bluuebunny/crossref_metadata_2025 huggingface dataset:
The challenges of obtaining ethics approval for a randomized, double-blind, placebo-controlled research study in Jersey
Authors: Haresnape Claire
Published: October 2013

Background and objective

A PhD project involving designing and implementing a small-scale clinical trial at Jersey General Hospital encountered a variety of difficulties in obtaining ethics approval due to Jersey’s unique legal and constitutional position. Clarification of the necessary route of application took some 28 months. It was established that only local ethics approval is required for clinical trials taking place in the Channel Islands and that there is no need for Medicines and Healthcare products Regulatory Agency (MHRA) approval in the form of Clinical Trials Authorization (CTA), because Jersey falls outside the existing legal and regulatory framework. The experiences and findings gained from this project would prove of use to other researchers planning to conduct clinical trials in the Channel Islands.
Trouble with ataxia: A longitudinal qualitative study of the diagnosis and medical management of a group of rare, progressive neurological conditions
Authors: Daker-White Gavin , Ealing John , Greenfield Julie , Kingston Helen , Sanders Caroline , Payne Katherine
Published: October 2013

Objectives:

An exploratory investigation of diagnosis and management in progressive ataxias: rare neurological conditions usually affecting balance, mobility and speech.

Methods:

A longitudinal qualitative study into the experiences of people with ataxia and neurologists. Thematic analysis and follow-up interviews were used to determine diagnosis and management issues over time.

Results:

People with ataxia recruited via two hospital departments and Ataxia UK were interviewed at baseline (n = 38) and 12-month follow-up (n = 31). Eight consultant neurologists were interviewed once. Patient accounts were diverse, but many expressed frustration at having an incurable condition and dissatisfaction with service outcomes. At follow-up, there was variation in their contact and satisfaction with helping agencies. Service issues regarding continuity of care and the primary/secondary care interface were evident. Neurologists’ accounts also varied. One-half reported that there is nothing that can be done, and one-half favoured specialist referral to increase the likelihood of finding an underlying aetiology within budget constraints.

Conclusions:

Diagnostic uncertainties existing at baseline remained for patients at follow-up interviews, although some had learned to deal with the uncertainties brought by the diagnosis of a largely untreatable condition. Care pathways only seemed to operate in the case of defined conditions, such as Friedreich’s Ataxia, the most commonly inherited cause. The findings point to a need to develop the evidence base to inform the relative utility of diagnostic procedures in the context of finite resources for patient care and support.
Impaired Decision Making in Alzheimer’s Disease
Authors: Hot Pascal , Ramdeen Kylee T. , Borg Céline , Bollon Thierry , Couturier Pascal
Published: October 2013

To assess whether the decline of decision-making processes in people diagnosed with Alzheimer’s disease (AD) is explained by the use of an inappropriate analytic strategy induced by their high level of uncertainty about their ability, we used happiness induction to activate an appropriate heuristic processing of information. Healthy older adults and AD patients performed the Iowa Gambling Task either in a standard condition or after viewing a funny film clip. Although AD patients had impaired performances in the standard condition, the happiness condition significantly increased AD patient performance level compared with that of the control subgroups. Additional analyses showed that uncertainty levels were reduced in happy AD patients and that performances in the Iowa Gambling Task were not due to impairment in executive or memory functions. We suggest that higher uncertainty levels in patients with mild AD, which induce an inappropriate analytic strategy, can be reduced through emotional remediation techniques.
Early Farming in Finland: Was there Cultivation before the Iron Age (500 BC)?
Authors: Lahtinen Maria , Rowley-Conwy Peter
Published: October 2013

We review the evidence for the earliest agriculture in Finland. The claims are all based on pollen analysis. Some claims go back to the Neolithic period. We contest these claims critically and argue that the ‘early cereal-type’ pollen grains may in fact come from large-grained wild grasses, and cannot be taken as clear evidence for cultivation in the absence of other lines of evidence. Cultivation of cereals in Finland may have started as late as the start of the Iron Age in c. 500 BC.
Eradicating acute myeloid leukemia in a MllPTD/wt:Flt3ITD/wt murine model: a path to novel therapeutic approaches for human disease
Authors: Bernot Kelsie M. , Nemer John S. , Santhanam Ramasamy , Liu Shujun , Zorko Nicholas A. , Whitman Susan P. , Dickerson Kathryn E. , Zhang Mengzi , Yang Xiaojuan , McConnell Kathleen K. , Ahmed Elshafa H. , Muñoz Maura R. , Siebenaler Ronald F. , Marcucci Gabriel G. , Mundy-Bosse Bethany L. , Brook Daniel L. , Garman Sabrina , Dorrance Adrienne M. , Zhang Xiaoli , Zhang Jianying , Lee Robert J. , Blum William , Caligiuri Michael A. , Marcucci Guido
Published: October 2013

