bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of the in vitro transgene mutation assay in MutaMouse FE1 cells: Evaluation of nine misleading (“False”) positive chemicals
Authors: Maertens Rebecca M. , Long Alexandra S. , White Paul A.
Published: August 2017

The screening of chemicals for the protection of human health and the environment requires the assessment of genetic toxicity. However, existing, internationally‐accepted in vitro mammalian genotoxicity tests have been criticized for their low specificity (i.e. high frequency of “false” or “misleading” positive results for compounds that are negative in vivo). An in vitro transgene mutation assay has been established that uses a metabolically competent cell line derived from MutaMouse lung (i.e. FE1 cells). Mutation scoring employs the well‐characterized lacZ positive selection system, and the assay is proposed as an alternative in vitro assessment tool. In this study, the performance of the FE1 cell assay was evaluated by examining responses to nine non‐DNA‐reactive chemicals that previously elicited misleading positive results in other mammalian cell genotoxicity assays. FE1 cells were exposed to concentrations up to approximately 10 mM and/or concentrations that yielded approximately 80‐90% cytotoxicity (as measured by relative increase in cell count). The assay demonstrated excellent specificity; exposures to the chemicals examined did not yield any positive responses even when tested in the presence of an exogenous metabolic activation system (i.e. S9) or with an extended sampling time. These results indicate that the FE1 cell mutagenicity assay is an effective and practical alternative to traditional mammalian cell gene mutation assays. The development and validation of effective in vitro tools such as the MutaMouse FE1 cell assay will contribute to international efforts to reduce, refine, and replace experimental animals for toxicity assessment. Environ. Mol. Mutagen. 58:582–591, 2017. © 2017 Wiley Periodicals, Inc.
Bcl‐2 protects TK6 cells against hydroquinone‐induced apoptosis through PARP‐1 cytoplasm translocation and stabilizing mitochondrial membrane potential
Authors: Chen Yuting , Chen Shaoyun , Liang Hairong , Yang Hui , Liu Linhua , Zhou Kairu , Xu Longmei , Liu Jiaxian , Yun Lin , Lai Bei , Song Li , Luo Hao , Peng Jianming , Liu Zhidong , Xiao Yongmei , Chen Wen , Tang Huanwen
Published: August 2017

B cell leukemia/lymphoma‐2 (Bcl‐2) suppresses apoptosis by binding the BH3 domain of proapoptotic factors and thereby regulating mitochondrial membrane potential (MMP). This study aimed to investigate the role of Bcl‐2 in controlling the mitochondrial pathway of apoptosis during hydroquinone (HQ)‐induced TK6 cytotoxicity. In this study, HQ, one metabolite of benzene, decreased the MMP in a concentration‐dependent manner and induced the generation of reactive oxygen species (ROS), the activation of the DNA damage marker γ‐H2AX, and production of the DNA damage‐responsive enzyme poly(ADP‐ribose)polymerase‐1 (PARP‐1). Exposure of TK6 cells to HQ leads to an increase in Bcl‐2 and co‐localization with PARP‐1 in the cytoplasm. Inhibition of Bcl‐2 using the BH3 mimetic, ABT‐737, suppressed the PARP‐1 nuclear to cytoplasm translocation and sensitized TK6 cells to HQ‐induced apoptosis through depolarization of the MMP. Western blot analysis indicated that ABT‐737 combined with HQ increased the levels of cleaved PARP and γ‐H2AX, but significantly decreased the level of P53. Thus, ABT‐737 can influence PARP‐1 translocation and induce apoptosis via mitochondria‐mediated apoptotic pathway, independently of P53. In addition, we found that knockdown of PARP‐1 attenuated the HQ‐induced production of cleaved PARP and P53. These results identify Bcl‐2 as a protective mediator of HQ‐induced apoptosis and show that upregulation of Bcl‐2 helps to localize PARP‐1 to the cytoplasm and stabilize MMP. Environ. Mol. Mutagen. 59:49–59, 2018. © 2017 Wiley Periodicals, Inc.
Telomerase activity, telomere length and hTERT DNA methylation in peripheral blood mononuclear cells from monozygotic twins with discordant smoking habits
Authors: Marcon Francesca , Siniscalchi Ester , Andreoli Cristina , Allione Alessandra , Fiorito Giovanni , Medda Emanuela , Guarrera Simonetta , Matullo Giuseppe , Crebelli Riccardo
Published: August 2017

Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco smoke exposure and telomerase activity (TA) in peripheral blood mononuclear cells of healthy smokers. The methylation status of the catalytic subunit of telomerase hTERT was concurrently investigated to assess the possible association between epigenetic modifications of hTERT and TA. Besides, the association between smoke and telomere length (TL) has been evaluated. Healthy monozygotic twins with discordant smoking habits were selected as study population to minimize inter‐individual differences because of demographic characteristics and genetic heterogeneity. Statistically significant higher values of TA and TL were observed in smokers compared to nonsmoker co‐twins. The multivariate analysis of data showed, besides smoking habits (P = 0.02), an influence of gender (P = 0.006) and BMI (P = 0.001) on TA and a borderline effect of gender (P = 0.05) on TL. DNA methylation analysis, focused on 100 CpG sites mapping in hTERT, highlighted nine CpG sites differentially methylated in smokers. When co‐twins were contrasted, selecting as variables the intra‐twin difference in TA and hTERT DNA methylation, a statistically significant inverse correlation (P = 0.003) was observed between TA and DNA methylation at the cg05521538 site. In conclusion, these results indicate an association of tobacco smoke with TA and TL and suggest a possible association between smoke‐induced epigenetic effects and TA in healthy smokers. Environ. Mol. Mutagen. 58:551–559, 2017. © 2017 Wiley Periodicals, Inc.
Single nucleotide polymorphisms rs911160 in AURKA and rs2289590 in AURKB mitotic checkpoint genes contribute to gastric cancer susceptibility
Authors: Mesic Aner , Markocic Ela , Rogar Marija , Juvan Robert , Hudler Petra , Komel Radovan
Published: August 2017

