bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating diagnostic tests
Authors: Kennedy Ashley Graham
Published: April 2016

Although much has been written on the role of randomized controlled trials and mechanistic reasoning in the evaluation of therapeutic treatments, philosophers of medicine have not yet turned their attention to the question of how diagnostic tests and procedures should be evaluated. I aim to begin to fill this gap by examining each of the following questions:

What is the best way to determine the accuracy of a diagnostic test?

What is the best way to determine the clinical effectiveness of a diagnostic test?

Can an accurate diagnostic test be considered medically valuable even if it is not clinically effective?

I argue that while diagnostic accuracy is a minimum requirement for both clinical effectiveness and medical value, accuracy and effectiveness are not sufficient for determining the value of a diagnostic test, because diagnostic value extends beyond patient outcomes.
Effect of Selected Physico‐Chemical Factors on Bacterial Β‐Cryptoxanthin Degradation: Stability and Kinetic Study
Authors: Mitra Ruchira , Samanta Amit Kumar , Chaudhuri Surabhi , Dutta Debjani
Published: April 2016

Carotenoids are promising dietary supplements to human population due to its potential nutraceutical benefits. Their stability in food system is a big concern for food industry. In this study, stability of β‐cryptoxanthin (β‐CRX), a yellow colored pro‐vitamin A xanthophyll, extracted from a previously isolated bacterium Kocuria marina DAGII, was studied under different processing conditions by first‐order linear regression analysis and two‐way ANOVA. The results indicated that the β‐CRX resisted thermal treatments up to 50°C with degradation rate constants (k) of 0.3731–0.8661 h−1, thermal death times (D values) of 6.1715–2.6586 h, a z value of 169.5°C, an activation energy (
) of

, enthalpy
and entropy of activation (ΔS) of
and
, respectively, over the temperature range of
–
. The resulting positive Gibbs free energy change (
) indicated the non‐spontaneous nature of the degradation reaction. Neutral to basic pH was favorable for the β‐CRX processing. Light induced degradation was high
resulting into complete degradation of the β‐CRX. Furthermore, addition of metallic ions significantly affected the β‐CRX stability, however, it was stable in presence of
,
, oxidant
and reductant
. Till date there has been no detailed report on the degradation kinetics of β‐CRX, obtained from microbial source. Hence considering all the tested parameters, this study is significant for using the extracted bacterial β‐CRX as a dietary supplement.

Practical Applications

β‐CRX is a bioactive compound having great potential as a dietary supplement because of its therapeutic and immune‐enhancing properties, especially the pro‐vitamin A activity, anti‐oxidant and anti‐cancer properties. But, the stability of β‐CRX during food processing is a big concern due to the presence of polyunsaturated chains of conjugated double bonds. Thus, the present research work explores the stability of β‐CRX, extracted from Kocuria marina DAGII, under different selected parameters that are important for processing of food. This study gives an idea about the effective β‐CRX remaining after it is being exposed to high temperature, acidic pH, light and oxidizing environment. Results indicate the favorable conditions that should be maintained during the β‐CRX processing for industrial application. Assessment of the chemical kinetics and application of the mathematical model will also provide information for designing an optimum process so that minimum degradation of β‐CRX takes place.
Adiponectin regulates aquaglyceroporin expression in hepatic stellate cells altering their functional state
Authors: Tardelli Matteo , Moreno‐Viedma Veronica , Zeyda Maximilian , Itariu Bianca K , Langer Felix B , Prager Gerhard , Stulnig Thomas M
Published: April 2016

Background and Aim

Obesity is a major risk factor for liver fibrosis and tightly associated with low levels of adiponectin. Adiponectin has antifibrogenic activity protecting from liver fibrosis, which is mainly driven by activated hepatic stellate cells (HSC). Aquaporins are transmembrane proteins that allow the movement of water and, in case of aquaglyceroporins (AQPs), of glycerol that is needed in quiescent HSC for lipogenesis. Expression of various AQPs in liver is altered by obesity; however, the mechanisms through which obesity influences HSCs activation and AQPs expression remain unclear. This study aimed to identify obesity‐associated factors that are related to HSC AQPs expression activation and lipid storage.

Methods

Correlations between serum adipokine levels and hepatic AQPs gene expression were analyzed from a cohort of obese patients. AQP and fibrotic gene expression was determined in a HSC line (LX2) and in a hepatocyte cell line (HepG2) after stimulation with adiponectin using quantitative real‐time polymerase chain reaction.

Results

We found that serum adiponectin significantly correlated with liver AQP3, AQP7, AQP9 gene expressions. In vitro, adiponectin induced upregulation of AQP3 gene and AQP3 protein expression in human HSCs, but not in hepatocytes, while AQP7, AQP9 remained undetectable. Accordingly, HSC stimulated with adiponectin increased glycerol uptake, lipogenic gene expression, and lipid storage while downregulating activation/fibrosis markers.