Key Points

The MllPTD/wt:Flt3ITD/wt mouse is a relevant AML model in which the miR-29b–mediated epigenetics-kinome crosstalk is targetable by bortezomib. An original liposomal formulation of bortezomib eradicates AML and yields curative therapy for MllPTD/wt:Flt3ITD/wt AML.
Maintaining genetic diversity using molecular coancestry: the effect of marker density and effective population size
Authors: Gómez-Romano Fernando , Villanueva Beatriz , Rodríguez de Cara María Ángeles , Fernández Jesús
Published: October 2013

Background

The most efficient method to maintain genetic diversity in populations under conservation programmes is to optimize, for each potential parent, the number of offspring left to the next generation by minimizing the global coancestry. Coancestry is usually calculated from genealogical data but molecular markers can be used to replace genealogical coancestry with molecular coancestry. Recent studies showed that optimizing contributions based on coancestry calculated from a large number of SNP markers can maintain higher levels of diversity than optimizing contributions based on genealogical data. In this study, we investigated how SNP density and effective population size impact the use of molecular coancestry to maintain diversity.

Results

At low SNP densities, the genetic diversity maintained using genealogical coancestry for optimization was higher than that maintained using molecular coancestry. The performance of molecular coancestry improved with increasing marker density, and, for the scenarios evaluated, it was as efficient as genealogical coancestry if SNP density reached at least 3 times the effective population size.

However, increasing SNP density resulted in reduced returns in terms of maintained diversity. While a benefit of 12% was achieved when marker density increased from 10 to 100 SNP/Morgan, the benefit was only 2% when it increased from 100 to 500 SNP/Morgan.

Conclusions

The marker density of most SNP chips already available for farm animals is sufficient for molecular coancestry to outperform genealogical coancestry in conservation programmes aimed at maintaining genetic diversity. For the purpose of effectively maintaining genetic diversity, a marker density of around 500 SNPs/Morgan can be considered as the most cost effective density when developing SNP chips for new species. Since the costs to develop SNP chips are decreasing, chips with 500 SNPs/Morgan should become available in a short-term horizon for non domestic species.
Influence of developmental stage and genotype on liver mRNA levels among wild, domesticated, and hybrid rainbow trout (Oncorhynchus mykiss)
Authors: White Samantha L , Sakhrani Dionne , Danzmann Roy G , Devlin Robert H
Published: October 2013

Background

Release of domesticated strains of fish into nature may pose a threat to wild populations with respect to their evolved genetic structure and fitness. Understanding alterations that have occurred in both physiology and genetics as a consequence of domestication can assist in evaluating the risks posed by introgression of domesticated genomes into wild genetic backgrounds, however the molecular causes of these consequences are currently poorly defined. The present study has examined levels of mRNA in fast-growing pure domesticated (D), slow-growing age-matched pure wild (Wa), slow-growing size-matched pure wild (Ws), and first generation hybrid cross (W/D) rainbow trout (Oncorhynchus mykiss) to investigate the influence of genotype (domesticated vs. wild, and their interactions in hybrids) and developmental stage (age- or size-matched animals) on genetic responses (i.e. dominant vs. recessive) and specific physiological pathways.

Results

Highly significant differences in mRNA levels were found between domesticated and wild-type rainbow trout genotypes (321 mRNAs), with many mRNAs in the wild-domesticated hybrid progeny showing intermediate levels. Differences were also found between age-matched and size-matched wild-type trout groups (64 mRNAs), with unique mRNA differences for each of the wild-type groups when compared to domesticated trout (Wa: 114 mRNAs, Ws: 88 mRNAs), illustrating an influence of fish developmental stage affecting findings when used as comparator groups to other genotypes. Analysis of differentially expressed mRNAs (found for both wild-type trout to domesticated comparisons) among the genotypes indicates that 34.8% are regulated consistent with an additive genetic model, whereas 39.1% and 26.1% show a recessive or dominant mode of regulation, respectively. These molecular data are largely consistent with phenotypic data (growth and behavioural assessments) assessed in domesticated and wild trout strains.