Background: Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes could confer increased susceptibility to gastric cancer (GC). We investigated the association of Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC), Polo‐like kinase 1 (PLK1) and Budding uninhibited by benzimidazol 3, yeast (BUB3) gene polymorphisms with GC risk. Materials and methods: Genotyping of 6 SNPs in AURKA (rs911160 and rs8173), AURKB (rs2289590), AURKC (rs11084490), PLK1 (rs42873), and BUB3 (rs7897156) was performed using TaqMan genotyping assays. Results: Our study demonstrated that rs911160 (AURKA) heterozygous genotype was associated with an increased GC risk (OR = 1.50, 95% CI = 1.01‐2.22, P = 0.043). Analysis of rs911160 (AURKA) showed significant association with an increased risk for intestinal type GC (OR = 1.80, 95%CI = 1.01–3.21, P = 0.040) and the risk was significantly higher in women than men (OR = 2.65, 95%CI = 1.02–6.87, P = 0.033). SNP rs2289590 in AURKB might contribute to susceptibility for the development of gastric cancer, particularly in women (OR = 2.08, 95% CI = 1.05–4.09, P = 0.032). Conclusion: Our findings suggested that AURKA (rs911160) and AURKB (rs2289590) polymorphisms could affect GC risk. Further validation studies in larger and multi‐ethnical populations are needed to elucidate their functional impact on the development of GC. Environ. Mol. Mutagen. 58:701–711, 2017. © 2017 Wiley Periodicals, Inc.
The effect of tides and storms on the sediment transport across a Dutch barrier island
Authors: Wesselman Daan , de Winter Renske , Engelstad Anita , McCall Robert , van Dongeren Ap , Hoekstra Piet , Oost Albert , van der Vegt Maarten
Published: August 2017

Under natural conditions, barrier islands might grow vertically and migrate onshore under the influence of long‐term sea level rise. Sediment is transported onshore during storm‐induced overwash and inundation. However, on many Dutch Wadden Islands, dune openings are closed off by artificial sand‐drift dikes that prevent the influx of sediment during storms. It has been argued that creating openings in the dune row to allow regular flooding on barrier islands can have a positive effect on the sediment budget, but the dominant hydrodynamic processes and their influence on sediment transport during overwash and inundation are unknown. Here, we present an XBeach model study to investigate how sediment transport during overwash and inundation across the beach of a typical mesotidal Wadden Sea barrier island is influenced by wave, tide and storm surge conditions. Firstly, we validated the model XBeach with field data on waves and currents during island inundation. In general, the XBeach model performed well. Secondly, we studied the long‐term sediment transport across the barrier island. We distinguished six representative inundation classes, ranging from frequently occurring, low‐energy events to infrequent, high‐energy events, and simulated the hydrodynamics and sediment transport during these events. An analysis of the model simulations shows that larger storm events cause larger cross‐shore sediment transport, but the net sediment exchange during a storm levels off or even becomes smaller for the largest inundation classes because it is counteracted by larger mean water levels in the Wadden Sea that oppose or even reverse sediment transport during inundation. When taking into account the frequency of occurrence of storms we conclude that the cumulative effect of relatively mild storms on long‐term cross‐shore sediment transport is much larger than that of the large storm events. © 2017 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd.
Parsimonious sediment transport equations based on Bagnold's stream power approach
Authors: Lammers Roderick W. , Bledsoe Brian P.
Published: August 2017

It is increasingly recognized that effective river management requires a catchment scale approach. Sediment transport processes are relevant to a number of river functions but quantifying sediment fluxes at network scales is hampered by the difficulty of measuring the variables required for most sediment transport equations (e.g. shear stress, velocity, and flow depth). We develop new bedload and total load sediment transport equations based on specific stream power. These equations use data that are relatively easy to collect or estimate throughout stream networks using remote sensing and other available data: slope, discharge, channel width, and grain size. The new equations are parsimonious yet have similar accuracy to other, more established, alternatives. We further confirm previous findings that the dimensionless critical specific stream power for incipient particle motion is generally consistent across datasets, and that the uncertainty in this parameter has only a minor impact on calculated sediment transport rates. Finally, we test the new bedload transport equation by applying it in a simple channel incision model. Our model results are in close agreement to flume observations and can predict incision rates more accurately than a more complicated morphodynamic model. These new sediment transport equations are well suited for use at stream network scales, allowing quantification of this important process for river management applications. Copyright © 2017 John Wiley & Sons, Ltd.
Clinicopathological characteristics and outcomes of squamous cell carcinoma of the tongue in different age groups
Authors: Zhang Yan‐Yan , Wang Dian‐Can , Su Jia‐Zeng , Jia Ling‐Fei , Peng Xin , Yu Guang‐Yan
Published: August 2017

Background

The clinicopathological features and outcomes of squamous cell carcinoma (SCC) of the tongue in patients of different age groups remain debatable.

Methods

Medical records of 457 patients with tongue SCC were reviewed, grouped by age, followed up, and compared.