Conclusions

These findings demonstrate that adiponectin is a potent inhibitor of HSC activation and induces AQPs expression. Thus, low serum levels of adiponectin could be a mechanism how obesity affects the functional state of HSC, thereby contributing to obesity‐associated liver fibrosis.
Phase equilibria modelling and zircon age dating of pelitic granulites in Zhaojiayao, from the Jining Group of the Khondalite Belt, North China Craton
Authors: Li X. W. , Wei C. J.
Published: April 2016

The Jining Group occurs as the eastern segment of the Khondalite Belt, North China Craton and is dominated by a series of granulite facies rocks involving ‘normal’ pelitic granulites recording peak temperatures of ~850 °C and ultrahigh‐temperature (UHT) pelitic granulites recording peak temperatures of 950–1100 °C. The P–T paths and ages of these two types of granulites are controversial. Three pelitic granulite samples in the Jining Group comprising two sillimanite–garnet gneiss samples (J1208 and J1210) and one spinel–garnet gneiss sample (J1303) were collected from Zhaojiayao, where ‘normal’ pelitic granulites occur, for determination of their metamorphic evolution and ages. Samples J1208 and J1210 are interpreted to record cooling paths from the Tmax stages with P–T conditions respectively of ~870–890 °C/7–8 kbar and >840 °C/>7.5 kbar constrained from the stability fields of the observed mineral assemblages and the isopleths of plagioclase, garnet and biotite compositions in pseudosections. Sample J1303 is interpreted to record pre‐Tmax decompression from the kyanite‐stability fields to the Tmax stage of 950–1020 °C/8–9 kbar and a post‐Tmax cooling path revealed mainly from the stability field of the observed mineral assemblage, the plagioclase zoning and the biotite composition isopleth in pseudosections. The post‐Tmax cooling stage can be divided into suprasolidus and subsolidus stages. The suprasolidus cooling may not result in an equilibrium state at the solidus in a rock. Therefore, different minerals may record different P–T conditions along the cooling path; the inferred maximum temperature is commonly higher than the solidus as well as different solidi being recorded for different samples from the same outcrop but experiencing different degrees of melt loss. Plagioclase compositions, especially its zoning in plagioclase‐rich granulites, are predicted to be useful for recording the higher temperature conditions of a granulite's thermal history. The three samples studied seem to record the temperature range covering those of the ‘normal’ and UHT pelitic granulites in the Jining Group, suggesting that UHT conditions may be reached in ‘normal’ granulites without diagnostic UHT indicators. LA‐ICP‐MS zircon U–Pb data provide a continuous trend of concordant 207Pb/206Pb ages from 1.89 to 1.79 Ga for sample J1210, and from 1.94 to 1.80 Ga for sample J1303. These continuous and long age spectrums are interpreted to represent a slow cooling and exhumation process corresponding to the post‐Tmax cooling P–T paths recorded by the pelitic granulites, which may have followed the exhumation of deeply buried rocks in a thickened crust region resulted from a collision event at c. 1.95 Ga as suggested by the pre‐Tmax decompression P–T path.
BRAFV600E mutation in the diagnosis of unicystic ameloblastoma
Authors: Pereira Núbia Braga , Pereira Karuza Maria Alves , Coura Bruna Pizziolo , Diniz Marina Gonçalves , de Castro Wagner Henriques , Gomes Carolina Cavalieri , Gomez Ricardo Santiago
Published: April 2016

Background

Unicystic ameloblastoma, an odontogenic neoplasm, presents clinical and radiographic similarities with dentigerous and radicular cysts, non‐neoplastic lesions. It is not always possible to reach a final diagnosis with the incisional biopsy, leading to inappropriate treatment. The BRAFV600E activating mutation has been reported in a high proportion of ameloblastomas. The purpose of the study was to assess the utility of the detection of the BRAFV600E mutation in the differential diagnosis of unicystic ameloblastoma with dentigerous and radicular cysts.

Methods

Twenty‐six archival samples were included, comprising eight unicystic ameloblastomas (UAs), nine dentigerous and nine radicular cysts. The mutation was assessed in all samples by anti‐BRAFV600E (clone VE1) immunohistochemistry (IHC) and by TaqMan mutation detection qPCR assay. Sanger sequencing was further carried out when samples showed conflicting results in the IHC and qPCR.

Results

Although all UAs (8/8) showed positive uniform BRAFV600E staining along the epithelial lining length, the mutation was not confirmed by qPCR and Sanger sequencing in three samples. Positive staining for the BRAFV600E protein was observed in one dentigerous cyst, but it was not confirmed by the molecular methods. Furthermore, 2/9 dentigerous cysts and 2/9 radicular cysts showed non‐specific immunostaining of the epithelium or plasma cells. None of the dentigerous or radicular cysts cases presented the BRAFV600E mutation in the qPCR assay.

Conclusions

The BRAFV600E antibody (clone VE1) IHC may show non‐specific staining, but molecular assays may be useful for the diagnosis of unicystic ameloblastoma, in conjunction with clinical, radiological and histopathological features.
Regulatory T cells in oral squamous cell carcinoma
Authors: Liu Sai , Liu Dongjuan , Li Jing , Zhang Dunfang , Chen Qianming
Published: April 2016

Regulatory T cells (Tregs) play a critical role in modulating and maintaining immune homeostasis and tolerance. They accumulate in many types of tumors and play a critical role in tumor evasion of immune surveillance. Oral cancer is characterized by an increase in the number of infiltrating Tregs; however, the significance of this increase on the prognosis of oral cancer is controversial. This review focuses on the function of Tregs in oral squamous cell carcinoma and its implications on prognosis. We also discuss potential therapeutic strategies aimed at Tregs modification in oral SCC.
Phenotypically non‐suppressive cells predominate among FoxP3‐positive cells in oral lichen planus
Authors: Schreurs Olav , Karatsaidis Andreas , Schenck Karl
Published: April 2016

Background

Oral lichen planus (OLP) is a common T‐cell‐dominated oral chronic inflammatory disease occurring in periods of remission, quiescence, activity with pronounced inflammation, and acute ulceration. Cell infiltrates in OLP contain varying numbers of CD4+ T cells expressing the transcription factor FoxP3. FoxP3+CD4+ T cells are, however, a heterogeneous cell population containing suppressive and non‐suppressive cells, and their distribution in infiltrates from OLP is unknown.