Conclusions

The present molecular data are concordant with domestication having clearly altered rainbow trout genomes and consequent phenotype from that of native wild populations. Although mainly additive responses were noted in hybrid progeny, the prevalence of dominant and non-additive responses reveals that introgression of domesticated and wild genotypes alters the type of genetic control of mRNA levels from that of wild-type, which may lead to disruption of gene regulation systems important for developing phenotypes for optimal fitness in nature. A clear influence of both fish age and size (developmental stage) on mRNA levels was also noted in this study, which highlights the importance of examining multiple control samples to provide a comprehensive understanding of changes observed between strains possessing differences in growth rate.
RETRACTED ARTICLE: MicroRNA-302b suppresses cell proliferation by targeting EGFR in human hepatocellular carcinoma SMMC-7721 cells
Authors: Wang Lumin , Yao Jiayi , Shi Xin , Hu Lili , Li Zongfang , Song Tusheng , Huang Chen
Published: October 2013

Background

MicroRNAs are regulators that can play an essential role in tumorigenesis. Although miR-302 families have been suggested to be tumor repressors in human cancer, the mechanism by which they suppress tumor development remains to be defined. In this study, we discover that miR302b suppresses tumor proliferation may due to directly targeting EGFR in human hepatocellular carcinoma (HCC).

Methods

QRT-PCR was used to assess miR-302b and EGFR expression in 27 pairs of clinical hepatocellular carcinoma tissues and their corresponding adjacent nontumorous liver tissues. MTT, colony formation, immunofluorescence staining, and cell cycle assays were used to examine the tumor suppressor role of miR302b in cell proliferation. Luciferase assays were performed to assess the EGFR was a novel target of miR-302b. Western blot assay was used to validate the protein expression level.

Results

We demonstrated that miR-302b was frequently down-regulated, whereas EGFR was up-regulated in 27 pairs of clinical HCC and non-tumorous counterparts. The dual-luciferase reporter assays revealed that EGFR was a novel target of miR-302b. Re-expression of miR-302b resulted in the inhibition of proliferation in hepatocellular carcinoma SMMC-7721 cells. The silencing of EGFR by miR-302b or siEGFR led to down-regulation of proliferation-related proteins, such as AKT2, CCND1, and CDK2.

Conclusion

miR-302b suppresses HCC growth may due to targeting the EGFR/AKT2/CCND1 pathway.
The biomechanical properties of the cornea and anterior segment parameters
Authors: Hwang Ho Sik , Park Seh Kwang , Kim Man Soo
Published: October 2013

Background

To investigate the biomechanical properties of the cornea measured with the Ocular Response Analyzer (ORA) and their association with the anterior segment parameters representing the geometric dimensions including the corneal volume and anterior chamber volume.

Methods

A retrospective review of 1020 patients who visited the BGN Eye Clinic was done. The mean radius of the corneal curvature, corneal astigmatism, corneal volume, anterior chamber depth, and anterior chamber volume were measured with an anterior segment tomographer. The central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The corneal diameter was measured with an Orbscan as White to White. Cornea hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular pressure (IOPg), and cornea-compensated IOP (IOPcc) were measured with an ORA. Multiple linear regression models were constructed with CH and CRF as the dependent variables and age, gender, and the anterior segment parameters as the covariates.

Results

958 eyes from 958 patients (mean age 26.7 years; male 43.4%) were included in this study after excluding some eyes according to the exclusion criteria. The mean CH and CRF were 10.1 and 9.9 mmHg, respectively. The mean IOPg and IOPcc were 14.8 and 15.8 mmHg. The multivariate analysis showed that CH was negatively associated with the mean radius of the cornea curvature (regression coefficient = - 0.481, p = 0.023) and positively associated with CCT (regression coefficient =0.015, p < 0.001) and corneal volume (regression coefficient =0.059, p = 0.014). The association between CH and the corneal diameter, anterior chamber depth, and anterior chamber volume were not statistically significant. The evaluation of CRF showed that CRF was negatively associated with the mean radius of the cornea curvature (regression coefficient = - 0.540, p = 0.013), and positively associated with CCT (β = 0.026, p < 0.001). The association between CRF and the corneal diameter, corneal volume, anterior chamber depth, and anterior chamber volume were not statistically significant.

