bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes and histological findings of patients with advanced metastatic germ cell tumors undergoing post‐chemotherapy resection of retroperitoneal lymph nodes and residual extraretroperitoneal masses
Authors: Nakamura Terukazu , Oishi Masakatsu , Ueda Takashi , Fujihara Atsuko , Nakanishi Hiroyuki , Kamoi Kazumi , Naya Yoshio , Hongo Fumiya , Okihara Koji , Miki Tsuneharu
Published: April 2015

Objectives

To assess clinical outcomes of patients with advanced germ cell tumor undergoing post‐chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection.

Methods

Between 1998 and 2013, 175 retroperitoneal lymph node dissections for advanced metastatic germ cell tumors were carried out at Kyoto Prefectural University of Medicine, Kyoto, Japan. Of patients receiving retroperitoneal lymph node dissections, 156 underwent post‐chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection as first surgery after completion of chemotherapy. Of these 156 patients, 47 underwent both post‐chemotherapy retroperitoneal lymph node dissection and extraretroperitoneal mass resection.

Results

The histological findings were necrosis in 59.6%, teratoma in 31.4% and viable cancer in 9.0% at retroperitoneal lymph node. At extraretroperitoneal mass resection, necrosis was present in 59.6%, teratoma in 31.9% and viable cancer in 8.5%. Overall histological discordance between retroperitoneal lymph node and extraretroperitoneal mass was found in 31.9%. Five‐year disease‐free survival stratified by retroperitoneal lymph node histology in 156 patients was 91.3% for necrosis, 78.7% for teratoma and 63.5% for viable cancer (log–rank, P = 0.009). Antegrade ejaculation was preserved in 80.9%. In the worst histology of post‐chemotherapy retroperitoneal lymph node dissection or extraretroperitoneal mass resection in 156 patients, 5‐year disease‐free survival was 93.2% for necrosis, 79.0% for teratoma and 63.4% for viable cancer (log–rank, P < 0.001). Independent prognostic factors for disease‐free survival were presence of viable cancer in retroperitoneal lymph node histology and salvage chemotherapy.

Conclusion

The presence of viable cancer at the retroperitoneal lymph node is an independent predictor of disease recurrence. In approximately one‐third of cases, there is a histological discordance between retroperitoneal lymph node and extraretroperitoneal mass. Resection of residual retroperitoneal lymph node and extraretroperitoneal masses remains an important procedure in the management of advanced germ cell tumors.
Building Criminal Authority: A Comparative Analysis of Drug Gangs in Rio de Janeiro and Recife
Authors: Wolff Michael Jerome
Published: April 2015

Why do drug gangs develop sophisticated authority functions in some places and not in others? Comparing two Brazilian cities, Rio de Janeiro and Recife, this article argues that territorially embedded informal authority structures from earlier times, coupled with sporadic and extremely violent policing, encouraged drug gangs in Rio de Janeiro to develop authoritative functions and residents to acquiesce to them. In Recife, by contrast, drug gangs inherited diffuse and territorially independent authority structures and confronted a much less lethally violent police force. Consequently, they failed to find common cause with local residents, and their organizational development was truncated.
Voting for Democracy: Campaign Effects in Chile's Democratic Transition
Authors: Boas Taylor C.
Published: April 2015

In a global context in which authoritarian regimes often hold elections, defeating dictators at the polls can play a key role in transitions to democracy. When the opposition is allowed to campaign for votes in such elections, there are strong reasons to believe that its efforts will be more persuasive than those of the authoritarian incumbent. This article examines the effect of televised campaign advertising on vote choice in the 1988 plebiscite that inaugurated Chile's transition to democracy. Using matching to analyze postelectoral survey data, it shows that the advertising of the opposition's no campaign made Chileans more likely to vote against dictator Augusto Pinochet, whereas the advertising of the government's yes campaign had no discernible effect. These findings suggest that the no campaign played an important causal role in the change of political regime.
Notch receptor expression in human brain arteriovenous malformations
Authors: Hill‐Felberg Sandra , Wu Hope Hueizhi , Toms Steven A. , Dehdashti Amir R.
Published: April 2015

The roles of the Notch pathway proteins in normal adult vascular physiology and the pathogenesis of brain arteriovenous malformations are not well‐understood. Notch 1 and 4 have been detected in human and mutant mice vascular malformations respectively. Although mutations in the human Notch 3 gene caused a genetic form of vascular stroke and dementia, its role in arteriovenous malformations development has been unknown. In this study, we performed immunohistochemistry screening on tissue microarrays containing eight surgically resected human brain arteriovenous malformations and 10 control surgical epilepsy samples. The tissue microarrays were evaluated for Notch 1–4 expression. We have found that compared to normal brain vascular tissue Notch‐3 was dramatically increased in brain arteriovenous malformations. Similarly, Notch 4 labelling was also increased in vascular malformations and was confirmed by western blot analysis. Notch 2 was not detectable in any of the human vessels analysed. Using both immunohistochemistry on microarrays and western blot analysis, we have found that Notch‐1 expression was detectable in control vessels, and discovered a significant decrease of Notch 1 expression in vascular malformations. We have demonstrated that Notch 3 and 4, and not Notch 1, were highly increased in human arteriovenous malformations. Our findings suggested that Notch 4, and more importantly, Notch 3, may play a role in the development and pathobiology of human arteriovenous malformations.
Carbohydrate intake is associated with time spent in the euglycemic range in patients with type 1 diabetes
Authors: Ayano‐Takahara Shiho , Ikeda Kaori , Fujimoto Shimpei , Asai Kanae , Oguri Yasuo , Harashima Shin‐ichi , Tsuji Hidemi , Shide Kenichiro , Inagaki Nobuya
Published: April 2015

Aims/Introduction

Greater glycemic variability and lack of predictability are important issues for patients with type 1 diabetes. Dietary factors are one of the contributors to this variability, but how closely diet is linked to glycemic fluctuation on a daily basis has not been investigated. We examined the association between carbohydrate intake and glycemic excursion in outpatients.

