bluuebunny/crossref_metadata_2025 huggingface dataset:
Union responses to young workers since the Great Recession in Ireland, the Netherlands and Sweden: are youth structures reorienting the union agenda?
Authors: Vandaele Kurt
Published: August 2013

This article analyses how youth structures at the confederal level of trade unions are influencing the union agenda in the face of the growing problem of youth unemployment in Europe. Five youth structures from union confederations in Ireland, the Netherlands and Sweden have been studied. Although youth structures were already able to influence the union agenda in certain confederations before the crisis, the evidence demonstrates that youth issues have gained prominence today. A particular pattern discernible across countries is coalition-building between youth structures and student organizations for guiding the transition of the next generation of young workers from school to the labour market. More generally, youth structures’ possibilities for action can be explained not only by the confederations’ age composition and changing systems of union governance, but also by the specific national socio-economic context and political opportunity structures.
Labour market transitions of young workers in Nordic and southern European countries: the role of flexicurity
Authors: Madsen Per Kongshøj , Molina Oscar , Møller Jesper , Lozano Mariona
Published: August 2013

The economic crisis has revived interest in the increasingly vulnerable position of young people in the labour market. In this article we look at the labour market transitions of young workers in Nordic and southern European employment regimes, assessing differences in the degrees and forms of uncertainty they face in their transitions as well as the changes observed in the context of the economic crisis. It is argued that labour market policies coming under the ‘flexicurity’ title have had only a limited impact on mitigating the increasing dualization of EU labour markets. This applies particularly to young workers in southern Europe who are more exposed to the flexibility dimension and less protected by its compensating security measures. The analysis also shows how the crisis is widening the gap between the two groups of countries in the degree and forms of uncertainty facing young workers in their labour market transitions.
VEGFR-1, Bcl-2, and HO-1 Ratios in Pregnant Women With Hypertension
Authors: Varol Füsun , Uzunoğlu Renginar , Erbaş Hakan , Süt Necdet , Sayın Cenk
Published: August 2013

Backgound/Aim:

Preeclampsia (PE) is a multisystem disease resulting in high maternal–fetal morbidity and mortality. The aim of the study was to investigate antiangiogenesis-associated alterations in antiapoptotic and antioxidative proteins in PE.

Method:

Of the 46 patients with PE, 25 (54.3%) were with gestational hypertension (GH), 12 (26%) were with mild, and 9 (19.5%) were with severe PE. The serum levels of vascular endothelial growth factor receptor 1 (VEGFR-1), heme oxygenase 1 (HO-1), and B-cell lymphoma/leukemia (Bcl-2) levels were measured by enzyme-linked immunosorbent assay.

Results:

In the severe PE group, the VEGFR-1 serum levels (27.3 ± 16.8 vs 13.3 ± 10.7 ng/mL, P = .023) were higher, but the Bcl-2 levels (1.5 ± 0.2 vs 2.1 ± 1.7 ng/mL, P = .047) were lower than the levels in the GH-mild PE group ( P = .047). Also, VEGFR-1/Bcl-2 ratio in the severe PE group was significantly higher ( P = .003) than the ratio in the GH-mild PE group.

Conclusion:

The Bcl-2 and HO-1 proteins seem to have important roles in the antiangiogenic environment of preeclampsia.
Comparative Toxicokinetics of MMB4 DMS in Rats, Rabbits, Dogs, and Monkeys Following Single and Repeated Intramuscular Administration
Authors: Hong S. Peter , Gibbs Seth T. , Kobs Dean J. , Hawk Michael A. , Croutch Claire R. , Osheroff Merrill R. , Johnson Jerry D. , Burback Brian L.
Published: August 2013

1,1′-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Time courses of MMB4 concentrations in plasma were characterized following 7-day repeated intramuscular (IM) administrations of MMB4 DMS to male and female Sprague-Dawley rats, New Zealand White rabbits, beagle dogs (single dose only), and rhesus monkeys at drug dose levels used in earlier toxicology studies. In general, there were no significant differences in MMB4 toxicokinetic (TK) parameters between males and females for all the species tested in these studies. After a single IM administration to rats, rabbits, dogs, and monkeys, MMB4 DMS was rapidly absorbed, resulting in average Tmax values ranging from 5 to 30 minutes. Although Cmax values did not increase dose proportionally, the overall exposure to MMB4 in these preclinical species, as indicated by area under the curve (AUC) extrapolated to the infinity (AUC∞) values, increased in an approximately dose-proportional manner. The MMB4 DMS was extensively absorbed into the systemic circulation after IM administration as demonstrated by greater than 80% absolute bioavailability values for rats, rabbits, and dogs. Repeated administrations of MMB4 DMS for 7 days did not overtly alter TK parameters for MMB4 in rats, rabbits, and monkeys (150 and 300 mg/kg/d dose groups only). However, Cmax and AUC values decreased in monkeys given 450 and 600 mg/kg IM doses of MMB4 DMS following repeated administrations for 7 days. Based on the TK results obtained from the current study and published investigations, it was found that the apparent volume of distribution and clearance values were similar among various preclinical species, except for the rat.
Efficacy and Pharmacokinetic/Pharmacodynamic Study of 1,1′-Methylenebis{4-[(hydroxyimino)methyl] pyridinium} Dimethanesulfonate in Guinea Pigs and Rhesus Macaques Exposed to Cyclosarin
Authors: Harvilchuck Jill A. , Hong S. Peter , Richey Jamie S. , Osheroff Merrill R. , Johnson Jerry D.
Published: August 2013