Conclusion

The CH was shown to be positively associated with the corneal volume and the association between CH and the anterior chamber volume were not significant. The associations of CRF with the corneal volume or anterior chamber volume were not significant.
In vitro cytocidal effects of the essential oil from Croton cajucara (red sacaca) and its major constituent 7- hydroxycalamenene against Leishmania chagasi
Authors: Rodrigues Igor A , Azevedo Mariana M B , Chaves Francisco C M , Bizzo Humberto R , Corte-Real Suzana , Alviano Daniela S , Alviano Celuta S , Rosa Maria S S , Vermelho Alane B
Published: October 2013

Background

Visceral leishmaniasis is the most serious form of leishmaniasis and can be lethal if left untreated. Currently available treatments for these parasitic diseases are frequently associated to severe side effects. The leaves of Croton cajucara are used as an infusion in popular medicine to combat several diseases. Previous studies have demonstrated that the linalool-rich essential oil from C. cajucara (white sacaca) is extremely efficient against the tegumentary specie Leishmania amazonensis. In this study, we investigated the effects of the 7-hydroxycalamenene-rich essential oil from the leaves of C. cajucara (red sacaca) against Leishmania chagasi, as well as on the interaction of these parasites with host cells.

Methods

Promastigotes were treated with different concentrations of the essential oil for determination of its minimum inhibitory concentration (MIC). In addition, the effects of the essential oil on parasite ultrastructure were analyzed by transmission electron microscopy. To evaluate its efficacy against infected cells, mouse peritoneal macrophages infected with L. chagasi promastigotes were treated with the inhibitory and sub-inhibitory concentrations of the essential oil.

Results

The minimum inhibitory concentrations of the essential oil and its purified component 7-hydroxycalamenene against L. chagasi were 250 and 15.6 μg/mL, respectively. Transmission electron microscopy analysis revealed important nuclear and kinetoplastic alterations in L. chagasi promastigotes. Pre-treatment of macrophages and parasites with the essential oil reduced parasite/macrophage interaction by 52.8%, while it increased the production of nitric oxide by L. chagasi-infected macrophages by 80%.

Conclusion

These results indicate that the 7-hydroxycalamenene-rich essential oil from C. cajucara is a promising source of leishmanicidal compounds.
Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases
Authors: Huang Si-Yuan , Shen Shu-Jing , Li Xing-Ya
Published: October 2013

Background

Pulmonary sarcomatoid carcinoma is a diagnostically challenging group of tumors. It’s a rare histologic subtype of non-small cell lung cancer.There are five subgroups of pulmonary sarcomatoid carcinoma, they are identified as pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. We explored the clinicopathologic features and prognostic factors of this tumor.

Methods

We analyzed retrospectively the clinicopathological data of 51 patients with pulmonary sarcomatoid carcinoma who were treated in the First Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital and Henan People Hospital from January 2005 to December 2012. The correlation between prognosis and age, sex, smoking history, tumor size, TNM staging, and treatment modality was analyzed by the statistical software SPSS 17.0. The survival analysis was conducted using the Kaplan-Meier method. The factors influencing survival were analyzed using univariate (Log-rank) and multivariate (Cox) models.

Results

The overall survival rates at 1, 2, 3 and 5 years were 45.5%, 35.8%, 28.2% and 20.1%, respectively. Cox univariate analyses revealed that age, tumor size, T stage, M stage, surgery or not, and postoperative chemotherapy or not, were prognostic factors. Cox multivariate analysis found that tumor size and M stage were independent prognostic factors for PSC.

Conclusions

Due to its rarity and the lack of large-scale clinical trial evidence, few studies about PSC have been reported, its clinical and pathological characteristics remain unclear, and its preoperative diagnosis and investigation of novel treatment approaches are imperative. In our study, the main factors affecting the prognosis of tumor size and M staging are the crucial prognostic factors for PSC. Surgical resection and postoperative adjuvant chemotherapy might result in better prognosis.
The AKT inhibitor AZD5363 is selectively active in PI3KCA mutant gastric cancer, and sensitizes a patient-derived gastric cancer xenograft model with PTEN loss to Taxotere
Authors: Li Jing , Davies Barry R , Han Sufang , Zhou Minhua , Bai Yu , Zhang Jingchuan , Xu Yan , Tang Lily , Wang Huiying , Liu Yuan Jie , Yin Xiaolu , Ji Qunsheng , Yu De-Hua
Published: October 2013