Methods

Biopsies were taken from normal oral mucosa (n = 8) and OLP lesions (n = 19), and a set of in situ methods for the determination of the functional phenotype of FoxP3+CD4+ T cells was applied.

Results

Numbers of FoxP3+CD4+ T cells were highest in the atrophic form of the disease, yet low in the ulcerative form. The main FoxP3+CD4+ T‐cell population observed was FoxP3+CD45RA−CD25+CD45RO+ and CD15s−, a phenotype delineating a non‐suppressive subset. Numbers of cells with an actively suppressing phenotype (FoxP3+CD45RA−CD25+CD45RO+ and CD15s+) were, however, about twice as high in reticular lesions as compared with the atrophic form. Many FoxP3+CD4+ T cells expressed T‐bet, the hallmark transcription factor for IFN‐γ‐producing T cells, indicating that they may enhance immune and inflammatory responses rather than suppress them.

Conclusions

The absence of actively suppressing FoxP3+CD4+ T cells may in part explain why OLP is a remarkably persisting condition, in spite of the presence of substantially high numbers of FoxP3+CD4+ T cells. The findings emphasize that it is crucial to examine not only numbers but also functional phenotype of FoxP3+CD4+ T cells in human tissues.
Domain Specificity in Adolescents’ Concepts of Laws: Associations Among Beliefs and Behavior
Authors: Oosterhoff Benjamin , Metzger Aaron
Published: April 2016

Using detailed vignettes and scale measures, concepts of laws regulating domain‐specific issues and engagement in delinquency were assessed among 340 9th through 12th graders (Mage = 16.64, SD = 1.37). Adolescents distinguished between laws that regulate moral, drug‐related prudential, conventional, personal, and multifaceted issues in their criterion judgments and justifications. Youths’ ratings of the importance of laws, obligation to obey laws, and deserved punishment for breaking different laws also followed domain‐consistent patterns. Adolescents’ engagement in moral, drug‐related prudential, and multifaceted forms of delinquency was associated with less supportive judgments about laws within the same domain. Findings contribute to civic development research by demonstrating domain specificity in adolescents’ beliefs about laws and suggest that these beliefs are linked with engagement in similar types of delinquency.
Using nuclear genes to reconstruct angiosperm phylogeny at the species level: A case study with Brassicaceae species
Authors: Cai Liming , Ma Hong
Published: April 2016

Angiosperm phylogeny has been investigated extensively using organellar sequences; recent efforts using nuclear genes have also been successful in reconstructing angiosperm phylogenies at family or deeper levels. However, it is not clear whether nuclear genes are also effective in understanding relationships between species in a genus. Here we present a case study of phylogeny at generic and specific levels with nuclear genes, using Brassicaceae taxa as examples. Brassicaceae includes various crops and the model plant Arabidopsis thaliana. A recent study showed that nuclear genes can provide well‐resolved relationships between tribes and larger lineages in Brassicaceae, but few species were included in any given genus. We present a phylogeny with multiple species in each of five genera within Brassicaceae for a total of 65 taxa, using three protein‐coding nuclear genes, MLH1, SMC2, and MCM5, with up to approximately 10 200 base pairs (in both exons and introns). Maximum likelihood and Bayesian analyses of the separate gene regions and combined data reveal high resolution at various phylogenetic depths. The relationships between genera here were largely congruent with previous results, with further resolution at the species level. Also, we report for the first time the affinity of Cardamine rockii with tribe Camelineae instead of other Cardamine members. In addition, we report sequence divergence at three levels: across angiosperms, among Brassicaceae species, and between Arabidopsis ecotypes. Our results provide a robust species‐level phylogeny for a number of Brassicaceae members and support an optimistic perspective on the phylogenetic utility of conserved nuclear data for relatively recent clades.
SilE is an intrinsically disordered periplasmic “molecular sponge” involved in bacterial silver resistance
Authors: Asiani Karishma R. , Williams Huw , Bird Louise , Jenner Matthew , Searle Mark S. , Hobman Jon L. , Scott David J. , Soultanas Panos
Published: April 2016

Ag+ resistance was initially found on the Salmonella enetrica serovar Typhimurium multi‐resistance plasmid pMG101 from burns patients in 1975. The putative model of Ag+ resistance, encoded by the sil operon from pMG101, involves export of Ag+ via an ATPase (SilP), an effluxer complex (SilCFBA) and a periplasmic chaperon of Ag+ (SilE). SilE is predicted to be intrinsically disordered. We tested this hypothesis using structural and biophysical studies and show that SilE is an intrinsically disordered protein in its free apo‐form but folds to a compact structure upon optimal binding to six Ag+ ions in its holo‐form. Sequence analyses and site‐directed mutagenesis established the importance of histidine and methionine containing motifs for Ag+‐binding, and identified a nucleation core that initiates Ag+‐mediated folding of SilE. We conclude that SilE is a molecular sponge for absorbing metal ions.
Identification of phenolic compounds that suppress the virulence of Xanthomonas oryzae on rice via the type III secretion system
Authors: Fan Susu , Tian Fang , Li Jianyu , Hutchins William , Chen Huamin , Yang Fenghuan , Yuan Xiaochen , Cui Zining , Yang Ching‐Hong , He Chenyang
Published: April 2016