Materials and Methods

A total of 33 patients with type 1 diabetes were included in the analyses (age 44.5 ± 14.7 years, diabetes duration 15.1 ± 8.3 years, 64% female, 30% using insulin pump, glycated hemoglobin 8.1 ± 1.3%). Time spent in euglycemia (70–180 mg/dL), hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) of consecutive 48‐h periods of continuous glucose monitoring data were collected together with simultaneous records of dietary intake, insulin dose and physical activity. Correlation analyses and multiple regression analyses were used to evaluate the contribution of carbohydrate intake to time spent in the target glycemic range.

Results

In multiple regression analyses, carbohydrate intake (β = 0.53, P = 0.001), basal insulin dose per kg per day (β = −0.31, P = 0.034) and diabetes duration (β = 0.30, P = 0.042) were independent predictors of time spent in euglycemia. Carbohydrate intake (β = −0.51, P = 0.001) and insulin pump use (β = −0.34, P = 0.024) were independent predictors of time spent in hyperglycemia. Insulin pump use (β = 0.52, P < 0.001) and bolus insulin dose per kg per day (β = 0.46, P = 0.001) were independent predictors of time spent in hypoglycemia.

Conclusions

Carbohydrate intake is associated with time spent in euglycemia in patients with type 1 diabetes.
Expression of sexual ornaments in a polymorphic species: phenotypic variation in response to environmental risk
Authors: Winandy L. , Denoël M.
Published: April 2015

Secondary sexual traits may evolve under the antagonistic context of sexual and natural selection. In some polymorphic species, these traits are only expressed during the breeding period and are differently expressed in alternative phenotypes. However, it is unknown whether such phenotypes exhibit phenotypic plasticity of seasonal ornamentations in response to environmental pressures such as in the presence of fish (predation risk). This is an important question to understand the evolution of polyphenisms. We used facultative paedomorphosis in newts as a model system because it involves the coexistence of paedomorphs that retain gills in the adult stage with metamorphs that have undergone metamorphosis, but also because newts exhibit seasonal sexual traits. Our aim was therefore to determine the influence of fish on the development of seasonal ornamentation in the two phenotypes of the palmate newt (Lissotriton helveticus). During the entire newt breeding period, we assessed the importance of phenotype and fish presence with an information‐theoretic approach. Our results showed that paedomorphs presented much less developed ornamentation than metamorphs and those ornamentations varied over time. Fish inhibited the development of sexual traits but differently between phenotypes: in contrast to metamorphs, paedomorphs lack the phenotypic plasticity of sexual traits to environmental risk. This study points out that internal and external parameters act in complex ways in the expression of seasonal sexual ornamentations and that similar environmental pressure can induce a contrasted evolution in alternative phenotypes.
Genetic admixture supports an ancient hybrid origin of the endangered Hawaiian duck
Authors: Lavretsky P. , Engilis A. , Eadie J. M. , Peters J. L.
Published: April 2015

Speciation is regarded primarily as a bifurcation from an ancestral species into two distinct taxonomic units, but gene flow can create complex signals of phylogenetic relationships, especially among different loci. We evaluated several hypotheses that could account for phylogenetic discord between mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA) within Hawaiian duck (Anas wyvilliana), including stochastic lineage sorting, mtDNA capture and widespread genomic introgression. Our results best support the hypothesis that the contemporary Hawaiian duck is descended from an ancient hybridization event between the mallard (Anas platyrhynchos) and Laysan duck (Anas laysanensis). Whereas mtDNA clearly shows a sister relationship between Hawaiian duck and mallard, nuDNA is consistent with a genetic mosaic with nearly equal contributions from Laysan duck and mallard. In addition, coalescent analyses suggest that gene flow from either mallard or Laysan duck, depending on the predefined tree topology, is necessary to explain contemporary genetic diversity in Hawaiian ducks, and these estimates are more consistent with ancient, rather than contemporary, hybridization. Time since divergence estimates suggest that the genetic admixture event occurred around the Pleistocene–Holocene boundary, which is further supported by circumstantial evidence from the Hawaiian subfossil record. Although the extent of reproductive isolation from either putative parental taxon is not currently known, these species are phenotypically, genetically and ecologically different, and they meet primary criteria used in avian taxonomy for species designation. Thus, the available data are consistent with an admixed origin and support the hypothesis that the Hawaiian duck may represent a young hybrid species.
Selection and evolutionary potential of spring arrival phenology in males and females of a migratory songbird
Authors: Tarka M. , Hansson B. , Hasselquist D.
Published: April 2015