Introduction

Activation of the PI3K/AKT pathway is a common phenomenon in cancer due to multiple mechanisms, including mutation of PI3KCA, loss or mutation of PTEN, or over-expression of receptor tyrosine kinases. We recently developed a novel AKT kinase inhibitor, AZD5363, and demonstrated that HGC27, a cell line harboring both PI3KCA mutation and PTEN loss, displayed the greatest sensitivity to this AKT inhibitor in vitro and in vivo.

Case preparation

To further elucidate the correlation between AZD5363 response and genetic alterations in gastric cancer (GC) and identify GC patients with both PI3KCA mutations and PTEN loss, we investigated the effects of pharmacological inhibition of AKT on a panel of 20 GC cell lines and genetic aberrations in tumor samples from a cohort of Chinese GC patients. We demonstrated that GC cells with PI3KCA mutations were selectively sensitive to AZD5363. Disease linkage studies showed that PI3KCA activating mutations or PTEN loss were found in 2.7% (4/150) and 23% (14/61) of Chinese GC patients respectively. To further dissect the role of PI3KCA mutation and PTEN loss in response to AKT inhibition, we tested the antitumor activity of AZD5363 in two patient-derived GC xenograft (PDGCX) models harboring either PI3KCA mutation or PTEN loss. Our data indicated that AZD5363 monotherapy treatment led to a moderate response in the PI3KCA mutant PDGCX model. Whilst monotherapy AZD5363 or Taxotere were ineffective in the PTEN negative PDGCX model, significant anti-tumor activity was observed when AZD5363 was combined with Taxotere.

Conclusion

Our results indicated that PI3KCA mutation is an important determinant of response to AKT inhibition in GC and combination with AZD5363 can overcome innate resistance to Taxotere in a PTEN loss PDGCX model. It is suggested that AKT inhibitor is an attractive option for treatment of a new segment of GC patients with aberrant PI3K/AKT signaling.
A case report of adult lead toxicity following use of Ayurvedic herbal medication
Authors: Breeher Laura , Gerr Fred , Fuortes Laurence
Published: October 2013

Introduction

Ayurvedic medications consist of herbs that may be intentionally combined with metals, such as lead, mercury, iron, and zinc. Ayurvedic practitioners and their patients believe that the toxic properties of the metals are reduced or eliminated during preparation and processing.

Case report

A 69 year old Caucasian male retired professional with a prior history of stroke presented for evaluation of new onset depression, fatigue, generalized weakness, constipation, anorexia, and weight loss. History revealed that his symptoms were temporally related to initiation of an Ayurvedic herbal medication. The patient had been previously admitted to another hospital for these symptoms and was found to have a severe anemia for which no etiology was found. Laboratory tests revealed an elevated blood lead level and a diagnosis of symptomatic lead toxicity was made. The patient was treated with intramuscular, intravenous, and oral chelation therapy to promote lead excretion. Because of complaints of continued poor mental function, neuropsychological tests were administered before and after one of the chelation treatments and showed improvement in measures of attention and other cognitive domains. In addition, the patient was able to discontinue use of antidepressant medication after chelation.

Discussion

A high index of suspicion of metal toxicity is necessary among persons with characteristic symptoms and signs in the absence of occupational exposure. Despite limited evidence for chelation in adults and in those with modest blood lead levels, this patient appeared to benefit from repeated chelation therapy. Both allopathic and alternative medicine practitioners and public health specialists need to be aware of the potential for contamination of and side effects from alternative pharmacologic and herbal therapies.
Using neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy for nasopharyngeal carcinoma with intracranial invasion to protect critical normal tissue
Authors: Niu Xiaoshuang , Chang Xi , Gao Yunsheng , Hu Chaosu , Kong Lin
Published: October 2013

Purpose

To investigate the feasibility of neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy (IMRT) for intracranial invasion nasopharyngeal carcinoma (NPC).