Male Hartley guinea pigs and male rhesus macaques were used to determine an efficacious dose of 1,1′-methylenebis{4-[(hydroxyimino)methyl] pyridinium} dimethanesulfonate (MMB4 DMS) that would result in 80% survival, 24 hours following a single exposure to cyclosarin (GF). The pharmacokinetic/pharmacodynamic relationship between acetylcholinesterase activity and MMB4 plasma concentrations relative to survival was evaluated. Guinea pigs and non-human primates (NHPs) were concurrently administered MMB4 DMS (guinea pigs: 0, 10, 30, or 40 mg/kg, intramuscular [IM] and NHPs: 0.1, 1, 5, 10, or 20 mg/kg, IM), atropine, and diazepam following a 3 × median lethal dose (LD50) GF challenge. Clinical observations were evaluated using a quality-of-life (QOL) scoring system. All GF-exposed animals exhibited typical signs of nerve agent poisoning immediately following challenge. In guinea pigs, 24-hour survival was 0%, 50%, 90%, and 90% for 0, 10, 30, and 40 mg/kg MMB4 DMS groups, respectively. In addition, nearly all animals surviving to 24 hours were clinically normal, with many in the 30 and 40 mg/kg MMB4 DMS dose group observed as normal by 4 hours post-challenge. In NHPs, survival was 100% for all treatment groups, with all animals noted as clinically normal by 48 hours. Following treatment with atropine/MMB4 DMS/diazepam, NHPs exhibited dose- and temporal-related decreases in incidence and duration of the clinical signs of toxicity. The QOL scores improved with increasing MMB4 DMS dose in both species. The estimated ED80s were 25.5 mg/kg MMB4 DMS (human equivalent dose [HED] of 5.5 mg/kg) and ≤0.1 mg/kg (HED of 0.03 mg/kg) in guinea pigs and NHPs, respectively.
Discussion: A comparison of GAMLSS with quantile regression
Authors: Rigby RA , Stasinopoulos DM , Voudouris V
Published: August 2013

A discussion on the relative merits of quantile, expectile and GAMLSS regression models is given. We contrast the ‘complete distribution models’ provided by GAMLSS to the ‘distribution free models’ provided by quantile (and expectile) regression. We argue that in general, a flexibility parametric distribution assumption has several advantages allowing possible focusing on specific aspects of the data, model comparison and model diagnostics. A new method for concentrating only on the tail of the distributions is suggested combining quantile regression and GAMLSS.
Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway
Authors: Ha Tae Kwun , Kim Mi Eun , Yoon Ju Hwa , Bae Sung Jin , Yeom Jihye , Lee Jun Sik
Published: August 2013

Galangin is a member of flavonols and found in Alpinia officinarum, galangal root, and propolis. Previous studies have demonstrated that galangin has anti-cancer effects on several cancers, including melanoma, hepatoma, and leukaemia cells. However, anti-cancer activity of galangin on human colon cancer has not been established yet. In this study, we investigated the anti-cancer effects of galangin on two types of human colon cancer cells (HCT-15 and HT-29). We found that galangin induced apoptosis and DNA condensation of human colon cancer cells in a dose-dependent manner. We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis. In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.
Prediction of failure rates for new subsea systems: a practical approach and an illustrative example
Authors: Rahimi Maryam , Rausand Marvin
Published: August 2013

In the subsea oil and gas industry, new systems and new technologies are often met with skepticism, since the operators fear that they may fail and lead to production loss, costly repair interventions, and hydrocarbon leakages to the sea. Before a new system is accepted, the producer has to convince the operator that it is fit-for-use and has a high reliability. This is often done through a technology qualification program. An important part of the technology qualification program is to predict the failure rate of the new system in its future operational context. Identifying potential problems and estimating the failure rate at an early stage in the system development process are important owing to the high cost of design modifications later in the development process. This article presents a practical approach to reliability prediction of new subsea systems based on available operational data from similar, known systems from the topside environment and a comparison between the two systems. The application of the approach is illustrated by an example of a subsea pump.
Estimation of conditional moment by moving least squares and its application for importance analysis
Authors: Ruan Wenbin , Lu Zhenzhou , Wei Pengfei
Published: August 2013

Combined with advantages of moving least squares approximation, a new method for estimating higher-order conditional moment is established, which is useful for application in importance analysis and provides a supplement of the standard variance-based importance analysis. On the other hand, after obtaining the first four-order moments, the probability density function can be emulated by use of the Edgeworth expansion procedure, thereby a new method to compute the moment independent importance measure index [Formula: see text] proposed by Borgonovo is presented in this article. Two examples are employed to demonstrate that it is necessary to analyze higher-order conditional moment in importance analysis. At the same time, we study the feasibility of the Edgeworth expansion-based method for estimating the index [Formula: see text] by applying it to these examples.
Requirement for Lyl1 in a model of Lmo2-driven early T-cell precursor ALL
Authors: McCormack Matthew P. , Shields Benjamin J. , Jackson Jacob T. , Nasa Chayanica , Shi Wei , Slater Nicholas J. , Tremblay Cedric S. , Rabbitts Terence H. , Curtis David J.
Published: August 2013