Results

Sex and TNM stage showed no intergroup differences. Tongue SCC in patients ≤30 years had the most advanced TNM classification and greatest proportion of poorly differentiation tumors. Both disease‐free survival (DFS) and disease‐specific survival (DSS) showed no statistically significant difference between the youngest and the oldest groups (P = .605 and P = .520). However, there was a tendency of higher death rate caused by recurrence or metastasis in the youngest group compared with the others (91.7% vs 75.4% and 77.4%).

Conclusion

Young patients had a tendency of higher death rate caused by recurrence or metastasis than middle‐age and older patients; therefore, a larger case sample is needed for further confirmation.
Characterizing the role of the hippocampus during episodic simulation and encoding
Authors: Thakral Preston P. , Benoit Roland G. , Schacter Daniel L.
Published: August 2017

The hippocampus has been consistently associated with episodic simulation (i.e., the mental construction of a possible future episode). In a recent study, we identified an anterior‐posterior temporal dissociation within the hippocampus during simulation. Specifically, transient simulation‐related activity occurred in relatively posterior portions of the hippocampus and sustained activity occurred in anterior portions. In line with previous theoretical proposals of hippocampal function during simulation, the posterior hippocampal activity was interpreted as reflecting a transient retrieval process for the episodic details necessary to construct an episode. In contrast, the sustained anterior hippocampal activity was interpreted as reflecting the continual recruitment of encoding and/or relational processing associated with a simulation. In the present study, we provide a direct test of these interpretations by conducting a subsequent memory analysis of our previously published data to assess whether successful encoding during episodic simulation is associated with the anterior hippocampus. Analyses revealed a subsequent memory effect (i.e., later remembered > later forgotten simulations) in the anterior hippocampus. The subsequent memory effect was transient and not sustained. Taken together, the current findings provide further support for a component process model of hippocampal function during simulation. That is, unique regions of the hippocampus support dissociable processes during simulation, which include the transient retrieval of episodic information, the sustained binding of such information into a coherent episode, and the transient encoding of that episode for later retrieval.
Hippocampal mechanisms in impaired spatial learning and memory in male offspring of rats fed a low‐protein isocaloric diet in pregnancy and/or lactation
Authors: Reyes‐Castro L. A. , Padilla‐Gómez E. , Parga‐Martínez N. J. , Castro‐Rodríguez D. C. , Quirarte G. L. , Díaz‐Cintra S. , Nathanielsz P. W. , Zambrano E.
Published: August 2017

Maternal nutritional challenges during fetal and neonatal development result in developmental programming of multiple offspring organ systems including brain maturation and function. A maternal low‐protein diet during pregnancy and lactation impairs associative learning and motivation. We evaluated effects of a maternal low‐protein diet during gestation and/or lactation on male offspring spatial learning and hippocampal neural structure. Control mothers (C) ate 20% casein and restricted mothers (R) 10% casein, providing four groups: CC, RR, CR, and RC (first letter pregnancy, second lactation diet). We evaluated the behavior of young adult male offspring around postnatal day 110. Corticosterone and ACTH were measured. Males were tested for 2 days in the Morris water maze (MWM). Stratum lucidum mossy fiber (MF) area, total and spine type in basal dendrites of stratum oriens in the hippocampal CA3 field were measured. Corticosterone and ACTH were higher in RR vs. CC. In the MWM acquisition test CC offspring required two, RC three, and CR seven sessions to learn the maze. RR did not learn in eight trials. In a retention test 24 h later, RR, CR, and RC spent more time locating the platform and performed fewer target zone entries than CC. RR and RC offspring spent less time in the target zone than CC. MF area, total, and thin spines were lower in RR, CR, and RC than CC. Mushroom spines were lower in RR and RC than CC. Stubby spines were higher in RR, CR, and RC than CC. We conclude that maternal low‐protein diet impairs spatial acquisition and memory retention in male offspring, and that alterations in hippocampal presynaptic (MF), postsynaptic (spines) elements and higher glucocorticoid levels are potential mechanisms to explain these learning and memory deficits.
An analytical study on three‐dimensional versus two‐dimensional water table‐induced flow patterns in a Tóthian basin
Authors: Wang Jun‐Zhi , Jiang Xiao‐Wei , Zhang Zhi‐Yuan , Wan Li , Wang Xu‐Sheng , Li Hailong
Published: August 2017

Although it has been increasingly acknowledged that groundwater flow pattern is complicated in the three‐dimensional (3‐D) domain, two‐dimensional (2‐D) water table‐induced flow models are still widely used to delineate basin‐scale groundwater circulation. However, the validity of 2‐D cross‐sectional flow field induced by water table has been seldom examined. Here, we derive the analytical solution of 3‐D water table‐induced hydraulic head in a Tóthian basin and then examine the validity of 2‐D cross‐sectional models by comparing the flow fields of selected cross sections calculated by the 2‐D cross‐sectional model with those by the 3‐D model, which represents the “true” cases. For cross sections in the recharge or discharge area of the 3‐D basin, even if head difference is not significant, the 2‐D cross‐sectional models result in flow patterns absolutely different from the true ones. For the cross section following the principal direction of groundwater flow, although 2‐D cross‐sectional models would overestimate the penetrating depth of local flow systems and underestimate the recharge/discharge flux, the flow pattern from the cross‐sectional model is similar to the true one and could be close enough to the true one by adjusting the decay exponent and anisotropy ratio of permeability. Consequently, to determine whether a 2‐D cross‐sectional model is applicable, a comparison of hydraulic head difference between 2‐D and 3‐D solutions is not enough. Instead, the similarity of flow pattern should be considered to determine whether a cross‐sectional model is applicable. This study improves understanding of groundwater flow induced by more natural water table undulations in the 3‐D domain and the limitations of 2‐D models accounting for cross‐sectional water table undulation only.
Metabolic conditions and breast cancer risk among Los Angeles County Filipina Americans compared with Chinese and Japanese Americans
Authors: Wu Anna H. , Vigen Cheryl , Butler Lesley M. , Tseng Chiu‐Chen
Published: August 2017