The targeting of bacterial type III secretion systems (T3SSs), which are critical virulence factors in most Gram‐negative pathogens, is regarded as an alternative strategy for the development of novel anti‐microbial drugs. Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc) are two of the most important bacterial pathogens on rice, which cause leaf blight and leaf streak diseases, respectively. To identify potential anti‐virulence drugs against these two pathogens, we screened a library of plant phenolic compounds and derivatives for their effects on the Xoo T3SS. Ten of 56 compounds significantly inhibited the promoter activity of a harpin gene, hpa1. These inhibitors were further tested for their impact on the hypersensitive response (HR) caused by Xoo on non‐host tobacco plants. The results showed that pretreatment of Xoo with TS006 (o‐coumaric acid, OCA), TS010, TS015 and TS018 resulted in significantly attenuated HR without affecting bacterial growth or survival. In addition, Cya translocation assays demonstrated that the translocation of two T3 effectors was suppressed by the four inhibitors. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) analysis showed that mRNA levels of representative genes in the hrp (hypersensitive response and pathogenicity) cluster, as well as the regulatory genes hrpG and hrpX, were reduced by treatment with the four inhibitors, suggesting that expression of the Xoo T3SS was suppressed. The expression of other virulence factors was not suppressed, which indicated possible T3SS‐specific inhibition. Finally, we demonstrated that these inhibitors reduced the disease symptoms of Xoo and Xoc on the rice cultivar (Oryza sativa) IR24 to varying extents.
A case of intravascular large B cell lymphoma: New clinical and immunohistochemical findings
Authors: Mansueto Gelsomina , Di Vito Anna , Belluomo Clara , Murino Patrizia , Natella Valentina , Camastra Caterina , Presta Ivan , Malara Natalia , de Rosa Gaetano , Donato Giuseppe , Mignogna Chiara
Published: April 2016

Intravascular large B cell lymphoma (IVLBCL) is a rare extranodal non‐Hodgkin lymphoma characterized by proliferation of malignant cells within the lumen of small vessels, with a predilection for the CNS and the skin. IVLBCL clinical course is highly aggressive, clinical signs and symptoms are not specific and may consist of neurological and cognitive impairment, fever of unknown origin and cutaneous lesions, lacking of a typical neuroimaging pattern. For all these reasons the diagnosis is commonly missed and the exitus is frequent, therefore post mortem evaluation is necessary to clarify the clinical history. We present a case of IVLBCL in a 62‐year‐old woman with unusual symptomatology, mimicking a vascular, multi‐infarctual cerebropathy. Hachinski Ischemic Score was 7 suggesting a vascular dementia. Autopsy was unable to define the nature of the disease. Immunohistochemical analysis for cluster of differentiation 20 (CD20) revealed the ubiquitous presence of malignant lymphoid B‐cells into the vessel of all organs analyzed, allowing the definitive diagnosis of IVLBCL. The atypical cells expressed high levels of anti‐apoptotic proteins B‐cell lymphoma 2 (Bcl‐2) and Galectin‐3, and showed cellular myelocytomatosis (c‐Myc) staining in <50% of tumor nuclei. Conversely, cells were immunonegative for multiple myeloma‐1 (MUM1), CD3, CD44, CD30, CD34 and CD133. Fluorescent in situ hybridization analysis for MYC rearrangements was negative. The high expression of Galectin‐3 provides new insights in the understanding of molecular pathogenesis of IVLBCL; indeed, such a finding represents a prognostic factor for other types of lymphoma and should, in the same way, be taken into account in IVLBCL.
HD2C histone deacetylase and a SWI/SNF chromatin remodelling complex interact and both are involved in mediating the heat stress response in Arabidopsis
Authors: Buszewicz Daniel , Archacki Rafał , Palusiński Antoni , Kotliński Maciej , Fogtman Anna , Iwanicka‐Nowicka Roksana , Sosnowska Katarzyna , Kuciński Jan , Pupel Piotr , Olędzki Jacek , Dadlez Michał , Misicka Aleksandra , Jerzmanowski Andrzej , Koblowska Marta Kamila
Published: April 2016

Studies in yeast and animals have revealed that histone deacetylases (HDACs) often act as components of multiprotein complexes, including chromatin remodelling complexes (CRCs). However, interactions between HDACs and CRCs in plants have yet to be demonstrated. Here, we present evidence for the interaction between Arabidopsis HD2C deacetylase and a BRM‐containing SWI/SNF CRC. Moreover, we reveal a novel function of HD2C as a regulator of the heat stress response. HD2C transcript levels were strongly induced in plants subjected to heat treatment, and the expression of selected heat‐responsive genes was up‐regulated in heat‐stressed hd2c mutant, suggesting that HD2C acts to down‐regulate heat‐activated genes. In keeping with the HDAC activity of HD2C, the altered expression of HD2C‐regulated genes coincided in most cases with increased histone acetylation at their loci. Microarray transcriptome analysis of hd2c and brm mutants identified a subset of commonly regulated heat‐responsive genes, and the effect of the brm hd2c double mutation on the expression of these genes was non‐additive. Moreover, heat‐treated 3‐week‐old hd2c, brm and brm hd2c mutants displayed similar rates of growth retardation. Taken together, our findings suggest that HD2C and BRM act in a common genetic pathway to regulate the Arabidopsis heat stress response.
Effect of zinc plus multivitamin supplementation on growth in school children
Authors: Rerksuppaphol Sanguansak , Rerksuppaphol Lakkana
Published: April 2016

Background

Zinc and multiple vitamins are essential for growth. Zinc and vitamin deficiency is very common in developing countries. The aim of this study was to assess the efficacy of zinc plus multivitamin supplements in improving growth of healthy Thai schoolchildren.