Key Points

Lyl1 is required for Lmo2-induced T-cell leukemia in mice, whereas Scl is dispensable. LYL1 is required for growth of ETP-ALL cell lines.
Thalidomide corrects impaired mesenchymal stem cell function in inducing tolerogenic DCs in patients with immune thrombocytopenia
Authors: Ma Ji , Ning Yun-na , Xu Miao , Hou Yu , Wang Ning , Hou Xiao-yan , Yu Ying-yi , Li Hui , He Wei-dong , Shao Lin-lin , Zhou Hai , Min Ya-nan , Liu Xin-guang , Shi Yan , Qin Ping , Guo Cheng-shan , Hou Ming , Peng Jun
Published: August 2013

Key Points

The impaired function of MSCs in proliferation ability and in inducing tolerogenic DCs may play a role in the pathogenesis of ITP. The effect of THD in correcting dysfunctions of MSCs may suggests a therapeutic potential of THD in ITP patients.
Exploring the abomasal lymph node transcriptome for genes associated with resistance to the sheep nematode Teladorsagia circumcincta
Authors: Gossner Anton , Wilkie Hazel , Joshi Anagha , Hopkins John
Published: August 2013

This study exploited Blackface lambs that varied in their resistance to the abomasal nematode parasite,Teladorsagia circumcincta. Infection of these lambs over 3 months identified susceptible (high adult worm count, high faecal egg count and low IgA antibody) and resistant animals that had excluded all parasites. Previous work had shown that susceptibility and resistance is dependent on the differential immune response to the parasite, which occurs within the abomasal (gastric) lymph node (ALN) that drains the site of infection. The Affymetrix ovine gene array was used to interrogate the transcriptome of the ALN to identify genes and physiological pathways associated with resistance. We used a bovine RT-qPCR array of 84 genes to validate the gene array, and also report digital gene expression analysis on the same tissues, reanalysed using the Oar v3.1 sheep genome assembly. These analyses identified Humoral Immune Response, Protein Synthesis, Inflammatory Response and Hematological System Development and Function as the two top-ranked networks associated with resistance. Central genes within these networks wereIL4,IL5,IL13RA2and in particularIL13, which confirmed that differential activation of Th2 polarized responses is critical to the resistance phenotype. Furthermore, in resistant sheep there was up-regulation of genes linked to control and suppression of inflammation. The identity of differentially-expressed chemokines and receptors in the resistant and susceptible sheep also begins to explain the cellular nature of the host response to infection. This work will greatly help in the identification of candidate genes as potential selectable markers of genetic resistance.
Rapid quantification of sequence repeats to resolve the size, structure and contents of bacterial genomes
Authors: Williams David , Trimble William L , Shilts Meghan , Meyer Folker , Ochman Howard
Published: August 2013

Abstract

Background

The numerous classes of repeats often impede the assembly of genome sequences from the short reads provided by new sequencing technologies. We demonstrate a simple and rapid means to ascertain the repeat structure and total size of a bacterial or archaeal genome without the need for assembly by directly analyzing the abundances of distinctk-mers among reads.

Results

The sensitivity of this procedure to resolve variation within a bacterial species is demonstrated: genome sizes and repeat structure of five environmental strains ofE. colifrom shortIlluminareads were estimated by this method, and total genome sizes corresponded well with those obtained for the same strains by pulsed-field gel electrophoresis. In addition, this approach was applied to read-sets for completed genomes and shown to be accurate over a wide range of microbial genome sizes.

Conclusions

Application of these procedures, based solely onk-mer abundances in short read data sets, allows aspects of genome structure to be resolved that are not apparent from conventional short read assemblies. This knowledge of the repetitive content of genomes provides insights into genome evolution and diversity.
Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus
Authors: Liu Yingxia , Li Shaoyuan , Zhang Guoliang , Nie Guang , Meng Zhizhong , Mao Dongting , Chen Chang , Chen Xinchun , Zhou Boping , Zeng Gucheng
Published: August 2013

Background

Host genetic variations may contribute to disease susceptibility of influenza. IL-1A and IL-1B are important inflammatory cytokines that mediate the inflammation and initiate the immune response against virus infection. In this study, we investigated the relationship between single-nucleotide polymorphisms (SNPs) of Interleukin-1A (IL-1A) and Interleukin-1B (IL-1B) and the susceptibility to 2009 pandemic A/H1N1 influenza (A(H1N1)pdm09). 167 patients whom were confirmed with A(H1N1)pdm09 and 192 healthy controls were included in this study. Four SNPs (rs1304037, rs16347, rs17561, rs2071373) in IL1A gene and three SNPs (rs1143623, rs3917345, rs1143627) in IL1B gene were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform, and the associations of the genetic variants of IL-1 with susceptibility to A(H1N1)pdm09 were then assessed.

Results

The polymorphisms of rs17561 in IL1A gene and rs1143627 in IL1B gene were found to be associated with susceptibility to A(H1N1)pdm09 with P values of 0.003 (OR 2.08, 95% CI 1.27-3.41) and 0.002 (OR 1.62 , 95% CI 1.20-2.18), respectively. However, no significant difference in allelic frequency was observed for other SNPs between cases and controls.