The timing of annual life‐history events affects survival and reproduction of all organisms. A changing environment can perturb phenological adaptations and an important question is if populations can evolve fast enough to track the environmental changes. Yet, little is known about selection and evolutionary potential of traits determining the timing of crucial annual events. Migratory species, which travel between different climatic regions, are particularly affected by global environmental changes. To increase our understanding of evolutionary potential and selection of timing traits, we investigated the quantitative genetics of arrival date at the breeding ground using a multigenerational pedigree of a natural great reed warbler (Acrocephalus arundinaceus) population. We found significant heritability of 16.4% for arrival date and directional selection for earlier arrival in both sexes acting through reproductive success, but not through lifespan. Mean arrival date advanced with 6 days over 20 years, which is in exact accordance with our predicted evolutionary response based on the breeder's equation. However, this phenotypic change is unlikely to be caused by microevolution, because selection seems mainly to act on the nongenetic component of the trait. Furthermore, demographical changes could also not account for the advancing arrival date. Instead, a strong correlation between spring temperatures and population mean arrival date suggests that phenotypic plasticity best explains the advancement of arrival date in our study population. Our study dissects the evolutionary and environmental forces that shape timing traits and thereby increases knowledge of how populations cope with rapidly changing environments.
Decisional support to prevent adverse drug reactions of long latency: pilot randomized controlled intervention for glucocorticoid‐induced diabetes
Authors: Dischinger Hannah R. , Cheng Elizabeth , Mann Alyse D. , Grueber Tiffany M. , Hawk Sherri , Davis Lisa A. , Prochazka Allan V. , Hutt Evelyn , Caplan Liron
Published: April 2015

Rationale, aims, and objectives

Long‐term exposure to glucocorticoids can cause adverse drug reactions of long latency (ADRLLs), including glucocorticoid‐induced diabetes mellitus (GID). Providers can monitor for GID using the glycosylated haemoglobin blood (HbA1C) test. This study examined the utility of decisional support to improve HbA1C‐based screening for GID. US veterans were identified as chronic users of oral glucocorticoids (>120 days of oral glucocorticoids in the last 2 years). The primary care providers caring for these patients were the target of the intervention. Providers were randomized to receive automatic HbA1C orders for their patients receiving chronic glucocorticoid or usual care.

Methods

This study was a pilot two‐arm, group‐randomized, controlled trial (n = 12 providers, n = 38 patients). Data collection occurred from 5 May 2013 until 10 January 2014. A pharmacist generated the order for an HbA1C through the electronic medical record. The time between the intervention start date and the date on which an HbA1C order was signed were compared using Cox proportional and hierarchical linear regression.

Results

The time to sign HbA1C orders (mean 12.0 days for the intervention arm; 104.0 days for control arm) was associated with significant differences favouring the intervention [HR (Hazard Ratio) 50.2, P < 0.001, confidence interval (CI) 6.3 to 398.7]. For the intervention group, 95% of orders were signed, whereas only 12% of control providers signed orders (odds ratio 150, P < 0.001, CI 12.4 to 1812.9).

Conclusions

The results of this study strongly suggest that the clinical pharmacist‐triggered order intervention is effective. This method of computerized decisional support may be useful in improving screening for GID and ADRLLs.
Neuronally produced versican V2 renders C‐fiber nociceptors IB4‐positive
Authors: Bogen Oliver , Bender Olaf , Löwe Jana , Blenau Wolfgang , Thevis Beatrice , Schröder Wolfgang , Margolis Richard U. , Levine Jon D. , Hucho Ferdinand
Published: April 2015

A subpopulation of nociceptors, the glial cell line‐derived neurotrophic factor (GDNF)‐dependent, non‐peptidergic C‐fibers, expresses a cell‐surface glycoconjugate that can be selectively labeled with isolectin B4 (IB4), a homotetrameric plant lectin from Griffonia simplicifolia. We show that versican is an IB4‐binding molecule in rat dorsal root ganglion neurons. Using reverse transcriptase polymerase chain reaction (RT‐PCR), in situ hybridization and immunofluorescence experiments on rat lumbar dorsal root ganglion, we provide the first demonstration that versican is produced by neurons. In addition, by probing Western blots with splice variant‐specific antibodies we show that the IB4‐binding versican contains only the glycosaminoglycan alpha domain. Our data support V2 as the versican isoform that renders this subpopulation of nociceptors IB4‐positive (+).

image

A subset of nociceptors, the GDNF‐dependent non‐peptidergic C‐fibers can be characterized by its reactivity for isolectin B4 (IB4), a plant lectin from Griffonia simplicifolia. We have previously demonstrated that versican V2 binds IB4 in a Ca2 + ‐dependent manner. However, given that versican is thought to be the product of glial cells, it was questionable whether versican V2 can be accountable for the IB4‐reactivity of this subset of nociceptors. The results presented here prove – for the first time – a neuronal origin of versican and suggest that versican V2 is the molecule that renders GDNF‐dependent non‐peptidergic C‐fibers IB4‐positive.
Protocadherins and Hypothalamic Development: Do They Play An Unappreciated Role?
Authors: Coughlin G. M. , Kurrasch D. M.
Published: April 2015