Accumulating evidence suggests that the aggregation of common metabolic conditions (high blood pressure, diabetes and dyslipidemia) is a risk factor for breast cancer. Breast cancer incidence has risen steadily in Asian American women, and whether these metabolic conditions contribute to breast cancer risk in certain Asian American subgroups is unknown. We investigated the role of physician‐diagnosed hypertension, high cholesterol and diabetes separately, and in combination, in relation to the risk of breast cancer in a population‐based case–control study of 2,167 Asian Americans diagnosed with breast cancer and 2,035 age and ethnicity matched control women in Los Angeles County. Compared to Asian American women who did not have any of the metabolic conditions, those with 1, 2 or 3 conditions showed a steady increase in risk (respective odds ratios were 1.12, 1.42 and 1.62; P trend = 0.001) with adjustment for covariates including body mass index. Similar significant trends were observed in Filipina Americans (P trend = 0.021), postmenopausal women (P trend =0.001), Asian women who were born in the United States (US) (P trend = 0.052) and migrants who have lived in the US for at least 20 years (P trend = 0.004), but not migrants who lived in the US for <20 years (P trend = 0.64). These results suggest that westernization in lifestyle (diet and physical inactivity) and corresponding increase in adiposity have contributed to the rising prevalence of these metabolic conditions, which in turn, are associated with an increase in breast cancer.
Safety and efficacy of a novel three‐dimensional magnetic resonance imaging model for uterine incision in placenta previa
Authors: Cao Yanwen , Wei Yanxing , Yu Yanhong , Wang Zhijian
Published: August 2017

Objective

To assess a novel three‐dimensional (3D) magnetic resonance imaging (MRI) model for determining position of uterine incision during cesarean delivery among patients with placenta previa.

Methods

A prospective study was conducted among women with singleton pregnancies complicated by placenta previa who delivered by cesarean at a hospital in China between January 1, 2014, and January 1, 2016. Patients chose whether to undergo 3D MRI modeling to guide uterine incision (study group) or the standard intervention (control group). Medical records were reviewed to collect data on maternal, neonatal, and operative characteristics.

Results

Among 134 women enrolled, 45 were in the study group and 89 in the control group. When compared with the control group, patients in the study group experienced less intraoperative blood loss (678.65 ± 649.54 vs 933.96 ± 695.25 mL; P=0.042) and shorter operative times (65.13 ± 27.38 vs 86.88 ± 54.43 minutes; P=0.013). Fewer patients in the study group received transfusions (11 [24%] vs 38 [43%]; P=0.038). No between‐group differences were found for hysterectomy rate, hospitalization days and cost, or neonatal outcomes.

Conclusion

Uterine incision guided by a 3D MRI model could improve maternal outcomes during cesarean delivery, including reductions in intraoperative blood loss, transfusion frequency, and operative time.
Clinical outcomes after external cephalic version with spinal anesthesia after failure of a first attempt without anesthesia
Authors: Massalha Manal , Garmi Gali , Zafran Noah , Carmeli Julia , Gimburg Genady , Salim Raed
Published: August 2017

Objective

To determine whether repeat external cephalic version (ECV) with spinal anesthesia affects clinical outcomes and cesarean delivery rates.

Methods

A retrospective study was conducted using data collected at one hospital in Israel between January 1, 2009, and December 31, 2015. Women with non‐vertex singleton pregnancies (≥37 weeks) who had a failed ECV attempt without spinal anesthesia were included in the analysis. All women were offered a repeat ECV with spinal anesthesia. Outcomes assessed were rates of vertex presentation at delivery, successful repeat ECV, and cesarean delivery.

Results

Overall, 145 of 213 ECV attempts without spinal anesthesia were successful. Of the 68 women with a failed attempt, 5 (7%) experienced spontaneous version and 18 (26%) delivered at another institution or went into spontaneous labor. Among the remaining 45 women, 28 (62%) agreed to a repeat ECV with spinal anesthesia; 11 (39%) of these procedures were successful. All 11 women experienced vertex presentation at delivery versus none of the 17 women who refused repeat ECV (P=0.003). The cesarean delivery rate was 64% (18/28) versus 100% (17/17), respectively (P=0.007).

Conclusion

Repeat ECV with spinal anesthesia after a failed first attempt without spinal anesthesia increased vertex presentation at birth and decreased the rate of cesarean delivery.
FAMILY CONFLICT MODERATES EARLY PARENT–CHILD BEHAVIORAL TRANSACTIONS
Authors: Paschall Katherine W. , Barnett Melissa A. , Mastergeorge Ann M. , Mortensen Jennifer A.
Published: August 2017

