanine aminotransferase, HDL cholesterol, total cholesterol and triglyceride levels were measured. The carotid EMT and cIMT were measured by an expert radiologist in all patients.

Results

Body mass index (BMI) (28.8 ± 3 vs. 18.1 ± 2.2, p < 0.001), total cholesterol (167.9 ± 34.8 mg dL−1 vs. 150.5 ± 28.1 mg dL−1, p = 0.029), homeostatic model assessment of insulin resistance (HOMA‐IR) (4.3 vs. 1.7, p < 0.001), cIMT (0.51 ± 0.08 mm vs. 0.45 ± 0.06 mm, p < 0.001) and carotid EMT (0.74 ± 0.11 mm vs. 0.64 ± 0.1 mm, p < 0.001) were significantly higher in obese subjects than in controls, while HDL cholesterol (41.6 ± 6.5 mg dL−1 vs. 49.5 ± 7.5 mg dL−1, p < 0.001) was lower in obesity group. Among the obese subjects, the HOMA‐IR values (4.7 vs. 3.6, p = 0.027), cIMT (0.54 ± 0.07 mm vs. 0.49 ± 0.07 mm, p = 0.039) and carotid EMT (0.79 ± 0.1 mm vs. 0.7 ± 0.1 mm, p = 0.013) were significantly higher in post‐pubertal children compared with prepubertal children. BMI, cut‐off values of HOMA‐IR and cIMT were significantly associated with increased carotid EMT (p < 0.001, p = 0.023 and p < 0.001, respectively). The only independent risk factor affecting carotid EMT was BMI (p < 0.001).

Conclusion

We have found that carotid EMT is associated with cIMT, obesity and insulin resistance and the assessment of carotid EMT may provide additional information concerning early vascular disease.
Vois‐Tu Le Kem? Do You See the Bos? Foreign Word Learning at 14 Months
Authors: da Estrela Chelsea , Byers‐Heinlein Krista
Published: December 2015

How easily can infants regularly exposed to only one language begin to acquire a second one? In three experiments, we tested 14‐month‐old English and French monolingual infants’ ability to learn words presented in foreign language sentence frames. Infants were trained on two novel word‐object pairings and then tested using a preferential looking task. Word forms were phonetically and phonotactically legal in both languages, and cross‐spliced across conditions, so only the sentence frames established the word as native or foreign. In Experiment 1, infants were taught one native and one foreign word and successfully learned both. In Experiment 2 and 3, infants were taught two foreign words, but only showed successful learning of the first word they encountered. These results demonstrate that infants can successfully learn words embedded in foreign language sentences, but this is more challenging than native word learning. More broadly, they show that the sentential context of a novel word, and not just the word form itself, influences infants’ early word learning.
Efficacy of a self‐help manual in increasing resilience in carers of adults with depression in Thailand
Authors: McCann Terence V. , Songprakun Wallapa , Stephenson John
Published: December 2015

Caring for a person with a mental illness can have adverse effects on caregivers; however, little is known about how best to help such caregivers. The aim of the present study was to examine the efficacy of a cognitive behaviour therapy‐guided self‐help manual in increasing resilience in caregivers of individuals with depression, in comparison to caregivers who receive routine support only. A randomized, controlled trial was conducted, following CONSORT guidelines, with 54 caregivers allocated to parallel intervention (self‐help manual) (n = 27) or control (standard support) (n = 27) groups. Resilience was assessed at baseline, post‐test (week 8), and follow up (week 12). Intention‐to‐treat analyses were undertaken. Repeated‐measures ANOVA indicated a significant difference in resilience scores between the three time points, showing a large effect. Pairwise comparisons between intervention and control groups indicated resilience to be significantly different between baseline and post‐test, and between baseline and follow up, but not between post‐test and follow up. Overall, the intervention group showed a slightly greater increase in resilience over time than the control group; however, the time–group interaction was not significant. Guided self‐help is helpful in improving caregivers’ resilience and could be used as an adjunct to the limited support provided to carers by mental health nurses and other clinicians.
Divorce in sub‐Saharan Africa: Are Unions Becoming Less Stable?
Authors: Clark Shelley , Brauner‐Otto Sarah
Published: December 2015

Divorce is one of the main drivers of family instability in sub‐Saharan Africa. Using data from 101 Demographic and Health Surveys and novel estimation techniques, we 1) provide the first systematic estimates of divorce across 33 countries; 2) assess trends in divorce in 20 countries; and 3) investigate the key country‐level correlates of divorce both across and within countries. Despite considerable geographic variation, our estimates show that divorce is common in most countries. Contrary to expectations, however, we find no evidence that divorce is increasing. Instead, divorce has been either stable or declining in recent decades. We show that socioeconomic factors associated with industrialization have countervailing effects on divorce. Urbanization and female employment are associated with higher levels of divorce, while age at first marriage and female education correspond to lower rates. These findings have implications for current and future family dynamics in sub‐Saharan Africa.
Closing a Sociodemographic Chapter of Chinese History
Authors: Zhao Zhongwei
Published: December 2015