Conclusions

This study provides a new insight into pathogenesis of A(H1N1)pdm09, suggesting that genetic variants of IL-1A and IL-1B may exert a substantial impact on the susceptibility of A(H1N1)pdm09 virus infection.
Identification and characterization of the zinc-regulated transporters, iron-regulated transporter-like protein (ZIP) gene family in maize
Authors: Li Suzhen , Zhou Xiaojin , Huang Yaqun , Zhu Liying , Zhang Shaojun , Zhao Yongfeng , Guo Jinjie , Chen Jingtang , Chen Rumei
Published: August 2013

Background

Zinc (Zn) and iron (Fe) are essential micronutrients for plant growth and development, their deficiency or excess severely impaired physiological and biochemical reactions of plants. Therefore, a tightly controlled zinc and iron uptake and homeostasis network has been evolved in plants. The Zinc-regulated transporters, Iron-regulated transporter-like Proteins (ZIP) are capable of uptaking and transporting divalent metal ion and are suggested to play critical roles in balancing metal uptake and homeostasis, though a detailed analysis ofZIPgene family in maize is still lacking.

Results

Nine ZIP-coding genes were identified in maize genome. It was revealed that the ZmZIP proteins share a conserved transmembrane domain and a variable region between TM-3 and TM-4. Transiently expression in onion epidermal cells revealed that all ZmZIP proteins were localized to the endoplasmic reticulum and plasma membrane. The yeast complementation analysis was performed to test the Zn or Fe transporter activity of ZmZIP proteins. Expression analysis showed that theZmIRT1transcripts were dramatically induced in response to Zn- and Fe-deficiency, though the expression profiles of otherZmZIPchanged variously. The expression patterns ofZmZIPgenes were observed in different stages of embryo and endosperm development. The accumulations ofZmIRT1andZmZIP6were increased in the late developmental stages of embryo, whileZmZIP4was up-regulated during the early development of embryo. In addition, the expression ofZmZIP5was dramatically induced associated with middle stage development of embryo and endosperm.

Conclusions

These results suggest thatZmZIPgenes encode functional Zn or Fe transporters that may be responsible for the uptake, translocation, detoxification and storage of divalent metal ion in plant cells. The various expression patterns ofZmZIPgenes in embryo and endosperm indicates that they may be essential for ion translocation and storage during differential stages of embryo and endosperm development. The present study provides new insights into the evolutionary relationship and putative functional divergence of theZmZIPgene family during the growth and development of maize.
Economic burden of acute coronary syndrome in South Korea: a national survey
Authors: Kim Jinhyun , Lee Eunhee , Lee Taejin , Sohn Aeree
Published: August 2013

Background

Acute coronary syndrome (ACS) is highly prevalent in Korea and is the third-leading cause of death in Korea; however, the economic cost of ACS on Korean society has not been investigated. This study examined the economic effect of ACS on the Korean population during the period 2004 to 2009.

Methods

The analysis used the cost of illness (COI) framework. Data on direct medical costs, direct non-medical costs, and productivity loss related to ACS morbidity and mortality were included. The Korean National Health Insurance Corporation’s claim database was used to obtain data on annual healthcare utilization and expenditures for the entire South Korean population. By using a data mining technique, we identified healthcare claims with ACS-related disease codes. Costs were estimated by using a macro-costing method.

Results

In 2009, the prevalence of ACS in Korea was 6.4 persons per 1,000 population members and the associated mortality rate was 20.2 persons per 100,000 population members. The total cost of ACS in 2009 was USD 918.2 million. Of the total, direct medical cost was USD 425.3 million, direct non-medical cost was USD 11.4 million, and cost associated with morbidity and mortality was USD 481.5 million.

Conclusions

The results show that the total cost of ACS to the Korean society is high. Early and effective management of ACS is required to reduce ACS-associated mortality and morbidity. We suggest that further research be undertaken to determine ways to reduce the economic effects of ACS and its treatment.
Prevalence, correlates and pattern of Hepatitis B among antenatal clinic attenders in Yaounde-Cameroon: is perinatal transmission of HBV neglected in Cameroon?
Authors: Fomulu Nelson J , Morfaw Frederick LI , Torimiro Judith N , Nana Philip , Koh Mve V , William Takang
Published: August 2013

Background

Few studies have evaluated the prevalence of HBV in the general Cameroonian population or among antenatal attendants. The aim of this study was to determine the prevalence, correlates and patterns of Hepatitis B surface antigen among pregnant women attending antenatal care in Yaounde-Cameroon.

Methods

This was a cross-sectional multicenter study carried out in a referral hospital and two secondary hospitals in Yaounde, the capital of Cameroon. The study lasted 15 months (March 2011 to June 2012), and recruited 959 pregnant women. Patient recruitment was consecutive. The HBsAg was tested using the Monalisa HBsAg Ultra ELISA kit. Other hepatitis B markers were equally tested.