The reciprocal transactions that shape early parent–child relationships are influenced by contextual stress, such as family conflict. Although family conflict is a salient stressor to the family system, few studies have considered how parent–child transactions vary according to exposure to family conflict. The present study examined how family conflict alters early parent–child behavioral transactions. We utilized three waves of data from a multisite longitudinal study of low‐income families (N = 2, 876), child age 14 months, 24 months, and 36 months, to identify behavioral transactions of positive and negative maternal (supportiveness, negative regard) and child (engagement, negativity) behaviors. Results indicated that family conflict at 14 months diminished the positive association between maternal supportiveness and child engagement, and amplified the inverse association between maternal negativity and child engagement. Family conflict at 14 months also was associated with increased stability of child negativity and subsequent increased maternal negative regard at 36 months, in part via increases in 24‐month child negativity. In sum, family conflict occurring early in childhood predicted and moderated behavioral transactions between young children and their mothers.
MATERNAL INTERACTION QUALITY MODERATES EFFECTS OF PRENATAL MATERNAL EMOTIONAL SYMPTOMS ON GIRLS’ INTERNALIZING PROBLEMS
Authors: Endendijk Joyce J. , De Bruijn Anouk T.C.E. , Van Bakel Hedwig J.A. , Wijnen Hennie A.A. , Pop Victor J.M. , Van Baar Anneloes L.
Published: August 2017

The role of mother–infant interaction quality is studied in the relation between prenatal maternal emotional symptoms and child behavioral problems. Healthy pregnant, Dutch women (N = 96, M = 31.6, SD = 3.3) were allocated to the “exposed group” (n = 46), consisting of mothers with high levels of prenatal feelings of anxiety and depression, or the “low‐exposed group” (n = 50), consisting of mothers with normal levels of depressive or anxious symptoms during pregnancy. When the children (49 girls, 47 boys) were 23 to 60 months of age (M = 39.0, SD = 9.6), parents completed the Child Behavior Checklist (T.M. Achenbach & L.A. Rescorla, ), and mother–child interaction quality during a home visit was rated using the Emotional Availability Scales. There were no differences in mother–child interaction quality between the prenatally exposed and low‐exposed groups. Girls exposed to high prenatal emotional symptoms showed more internalizing problems, if maternal interaction quality was less optimal. No significant effects were found for boys.
EARLY HEAD START FAMILIES’ EXPERIENCES WITH STRESS: UNDERSTANDING VARIATIONS WITHIN A HIGH‐RISK, LOW‐INCOME SAMPLE
Authors: Hustedt Jason T. , Vu Jennifer A. , Bargreen Kaitlin N. , Hallam Rena A. , Han Myae
Published: August 2017

The federal Early Head Start program provides a relevant context to examine families’ experiences with stress since participants qualify on the basis of poverty and risk. Building on previous research that has shown variations in demographic and economic risks even among qualifying families, we examined possible variations in families’ perceptions of stress. Family, parent, and child data were collected to measure stressors and risk across a variety of domains in families’ everyday lives, primarily from self‐report measures, but also including assay results from child cortisol samples. A cluster analysis was employed to examine potential differences among groups of Early Head Start families. Results showed that there were three distinct subgroups of families, with some families perceiving that they experienced very high levels of stress while others perceived much lower levels of stress despite also experiencing poverty and heightened risk. These findings have important implications in that they provide an initial step toward distinguishing differences in low‐income families’ experiences with stress, thereby informing interventions focused on promoting responsive caregiving as a possible mechanism to buffer the effects of family and social stressors on young children.
Optimization of region‐of‐interest sampling strategies for hepatic MRI proton density fat fraction quantification
Authors: Hong Cheng William , Wolfson Tanya , Sy Ethan Z. , Schlein Alexandra N. , Hooker Jonathan C. , Fazeli Dehkordy Soudabeh , Hamilton Gavin , Reeder Scott B. , Loomba Rohit , Sirlin Claude B.
Published: August 2017

BACKGROUND

Clinical trials utilizing proton density fat fraction (PDFF) as an imaging biomarker for hepatic steatosis have used a laborious region‐of‐interest (ROI) sampling strategy of placing an ROI in each hepatic segment.

PURPOSE

To identify a strategy with the fewest ROIs that consistently achieves close agreement with the nine‐ROI strategy.

STUDY TYPE

Retrospective secondary analysis of prospectively acquired clinical research data.

POPULATION

A total of 391 adults (173 men, 218 women) with known or suspected NAFLD.

FIELD STRENGTH/SEQUENCE

Confounder‐corrected chemical‐shift‐encoded 3T MRI using a 2D multiecho gradient‐recalled echo technique.

ASSESSMENT

An ROI was placed in each hepatic segment. Mean nine‐ROI PDFF and segmental PDFF standard deviation were computed. Segmental and lobar PDFF were compared. PDFF was estimated using every combinatorial subset of ROIs and compared to the nine‐ROI average.

STATISTICAL TESTING

Mean nine‐ROI PDFF and segmental PDFF standard deviation were summarized descriptively. Segmental PDFF was compared using a one‐way analysis of variance, and lobar PDFF was compared using a paired t‐test and a Bland–Altman analysis. The PDFF estimated by every subset of ROIs was informally compared to the nine‐ROI average using median intraclass correlation coefficients (ICCs) and Bland–Altman analyses.

RESULTS

The study population's mean whole‐liver PDFF was 10.1 ± 8.9% (range: 1.1–44.1%). Although there was no significant difference in average segmental (P = 0.452) or lobar (P = 0.154) PDFF, left and right lobe PDFF differed by at least 1.5 percentage points in 25.1% (98/391) of patients. Any strategy with ≥4 ROIs had ICC >0.995. 115 of 126 four‐ROI strategies (91%) had limits of agreement (LOA) <1.5%, including four‐ROI strategies with two ROIs from each lobe, which all had LOA <1.5%. 14/36 (39%) of two‐ROI strategies and 74/84 (88%) of three‐ROI strategies had ICC >0.995, and 2/36 (6%) of two‐ROI strategies and 46/84 (55%) of three‐ROI strategies had LOA <1.5%.