Methods

A randomized controlled trial was conducted in healthy 4–13‐year‐old Thai schoolchildren attending public school in central Thailand. Participants were randomized to receive either chelated zinc in the form of zinc bis‐glycinate (20 mg elemental zinc) plus multivitamins (vitamin A, 1000 IU; vitamin D, 200 IU; B1, 10 mg; B2, 3 mg; B6, 1 mg; B12, 10 μg; nicotinamide, 40 mg) or placebo once per day, 5 days per week for 6 months. Primary outcome was change in height from baseline to the end of the study. Secondary outcomes were change in weight, body mass index, waist and hip circumferences and waist‐to‐height ratio. An intention‐to‐treat analysis was performed.

Results

Seventy children each were randomized to the treatment and placebo groups. The children who received zinc and multivitamins had significantly higher gain in height (4.9 ± 1.3 vs 3.6 ± 0.9 cm, respectively; P < 0.001). Subgroup analysis showed significant improvement in height, especially in preadolescents. The increased gain in height was irrespective of baseline height and weight. The extra gain in height occurred after 2 months of supplementation. The changes in other anthropometric indices were not significantly different.

Conclusion

Supplementation of chelated zinc plus multivitamins for 6 months significantly increased height gain in Thai schoolchildren and was well tolerated.
Neurodevelopment of preterm infants born after in vitro fertilization and spontaneous multiple pregnancy
Authors: Ramoğlu Mehmet , Kavuncuoğlu Sultan , Aldemir Esin , Yarar Coşkun , Eras Zeynep
Published: April 2016

Background

The aim of this study was to compare perinatal, neonatal characteristics and neurodevelopmental prognosis of preterm infants born after in vitro fertilization (IVF) and spontaneous multiple pregnancy, and to evaluate the factors affecting neurodevelopmental outcome at 24–36 months.

Methods

A total of 125 preterm infants, 65 from spontaneous and 60 from IVF multiple pregnancy were evaluated in terms of neurodevelopmental outcome at the age of 24–36 months. Mean maternal age, chronic maternal disease, birthweight, gestational week, gender, APGAR score, neonatal intensive care unit admission, presence of congenital anomalies, referral to follow up, rehospitalization and socioeconomic status were investigated. Gross Motor Function Classification System and Denver II Developmental Screening Test were carried out. Local ethics committee approved the study (12.10.2010; no: 305).

Results

Mean maternal age, chronic maternal illness, pregnancy‐related diseases, 5 min APGAR score, rate of cesarean delivery and referral to follow up were significantly higher in the IVF group (P < 0.05). Neurological examination identified increased muscle tone in two children (1.6%); only one infant in the IVF group had cerebral palsy. A total of 26 subjects (20.8%; spontaneous group, n =17, 26.2%; IVF group, n = 9, 15%) had abnormal Denver II findings, mostly in language (8.8%) and personal–social (8.0%) development.

Conclusion

Morbidity, length of hospitalization and neurodevelopmental outcome of preterm infants born after spontaneous and IVF multiple pregnancy are similar. Delays in language and personal–social development were the most common neurodevelopmental abnormalities. Even within similar socioeconomic status, parents in the IVF group were more compliant with follow up.
Postal contact with participating children and its impact on response rate: Japan Environment and Children's Pilot Study
Authors: Senju Ayako , Suga Reiko , Tsuji Mayumi , Shibata Eiji , Anan Ayumi , Yamamoto Yukiyo , Kusuhara Koichi , Kawamoto Toshihiro
Published: April 2016

Background

Communication with participating children and its effect on participation outcome is one of the most important but untouched issues in birth cohort studies. The purpose of this study was to assess the effect of postal communication with the participating preschool children on the response rate to postal questionnaires.

Methods

One hundred and five mother–preschool child pairs from the Japan Environment and Children's Study (JECS) pilot cohort were included. During the 6 month study period, letters addressed to the children were enclosed with our biannual questionnaires, and the response rate transition was observed. Additionally, the participants were allocated to two groups. One of these was sent the letter with the individual name of the child at the top, and the other without it. The response rates of the two groups were compared using chi‐squared test. Parents' impressions of the letters and the changes in their motivation to complete the questionnaires were surveyed using an evaluation form.

Results

The overall response rate was 83.8%, which was lower than the previous survey period. Response rate was not significantly different between the two letter types. The duration before questionnaire return was not changed. Despite their favorable impression based on parent evaluation, the letters were not associated with the parents' motivation to respond.

Conclusion

Letters to participating preschool children had no effect on response rate, but the long‐term impact of its favorability still remains to be evaluated. A similar trial at later ages may be more effective.
Brazilian infant motor and cognitive development: Longitudinal influence of risk factors
Authors: Pereira Keila RG , Valentini Nadia C , Saccani Raquel
Published: April 2016

Background

Infant developmental delays have been associated with several risk factors, such as familial environmental, individual and demographic characteristics. The goal of this study was to longitudinally investigate the effects of maternal knowledge and practices, home environment and biological factors on infant motor and cognitive outcomes.