Normal brain development requires coordinated cell movements at precise times. It has long been established that cell–cell adhesion proteins of the cadherin superfamily are involved in the adhesion and sorting of cells during tissue morphogenesis. In the present review, we focus on protocadherins, which form the largest subfamily of the cadherin superfamily and mediate homophilic cell–cell adhesion in the developing brain. These molecules are highly expressed during neural development and the exact roles that they play are still emerging. Although, historically, protocadherins were considered to provide mechanical and chemical connections between adjacent cells, recent research suggests that they may also serve as molecular identity markers of neurones to help guide cell recognition and sorting, cell migration, outgrowth of neuronal processes, and synapse formation. This phenomenon of single cell diversity stems, in part, from the vast variation in protein structure, genomic organisation and molecular function of the protocadherins. Although expression profiles and genetic manipulations have provided evidence for the role of protocadherins in the developing brain, we have only begun to construct a complete understanding of protocadherin function. We examine our current understanding of how protocadherins influence brain development and discuss the possible roles for this large superfamily within the hypothalamus. We conclude that further research into these underappreciated but vitally important genes will shed insight into hypothalamic development and perhaps the underlying aetiology of neuroendocrine disorders.
Self‐congruity effects: A critical review and an integrative model
Authors: Kim Ji‐Hern
Published: April 2015

This research conducts an extensive review study on the extant research on self‐congruity, and presents some recommendations and propositions for future research. It describes the differences between two constructs (i.e., self‐congruity and brand personality) regarding the symbolic benefits of a brand. It also suggests an integrative model to encompass important cognitive and motivational factors to moderate the relationship between self‐congruity and brand evaluation. Although there should be meaningful moderators of self‐congruity effects that are not addressed in the model, this research can be a starting point for future research in order to develop a better research model for analyzing self‐congruity effects.
Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients
Authors: Bril Fernando , Ortiz‐Lopez Carolina , Lomonaco Romina , Orsak Beverly , Freckleton Michael , Chintapalli Kedar , Hardies Jean , Lai Song , Solano Felipe , Tio Fermin , Cusi Kenneth
Published: April 2015

Background & Aims

Liver ultrasound (US) is usually used in the clinical setting for the diagnosis and follow‐up of patients with nonalcoholic fatty liver disease (NAFLD). However, no large study has carefully assessed its performance using a semiquantitative ultrasonographic scoring system in overweight/obese patients, in comparison to magnetic resonance spectroscopy (1H‐MRS) and histology.

Methods

We recruited 146 patients and performed: a liver US using a 5‐parameter scoring system, a liver 1H‐MRS to quantify liver fat content, and a liver biopsy to assess histology. All measurements were repeated in a subgroup of patients (n = 62) after 18 months of follow‐up.

Results

The performance of liver US (parenchymal echo alone) was rather modest, and significantly worse than 1H‐MRS (AUROC: 0.82 [0.69–0.94] vs. 0.96 [0.90–1.00]; P = 0.04). However, the AUROC improved when different echographic parameters were taken into account (AUROC: 0.89 [0.83–0.96], P = 0.15 against 1H‐MRS). Optimum sensitivity for liver US was achieved at a liver fat content ≥12.5%, suggesting that below this threshold, liver US is less sensitive. Liver 1H‐MRS showed a high accuracy for the diagnosis of NAFLD, and correlated strongly with histological steatosis (r = 0.73, P < 0.0001). None of the imaging tests was adequate enough to predict changes over time in histology.

Conclusions

Despite its widespread use, liver US has several important limitations that healthcare providers should recognize, particularly because of its low sensitivity. Using a combination of echographic parameters, liver US showed a significant improvement in its diagnostic performance, but still was of limited value for monitoring treatment over time.
The Kings Score refines prognostic prediction in hepatocellular carcinoma: a novel application
Authors: Pinato David J. , Karamanakos Georgios , Ishizuka Mitsuru , Smirne Carlo , Pirisi Mario , Kubota Keiichi , Sharma Rohini
Published: April 2015

Background & Aims

There are a number of prognostic scores in hepatocellular carcinoma (HCC), none of which is optimal in predicting overall survival (OS) in the individual patient, particularly in intermediate stage disease, where patients are not surgically treatable but may qualify for a wide range of palliative interventions. We evaluated the prognostic role of a biochemical algorithm, the Kings Score (KS), in the palliative setting of care.

Methods

We used the algorithm [age x AST x INR]/platelet count to derive the KS. Full clinical data including Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training set of 97 patients from the UK. Independent predictors of survival identified in multivariate analysis were validated in an independent cohort of 766 patients from Japan and Italy.

Results

In both training and validation sets, KS was confirmed as an independent predictor of OS (P < 0.01). Ad‐hoc subgroup analysis revealed the KS to be prognostic in the palliative setting, being able to subclassify patients presenting with intermediate and advanced disease according to BCLC criteria (P < 0.001).

Conclusion

The KS integrates into the BCLC system to improve prognostic substratification in the palliative setting of care. The KS may help reducing disease heterogeneity and refine treatment allocation in intermediate‐advanced HCC.
Conservation genetics and geographic patterns of genetic variation of the endangered officinal herb Fritillaria pallidiflora
Authors: Su Zhihao , Pan Borong , Sanderson Stewart C. , Jiang Xiaolong , Zhang Mingli
Published: April 2015