At its recent Fifth Plenary Session held in Beijing, the Eighteenth Central Committee of the Communist Party of China decided to abolish the one‐child policy and allow all couples to have two children, thus closing an important chapter of China's social and demographic history. Recent fertility trends make it clear why it is urgent to abandon this policy. Census and survey data show that China's TFR had already fallen below replacement in 1991. Since the mid‐1990s, TFRs in most years have been lower than 1.5 children per woman. Since 2010, even lower fertility rates have been recorded by the annual population change surveys. Since the mid‐1990s, fertility decline has been increasingly driven by generalized ideational changes resulting from the social, economic, and cultural transformation of recent decades. In recent years many couples who were entitled to have a second child have chosen not to do so. For this reason, the termination of the one‐child policy is unlikely to lead to a major upturn in fertility, but rather to the continuation of a low‐fertility regime with more diverse fertility patterns across different sub‐populations, a pattern that has been observed in many countries.
CD200 increases alternatively activated macrophages through cAMP‐response element binding protein – C/EBP‐beta signaling
Authors: Hayakawa Kazuhide , Wang Xiaohua , Lo Eng H.
Published: December 2015

The concept of macrophage polarization toward different phenotypes after CNS injury has been increasingly discussed. Here, we propose that CD200 treatment may help shift pro‐inflammatory macrophages to an arginase 1 (Arg1)‐, transglutaminase 2 (TGM2)‐, and transforming growth factor beta 1 (TGF‐β)‐positive phenotype. Rat macrophages were stimulated by interferon γ and lipopolysaccharide (LPS) to induce pro‐inflammatory phenotypes. Treatment with human CD200‐Fc up‐regulated expression levels of alternatively activated M2‐like markers such as Arg1 and TGM2 but suppressed pro‐inflammatory M1‐like markers such as toll‐like receptor 4, interleukin 1 beta (IL‐1β), IL‐6, and GM‐CSF. Concomitantly, CD200‐Fc enhanced (CCAAT/enhancer‐binding protein) C/EBP‐beta promoter activity, whereas NF‐κB activity was suppressed. Treatment with CD200‐Fc also up‐regulated potentially beneficial TGF‐β expression in macrophages. When C/EBP‐beta signaling was suppressed with siRNA, the effect of CD200‐Fc on Arg1, TGM2 and TGF‐β up‐regulation was canceled. Taken together, these data provide proof‐of‐principle that targeting CD200 signaling may be a novel therapeutic approach to shift macrophages toward M2‐like polarization via modulating cAMP‐response element binding protein‐C/EBP‐beta transcriptional activity.

image

We showed that CD200 treatment decreased pro‐inflammatory cytokines (IL‐1β, IL‐6, and GM‐CSF) along with suppressed inflammatory NF‐κB activity in pro‐inflammatory Mφ. On the other hand, CD200 increased Arg1, TGM2, and TGF‐β production through CREB‐C/EBPβ signaling. We think that these findings provide proof‐of‐concept that CD200 signaling may play a key role in regulating macrophage polarization toward anti‐inflammatory phenotypes.
Occurrence of 16SrIV Subgroup A Phytoplasmas in Roystonea regia and Acrocomia mexicana Palms with Lethal Yellowing‐like Syndromes in Yucatán, Mexico
Authors: Narvaez María , Córdova‐Lara Iván , Reyes‐Martínez Celso , Puch‐Hau Carlos , Mota‐Narvaez Luis , Collí Ana , Caamal Goretti , Harrison Nigel , Sáenz Luis , Oropeza Carlos
Published: December 2015

The lethal yellowing (LY) disease and LY‐type syndromes affecting several palm species are associated with 16SrIV phytoplasmas in the Americas. In Mexico, palms of the species Roystonea regia and the native Acrocomia mexicana were found to exhibit LY‐type symptoms, including leaf decay, starting with mature leaves, necrosis and atrophy of inflorescences. DNA extracts obtained from these palms could be amplified by nested‐PCR using phytoplasma‐universal primer pair P1/P7 followed by LY‐group‐specific primer pair LY16Sr/LY16Sf. Blast analysis of the sequences obtained revealed an identity of 100% for R. regia and 99.27% for A. mexicana with 16SrIV‐A strain associated with LY in Florida, USA (Acc. AF498309). Computer‐simulated RFLP analysis showed that the patterns for the phytoplasma DNA of the two palm species were highly similar to that for 16SrIV subgroup A strain. A neighbour‐joining tree was constructed, and the sequences of the two palm species clustered in the same clade of group 16SrIV subgroup A. The results therefore support that LY‐type syndromes observed in palms of R. regia and A. mexicana in the Yucatan region of Mexico are associated with 16SrIV subgroup A phytoplasmas.
Effect of dietary fibres on small intestine histomorphology and lipid metabolism in young broiler chickens
Authors: Rahmatnejad E. , Saki A. A.
Published: December 2015

Two experiments were conducted to determine the influence of dietary fibres on small intestine histomorphology and lipid metabolism in broilers from 1 to 21 day of age. In experiment 1, diets containing insoluble [cellulose (CEL); 2% and 4%] or soluble [carboxymethyl cellulose (CMC); 2% and 4%] fibre were fed to broilers from day 1 to 21 post‐hatch and ileal tissue was collected at day 21 of age for histological evaluation. In experiment 2, broilers diet was supplemented with 0%, 1% or 2% insoluble fibre (Arbocel) during day 7 to 21 post‐hatch and plasma and liver lipid metabolism were evaluated at day 21. In experiment 1, inclusion of CMC reduced body weight gain (BWG) and feed intake (FI) and increased feed conversion ratio (FCR) compared with others. Intestinal histomorphology was unaffected by CEL, but CMC led to an increase in crypt depth (CD) and serosa thickness and a decrease in villus height (VH), villus width (VW), VH:CD ratio and villus surface area (VSA), rather than control and CEL groups. Treatment did not affect goblet cell type. Moreover, the CMC‐fed birds had greater total goblet cell count (GCC) as compared with others. In experiment 2, fibre inclusion was associated with increases in BWG from 7 to 14 day of age and an improvement in FCR, whereas FI was not influenced by treatments. Inclusion of fibre in the diet decreased the weight of the abdominal fat and cholesterol concentrations of liver and plasma. No significant effects on fatty acid composition of liver lipid were observed by fibre supplementation. These findings suggest dietary fibre affects performance, intestinal histomorphology and lipid metabolism in young chicks, which may directly affect poultry feeding strategies.
Carbon regulation of environmental pH by secreted small molecules that modulate pathogenicity in phytopathogenic fungi
Authors: Bi Fangcheng , Barad Shiri , Ment Dana , Luria Neta , Dubey Amit , Casado Virginia , Glam Nofar , Mínguez Jose Diaz , Espeso Eduardo A. , Fluhr Robert , Prusky Dov
Published: December 2015