DATA CONCLUSION

Four‐ROI sampling strategies with two ROIs in the left and right lobes achieve close agreement with nine‐ROI PDFF.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;47:988–994.
The main beam correction term in kinetic energy release from metastable peaks
Authors: Petersen Allan Christian
Published: August 2017

The correction term for the precursor ion signal width in determination of kinetic energy release is reviewed, and the correction term is formally derived. The derived correction term differs from the traditionally applied term. An experimental finding substantiates the inaccuracy in the latter. The application of the “T‐value” to study kinetic energy release is found preferable to kinetic energy release distributions when the metastable peaks are slim and simple Gaussians. For electronically predissociated systems, a “borderline zero” kinetic energy release can be directly interpreted in reaction dynamics with strong curvature in the reaction coordinate.
Hepatitis C virus genotypes in the Middle East and North Africa: Distribution, diversity, and patterns
Authors: Mahmud Sarwat , Al‐Kanaani Zaina , Chemaitelly Hiam , Chaabna Karima , Kouyoumjian Silva P. , Abu‐Raddad Laith J.
Published: August 2017

Our objective was to characterize the distribution, diversity and patterns of hepatitis C virus (HCV) genotypes in the Middle East and North Africa (MENA). Source of data was a database of HCV genotype studies in MENA populated using a series of systematic literature searches. Pooled mean proportions were estimated for each genotype and by country using DerSimonian‐Laird random‐effects meta‐analyses. Genotype diversity within countries was assessed using Shannon Diversity Index. Number of chronic infections by genotype and country was calculated using the pooled proportions and country‐specific numbers of chronic infection. Analyses were conducted on 338 genotype studies including 82 257 genotyped individuals. Genotype 1 was dominant (≥50%) in Algeria, Iran, Morocco, Oman, Tunisia, and UAE, and was overall ubiquitous across the region. Genotype 2 was common (10‐50%) in Algeria, Bahrain, Libya, and Morocco. Genotype 3 was dominant in Afghanistan and Pakistan. Genotype 4 was dominant in Egypt, Iraq, Jordan, Palestine, Qatar, Saudi Arabia, and Syria. Genotypes 5, 6, and 7 had limited or no presence across countries. Genotype diversity varied immensely throughout MENA. Weighted by population size, MENA's chronic infections were highest among genotype 3, followed by genotype 4, genotype 1, genotype 2, genotype 5, and genotype 6. Despite ubiquitous presence of genotype 1, the vast majority of chronic infections were of genotypes 3 or 4, because of the sizable epidemics in Pakistan and Egypt. Three sub‐regional patterns were identified: genotype 3 pattern centered in Pakistan, genotype 4 pattern centered in Egypt, and genotype 1 pattern ubiquitous in most MENA countries.
Safety and immunogenicity of the novel seasonal preservative‐ and adjuvant‐free influenza vaccine: Blind, randomized, and placebo‐controlled trial
Authors: Sarsenbayeva Gulbanu , Volgin Yevgeniy , Kassenov Markhabat , Issagulov Timur , Bogdanov Nikolay , Sansyzbay Abylay , Abitay Ruslan , Nurpeisova Ainur , Sagymbay Altynay , Koshemetov Zhumagali , Stukova Marina , Buzitskaya Zhanna , Кulmagambetov Ilyas , Karabayeva Dinara , Davlyatshin Timur , Khairullin Berik
Published: August 2017

The producers of influenza vaccines are not capable today to meet the global demand for an influenza vaccine in case of pandemic, so the World Health Organization recommends to develop the own influenza vaccine production in each country. A domestic preservative‐ and adjuvant‐free trivalent split vaccine against seasonal influenza was developed at the Research Institute for Biological Safety Problems. The paper presents the results of assessing safety and immunogenicity of the influenza split vaccine after single immunization of healthy volunteers aged 18‐50 years in the course of Phase I Clinical Trials. This study was randomized, blind, and placebo‐controlled. The volunteers were intramuscularly vaccinated with a dose of split vaccine or placebo. The study has shown that all local and systemic reactions had low degree of manifestation and short‐term character, so there was no need in medication. Serious side effects were not observed. On day 21 post vaccination the portion of vaccinated persons with fourfold seroconversions to influenza А/H1N1pdm09 virus was 100.0%, to influenza А/H3N2 virus—95.5%, to influenza B virus—81.8%, and in placebo group this index was 0%. Seroprotection rates against influenza А/H1N1pdm09, А/H3N2 and B viruses were 95.5, 86.3, and 72.7%, respectively. Geometric mean titers (GMT) of antibodies by day 21 post vaccination reached 175.7 for influenza А/H1N1pdm09 virus, 64.2 for influenza А/H3N2 virus, and 37.6 for influenza B virus; in placebo group GMT growth was not observed. So, the seasonal influenza split vaccine is well tolerated and fits all immunogenicity criteria for human influenza vaccines.
Resistance characterization of hepatitis C virus genotype 2 from Japanese patients treated with ombitasvir and paritaprevir/ritonavir
Authors: Schnell Gretja , Tripathi Rakesh , Krishnan Preethi , Beyer Jill , Reisch Thomas , Irvin Michelle , Dekhtyar Tatyana , Setze Carolyn , Rodrigues‐Jr Lino , Alves Katia , Burroughs Margaret , Redman Rebecca , Chayama Kazuaki , Kumada Hiromitsu , Collins Christine , Pilot‐Matias Tami
Published: August 2017