We used the statistical package for social sciences (SPSS) version 14.0 software to conduct a quantitative analysis of the derived data. Simple descriptive statistics such as means, standard deviations, and proportions were used to describe the data. We tested for association in categorical variables using the chi-squared (χ2) test. The odds ratio (OR) and the corresponding 95% confidence intervals (95% CI) were used to summarise the strength of association between specific binary exposure and outcome variables. The level of statistical significance for the study was set at p < 0.05.

Results

The prevalence of hepatitis B infection (HBsAg) among antenatal clinic attenders in our setting was 7.7%. Amongst these women, just 5.4% were previously aware of their HBsAg status. The rate of HBV infectivity was high, with 28% of HBsAg positive women having evidence of HBeAg in their plasma, and up to 45.8% of these women lacking antibodies against hepatitis B e antigen (anti-HBe). About 41% of the pregnant women had had previous contact with HBV as evidenced by the positive status for anti-HBc.

Just 2.7% of the pregnant women had previously been vaccinated against HBV. The mean age for HBsAg positivity in our setting was 26.9 ±4.7 years, and the most affected age group was the 25 – 29 years age group. There was no statistically significant association between age or other socio-demographic risk factors and HBsAg status. Numerous risk factors for HBV acquisition exists in our settings, but amongst these, only a history of a contact with hepatitis B infection was found to be significantly associated with HBsAg positivity (OR 1.63, 95% C.I 1.15-2.30). Finally, the coinfection rate of HBV/HIV was 0.74%.

Conclusion

The prevalence of hepatitis B among pregnant women in Cameroon is high, and the pattern tends towards high infectivity and therefore increased risk of perinatal HBV transmission. These highlight the need to step up preventive efforts against hepatitis B infection and perinatal HBV transmission in our community.
Radiographic and safety details of vertebral body stenting: results from a multicenter chart review
Authors: Diel Peter , Röder Christoph , Perler Gosia , Vordemvenne Thomas , Scholz Matti , Kandziora Frank , Fürderer Sebastian , Eiskjaer Soren , Maestretti Gianluca , Rotter Robert , Benneker Lorin Michael , Heini Paul Friedhelm
Published: August 2013

Background

Up to one third of BKP treated cases shows no appreciable height restoration due to loss of both restored height and kyphotic realignment after balloon deflation. This shortcoming has called for an improved method that maintains the height and realignment reached by the fully inflated balloon until stabilization of the vertebral body by PMMA-based cementation. Restoration of the physiological vertebral body height for pain relief and for preventing further fractures of adjacent and distant vertebral bodies must be the main aim for such a method. A new vertebral body stenting system (VBS) stabilizes the vertebral body after balloon deflation until cementation. The radiographic and safety results of the first 100 cases where VBS was applied are presented.

Methods

During the planning phase of an ongoing international multicenter RCT, radiographic, procedural and followup details were retrospectively transcribed from charts and xrays for developing and testing the case report forms. Radiographs were centrally assessed at the institution of the first/senior author.

Results

100 patients (62 with osteoporosis) with a total of 103 fractured vertebral bodies were treated with the VBS system. 49 were females with a mean age of 73.2 years; males were 66.7 years old. The mean preoperative anterior-middle-posterior heights were 20.3-17.6-28.0 mm, respectively. The mean local kyphotic angle was 13.1°. The mean preoperative Beck Index (anterior edge height/posterior edge height) was 0.73, the mean alternative Beck Index (middle height/posterior edge height) was 0.63. The mean postoperative heights were restored to 24.5-24.6-30.4 mm, respectively. The mean local kyphotic angle was reduced to 8.9°. The mean postoperative Beck Index was 0.81, the mean alternative one was 0.82. The overall extrusion rate was 29.1%, the symptomatic one was 1%. In the osteoporosis subgroup there were 23.8% extrusions. Within the three months followup interval there were 9% of adjacent and 4% of remote new fractures, all in the osteoporotic group.

Conclusions

VBS showed its strengths especially in realignment of crush and biconcave fractures. Given that fracture mobility is present, the realignment potential is sound and increases with the severity of preoperative vertebral body deformation.
Levothyroxine and lung cancer in females: the importance of oxidative stress
Authors: Cornelli Umberto , Belcaro Gianni , Recchia Martino , Finco Annarosa
Published: August 2013

Background

Levothyroxine (LT4) treatment can lead to iatrogenic hyperthyroidism and oxidative stress that can cause patient discomfort. Oxidative stress is also recognized as one of the causes of chronic diseases and cancer.

Methods

The prevalence of breast, colorectal, gastric and lung cancer in 18 Italian Regions during 2010 was correlated with the sales of LT4 in 2009. The cancer prevalence was analyzed in women aged 30–84. This age range corresponds to more than 80% of the consumers of the drug and to about 99% of all malignant cancers. The correlation between sales of LT4 and cancers was determined with the technique of Density Ellipses. The age and smoking contribution for lung cancer was determined with the Sequential test.

Results

No significant correlation was seen between LT4 sales and breast, colorectal and gastric cancers. A significant correlation was instead found for lung cancer (p < 0.05) corrected for smoking and age.

