bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levothyroxine and lung cancer in females: the importance of oxidative stress
Authors: Cornelli Umberto , Belcaro Gianni , Recchia Martino , Finco Annarosa 
Published: August 2013

Abstract

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

Abstract
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

Abstract

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

Abstract

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

AbstractBackgroundEnvironmental 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).MethodsA 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.ResultsSome 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’.ConclusionsAlthough 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

Abstract

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

Abstract

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

AbstractBackgroundLung 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.MethodsWhole-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.ResultsIn 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.ConclusionsFollowing 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.
Spectral discrimination of breast pathologies in situusing spatial frequency domain imaging
Authors: Laughney Ashley M , Krishnaswamy Venkataramanan , Rizzo Elizabeth J , Schwab Mary C , Barth Richard J , Cuccia David J , Tromberg Bruce J , Paulsen Keith D , Pogue Brian W , Wells Wendy A 
Published: August 2013

Abstract
Introduction
Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing.

Methods
Spatial frequency domain imaging (SFDI) was used to quantify near-infrared (NIR) optical parameters at the surface of 47 lumpectomy tissue specimens. Spatial frequency and wavelength-dependent reflectance spectra were parameterized with matched simulations of light transport. Spectral images were co-registered to histopathology in adjacent, stained sections of the tissue, cut in the geometry imaged in situ. A supervised classifier and feature-selection algorithm were implemented to automate discrimination of breast pathologies and to rank the contribution of each parameter to a diagnosis.

Results
Spectral parameters distinguished all pathology subtypes with 82% accuracy and benign (fibrocystic disease, fibroadenoma) from malignant (DCIS, invasive cancer, and partially treated invasive cancer after neoadjuvant chemotherapy) pathologies with 88% accuracy, high specificity (93%), and reasonable sensitivity (79%). Although spectral absorption and scattering features were essential components of the discriminant classifier, scattering exhibited lower variance and contributed most to tissue-type separation. The scattering slope was sensitive to stromal and epithelial distributions measured with quantitative immunohistochemistry.

Conclusions
SFDI is a new quantitative imaging technique that renders a specific tissue-type diagnosis. Its combination of planar sampling and frequency-dependent depth sensing is clinically pragmatic and appropriate for breast surgical-margin assessment. This study is the first to apply SFDI to pathology discrimination in surgical breast tissues. It represents an important step toward imaging surgical specimens immediately ex vivo to reduce the high rate of secondary excisions associated with breast lumpectomy procedures.