Fruit pathogens can contribute to the acidification or alkalinization of the host environment. This capability has been used to divide fungal pathogens into acidifying and/or alkalinizing classes. Here, we show that diverse classes of fungal pathogens—Colletotrichum gloeosporioides, Penicillium expansum, Aspergillus nidulans and Fusarium oxysporum—secrete small pH‐affecting molecules. These molecules modify the environmental pH, which dictates acidic or alkaline colonizing strategies, and induce the expression of PACC‐dependent genes. We show that, in many organisms, acidification is induced under carbon excess, i.e. 175 mm sucrose (the most abundant sugar in fruits). In contrast, alkalinization occurs under conditions of carbon deprivation, i.e. less than 15 mm sucrose. The carbon source is metabolized by glucose oxidase (gox2) to gluconic acid, contributing to medium acidification, whereas catalysed deamination of non‐preferred carbon sources, such as the amino acid glutamate, by glutamate dehydrogenase 2 (gdh2), results in the secretion of ammonia. Functional analyses of Δgdh2 mutants showed reduced alkalinization and pathogenicity during growth under carbon deprivation, but not in high‐carbon medium or on fruit rich in sugar, whereas analysis of Δgox2 mutants showed reduced acidification and pathogencity under conditions of excess carbon. The induction pattern of gdh2 was negatively correlated with the expression of the zinc finger global carbon catabolite repressor creA. The present results indicate that differential pH modulation by fruit fungal pathogens is a host‐dependent mechanism, affected by host sugar content, that modulates environmental pH to enhance fruit colonization.
Identification of signature volatiles to discriminate Candida albicans, glabrata, krusei and tropicalis using gas chromatography and mass spectrometry
Authors: Hertel Moritz , Hartwig Stefan , Schütte Eyke , Gillissen Bernhard , Preissner Robert , Schmidt‐Westhausen Andrea Maria , Paris Sebastian , Kastner Isabell , Preissner Saskia
Published: December 2015

Oral candidiasis is the most frequent fungal infection of the oral cavity. Clinical diagnoses require mycological confirmation, which is time‐consuming in case of culture testing. The aim of the study was to identify signature volatiles to develop a chairside breath test to diagnose oral candidiasis. Headspaces above Candida albicans, glabrata, tropicalis, krusei cultures, and growth media as control were analysed after eight and 24 h using offline gas chromatography and mass spectrometry. The identification of signature volatiles was assisted using various microbial databases. Retrieved volatile patterns enabled Candida species discrimination in vitro. For C. albicans 3‐methyl‐2‐butanone and styrene and for C. krusei a combination of p‐xylene, 2‐octanone, 2‐heptanone and n‐butyl acetate were found to be specific. 1‐hexanol was found in C. tropicalis, but is emitted by a variety of other microorganisms. C. glabrata was characterised through the absence of these volatiles. The development of a breath test is a promising approach in confirming suspicions of oral candidiasis. To confirm the retrieved results in vivo, breath tests in affected and healthy subjects have to be performed.
Taylor's law and related allometric power laws in New Zealand mountain beech forests: the roles of space, time and environment
Authors: Cohen Joel E. , Lai Jiangshan , Coomes David A. , Allen Robert B.
Published: December 2015

Taylor's law says that the variance of population density of a species is proportional to a power of mean population density. Density–mass allometry says that mean population density is proportional to a power of mean biomass per individual. These power laws predict a third, variance–mass allometry: the variance of population density of a species is proportional to a power of mean biomass per individual. We tested these laws using 10 censuses of New Zealand mountain beech trees in 250 plots over 30 years at spatial scales from 5 m to kilometers. We found that: 1) a single‐species forest not disrupted by humans obeyed all three laws; 2) random sampling explained the parameters of Taylor's law at a large spatial scale in 8 of 10 censuses, but not at a fine spatial scale; 3) larger spatial scale increased the exponent of Taylor's law and decreased the exponent of variance–mass allometry (this is the first empirical demonstration that the latter exponent depends on spatial scale), but affected the exponent of density–mass allometry slightly; 4) despite varying natural disturbance, the three laws varied relatively little over the 30 years; 5) self‐thinning and recruiting plots had significantly different intercepts and slopes of density–mass allometry and variance–mass allometry, but the parameters of Taylor's law were not usually significantly affected; and 6) higher soil calcium was associated with higher variance of population density in all censuses but not with a difference in the exponent of Taylor's law, while elevation above sea level and soil carbon‐to‐nitrogen ratios had little effect on the parameters of Taylor's law. In general, the three laws were remarkably robust. When their parameters were influenced by spatial scale and environmental factors, the parameters could not be species‐specific indicators. We suggest biological mechanisms that may explain some of these findings.
Differential induction of plant chemical defenses by parasitized and unparasitized herbivores: consequences for reciprocal, multitrophic interactions
Authors: Ode Paul J. , Harvey Jeffrey A. , Reichelt Michael , Gershenzon Jonathan , Gols Rieta
Published: December 2015