Conclusions

LT4 consumption in Italy is about 0.7 boxes/women/year. There is a correlation between lung cancer and LT4 treatment and oxidative stress caused by LT4 supplementation can be one of the causes. Although we cannot exclude that dysthyroidism needing LT4 supplementation might be the ground for lung cancer itself and measuring oxidative stress could be helpful in avoiding excessive use of the drug.
On nonlinear discrete weakly singular inequalities and applications to Volterra-type difference equations
Authors: Zheng Kelong , Wang Hong , Guo Chunxiang
Published: August 2013

Some nonlinear discrete weakly singular inequalities, which generalize some known results are discussed. Under suitable parameters, prior bounds on solutions to nonlinear Volterra-type difference equations are obtained. Two examples are presented to show the applications of our results in boundedness and uniqueness of solutions of difference equations, respectively.

MSC:34A34, 45J05.
The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus
Authors: Xu Lili , Bao Linlin , Deng Wei , Zhu Hua , Chen Ting , Lv Qi , Li Fengdi , Yuan Jing , Xiang Zhiguang , Gao Kai , Xu Yanfeng , Huang Lan , Li Yanhong , Liu Jiangning , Yao Yanfeng , Yu Pin , Yong Weidong , Wei Qiang , Zhang Lianfeng , Qin Chuan
Published: August 2013

Background

The current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin H7N9 influenza virus.

Findings

A/Anhui/1/2013 (H7N9) virus was administered by intranasal instillation to groups of mice and ferrets, and animals developed typical clinical signs including body weight loss (mice and ferrets), ruffled fur (mice), sneezing (ferrets), and death (mice). Peak virus shedding from respiratory tract was observed on 2 days post inoculation (d.p.i.) for mice and 3–5 d.p.i. for ferrets. Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets. The inoculation of H7N9 could elicit seroconversion titers up to 1280 in ferrets and 160 in mice. Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models.

Conclusions

The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.
Nav1.7: Stress-Induced Changes in Immunoreactivity within Magnocellular Neurosecretory Neurons of the Supraoptic Nucleus
Authors: Black Joel A , Hoeijmakers Janneke GJ , Faber Catharina G , Merkies Ingemar SJ , Waxman Stephen G
Published: August 2013

Background

Nav1.7 is preferentially expressed, at relatively high levels, in peripheral neurons, and is often referred to as a “peripheral” sodium channel, and Nav1.7-specific blockers are under study as potential pain therapeutics which might be expected to have minimal CNS side effects. However, occasional reports of patients with Nav1.7 gain-of-function mutations and apparent hypothalamic dysfunction have appeared. The two sodium channels previously studied within the rat hypothalamic supraoptic nucleus, Nav1.2 and Nav1.6, display up-regulated expression in response to osmotic stress.

Results

Here we show that Nav1.7 is present within vasopressin-producing neurons and oxytocin-producing neurons within the rat hypothalamus, and demonstrate that the level of Nav1.7 immunoreactivity is increased in these cells in response to osmotic stress.

Conclusions

Nav1.7 is present within neurosecretory neurons of rat supraoptic nucleus, where the level of immunoreactivity is dynamic, increasing in response to osmotic stress. Whether Nav1.7 levels are up-regulated within the human hypothalamus in response to environmental factors or stress, and whether Nav1.7 plays a functional role in human hypothalamus, is not yet known. Until these questions are resolved, the present findings suggest the need for careful assessment of hypothalamic function in patients with Nav1.7 mutations, especially when subjected to stress, and for monitoring of hypothalamic function as Nav1.7 blocking agents are studied.
Acute and Chronic Phases of Complex Regional Pain Syndrome in Mice are Accompanied by Distinct Transcriptional Changes in the Spinal Cord
Authors: Gallagher Joseph J , Tajerian Maral , Guo Tianzhi , Shi Xiaoyou , Li Wenwu , Zheng Ming , Peltz Gary , Kingery Wade S , Clark J David
Published: August 2013

Background

CRPS is a painful, debilitating, and often-chronic condition characterized by various sensory, motor, and vascular disturbances. Despite many years of study, current treatments are limited by our understanding of the underlying mechanisms. Little is known on the molecular level concerning changes in gene expression supporting the nociceptive sensitization commonly observed in CRPS limbs, or how those changes might evolve over time.

Results

We used a well-characterized mouse tibial fracture/cast immobilization model of CRPS to study molecular, vascular and nociceptive changes. We observed that the acute (3 weeks after fracture) and chronic (7 weeks after fracture) phases of CRPS-like changes in our model were accompanied by unique alterations in spinal gene expression corresponding to distinct canonical pathways. For the acute phase, top regulated pathways were: chemokine signaling, glycogen degradation, and cAMP-mediated signaling; while for the chronic phase, the associated pathways were: coagulation system, granzyme A signaling, and aryl hydrocarbon receptor signaling. We then focused on the role of CcL2, a chemokine that we showed to be upregulated at the mRNA and protein levels in spinal cord tissue in our model. We confirmed its association with the nociceptive sensitization displayed in this model by demonstrating that the spinal but not peripheral administration of a CCR2 antagonist (RS504393) in CRPS animals could decrease mechanical allodynia. The spinal administration of CcL2 itself resulted in mechanical allodynia in control mice.