Methods

This was a prospective cohort study with a sample of 49 infants from Southern Brazil. The infants were assessed three times over 4 months using the Alberta Infant Motor Scale and the Bayley Scale of Infant Development (Mental Development Scale). Parents completed the Daily Activities Scale of Infants, the Affordances in The Home Environment for Motor Development – Infant Scale, the Knowledge of Infant Development Inventory and a demographic questionnaire. Generalized estimating equation with Bonferroni method as the follow‐up test and Spearman correlation and multivariate linear backward regression were used.

Results

Cognitive and motor scores were strongly associated longitudinally and increased over time. Associations between the home affordances, parental practices and knowledge, and motor and cognitive development over time were observed. This relationship explained more variability in motor and cognitive scores compared with biological factors.

Conclusions

Variability in motor and cognitive development is better explained by environment and parental knowledge and practice. The investigation of factors associated with infant development allows the identification of infants at risk and the implementation of educational programs and parental training to minimize the effects of developmental delay.
Factors associated with cessation of sunbed use among Danish women
Authors: Wøhlk Ida Marie Rye , Philipsen Peter Alshede , Wulf Hans Christian
Published: April 2016

Background/purpose

Sunbed use is a known risk factor for malignant melanoma and non‐melanoma skin cancer. This study characterizes current and past female Danish sunbed users for the purpose of finding factors leading to cessation of sunbed use.

Methods

An online questionnaire was distributed via social media and email on February 25, 2014. 561 women responded.

Results

Sunbed use was found to be associated with smoking, light and light brown skin colour, and knowledge about the risks associated with sunbed use. Motivation for tanning was found to be increased attractiveness. Factors associated with cessation were: age above 24, medium to high level of education, non‐smoking, not being bothered by appearing white on the beach, and being unconcerned about friends' sunbed use. Binary logistic regression further showed a significant association between cessation and low income, after adjusting for age. The most indicated reason for cessation was fear of skin cancer.

Conclusion

Sunbed use could possibly be reduced by introducing a lower age limit of 18 and demanding staffed tanning salons. The age limit would allow young people to become more mature and self‐confident before deciding on using a sunbed. Our results suggest that future interventions and campaigns against the use of sunbeds should target young women with no or little postschool education.
The clinical severity score of chronic actinic dermatitis correlates with in vivo photoallergic reactions and the immunologic parameters related to a shift towards Th2 immunity from the Th2/Th1 balanced status in patients with chronic actinic dermatitis
Authors: Ko Dong‐Yeob , Choi Seung‐Hwan , Ha Seung‐Min , Kim Tae‐Hoon , Song Ki‐Hoon , Kim Kyeong Hee , Kim Ki‐Ho
Published: April 2016

Background

Chronic actinic dermatitis (CAD) has a more complicated pathogenetic basis than others. The clinical grading system and its correlations with the clinical and immunological parameters still remained to be investigated to define the nature of CAD in a more detailed manner.

Objectives

We investigated correlations of the clinical severity score of CAD (CSS‐CAD) with the clinical and immunological parameters.

Methods

We evaluated 72 patients with CAD and classified them into three groups according to the CSS‐CAD. We analysed total IgE level, peripheral blood (PB) eosinophil count, the ratio of Th2cell (CCR4 + CD4 +) percentage over Th1 cell (CXCR3 + CD4 +) percentage (Th2/Th1) and/or the sum of suppressor/cytotoxic T cells.

Results

The total IgE levels and the percentage of PB eosinophils were higher in the severer group than other groups. A shift towards Th2 from Th2/Th1 balanced status may be affected by total counts of suppressor T cells, and the patient with higher Th2/Th1 ratio than balanced status had the more proportion in the severer CSS‐CAD group than other groups.

Conclusion

The CSS‐CAD correlates with total IgE level, PB eosinophil count and a shift towards Th2 immunity from Th2/Th1. So we suggest the Th1/Th2 dysbalance may be affected by the CSS‐CAD.
Craniofacial phenotyping for prediction of obstructive sleep apnoea in a Chinese population
Authors: Sutherland Kate , Lee Richard W. W. , Petocz Peter , Chan Tat On , Ng Susanna , Hui David S. , Cistulli Peter A.
Published: April 2016

Background and objective

Craniofacial morphology is a risk factor for obstructive sleep apnoea (OSA). Facial photography has previously shown utility in predicting OSA in a Caucasian sleep clinic. However, ethnic differences in OSA risk factors may influence these facial predictors. Our aim was to assess phenotypical facial measurements for OSA prediction in a Chinese population.

Methods

Calibrated frontal and profile facial photographs were taken before polysomnography. Photographs were analysed to derive head, face and neck measurements. Demographical, anthropometrical and facial photographical variables were considered in prediction models for OSA. OSA prediction models were derived using logistic regression and classification and regression tree techniques.

Results

Two‐hundred subjects were recruited (146 OSA, 54 controls). The OSA group contained more men (77% vs 61%) and were more obese. Logistic regression modelling found cervicomental angle (OR 1.06/degree, 95% CI: 1.03–1.09, P < 0.001) and face width (OR 1.7/cm, 95% CI: 1.1–2.7, P = 0.02) predicted OSA (area under the receiver operating characteristics curve 0.76). Classification and regression tree analysis identified cricomental space area, mandibular width, mandibular plane angle and neck soft tissue area as predictors (area under receiver operating characteristics curve 0.81).