Treatment of HCV genotype (GT) 2‐infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) without ribavirin for 12 weeks in the phase 2 study M12‐536, and with ribavirin for 16 weeks in phase 3 study GIFT II resulted in SVR rates of 72.2% to 91.5%. Overall, 11 out of 125 patients with GT2a and 37 out of 79 patients with GT2b infection experienced virologic failure. The prevalence of baseline polymorphisms in NS3 and NS5A and their the impact on treatment outcome, as well as the development of viral resistance in GT2‐infected patients experiencing virologic failure were evaluated by HCV NS3 and NS5A population and clonal sequence analyses. Baseline polymorphisms in NS3 that confer resistance to paritaprevir were rare in both GT2a‐ and GT2b‐infected patients, while baseline polymorphisms in NS5A that confer resistance to ombitasvir were detected in 11.2% and 14.1% of the GT2a‐ and GT2b‐infected patients, respectively. There was no significant impact of baseline polymorphisms on treatment outcome in Japanese patients. The most common treatment‐emergent substitutions at the time of virologic failure occurred at amino acid positions 168 in NS3 and 28 in NS5A in both GT2a‐ and GT2b‐infected patients. Although there was a higher rate of virologic failure in patients with GT2b infection, the resistance analyses presented in this report support the conclusion that testing for baseline resistance‐associated polymorphisms is not warranted for HCV GT2‐infected patients treated with a regimen of ombitasvir/paritaprevir/ritonavir + ribavirin for 16 weeks.
Sevoflurane neurotoxicity in neonatal rats is related to an increase in the GABAAR α1/GABAAR α2 ratio
Authors: Xie Si‐Ning , Ye Hong , Li Jun‐Fa , An Li‐Xin
Published: August 2017

Exposure of neonatal rat to sevoflurane leads to neurodegeneration and deficits of spatial learning and memory in adulthood. However, the underlying mechanisms remain unclear. The type A γ‐aminobutyric acid receptor (GABAAR) is a target receptor for sevoflurane. The present study intends to investigate the changes in GABAAR α1/α2 expression and its relationship with the neurotoxicity effect due to sevoflurane in neonatal rats. After a dose–response curve was constructed to determine minimum alveolar concentration (MAC) and safety was guaranteed in our 7‐day‐old neonatal rat pup mode, we conducted two studies among the following groups: (A) the control group; (B) the sham anesthesia group; and (C) the sevoflurane anesthesia group and all three groups were treated in the same way as the model. First, poly(ADP‐ribose) polymerase‐1 protein (PARP‐1) expression was determined in the different brain areas at 6 hr after anesthesia. Second, the expression of PARP‐1 and GABAAR α1/GABAAR α2 in the hippocampus area was tested by Western blotting at 6 hr, 24 hr, and 72 hr after anesthesia in all three groups. After 4 hr, with 0.8 MAC (2.1%) sevoflurane anesthesia, the PARP‐1 expression was significantly higher in the hippocampus than the other brain areas (p < .05). Compared with Groups A and B, the expression of PARP‐1 in the hippocampus of Group C significantly increased at 6 hr after sevoflurane exposure (216% ± 15%, p < .05), and the ratio of the α1/α2 subunit of GABAAR surged at 6 hr (126% ± 6%), 24 hr (127% ± 8%), and 72 hr (183% ± 22%) after sevoflurane exposure in the hippocampus (p < .05). Our study showed that sevoflurane exposure of 0.8 MAC (2.1%)/4 hr was a suitable model for 7‐day‐old rats. And the exposure to sevoflurane could induce the apoptosis of neurons in the early stage, which may be related to the transmission from GABAAR α2 to GABAAR α1.
Interaction between optineurin and Rab1a regulates autophagosome formation in neuroblastoma cells
Authors: Song Gyun Jee , Jeon Hyejin , Seo Minchul , Jo Myungjin , Suk Kyoungho
Published: August 2017

Optineurin (OPTN) is an autophagy receptor protein that has been implicated in glaucoma and amyotrophic lateral sclerosis. OPTN‐mediated autophagy is a complex process involving many autophagy‐regulating proteins. Autophagy plays a critical role in removing damaged organelles, intracellular pathogens, and protein aggregates to maintain cellular homeostasis. We identified Ypt1 as a novel interaction partner of OPTN by performing a large‐scale yeast‐human two‐hybrid assay. Coimmunoprecipitation assay showed that OPTN interacted with Rab1, the mammalian homolog of yeast Ypt1, in N2a mouse neuroblastoma cell line. We confirmed this interaction by confocal microscopy showing intracellular colocalization of the two proteins. We observed that a zinc finger domain of OPTN is important for Rab1a binding. Rab1a activity is also required for the binding with OPTN. The role of the OPTN‐Rab1a complex in neuronal autophagy was determined by measuring the translocation of microtubule‐associated protein light chain 3–EGFP to autophagosomes. In N2a cells, OPTN‐induced autophagosome formation was inhibited by Rab1a knockdown, indicating the important role of OPTN‐Rab1a interaction in neuronal autophagy processes. Similarly, in N2a cells overexpressing Rab1a, serum starvation–induced formation of autophagosome was enhanced, while OPTN knockdown reduced the Rab1a‐induced autophagy. These results show that the OPTN‐Rab1a complex modulates autophagosome formation in neuroblastoma cells.
Impact of nitrogen source and supply level on growth, yield and nutritional value of two contrasting ecotypes of Cichorium spinosum L. grown hydroponically
Authors: Chatzigianni Martina , Alkhaled Bara'a , Livieratos Ioannis , Stamatakis Aristidis , Ntatsi Georgia , Savvas Dimitrios
Published: August 2017

BACKGROUND

In the present study, two contrasting stamnagathi (Cichorium spinosum L.) ecotypes originating either from a mountainous or from a seaside habitat were grown hydroponically and supplied with a nutrient solution differing in the total‐N level (4 or 16 mmol L–1) and the N source (NH4+‐N/total‐N: 0.05, 0.25 or 0.50). The aim was to search for genotypic differences in nitrogen nutrition.