Conclusions

Our data provide a global look at the transcriptional changes in the spinal cord that accompany the acute and chronic phases of CRPS as modeled in mice. Furthermore, it follows up on one of the top-regulated genes coding for CcL2 and validates its role in regulating nociception in the fracture/cast model of CRPS.
Functional characterization of three MicroRNAs of the Asian Tiger Mosquito, Aedes albopictus
Authors: Puthiyakunnon Santhosh , Yao Yunying , Li Yiji , Gu Jinbao , Peng Hongjuan , Chen Xiaoguang
Published: August 2013

Background

Temporal and stage specific expression of microRNAs (miRNAs) in embryos, larvae, pupae and adults of Aedes albopictus showed differential expression levels across the four developmental stages, indicating their potential regulatory roles in mosquito development. The functional characterization of these miRNAs was not known. Accordingly our study evaluated the functional characterization of three miRNAs, which are temporally up-regulated in the various developmental stages of Ae. albopictus mosquitoes.

Methods

miRNA mimics, inhibitors and negative controls were designed and their knock-in and knock-down efficiency were analyzed by qRT-PCR after transfecting the mosquito cell lines C6/36, and also by injecting in their specific developmental stages. The functional role of each individual miRNA was analyzed with various parameters of development such as, hatching rate and hatching time in embryos, eclosion rate in larvae, longevity and fecundity in the adult mosquitoes.

Results

The knock-in with the specifically designed miRNA mimics showed increased levels of expression of miRNA compared with their normal controls. We confirmed these findings using qRT-PCR, both by in vitro expression in C6/36 mosquito cell lines after transfection as well as in in vivo expression in developmental stages of mosquitoes by microinjection. The knock-down of expression with the corresponding inhibitors showed a considerable decrease in the expression levels of these miRNAs and obvious functional effects in Ae. albopictus development, detected by a decrease in the hatching rate of embryos and eclosion rate in larvae and a marked reduction in longevity and fecundity in adults.

Conclusion

This study carried out by knock-in and knock-down of specifically and temporally expressed miRNAs in Ae. albopictus by microinjection is a novel study to delineate the importance of the miRNA expression in regulating mosquito development. The knock-down and loss of function of endogenously expressed miRNAs by the miRNA inhibitors in specific developmental stages had considerable effects on development, but enhancement of their gain of function was not observed on knock-in of these specific miRNAs. Hence, our study indicates that an optimal level of endogenous expression of miRNA is indispensable for the normal development and maintenance of the vectorial population density and pathogen transmissibility of this mosquito vector.
Lessons from history: morbidity of cold injury in the Royal Marines during the Falklands Conflict of 1982
Authors: St Clair Golden Francis , Francis Thomas James Roose , Gallimore Deborah , Pethybridge Roger
Published: August 2013

Background

Environmental conditions in the Falklands Conflict of 1982 favoured the genesis of cold injuries. Immediately, post-war, cold injury morbidity and its contributory factors were assessed, in the personnel of UK 3 Commando Brigade (3 Cdo Bde).

Methods

A questionnaire survey of the 3,006 members of 3 Cdo Bde who landed on the islands was conducted within 6–10 weeks of the end of hostilities. Questions included those relating to features of cold injury, body morphology, age, symptoms experienced, past medical history and other possible contributory causes. Additionally, the unit medical team conducted a cursory examination. Data were sent to the Royal Navy Institute of Naval Medicine (INM), where the degree of likely cold injury was broadly classified (‘asymptomatic’ ‘mild’, ‘moderate’ or ‘severe’). A sample (total 109) was then selected at random from each category and subsequently examined and tested at the INM (nerve conduction, photoplethysmography and thermography testing). Forty-seven non-cold exposed sailors acted as a control group. These contemporaneous records have now been identified and interrogated.

Results

Some 2,354 (78%) completed questionnaires were returned, revealing that 1,505 (64%) had experienced symptoms of non-freezing cold injury. The morbidity in the infantry units was significantly greater than that in the support troops (1,051 (76%) vs 454 (46%),p < 0.05). No evidence was found to support an influence of a number of factors, commonly believed to have an aetiological role in the production of cold injury. Whilst there was no significant relationship between past history and cold injury morbidity in the brigade as a whole, or within the infantry units alone, an associationwasidentified in the collective infantry units (73%) and the support/headquarter units (59%) (p < 0.05).

In comparison with uninjured sailors who acted as controls (n = 47), nerve conduction was impaired in 35% of those screened some months after returning to the UK, while the photoplethysmography and thermographic responses to a cold sensitivity test showed that most (including those classed by questionnaire as asymptomatic) had residual ‘cold sensitivity’.

Conclusions

Although the passage of time has made retrospective interrogation of historical documents hard, the available data do appear to offer valuable historical and clinical insights. Cold injury affected the majority of those fighting in the cold temperate climate of the Falklands. The overwhelming environmental conditions meant that, for most, a past history of cold injury did not appear to represent a risk factor for subsequent injury, as is the case for less severe conditions. Importantly, even asymptomatic individuals when tested often showed physiological evidence of cold injury—perhaps predisposing them to subsequent elevation in risk.
Disorganization of neocortical lamination in focal cortical dysplasia is brain-region dependent: evidence from layer-specific marker expression
Authors: Fauser Susanne , Häussler Ute , Donkels Catharina , Huber Susanne , Nakagawa Julia , Prinz Marco , Schulze-Bonhage Andreas , Zentner Josef , Haas Carola A
Published: August 2013

Background

Focal cortical dysplasias (FCD) are local disturbances of neocortical architecture and a common cause of pharmaco-resistant focal epilepsy. Little is known about the pathomechanisms leading to architectural abnormalities associated with FCD.