Fritillaria pallidiflora is an endangered officinal herb distributed in the Tianshan Mountains of northwestern China. We examined its phylogeography to study evolutionary processes and suggest implications for conservation. Six haplotypes were detected based on three chloroplast non‐coding spacers (psbA‐trnH, rps16, and trnS‐trnG); genetic variation mainly occurred among populations and SAMOVA groups. This species is distributed in different deep valleys, and we speculate that these fragmented habitats cause gene flow barriers among populations and groups. We also speculate that during glacial periods, extremely low temperatures and aridity caused additional range shrinkage and fragmentation, factors consequently resulting in significant intraspecific differentiation in allopatric regions. For setting a conservation management plan, we identified the Lucaogou region as the most important area, and we designated two ESUs for separate management.
The Impact of Left Atrial Surface Area and the Second Generation Cryoballoon on Clinical Outcome of Atrial Fibrillation Cryoablation
Authors: GREISS HARALD , BERKOWITSCH ALEXANDER , WOJCIK MACIEJ , ZALTSBERG SERGEJ , PAJITNEV DIMITRI , DEUBNER NIKOLAS , AKKAYA ERSAN , GÜTTLER NORBERT , HAMM CHRISTIAN , NEUMANN THOMAS , KUNISS MALTE
Published: April 2015

Aims

In this observational study, we examine the significance of the left atrial (LA) surface area and compare the clinical usage of the Arctic Front Advance (CBA) versus Arctic Front (CB) cryoballoon with the intent to investigate the impact of each in terms of long‐term freedom from atrial fibrillation (AF) for patients with nonvalvular AF.

Methods

Pulmonary vein isolation (PVI) was performed while using a cryoballoon ablation catheter in conjunction with an intraluminal circular diagnostic mapping catheter, Achieve. The consecutive patients ablated with CBA were matched with patients previously ablated with CB, using propensity score matching. The primary endpoint of this observational single‐center retrospective study was the first observation of electrocardiogram‐documented recurrence of atrial arrhythmias lasting >30 seconds.

Results

The patient demographic data were similar in the CBA‐ and CB‐group (N = 188 patients each group). In all patients in the CBA‐group and in 95% of the patients in the CB group, acute procedural PVI of all veins was achieved with the single usage of a 28‐mm cryoballoon. The one‐year freedom from atrial arrhythmias was significantly better in the CBA‐ versus the CB‐group of patients, 90% versus 64%, respectively. During 15‐month clinical follow‐up in CBA group, patients with LA area above 23 cm2 were more likely to experience recurrence of AF (23%) than patients with LA area below 23 cm2 (7%).

Conclusions

Comparing one‐year outcomes, the CBA is superior to the CB with regards to maintenance of normal sinus rhythm. When using the CBA catheter, an enlarged LA is associated with a higher recurrence of arrhythmia.
Maternal vitamin D levels are inversely related to allergic sensitization and atopic diseases in early childhood
Authors: Chiu Chih‐Yung , Huang Shih‐Yin , Peng Yu‐Chieh , Tsai Ming‐Han , Hua Man‐Chin , Yao Tsung‐Chieh , Yeh Kuo‐Wei , Huang Jing‐Long
Published: April 2015

Background

There are few studies addressing the impact of maternal vitamin D status on the vitamin D levels in offspring, their sensitization to common allergens and atopic disease development.

Methods

Children aged 0 through 4 yr from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Time series of serum 25‐hydroxyvitamin D (25(OH)D) levels were measured in maternal blood before delivery, cord blood, and at age 1.5, 3, and 4 using an electrochemiluminescence‐based assay. Specific IgE antibodies against food and inhalant allergens were measured at 6 months, and 1, 1.5, 2, 3, and 4 yr of age.

Results

A total of 164 mother–child pairs from a birth cohort were recruited in this study. The mean levels of maternal 25(OH)D were 23.2 ± 7.7 ng/ml with a high (up to 80%) prevalence of insufficient vitamin D status (< 30 ng/ml). A significant correlation was seen between maternal and cord blood 25(OH)D levels (p < 0.001), and a persistent lower 25(OH)D level was found in children born to mothers with deficient 25(OH)D levels. Deficient maternal 25(OH)D levels (<20 ng/ml) appeared to be associated with a higher prevalence of allergen sensitization before age 2. Higher maternal 25(OH)D levels were significantly associated with lower risk of eczema (OR 0.12; 95% CI 0.02–0.63; p = 0.012) and asthma (OR 0.22; 95% CI 0.06–0.92; p = 0.038) at age 4.

Conclusions

Low maternal 25(OH)D levels appear not only to be associated with an increase in the prevalence of allergic sensitization but also the risk of eczema and asthma in early childhood.
Mode of delivery and childhood fractional exhaled nitric oxide, interrupter resistance and asthma: the Generation R study
Authors: van Berkel Annemaria C. , den Dekker Herman T. , Jaddoe Vincent W. V. , Reiss Irwin K. , Gaillard Romy , Hofman Albert , de Jongste Johan C. , Duijts Liesbeth
Published: April 2015

Background

Previous studies suggest that caesarean section may influence the risk of childhood asthma. We examined the associations of different modes of delivery with childhood wheezing patterns, asthma, fractional exhaled nitric oxide (FeNO) and airway interrupter resistance (Rint) up to school age.

Methods

This study among 6,128 children was embedded in a population‐based prospective cohort study. Information on mode of delivery was obtained from midwives and hospital registries. Wheezing patterns from birth onwards and ever physician‐diagnosed asthma at age 6 yr were assessed by questionnaires. FeNO and Rint were measured at age 6 yr. We used multivariate polynomial, logistic and linear regression models.

Results

Compared with vaginal delivery, caesarean section was associated with increased risks of early and persistent wheezing up to school age [odds ratios (95% confidence interval): 1.36 (1.06, 1.75) and 1.73 (1.24, 2.40), respectively]. The effect sizes of elective and emergency caesarean section with wheezing outcomes were similar. Only elective caesarean section was associated with a higher FeNO level [sympercent (95% CI): 12.7 (0.6, 24.8)]. We did not observe associations of mode of delivery with asthma or Rint. Also, vacuum‐ or forceps‐assisted vaginal delivery was not associated with any asthma or related outcome.