Insect parasitoids can play ecologically important roles in virtually all terrestrial plant–insect herbivore interactions, yet whether parasitoids alter the defensive traits that underlie interactions between plants and their herbivores remains a largely unexplored question. Here, we examined the reciprocal trophic interactions among populations of the wild cabbage Brassica oleracea that vary greatly in their production of defensive secondary compounds – glucosinolates (GSs), a generalist herbivore, Trichoplusia ni, and its polyembryonic parasitoid Copidosoma floridanum. In a greenhouse environment, plants were exposed to either healthy (unparasitized), parasitized, or no herbivores. Feeding damage by herbivores induced higher levels of the indole GSs, glucobrassicin and neoglucobrassicin, but not any of the other measured GSs. Herbivores parasitized by C. floridanum induced cabbage plants to produce 1.5 times more indole GSs than levels induced by healthy T. ni and five times more than uninduced plants. As a gregarious endoparasitoid, C. floridanum causes its host T. ni to feed more than unparasitized herbivores resulting in increased induction of indole GSs. In turn, herbivore fitness parameters (including differential effects on male and female contributions to lifetime fecundity in the herbivore) were negatively correlated with the aliphatic GSs, sinigrin and gluconapin, whereas parasitoid fitness parameters were negatively correlated with the indole GSs, glucobrassicin and neoglucobrassicin. That herbivores and their parasitoids appear to be affected by different sets of GSs was unexpected given the intimate developmental associations between host and parasitoid. This study is the first to demonstrate that parasitoids, through increasing feeding by their herbivorous hosts, can induce higher levels of non‐volatile plant chemical defenses. While parasitoids are widely recognized to be ubiquitous in most terrestrial insect herbivore communities, their role in influencing plant–insect herbivore relationships is still vastly underappreciated.
Xpert MTB/Rif for the diagnosis of extrapulmonary tuberculosis – an experience from a tertiary care centre in South India
Authors: Suzana Shirly , Ninan Marilyn M. , Gowri Mahasampath , Venkatesh Krishnan , Rupali Priscilla , Michael Joy S.
Published: December 2015

Objective

The Xpert MTB/Rif, with a detection limit of 131 CFU/ml, plays a valuable role in the diagnosis of extrapulmonary tuberculosis, both susceptible and resistant. This study aims at evaluating the Xpert MTB/Rif for the same, at a tertiary care centre in south India, assessing it against both culture and a composite gold standard (CGS).

Methods

We tested consecutive samples from patients suspected of extrapulmonary tuberculosis with Xpert MTB/Rif, evaluated its sensitivity and specificity against solid and/or liquid culture and CGS. An individual analysis of different sample types (tissue biopsies, fluids, pus, lymph node biopsies and CSF) given an adequate sample size, against both culture and CGS, was also performed.

Results

In total, 494 samples were analysed against culture. Compared to culture, the sensitivity of Xpert MTB/Rif was 89% (95% CI 0.81–0.94) and its specificity was 74% (95% CI 0.70–0.78). When Xpert MTB/Rif was compared to the CGS, pooled sensitivity was 62% (95% CI 0.56–0.67) and specificity was 100% (95% CI 0.91–1.00).

Conclusion

This assay performs better than the currently available conventional laboratory methods. The rapidity with which results are obtained is an added advantage, and its integration into a routine diagnostic protocol must be considered.
Class I and II HLA antibodies in pediatric patients with thalassemia major
Authors: Yee Marianne E. McPherson , Shah Ankoor , Anderson Alan R. , Boudreaux Jeanne , Bray Robert A. , Gebel Howard M. , Josephson Cassandra D.
Published: December 2015

BACKGROUND

HLA alloimmunization is a potential complication of red blood cell (RBC) transfusion with detrimental consequences for future organ or hematopoietic stem cell transplantation.

STUDY DESIGN AND METHODS

The study aimed to determine the prevalence and specificity of HLA antibodies among pediatric patients with thalassemia major (TM) and antibody changes over time while on leukoreduced chronic transfusion therapy. HLA antibodies were measured at two or more time points in children and young adults ages 3 to 21 years with TM. HLA Class I and II antibodies were measured by FlowPRA screening. Positive screening assays were confirmed with LabScreen single‐antigen bead assays for antibody specificity.

RESULTS

HLA antibodies were detected in 10 of 19 (53%) subjects: seven of 19 (37%) with HLA Class I and II antibodies, two of 19 (11%) with only HLA Class I antibodies, and one of 19 (5%) with only HLA Class II antibodies. Subjects with HLA antibodies were older (14.6 years vs. 7.1 years, p = 0.05), predominantly male (80%), and more likely to have a remote history of nonleukoreduced transfusions (p = 0.057). Median time between testing was 3.7 years. De novo HLA antibodies were detected in two of 11 patients who initially had negative panel‐reactive antibody screens, while one subject lost detection of Class II antibody. Two of seven patients with HLA antibodies had antibodies to self‐HLA.