RESULTS

At commercial maturity, the dry weight of mountainous plants was higher than that of seaside plants. The shoot mineral concentrations were higher in seaside plants than in mountainous plants in both harvests. The leaf nitrate concentration was influenced by the levels of both total‐N and NH4+‐N/total‐N at both harvests, whereas plants with a seaside origin exhibited higher nitrate concentrations than those originating from a mountainous site in all total‐N and NH4+‐N/total‐N treatments.

CONCLUSION

The two stamnagathi ecotypes differed considerably in their responses to nitrogen nutrition and tissue nitrate content. The mountainous ecotype was superior in terms of growth, tissue nitrate concentration and antioxidant capacity, whereas the seaside ecotype accumulated more nutrient microcations in leaves. A low total‐N concentration (up to 4 mmol L–1) combined with a high NH4+‐N/total‐N ratio (up to 0.05) could minimize tissue NO3– concentrations without compromising yield. © 2017 Society of Chemical Industry
Synthesis of novel octyl sinapate to enhance antioxidant capacity of rapeseed–linseed oil mixture
Authors: Szydłowska‐Czerniak Aleksandra , Rabiej Dobrochna , Krzemiński Marek
Published: August 2017

BACKGROUND

Lipophilisation allows the formation of new functionalised antioxidants having beneficial properties compared to natural hydrophilic phenolic acids. Therefore, this work focused on the synthesis of lipophilic antioxidants, such as a new octyl sinapate, octyl caffeate and octyl ferulate using the modified Fischer esterification of selected hydroxycinnamic acids with 1‐octanol.

RESULTS

The lipophilic octyl sinapate was obtained for the first time with satisfactory yield (83%) after purification by column chromatography. The identity of the synthesised phenolipids was confirmed by chromatographic and spectroscopic analyses. Antioxidant capacity of phenolipids was determined by DPPH (IC50 = 35.87–52.24 μg mL−1) and ABTS (IC50 = 39.45–48.72 μg mL−1) methods and compared with IC50 values (7.37–35.30 μg mL−1 and 7.55–41.67 μg mL−1, respectively) for well known antioxidants. The antioxidant capacity of rapeseed–linseed oil enriched with the purified esters was about two to 30 times higher in comparison with a non‐supplemented oil.

CONCLUSION

The novel octyl sinapate as well as octyl caffeate and octyl ferulate have antioxidant properties and lipophilic character, therefore they may be added to vegetable oils as potential antioxidants for tackling oxidative processes. © 2017 Society of Chemical Industry
Effect of pre‐bloom leaf removal on grape aroma composition and wine sensory profile of Semillon cultivar
Authors: Alessandrini Massimiliano , Battista Fabrizio , Panighel Annarita , Flamini Riccardo , Tomasi Diego
Published: August 2017

BACKGROUND

Early leaf removal at pre‐bloom is an innovative viticultural practice for regulating yield components and improving grape quality. The effects of this technique on vine performance, grape composition and wine sensory profile of Semillon variety were assessed.

RESULTS

Pre‐bloom leaf removal enhanced canopy porosity, total soluble solids in musts and reduced cluster compactness. This practice had a strong effect on glycoside aroma precursors, in particular by increasing glycoside terpenols and norisoprenoids. Metabolites of linalool were the most responsive to leaf removal. Wine produced from defoliated vines was preferred in tasting trials for its more intense fruity notes and mouthfeel attributes.

CONCLUSION

Pre‐bloom leaf removal is a powerful technique for modifying canopy microclimate, vine yield, grape composition and wine quality. The increase of glycoside aroma compounds in treated grapes has potential positive effect in improving the sensory profile of the resulting wines. © 2017 Society of Chemical Industry
Polyphenol‐rich pomegranate juice reduces IgE binding to cashew nut allergens
Authors: Li Yichen , Mattison Christopher P
Published: August 2017

BACKGROUND

Food allergy negatively impacts quality of life and can be life‐threatening. Cashew nuts can cause severe reactions in very small amounts, and they are included in a group of foods most commonly responsible for causing food allergy. Polyphenols and polyphenol‐rich juices have been demonstrated to complex with peanut allergens. Here, the interaction between cashew nut allergens and polyphenol‐rich juices is evaluated biochemically and immunologically.

RESULTS

Various juices, including pomegranate (POM), blueberry (BB), and concord grape (CG) juices, were evaluated for polyphenol content and formation of polyphenol–cashew allergen complexes. Among the various juices studied, POM juice showed a greater capacity to form complexes with cashew proteins. Dynamic light scattering (DLS) demonstrated a sharp increase in cashew protein extract particle size to around 3580 nm, and fewer cashew proteins were resolved by electrophoresis after treatment with POM juice. Immunoassays demonstrated reduced IgG and IgE binding to cashew allergens due to allergen precipitation by POM juice. These observations support the formation of complexes between polyphenol and cashew proteins that can prevent antibody recognition of cashew allergens through allergen precipitation.

CONCLUSION

POM juice treatment of cashew extract effectively reduces antibody binding through allergen precipitation, and these findings could be applied to the development of less allergenic cashew nut products and oral immunotherapy. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.