Conclusions

Both elective and emergency caesarean sections are associated with increased risks of early and persistent wheezing up to school age. This might be explained by increased airway inflammation reflected by higher FeNO levels.
A multinational study to compare prevalence of atopic dermatitis in the first year of life
Authors: Draaisma Eelco , Garcia‐Marcos Luis , Mallol Javier , Solé Dirceu , Pérez‐Fernández Virginia , Brand Paul L. P. ,   the EISL Study Group
Published: April 2015

Background

Atopic dermatitis (AD) is common in childhood, with peak prevalence in early childhood. However, international comparisons of prevalence have focused on older children. We analysed differences in prevalence rates of AD and the associations with putative risk and protective factors, among infants in two European and two Central American countries.

Methods

In 1‐yr old infants participating in the International Study of Wheezing in Infants (EISL), prevalence of AD and putative risk and protective factors were assessed by a questionnaire applied to parents. For each risk/protective factor summary, odds ratios with 95% confidence intervals were calculated by means of random effects meta‐analysis.

Results

Data from 9803 infants were analysed. AD prevalence varied from 10.6% (Valencia, Spain) to 28.2% (San Pedro Sula, Honduras). Average AD prevalences were lower in Europe (14.2%) than in Central America (18.2%, p < 0.01). Consistent with older children, presence of siblings decreased (OR 0.82 [0.72–0.94]), whereas family history of asthma (OR 1.32 [1.10–1.59]), rhinitis (OR 1.33 [1.14–1.54]) and atopic dermatitis (OR 2.40 [1.89–3.05]) increased the risk of infantile AD. However, gender, family size, breastfeeding and socio‐economic status were not associated with AD prevalence.

Conclusions

This study shows almost threefold differences in the prevalence of AD in infancy between countries. Risk and protective factors involved in the expression of infantile AD differ from those in older children, possibly suggesting a different pathophysiology. There is a need for additional international epidemiological surveys on AD in young children, the peak prevalence age of this condition.
Allergy‐test‐driven elimination diet is useful in children with eosinophilic esophagitis, regardless of the severity of symptoms
Authors: Syrigou Ekaterini , Angelakopoulou Aspasia , Zande Maria , Panagiotou Ioanna , Roma Eleftheria , Pitsios Constantinos
Published: April 2015

Background

A combination of PPIs and corticosteroids is the pharmacotherapy mostly used to treat eosinophilic esophagitis (EoE), while dietetic manipulations consist also an efficient option. The aim of this study was to compare the efficacy of allergy‐test‐driven elimination diet in children with mild symptoms of EoE to a group of children with moderate/severe symptoms.

Methods

Thirty‐five children, aged 7 months to 12 yr, with EoE were enrolled in the study. They had a clinical history of GERD‐like (21 children, Group A) or more severe symptoms (14 children, Group B). The diagnosis had been confirmed after two preliminary months of therapy with PPIs and an esophagogastroduodenoscopy. Soon after diagnosis, they were allergy‐tested, using IgE detection (SPT and serum‐specific IgE) and atopy patch tests (APTs). A 12‐month tailor‐made diet was prescribed according to the tests. Patients of Group B continued PPIs for two more months, while swallowed topical steroids were also prescribed to them for the first 5 months after diagnosis, followed by an ‘as‐needed’ use of them for the rest of the study. Endoscopy was repeated at the end of the study.

Results

Milk and egg were the most common APT‐positive allergens. Thirty‐two patients were instructed to follow an elimination diet, which was completed by 15/18 of Group A and 12/14 of Group B. An improvement of symptoms was reported by 26/27 patients that completed the study. The use of swallowed corticosteroids was noticeably decreased during the as‐needed period, in Group B. A remarkable reduce of eosinophils was noticed in biopsies; from 42.84 ± 18.08, they decreased to 6.41 ± 3.20, a year after.

Conclusion

All children with EoE and mild symptoms had resolution of symptoms and normal eosinophils in the esophageal mucosa a year after an allergy‐driven elimination diet. Patients with moderate/severe EoE symptoms had the same improvement, indicating that an elimination diet is an efficient complementary treatment to corticosteroids.
T‐DNA insertion in aquaporin gene AtPIP1;2 generates transcription profiles reminiscent of a low CO2 response
Authors: Boudichevskaia Anastassia , Heckwolf Marlies , Kaldenhoff Ralf
Published: April 2015

Results from CO2 diffusion studies and characterization of Arabidopsis thaliana aquaporin AtPIP1;2 T‐DNA insertion lines support the idea that specific aquaporins facilitate the diffusion of CO2 through biological membranes. However, their function as CO2 diffusion facilitators in plant physiology is still a matter of debate. Assuming that a lack of AtPIP1;2 causes a characteristic transcriptional response, we compared data from a AtPIP1;2 T‐DNA insertion line obtained by Illumina sequencing, Affymetrix chip analysis and quantitative RT‐PCR to the transcriptome of plants grown under drought stress or under low CO2 conditions. The plant reaction to the deficit of AtPIP1;2 was unlike drought stress responses but comparable with that of low CO2 conditions. In addition, we observed a phenotype characteristic to plants grown under low CO2. The findings support the hypothesis that the AtPIP1;2 function in plant physiology is not to facilitate water but CO2 diffusion.
Maintenance of distinct melanocyte populations in the interfollicular epidermis
Authors: Glover James D. , Knolle Stefan , Wells Kirsty L. , Liu Dianbo , Jackson Ian J. , Mort Richard L. , Headon Denis J.
Published: April 2015