CONCLUSION

HLA antibodies have a high prevalence in TM patients and may be associated with nonleukoreduced transfusions and older age. For such patients, antibody identification will be useful if subsequent organ or stem cell transplantation is needed.
On -invariants attached to cyclic cubic number fields
Authors: Delbourgo Daniel , Chao Qin
Published: December 2015

We describe an algorithm for finding the coefficients of $F(X)$ modulo powers of $p$, where $p\neq 2$ is a prime number and $F(X)$ is the power series associated to the zeta function of Kubota and Leopoldt. We next calculate the 5-adic and 7-adic ${\it\lambda}$-invariants attached to those cubic extensions $K/\mathbb{Q}$ with cyclic Galois group ${\mathcal{A}}_{3}$ (up to field discriminant ${<}10^{7}$), and also tabulate the class number of $K(e^{2{\it\pi}i/p})$ for $p=5$ and $p=7$. If the ${\it\lambda}$-invariant is greater than zero, we then determine all the zeros for the corresponding branches of the $p$-adic $L$-function and deduce ${\rm\Lambda}$-monogeneity for the class group tower over the cyclotomic $\mathbb{Z}_{p}$-extension of $K$.

Supplementary materials are available with this article.
Application of Artificial Neural Network–Particle Swarm Optimization Algorithm for Prediction of Gas Condensate Dew Point Pressure and Comparison With Gaussian Processes Regression–Particle Swarm Optimization Algorithm
Authors: Khaksar Manshad Abbas , Rostami Habib , Moein Hosseini Seyed , Rezaei Hojjat
Published: December 2015

For gas condensate reservoirs, as the reservoir pressure drops below the dew point pressure (DPP), a large amount of valuable condensate drops out and remains in the reservoir. Thus, prediction of accurate values for DPP is important and leads to successful development of gas condensate reservoirs. There are some experimental methods such as constant composition expansion (CCE) and constant volume depletion (CVD) for DPP measurement but difficulties in experimental measurement especially for lean retrograde gas condensate causes to develop of different empirical correlations and equations of state for DPP calculation. Equations of state and empirical correlations are developed for special and limited data sets and for unseen data sets they are not generalizable. To mitigate this problem, in this paper we developed new artificial neural network optimized by particle swarm optimization (ANN-PSO) for DPP prediction. Reservoir fluid composition, temperature and characteristics of the C7+ considered as input parameters to neural network and DPP as target parameter. Comparing results of the developed model in this research with Gaussian processes regression by particle swarm optimization (GPR-PSO), previous models and correlations shows that the predictive model is accurate and is generalizable to new unseen data sets.
The Effect of Viscosity on Low Concentration Particle Transport in Single-Phase (Liquid) Horizontal Pipes
Authors: Najmi Kamyar , McLaury Brenton S. , Shirazi Siamack A. , Cremaschi Selen
Published: December 2015

Particle transport has been an active area of research for many years. Despite many excellent experimental and modeling studies contributing to the fundamental understanding of particle transport, the effect of viscosity is still not well-understood. There are limited experimental studies addressing the effect of viscosity on particle transport. Even among those limited studies, contradictory conclusions have been reported in the literature. A review of the single-phase proposed models also reveals that fluid viscosity has not been well addressed in the models as well. The main focus of this study is to investigate the effect of viscosity on particle transport in laminar and turbulent flows. Experiments were performed using a 0.05 m diameter pipe. Comparisons of the obtained data with previously reported data in the literature show similar characteristics. The current study finds that liquid flow regime in the pipe plays an important role on how viscosity affects the particle transport phenomenon. Discussions presented in this work to explain the obtained experimental data shed light on this less addressed physical parameter.
Recent experimental advances on hydrophobic interactions at solid/water and fluid/water interfaces
Authors: Zeng Hongbo , Shi Chen , Huang Jun , Li Lin , Liu Guangyi , Zhong Hong
Published: December 2015

Hydrophobic effects play important roles in a wide range of natural phenomena and engineering processes such as coalescence of oil droplets in water, air flotation of mineral particles, and folding and assembly of proteins and biomembranes. In this work, the authors highlight recent experimental attempts to reveal the physical origin of hydrophobic effects by directly quantifying the hydrophobic interaction on both solid/water and fluid/water interfaces using state-of-art nanomechanical techniques such as surface forces apparatus and atomic force microscopy (AFM). For solid hydrophobic surfaces of different hydrophobicity, the range of hydrophobic interaction was reported to vary from ∼10 to >100 nm. With various characterization techniques, the very long-ranged attraction (>100 nm) has been demonstrated to be mainly attributed to nonhydrophobic interaction mechanisms such as pre-existing nanobubbles and molecular rearrangement. By ruling out these factors, intrinsic hydrophobic interaction was measured to follow an exponential law with decay length of 1–2 nm with effective range less than 20 nm. On the other hand, hydrophobic interaction measured at fluid interfaces using AFM droplet/bubble probe technique was found to decay with a much shorter length of ∼0.3 nm. This discrepancy of measured decay lengths is proposed to be attributed to inherent physical distinction between solid and fluid interfaces, which impacts the structure of interface-adjacent water molecules. Direct measurement of hydrophobic interaction on a broader range of interfaces and characterization of interfacial water molecular structure using spectroscopic techniques are anticipated to help unravel the origin of this rigidity-related mismatch of hydrophobic interaction and hold promise to uncover the physical nature of hydrophobic effects. With improved understanding of hydrophobic interaction, intrinsic interaction mechanisms of many biological and chemical pathways can be better elucidated, and novel devices/processes can be developed with capacity to modulate and control the hydrophobic effects from the molecular to the macroscopic scale.
ToF-SIMS and laser-SNMS analysis of Madin–Darby canine kidney II cells with silver nanoparticles using an argon cluster ion beam
Authors: Nees Ricarda , Pelster Andreas , Körsgen Martin , Jungnickel Harald , Luch Andreas , Galla Hans-Joachim , Arlinghaus Heinrich F.
Published: December 2015