Results

In the present study we compared 52 FCD cases originating from the frontal or temporal lobe with or without Ammon’s horn sclerosis (AHS) with regard to structural and molecular differences. We applied layer-specific (ER81, RORß, SMI32, TLE4) and interneuron (calbindin, parvalbumin) markers by means of immunohistochemistry, in situ hybridization (ISH), and real time RT-PCR and correlated our findings with clinical parameters. We found that: (1) Structural abnormalities were most prominent in layers III-VI including changed morphology of individual neurons or dispersion, blurring and thinning of layers. These alterations were most pronounced in isolated frontal FCD, whereas the most homogeneous group was FCD IIIa. (2) Numbers of calbindin- and parvalbumin-positive interneurons varied considerably within the different FCD groups, but were not generally reduced. A significant decrease was only found for calbindin-positive interneurons in frontal FCD, and for parvalbumin-positive interneurons in FCD IIIa. (3) Interestingly, FCD IIIa presented with significant changes in the numbers of calbindin- or TLE4-positive neurons when compared to isolated FCD or controls. (4) Correlations between clinical and cellular parameters strongly depended on FCD localisation and age of the patients.

Conclusions

In summary, our data suggest that late cortical development is disturbed in FCD, yet most likely by different causes depending on brain region, FCD type and FCD severity.
Suitable test substances for proof of concept regarding infochemical effects in surface waters
Authors: Nendza Monika , Klaschka Ursula , Berghahn Rüdiger
Published: August 2013

Background

Infochemical effects have been defined as the manipulation of the odour perception of organisms by anthropogenic substances which may result in ecologically relevant behavioural disorder. However, the environmental relevance of infochemical effects has not yet been confirmed by experimental observations. This project aims to test for infochemical effects on chemical communication in water bodies with systematic experimental investigations. The first crucial step is to select suitable test substances. Repellents (PT 19 biocides) and odourants may be assumed to affect the response of aquatic populations and communities. These mostly polar and stable compounds may disturb chemical communication between organisms and may cause organismic effects like drift (downstream dislocation of e.g. crustacean and insect larvae in streams). Repellents enter surface waters mainly indirectly via wastewater discharges from sewage treatment plants or directly by being washed off from the skin and clothes of bathers.

Results

In this literature study, suitable chemicals were selected for confirmatory assessments of suspected infochemical effects by laboratory tests in a subsequent second part of the project. The use pattern and physico-chemical properties of the substances selected, in combination with their limited biological degradability, indicate potential aquatic relevance with possible chronic impact caused by disturbed communication. After due consideration of advantages and limitations, three PT 19 repellents appear suitable test compounds for proof of concept in the subsequent experimental part of the project:

• DEET (CAS 134-62-3)

• Icaridine (CAS 119515-38-7)

• EBAAP (CAS 52304-36-6)

Another promising candidate for infochemical effects is isophorone (CAS 78-59-1), a natural attractant and an anthropogenic high production volume solvent.

Conclusions

Four chemicals were selected with the expectation that they may be suitable test substances for experimental proof of concept of infochemical effects in the subsequent part of the project. The experimental results may then help to answer the question of whether PT 19 biocides and other odourants entering aquatic ecosystems give rise for concern about potential infochemical effects.
MicroRNAs implicated in dysregulation of gene expression following human lung transplantation
Authors: Zhang Wei , Zhou Tong , Ma Shwu-Fan , Machado Robert F , Bhorade Sangeeta M , Garcia Joe GN
Published: August 2013

Background

Lung transplantation remains the only viable treatment option for the majority of patients with advanced lung diseases. However, 5-year post-transplant survival rates remain low primarily secondary to chronic rejection. Novel insights from global gene expression profiles may provide molecular phenotypes and therapeutic targets to improve outcomes after lung transplantation.

Methods

Whole-genome gene expression profiling was performed in a cohort of patients that underwent lung transplantation as well as healthy controls using the Affymetrix Human Exon 1.0ST Array. To explore the potential roles of microRNAs (miRNAs) in regulating lung transplantation-associated gene dysregulation, miRNA expression levels were also profiled in the same samples using the Exiqon miRCURY LNA Array.

Results

In a cohort of 18 lung transplant patients, 364 dysregulated genes were identified in Caucasian patients relative to normal individuals without pulmonary disorders. Pathway enrichment analysis of the dysregulated genes pointed to Gene Ontology biological processes such as “defense response”, “immune response” and “response to wounding”. We then compared the expression profiles of potential regulating miRNAs, suggesting that dysregulation of a number of lung transplantation-associated genes (e.g.,ATR,FUT8,LRRC8B,NFKBIA) may be attributed to the dysregulation of their respective regulating miRNAs.

Conclusions

Following human lung transplantation, a substantial proportion of genes, particularly those genes involved in certain biological processes like immune response, were dysregulated in patients relative to their healthy counterparts. This exploratory analysis of the relationships between miRNAs and their gene targets in the context of lung transplantation warrants further investigation and may serve as novel therapeutic targets in lung transplant complications.