Hair follicles and sweat glands are recognized as reservoirs of melanocyte stem cells (MSCs). Unlike differentiated melanocytes, undifferentiated MSCs do not produce melanin. They serve as a source of differentiated melanocytes for the hair follicle and contribute to the interfollicular epidermis upon wounding, exposure to ultraviolet irradiation or in remission from vitiligo, where repigmentation often spreads outwards from the hair follicles. It is unknown whether these observations reflect the normal homoeostatic mechanism of melanocyte renewal or whether unperturbed interfollicular epidermis can maintain a melanocyte population that is independent of the skin's appendages. Here, we show that mouse tail skin lacking appendages does maintain a stable melanocyte number, including a low frequency of amelanotic melanocytes, into adult life. Furthermore, we show that actively cycling differentiated melanocytes are present in postnatal skin, indicating that amelanotic melanocytes are not uniquely relied on for melanocyte homoeostasis.
Ex vivo evaluation of the effect of photodynamic therapy on skin scars and striae distensae
Authors: Mendoza‐Garcia Jenifer , Sebastian Anil , Alonso‐Rasgado Teresa , Bayat Ardeshir
Published: April 2015

Background

Skin scars and striae distensae (SD) are common dermal disorders with ill‐defined treatment options. There is emerging clinical evidence for use of photodynamic therapy (PDT) in treating skin fibrosis. Therefore, the aim here was to investigate the effect of PDT on skin scars and SD in an ex vivo model of human skin scarring.

Methods

Photodynamic therapy, with 5ALA or MALA in addition to illumination with 40 J/cm2 of red light, was applied to striae alba, fine line, hypertrophic and keloid scars ex vivo (n = 18). General morphology was assessed by H&E, Herovici's and Weigert's differential staining. Apoptosis, proliferation, metalloproteinase 3 and tropoelastin expression were quantified immunohistochemically, and differential gene expression of proliferating cell nuclear antigen (PCNA), collagen (COL) type I and type III, matrix metalloproteinase 3 (MMP3) and tropoelastin (ELN) was assessed by real‐time quantitative reverse transcription polymerase chain reaction.

Results

Apoptosis increased, which correlated with decreased proliferation and PCNA gene expression. Post‐PDT, matrix components were found to be re‐organised in both hypertrophic and keloid scars. COLI and COLIII gene expression levels decreased, whilst MMP3 and ELN increased significantly post‐PDT compared to normal skin and untreated controls (P < 0.05). However, no significant difference between 5ALA and MALA‐PDT treatments was observed.

Conclusion

Using our unique ex vivo model, we show for the first time morphological and cellular effect of application of PDT, which correlates with the degree and severity of dermal fibrosis. In view of this, PDT may be ideal in targeting treatment of abnormal skin scarring.
Immune responses of wild birds to emerging infectious diseases
Authors: Staley M. , Bonneaud C.
Published: April 2015

Over the past several decades, outbreaks of emerging infectious diseases (EIDs) in wild birds have attracted worldwide media attention, either because of their extreme virulence or because of alarming spillovers into agricultural animals or humans. The pathogens involved have been found to infect a variety of bird hosts ranging from relatively few species (e.g. Trichomonas gallinae) to hundreds of species (e.g. West Nile Virus). Here we review and contrast the immune responses that wild birds are able to mount against these novel pathogens. We discuss the extent to which these responses are associated with reduced clinical symptoms, pathogen load and mortality, or conversely, how they can be linked to worsened pathology and reduced survival. We then investigate how immune responses to EIDs can evolve over time in response to pathogen‐driven selection using the illustrative case study of the epizootic outbreak of Mycoplasma gallisepticum in wild North American house finches (Haemorhous mexicanus). We highlight the need for future work to take advantage of the substantial inter‐ and intraspecific variation in disease progression and outcome following infections with EID to elucidate the extent to which immune responses confer increased resistance through pathogen clearance or may instead heighten pathogenesis.
Old sleeping Sicilian beauty: seed germination in the palaeoendemic Petagnaea gussonei (Spreng.) Rauschert (Saniculoideae, Apiaceae)
Authors: De Castro O. , Gianguzzi L. , Carucci F. , De Luca A. , Gesuele R. , Guida M.
Published: April 2015

Petagnaea gussonei (Apiaceae) is a perennial herbaceous species endemic to northeast Sicily (Nebrodi Mountains). It is considered a remnant of the Sicilian Tertiary flora, and is endangered according to the Red List. There is no information in the literature about the germinability of its seeds, even though seed production is know to occur. The aim of this study was to obtain data to better understand seed germination of this species and its biological implications. Thus, several approaches were employed: vitality analyses, gibberellic acid supply, germination and soil microbial flora analyses via end‐point and qPCR. The results suggest that seed germination occurs after ca. 1.5 years at a rate of ca. 11%. The seeds can be classified as physiologically dormant, and probably require prolonged cold stratification for germination. Because seed germination is low, it is likely that agamic reproduction represents an important mean for its conservation and survival. These results have important implications for P. gussonei survival and should be considered in possible re‐introduction attempts aimed at restoring threatened populations.
Monitoring the Foetal Phase of Gestation in the Queen With a 12.5‐MHz Ultrasound Probe and Prediction of the Parturition by Combining the Measurements of Head and Abdominal Diameters
Authors: Topie E , Bencharif D , Briand L , Tainturier D
Published: April 2015