Conclusion

In a Hong Kong Chinese sleep clinic, facial photographical measurements had predictive utility for OSA. Prediction models had similar accuracy and included variables to a previous Caucasian population.
Shape remodeling and blebbing of active cytoskeletal vesicles
Authors: Loiseau Etienne , Schneider Jochen A. M. , Keber Felix C. , Pelzl Carina , Massiera Gladys , Salbreux Guillaume , Bausch Andreas R.
Published: April 2016

Cell-sized biomimetic active cytoskeletal vesicles undergo blebbing and shape remodeling due to myosin contractile activity.
Record Balkan floods of 2014 linked to planetary wave resonance
Authors: Stadtherr Lisa , Coumou Dim , Petoukhov Vladimir , Petri Stefan , Rahmstorf Stefan
Published: April 2016

Resonating atmospheric waves slowed down a cyclone’s movement, leading to four successive days of heavy rainfall over the Balkans.
Evidence for partial melt in the crust beneath Mt. Paektu (Changbaishan), Democratic People’s Republic of Korea and China
Authors: Kyong-Song Ri , Hammond James O. S. , Chol-Nam Ko , Hyok Kim , Yong-Gun Yun , Gil-Jong Pak , Chong-Song Ri , Oppenheimer Clive , Liu Kosima W. , Iacovino Kayla , Kum-Ran Ryu
Published: April 2016

Magma beneath Mt. Paektu may be associated with an episode of volcanic unrest that occurred between 2002 and 2005.
Room temperature detection of individual molecular physisorption using suspended bilayer graphene
Authors: Sun Jian , Muruganathan Manoharan , Mizuta Hiroshi
Published: April 2016

Researchers detect individual CO
2
physisorption with suspended bilayer graphene based on induced Coulomb impurity scattering.
Direct visualization of the thermomagnetic behavior of pseudo–single-domain magnetite particles
Authors: Almeida Trevor P. , Muxworthy Adrian R. , Kovács András , Williams Wyn , Brown Paul D. , Dunin-Borkowski Rafal E.
Published: April 2016

In situ electron microscopy is used to visualize the thermomagnetic behavior of vortex domain states within magnetic minerals.
Ultraflexible organic photonic skin
Authors: Yokota Tomoyuki , Zalar Peter , Kaltenbrunner Martin , Jinno Hiroaki , Matsuhisa Naoji , Kitanosako Hiroki , Tachibana Yutaro , Yukita Wakako , Koizumi Mari , Someya Takao
Published: April 2016

Optoelectronic electronic skins, or e-skins, introduce electronic sensing and displays on the surface of human skin.
Large anomalous Hall effect driven by a nonvanishing Berry curvature in the noncolinear antiferromagnet Mn
3
Ge
Authors: Nayak Ajaya K. , Fischer Julia Erika , Sun Yan , Yan Binghai , Karel Julie , Komarek Alexander C. , Shekhar Chandra , Kumar Nitesh , Schnelle Walter , Kübler Jürgen , Felser Claudia , Parkin Stuart S. P.
Published: April 2016

A large anomalous Hall effect is observed in the triangular antiferromagnet Mn
3
Ge arising from an intrinsic electronic Berry phase.
Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure
Authors: Nicklisch Sascha C. T. , Rees Steven D. , McGrath Aaron P. , Gökirmak Tufan , Bonito Lindsay T. , Vermeer Lydia M. , Cregger Cristina , Loewen Greg , Sandin Stuart , Chang Geoffrey , Hamdoun Amro
Published: April 2016

Common seafood pollutants inhibit a crucial cellular defense protein.
Two faces of WNT signaling
Authors: Gough Nancy R.
Published: April 2016

Endogenous WNT antagonists have roles in both childhood brain cancer and melanoma in the elderly.
New connections: T cell actin dynamics
Authors: Gough Nancy R.
Published: April 2016

Live-cell imaging reveals the dynamics of the cytoskeleton in activated T cells.
New connections: Species-specific immune responses
Authors: Foley John F.
Published: April 2016

Mouse and human macrophages use distinct signaling molecules to respond to similar stimuli.
Complete Sequences of
mcr-1
-Harboring Plasmids from Extended-Spectrum-β-Lactamase- and Carbapenemase-Producing Enterobacteriaceae
Authors: Li Aiqing , Yang Yong , Miao Minhui , Chavda Kalyan D. , Mediavilla José R. , Xie Xiaofang , Feng Ping , Tang Yi-Wei , Kreiswirth Barry N. , Chen Liang , Du Hong
Published: April 2016

Here we completely sequenced four
mcr-1
-haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing
Escherichia coli
and two carbapenemase-producing
Klebsiella pneumoniae
clinical isolates. The
mcr-1
-harboring plasmids from an
E. coli
sequence type 2448 (ST2448) isolate and two
K. pneumoniae
ST25 isolates were identical (all pMCR1-IncX4), belonging to the IncX4 incompatibility group, while the plasmid from an
E. coli
ST2085 isolate (pMCR1-IncI2) belongs to the IncI2 group. A nearly identical 2.6-kb
mcr-1-pap2
element was found to be shared by all
mcr-1
-carrying plasmids.
Synthesis and Antimicrobial Evaluation of Amixicile-Based Inhibitors of the Pyruvate-Ferredoxin Oxidoreductases of Anaerobic Bacteria and Epsilonproteobacteria
Authors: Kennedy Andrew J. , Bruce Alexandra M. , Gineste Catherine , Ballard T. Eric , Olekhnovich Igor N. , Macdonald Timothy L. , Hoffman Paul S.
Published: April 2016