The use of nanoparticles is one of the fastest expanding fields in industrial as well as in medical applications, owing to their remarkable characteristics. Silver nanoparticles (AgNPs) are among the most-commercialized nanoparticles because of their antibacterial effects. Laser postionization secondary neutral mass spectrometry (laser-SNMS) and time-of-flight secondary ion mass spectrometry in combination with argon cluster ion sputtering was used for the first time to investigate the effects of AgNPs on Madin-Darby canine kidney (MDCK) II cells. Depth profiles and high-resolution three dimensional (3D) images of nanoparticles and organic compounds from cells were obtained using an Ar cluster ion beam for sputtering and Bi3+ primary ions for the analysis. The 3D distribution of AgNPs and other organic compounds in MDCK II cells could be readily detected with very high efficiency, sensitivity, and submicron lateral resolution. The argon cluster ion beam is well suited for the sputtering of biological samples. It enables a high sample removal rate along with low molecular degradation. The outer membrane, the cytoplasm, and the nuclei of the cells could be clearly visualized using the signals PO+ and C3H8N+ or CN+ and C3H8N+. The laser-SNMS images showed unambiguously that AgNPs are incorporated by MDCK II cells and often form silver aggregates with a diameter of a few micrometers, mainly close to the outside of the cell nuclei.
To be parasitic or symbiotic?
Authors: Prabakaran Sudhakaran
Published: December 2015

Rhizobial strains with HrrP degrade host-derived signaling peptides to become parasitic.
Altering timing perturbs cell signaling
Authors: Ray L. Bryan
Published: December 2015

A signaling pathway is vulnerable to disruption by suitably timed input.
Unsilencing antitumor T cell activity
Authors: Foley John F.
Published: December 2015

The suppressor of cytokine signaling protein Cish inhibits T cell receptor signaling to suppress the antitumor activity of cytotoxic T cells.
β-Lactamase Characterization of Gram-Negative Pathogens Recovered from Patients Enrolled in the Phase 2 Trials for Ceftazidime-Avibactam: Clinical Efficacies Analyzed against Subsets of Molecularly Characterized Isolates
Authors: Mendes Rodrigo E. , Castanheira Mariana , Gasink Leanne , Stone Gregory G. , Nichols Wright W. , Flamm Robert K. , Jones Ronald N.
Published: December 2015

The correlation of the clinical efficacies of ceftazidime-avibactam and comparators (carbapenems) was evaluated against baseline Gram-negative isolates having characterized β-lactam resistance mechanisms from complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) phase 2 trials.
Enterobacteriaceae
displaying ceftriaxone and/or ceftazidime MICs of ≥2 μg/ml (69 isolates) and nonfermentative Gram-negative bacilli (NF-GNB [three isolates]) with ceftazidime MICs of ≥16 μg/ml were characterized for their narrow- and extended-spectrum β-lactamase (ESBL) content.
Enterobacteriaceae
(one isolate) and NF-GNB (three isolates) with imipenem/meropenem MICs of ≥2 and ≥16 μg/ml, respectively, were tested for carbapenemases. All cUTI
E. coli
had the lineage background investigated (ST131-like versus non-ST131-like). The primary efficacy endpoint was microbiological response (eradication) at test of cure (TOC) for cUTI and clinical response (inferred microbiological eradication) at TOC for cIAI. A total of 34.1% of baseline cUTI (36.4%) and cIAI (33.1%) pathogens met the MIC-based screening criteria (screen positive). All screen-positive cUTI pathogens were CTX-M-producing
E. coli
, except for one
E. cloacae
isolate with AmpC overexpression. The majority (66.7%) of screen-positive cIAI isolates produced CTX-M-type coupled with a diverse array of other β-lactamases. Similar favorable responses were observed with ceftazidime-avibactam (93.3%) and carbapenems (90.9%), when a non-ESBL
Enterobacteriaceae
isolate was recovered at the baseline visit. When an ESBL
Enterobacteriaceae
isolate was present, the favorable responses were 85.7% and 80.0% with ceftazidime-avibactam and carbapenems, respectively. Higher favorable responses were observed with ceftazidime-avibactam (75.0%) than with carbapenems (66.7%) when an ST131-like
E. coli
isolate was recovered at baseline, as when a non-ST131-like isolate was present (93.8% versus 86.7%, respectively). The efficacy of ceftazidime-avibactam was similar to that of carbapenems for treatment of cUTI and cIAI caused by ESBL organisms.
Role of the Outer Membrane and Porins in Susceptibility of β-Lactamase-Producing Enterobacteriaceae to Ceftazidime-Avibactam
Authors: Pagès Jean-Marie , Peslier Sabine , Keating Thomas A. , Lavigne Jean-Philippe , Nichols Wright W.
Published: December 2015