Contents

Ten gestations in six domestic shorthair cats (Europeans) were monitored daily during the foetal phase of gestation, from the 28th day after the first mating until parturition, using ultrasound with a 12.5‐MHz probe. The development of the various organs over this period was recorded. The diameters of the head (HD) and abdomen (AD) were measured. Skeletal calcification visible on ultrasound occurred in a defined order between the 34th and 40th day of gestation. During the last 30 days of gestation, there was a significant correlation between HD and days before parturition (DBP) (r2 = 0.99) and between AD and DBP (r2 = 0.98). The following equations were obtained: DBP = −2.10*HD (mm) + 50.74; DBP = −1.01*AD (mm) + 42.19. The confidence intervals were stable over the last 30 days of gestation. For the HD, the confidence interval was ±1 day in 53% of cases and ±2 days in 85% of cases. For the AD, the confidence interval was ±1 day in 45% of cases and ±2 days in 77% of cases. A table obtained by combining the HD and AD measurements made it possible to estimate the date of parturition within 2 days with a reliability of over 85%.
The effectiveness of lung cancer MDT and the role of respiratory physicians
Authors: Prabhakar Charles N. , Fong Kwun M. , Peake Michael D. , Lam David C. , Barnes David J.
Published: April 2015

There is an increasing trend for the use of multi‐disciplinary teams (MDT) in the management of complex medical conditions. The latter may include various cancers, including lung cancer. However, the use of MDT is not restricted to cancer management, but may include complex conditions like diabetes and other non‐malignant disorders. There is an increasing trend to use MDT in the investigation and management of patients with suspected or proven lung cancer. This review examines the evidence that supports the efficacy, or otherwise, of lung cancer management in a MDT as opposed to individual care, who should be a member of a lung cancer MDT, and the specific role of the respiratory physician in a lung cancer MDT. Although it may seem to make common sense to manage lung cancer in a MDT setting, there is actually little in the way of high quality data to support this concept. The logistic and ethical difficulties in researching this issue are highlighted in this review.
Defense of Cyber Infrastructures Against Cyber‐Physical Attacks Using Game‐Theoretic Models
Authors: Rao Nageswara S. V. , Poole Stephen W. , Ma Chris Y. T. , He Fei , Zhuang Jun , Yau David K. Y.
Published: April 2015

The operation of cyber infrastructures relies on both cyber and physical components, which are subject to incidental and intentional degradations of different kinds. Within the context of network and computing infrastructures, we study the strategic interactions between an attacker and a defender using game‐theoretic models that take into account both cyber and physical components. The attacker and defender optimize their individual utilities, expressed as sums of cost and system terms. First, we consider a Boolean attack‐defense model, wherein the cyber and physical subinfrastructures may be attacked and reinforced as individual units. Second, we consider a component attack‐defense model wherein their components may be attacked and defended, and the infrastructure requires minimum numbers of both to function. We show that the Nash equilibrium under uniform costs in both cases is computable in polynomial time, and it provides high‐level deterministic conditions for the infrastructure survival. When probabilities of successful attack and defense, and of incidental failures, are incorporated into the models, the results favor the attacker but otherwise remain qualitatively similar. This approach has been motivated and validated by our experiences with UltraScience Net infrastructure, which was built to support high‐performance network experiments. The analytical results, however, are more general, and we apply them to simplified models of cloud and high‐performance computing infrastructures.
Polarized currents inhibit in vitro growth of bacteria colonizing cutaneous ulcers
Authors: Gomes Rosana Caetano , Brandino Hugo Evangelista , Alves de Sousa Natanael Teixeira , Santos Marcos Ferracioli , Martinez Roberto , de Jesus Guirro Rinaldo Roberto
Published: April 2015

Infections caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli are among the microorganisms that often lead to infection in pressure ulcers. Polarized current has emerged as a possible intervention to limit bacterial proliferation. We analyzed the effect of fixed diphasic – Bernard (FD‐B) and high voltage monophasic pulsed (HVMP) currents on bacteria S. aureus ATCC 25923 (Gram +), P. aeruginosa ATCC 27853 (Gram –), and E. coli ATCC 25922 (Gram –). After the bacterial strains were activated the bacteria were suspended in physiological solution (0.9%) and the concentration adjusted to 1.5 × 103 CFU/mL. The cultures were stimulated with FD‐B current at (3, 6, and 9 mA, 100 Hz, 15 and 30 minutes) and HVMP (32, 64, and 95 V, 100 Hz, 30 and 60 min) while monitoring the pH and temperature. After the stimulation, the suspensions were plated and incubated for 24 hours at 37°C. Then the counts were made of colony forming units (CFU). Data were submitted to normality Shapiro–Wilk test followed by nonparametric ANOVA test and post hoc Tukey test with p < 0.05. There was a decrease in the CFU for the two currents, but the most effective reduction was in FD‐B. The temperature remained constant and the pH measured alkaline at the negative pole and acid at the positive pole during stimulation. The application of FD‐B and HVMP currents promoted inhibition of bacterial proliferation when stimulated in vitro, acting as an adjuvant resource in the healing process.