Amixicile is a promising derivative of nitazoxanide (an antiparasitic therapeutic) developed to treat systemic infections caused by anaerobic bacteria, anaerobic parasites, and members of the
Epsilonproteobacteria
(
Campylobacter
and
Helicobacter
). Amixicile selectively inhibits pyruvate-ferredoxin oxidoreductase (PFOR) and related enzymes by inhibiting the function of the vitamin B
1
cofactor (thiamine pyrophosphate) by a novel mechanism. Here, we interrogate the amixicile scaffold, guided by docking simulations, direct PFOR inhibition assays, and MIC tests against
Clostridium difficile
,
Campylobacter jejuni
, and
Helicobacter pylori
. Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4′-aminopyrimidine of thiamine pyrophosphate (TPP). The
ortho
-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biological activity against
C. difficile
. Docking simulation results correlate well with mechanistic enzymology and nuclear magnetic resonance (NMR) studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B
1
function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance.
Identification of a Third Mn(II) Oxidase Enzyme in Pseudomonas putida GB-1
Authors: Geszvain Kati , Smesrud Logan , Tebo Bradley M.
Published: April 2016

The oxidation of soluble Mn(II) to insoluble Mn(IV) is a widespread bacterial activity found in a diverse array of microbes. In the Mn(II)-oxidizing bacterium
Pseudomonas putida
GB-1, two Mn(II) oxidase genes, named
mnxG
and
mcoA
, were previously identified; each encodes a multicopper oxidase (MCO)-type enzyme. Expression of these two genes is positively regulated by the response regulator MnxR. Preliminary investigation into putative additional regulatory pathways suggested that the flagellar regulators FleN and FleQ also regulate Mn(II) oxidase activity; however, it also revealed the presence of a third, previously uncharacterized Mn(II) oxidase activity in
P. putida
GB-1. A strain from which both of the Mn(II) oxidase genes and
fleQ
were deleted exhibited low levels of Mn(II) oxidase activity. The enzyme responsible was genetically and biochemically identified as an animal heme peroxidase (AHP) with domain and sequence similarity to the previously identified Mn(II) oxidase MopA. In the Δ
fleQ
strain,
P. putida
GB-1 MopA is overexpressed and secreted from the cell, where it actively oxidizes Mn. Thus, deletion of
fleQ
unmasked a third Mn(II) oxidase activity in this strain. These results provide an example of an Mn(II)-oxidizing bacterium utilizing both MCO and AHP enzymes.

IMPORTANCE
The identity of the Mn(II) oxidase enzyme in
Pseudomonas putida
GB-1 has been a long-standing question in the field of bacterial Mn(II) oxidation. In the current work, we demonstrate that
P. putida
GB-1 employs both the multicopper oxidase- and animal heme peroxidase-mediated pathways for the oxidation of Mn(II), rendering this model organism relevant to the study of both types of Mn(II) oxidase enzymes. The presence of three oxidase enzymes in
P. putida
GB-1 deepens the mystery of why microorganisms oxidize Mn(II) while providing the field with the tools necessary to address this question. The initial identification of MopA as a Mn(II) oxidase in this strain required the deletion of FleQ, a regulator involved in both flagellum synthesis and biofilm synthesis in
Pseudomonas aeruginosa
. Therefore, these results are also an important step toward understanding the regulation of Mn(II) oxidation.
Metrics Proposed To Prevent the Harvest of Leafy Green Crops Exposed to Floodwater Contaminated with Escherichia coli
Authors: Callahan Mary Theresa , Micallef Shirley A. , Sharma Manan , Millner Patricia D. , Buchanan Robert L.
Published: April 2016

The California Leafy Green Products Handler Marketing Agreement (LGMA) requires leafy green crops within 9 m of the edge of a flooded field not be harvested due to potential contamination (California Leafy Green Products Handler Marketing Board,
Commodity Specific Flood Safety Guidelines for the Production and Harvest of Lettuce and Leafy Greens
, 2012). Further, previously flooded soils should not be replanted for 60 days. In this study, the suitability of the LGMA metrics for farms in the Mid-Atlantic region of the United States was evaluated. The upper end of a spinach bed (in Beltsville, MD) established on a −5% grade was flooded with water containing 6 log CFU/ml
Escherichia coli
to model a worst-case scenario of bacterial movement through soil.
Escherichia coli
prevalence in soil and on foliar tissue was determined by most probable number (MPN) analysis at distances up to 9 m from the edge of the flood for 63 days. While
E. coli
was quickly detected at the 9-m distance within 1 day in the spring trial and within 3 days in the fall trial, no
E. coli
was detected on plants outside the flood zone after 14 days. On day 63 for the two trials,
E. coli
populations in the flood zone soil were higher in the fall than in the spring. Regression analysis predicted that the time required for a 3-log MPN/g (dry weight) decrease in
E. coli
populations inside the flood zone was within the 60-day LGMA guideline in the spring but would require 90 days in the fall. Overall, data suggest that the current guidelines should be revised to include considerations of field and weather conditions that may promote bacterial movement and survival.

IMPORTANCE
This study tracked the movement of
Escherichia coli
from floodwater across a horizontal plane of soil and the potential for the contamination of distant leafy green produce. The purpose of this study was to address the validity of the California Leafy Green Products Handler Marketing Agreement recommendations for the harvest of leafy green crops after a flooding event. These recommendations were based on the turning radius of farming equipment but did not take into consideration the potential subsurface movement of pathogens in the water through soil. This research shows that further considerations of field slope, temperature, and additional rainfall events may be necessary to provide appropriate guidelines to prevent the harvest of leafy green crops contaminated by enteric pathogens in floodwaters. This study may be used to provide a framework for comprehensive recommendations to growers for good harvesting practices after a flooding event.