This study examined the activity of the novel antimicrobial combination ceftazidime-avibactam against
Enterobacteriaceae
exhibiting different outer membrane permeability profiles, specifically with or without porins and with or without expression of the main efflux pump (AcrAB-TolC). The addition of the outer membrane permeabilizer polymyxin B nonapeptide increased the antibacterial activities of avibactam alone, ceftazidime alone, and ceftazidime-avibactam against the characterized clinical isolates of
Escherichia coli
,
Enterobacter aerogenes
, and
Klebsiella pneumoniae
. This enhancement of activities was mainly due to increased passive penetration of compounds since inhibition of efflux by the addition of phenylalanine-arginine β-naphthylamide affected the MICs minimally. OmpF (OmpK35) or OmpC (OmpK36) pores were not the major route by which avibactam crossed the outer membranes of
E. coli
and
K. pneumoniae
. In contrast, Omp35 and Omp36 allowed diffusion of avibactam across the outer membrane of
E. aerogenes
, although other diffusion channels for avibactam were also present in that species. It was clear that outer membrane permeability and outer membrane pore-forming proteins play a key role in the activity of ceftazidime-avibactam. Nevertheless, the MICs of ceftazidime-avibactam (with 4 mg/liter avibactam) against the ceftazidime-resistant clinical isolates of the three species of
Enterobacteriaceae
studied were ≤8 mg/liter, regardless of outer membrane permeability changes resulting from an absence of defined porin proteins or upregulation of efflux.
Porin Loss Impacts the Host Inflammatory Response to Outer Membrane Vesicles of Klebsiella pneumoniae
Authors: Turner Kelli L. , Cahill Bethaney K. , Dilello Sarah K. , Gutel Dedra , Brunson Debra N. , Albertí Sebastián , Ellis Terri N.
Published: December 2015

Antibiotic-resistant strains ofKlebsiella pneumoniaeoften exhibit porin loss. In this study, we investigated how porin loss impacted the composition of secreted outer membrane vesicles as well as their ability to trigger proinflammatory cytokine secretion by macrophages. We hypothesize that porin loss associated with antibiotic resistance will directly impact both the composition of outer membrane vesicles and their interactions with phagocytic cells. Using clonally related clinical isolates of extended-spectrum beta-lactamase (ESBL)-positiveKlebsiella pneumoniaewith different patterns of porin expression, we demonstrated that altered expression of OmpK35 and OmpK36 results in broad alterations to the protein profile of secreted vesicles. Additionally, the level of OmpA incorporation was elevated in strains lacking a single porin. Porin loss significantly impacted macrophage inflammatory responses to purified vesicles. Outer membrane vesicles lacking both OmpK35 and OmpK36 elicited significantly lower levels of proinflammatory cytokine secretion than vesicles from strains expressing one or both porins. These data demonstrate that antibiotic resistance-associated porin loss has a broad and significant effect on both the composition of outer membrane vesicles and their interactions with phagocytic cells, which may impact bacterial survival and inflammatory reactions in the host.
Stearylamine Liposomal Delivery of Monensin in Combination with Free Artemisinin Eliminates Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection in Murine Malaria
Authors: Rajendran Vinoth , Rohra Shilpa , Raza Mohsin , Hasan Gulam Mustafa , Dutt Suparna , Ghosh Prahlad C.
Published: December 2015

The global emergence of drug resistance in malaria is impeding the therapeutic efficacy of existing antimalarial drugs. Therefore, there is a critical need to develop an efficient drug delivery system to circumvent drug resistance. The anticoccidial drug monensin, a carboxylic ionophore, has been shown to have antimalarial properties. Here, we developed a liposome-based drug delivery of monensin and evaluated its antimalarial activity in lipid formulations of soya phosphatidylcholine (SPC) cholesterol (Chol) containing either stearylamine (SA) or phosphatidic acid (PA) and different densities of distearoyl phosphatidylethanolamine-methoxy-polyethylene glycol 2000 (DSPE-mPEG-2000). These formulations were found to be more effective than a comparable dose of free monensin in
Plasmodium falciparum
(3D7) cultures and established mice models of
Plasmodium berghei
strains NK65 and ANKA. Parasite killing was determined by a radiolabeled [
3
H]hypoxanthine incorporation assay (
in vitro
) and microscopic counting of Giemsa-stained infected erythrocytes (
in vivo
). The enhancement of antimalarial activity was dependent on the liposomal lipid composition and preferential uptake by infected red blood cells (RBCs). The antiplasmodial activity of monensin in SA liposome (50% inhibitory concentration [IC
50
], 0.74 nM) and SPC:Chol-liposome with 5 mol% DSPE-mPEG 2000 (IC
50
, 0.39 nM) was superior to that of free monensin (IC
50
, 3.17 nM), without causing hemolysis of erythrocytes. Liposomes exhibited a spherical shape, with sizes ranging from 90 to 120 nm, as measured by dynamic light scattering and high-resolution electron microscopy. Monensin in long-circulating liposomes of stearylamine with 5 mol% DSPE-mPEG 2000 in combination with free artemisinin resulted in enhanced killing of parasites, prevented parasite recrudescence, and improved survival. This is the first report to demonstrate that monensin in PEGylated stearylamine (SA) liposome has therapeutic potential against malaria infections.
Emergence of
cfr
-Mediated Linezolid Resistance in a Methicillin-Resistant Staphylococcus aureus Epidemic Clone Isolated from Patients with Cystic Fibrosis
Authors: de Dios Caballero Juan , Pastor María Dolores , Vindel Ana , Máiz Luis , Yagüe Genoveva , Salvador Carme , Cobo Marta , Morosini María-Isabel , del Campo Rosa , Cantón Rafael ,   the GEIFQ Study Group
Published: December 2015

Resistance to linezolid (LZD) in methicillin-resistant
Staphylococcus aureus
(MRSA) isolates from patients with cystic fibrosis (CF) is due mainly to ribosomal mutations. We report on four CF patients with LZD-resistant MRSA bronchopulmonary infections by strains carrying the
cfr
gene. Strains from one patient also harbored the G2576U mutation (23S rRNA) and the G139R substitution (L3 protein). All strains belonged to the epidemic clone ST125 MRSA IVc. Our results support the monitoring of LZD resistance emergence in CF and non-CF MRSA isolates.
Does Critical Illness Change Levofloxacin Pharmacokinetics?
Authors: Roberts Jason A. , Cotta Menino Osbert , Cojutti Piergiorgio , Lugano Manuela , Rocca Giorgio Della , Pea Federico
Published: December 2015

Levofloxacin is commonly used in critically ill patients for which existing data suggest nonstandard dosing regimens should be used. The objective of this study was to compare the population pharmacokinetics of levofloxacin in critically ill and in non-critically ill patients. Adult patients with a clinical indication for levofloxacin were eligible for participation in this prospective pharmacokinetic study. Patients were given 500 mg or 750 mg daily by intravenous administration with up to 11 blood samples taken on day 1 or 2 of therapy. Plasma samples were analyzed and population pharmacokinetic analysis was undertaken using Pmetrics. Thirty-five patients (18 critically ill) were included. The mean (standard deviation [SD]) age, weight, and Cockcroft-Gault creatinine clearance for the critically ill and for the non-critically ill patients were 60.3 (16.4) and 72.0 (11.6) years, 78.5 (14.8) and 70.9 (15.8) kg, and 71.9 (65.8) and 68.2 (30.1) ml/min, respectively. A two-compartment linear model best described the data. Increasing creatinine clearance was the only covariate associated with increasing drug clearance. The presence of critical illness did not significantly affect any pharmacokinetic parameter. The mean (SD) parameter estimates were as follows: clearance, 8.66 (3.85) liters/h; volume of the central compartment (Vc), 41.5 (24.5) liters; intercompartmental clearance constants from central to peripheral, 2.58 (3.51) liters/h; and peripheral to central compartments, 0.90 (0.58) liters/h. Monte Carlo dosing simulations demonstrated that achievement of therapeutic exposures was dependent on renal function, pathogen, and MIC. Critical illness appears to have no independent effect on levofloxacin pharmacokinetics that cannot be explained by altered renal function.
Characterization of an Acinetobacter baumannii
lptD
Deletion Strain: Permeability Defects and Response to Inhibition of Lipopolysaccharide and Fatty Acid Biosynthesis
Authors: Bojkovic Jade , Richie Daryl L. , Six David A. , Rath Christopher M. , Sawyer William S. , Hu Qijun , Dean Charles R.
Published: December 2015

Lipid A on the Gram-negative outer membrane (OM) is synthesized in the cytoplasm by the Lpx pathway and translocated to the OM by the Lpt pathway. Some
Acinetobacter baumannii
strains can tolerate the complete loss of lipopolysaccharide (LPS) resulting from the inactivation of early LPS pathway genes such as
lpxC
. Here, we characterized a mutant deleted for
lptD
, which encodes an OM protein that mediates the final translocation of fully synthesized LPS to the OM. Cells lacking
lptD
had a growth defect comparable to that of an
lpxC
deletion mutant under the growth conditions tested but were more sensitive to hydrophobic antibiotics, revealing a more significant impact on cell permeability from impaired LPS translocation than from the loss of LPS synthesis. Consistent with this, ATP leakage and
N
-phenyl-1-naphthylamine (NPN) fluorescence assays indicated a more severe impact of
lptD
deletion than of
lpxC
deletion on inner and outer membrane permeability, respectively. Targeted liquid chromatography-mass spectrometry (LCMS) analysis of LPS intermediates from UDP-3-
O-R
-3-hydroxylauroyl-
N
-acetyl-α-
d
-glucosamine through lipid IV
A
showed that the loss of LptD caused an accumulation of lipid IV
A
. This suggested that pathway intermediate accumulation or mislocalization caused by the blockage of later LPS pathway steps impacts envelope integrity. Supporting this notion, chemical inhibition of lipid A precursor enzymes, including LpxC and FabB/F, in the
lptD
deletion strain partially rescued growth and permeability defects.

IMPORTANCE
New antibiotics to treat Gram-negative bacterial infections are urgently needed. Inhibition of LPS biosynthesis is attractive because this would impact viability and cell permeability. Therefore, a better understanding of this pathway is important, especially in strains such as
A. baumannii
ATCC 19606, where LPS biosynthesis is not essential
in vitro
. We show that ATCC 19606 also survives the loss of the final translocation of LPS into the OM (
lptD
deletion). Intriguingly, this impaired cell envelope integrity more than the loss of LPS biosynthesis (
lpxC
deletion), presumably due to the accumulation of toxic intermediates. Supporting this, chemical inhibition of LPS biosynthesis partially reversed this permeability defect. This extends our understanding of the LPS machinery and provides insights into potential interrelationships of the target steps along this important pathway.
Nucleotide Manipulatives to Illustrate the Central Dogma
Authors: Yung Sonja B. , Primm Todd P.
Published: December 2015

The central dogma is a core concept that is critical for introductory biology and microbiology students to master. However, students often struggle to conceptualize the processes involved, and fail to move beyond simply memorizing the basic facts. To encourage critical thinking, we have designed a set of magnetic nucleotide manipulatives that allow students to model DNA structure, along with the processes of replication, transcription, and translation.