Methods and materials

From June 2007 to January 2012, 32 patients with intracranial invasion NPC treated with TPF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, 5-FU 2500 mg/m2 every 3 weeks for 3 cycles) neoadjuvant chemotherapy, and replanning IMRT with concurrent chemotherapy were retrospectively studied. The first IMRT plan for each patient was generated based on the original planning CT scan acquired before the start of treatment. Because of tumor shrinkage during radiotherapy, modified gross tumor volume of primary tumor (GTV-P) and high risk clinical target volume (CTV-H), and a new plan was generated and used to complete the course of IMRT. The DVHs of IMRT plan with or without replanning were compared.

Results

There weren’t statistically significant differences in the V95, D-mean, D-95, and D-99 to the modified PTVGTV-P and PTVCTV-H with and without replanning IMRT. Replanning reduced the doses to the brain stem, optic nerve, optic chiasm and temporal lobe. Objective responses were 100.0% 3 months after completion of radiotherapy. Acute toxicities were well tolerated, except for the relatively high incidence of neutropenia. The 2-year local control rates and distant-metastasis free survival were 88.2% (95% CI, 72.9% to 100.0%) and 89.6% (95% CI, 75.9% to 100.0%).

Conclusion

Neoadjuvant chemotherapy and replanning IMRT according to tumor shrinkage during the treatment is essential to ensure safe doses to normal tissues, and produces encouraging outcome for intracranial invasion NPC.
Effects of abscisic acid and brassinolide on photosynthetic characteristics of Leymus chinensis from Songnen Plain grassland in Northeast China
Authors: Hu Yong-Jun , Shi Lian-Xuan , Sun Wei , Guo Ji-Xun
Published: October 2013

Background

It has been well demonstrated that plant growth regulators have important functions in multiple physiological processes. ABA and BR play crucial roles in response of crops to stresses. Photosynthetic capacity of Leymus. chinensis treated by various concentrations of ABA and BR in combination was determined. Further more, the mechanisms of ABA and BR treatments and potential for recovery of saline-alkali grasslands were discussed.

Results

Abscisic acid (ABA) and brassinolide (BR) affected leaf gas exchange, growth and biomass of L. chinensis. The application of ABA and BR mixtures, especially that of 0.01 mM ABA and 2 × 10-4 mM BR, increased the net photosynthetic rate, stomatal conductance, water use efficiency, the maximum net photosynthetic rate, light-saturated rate, leaf respiration rate, the maximum RUBP carboxylation rate, the maximum electron transport rate, the maximum triose-phosphate utilization, carboxylation efficiency and the quantum efficiency of PSII and subsequently enhanced density, height and biomass in L. chinensis. We also observed reduction in the light compensation and saturation points following the application of ABA and BR treatments.

Conclusions

We concluded that proper use of plant growth regulators can enhance the plant growth and productivity on the Songnen grassland, which is particularly important for the improvement of saline – alkaline grassland and the yield of grazing lands.
Localization of organic anion transporting polypeptide (Oatp) 1a4 and Oatp1c1 at the rat blood-retinal barrier
Authors: Akanuma Shin-ichi , Hirose Shiro , Tachikawa Masanori , Hosoya Ken-ichi
Published: October 2013

Background

Organic anion transporting polypeptide (Oatp) transporters at the blood–brain barrier (BBB) and the blood-retinal barrier (BRB), which consists of retinal capillary endothelial cells and retinal pigment epithelial cells, are major determinants of the control of anionic drugs into the brain and retina. Although Oatp1a4 (Slco1a4) and Oatp1c1 (Slco1c1) are known to be expressed in the abluminal and luminal membrane of the rat BBB and Oatp1a4 is known to be expressed at the BRB, the expression and localization of Oatp1c1 at the BRB and subcellular localization of Oatp1a4 at the BRB have received little attention. Therefore, the purpose of present study was to determine the cellular and subcellular localization of Oatp1a4 and 1c1 at the BRB.

Methods

We used guinea pig polyclonal antibodies to Oatp1a4 and 1c1 for immunoblot and immunohistochemical analysis to determine their cellular and subcellular distributions in the rat retina. We compared these distributions with those of the glucose transporter 1 (GLUT1/Slc2a1). Whole brain, brain capillary fractions and kidney were used as control.

Results

Oatp1a4 and 1c1 immunoreactivities were detected in the rat retinal capillaries and co-localized with GLUT1, suggesting that both proteins are located on the abluminal and luminal membrane of the retinal capillary endothelial cells. Oatp1a4 and 1c1 immunoreactivities were preferentially detected on the apical and basolateral membrane of rat retinal pigment epithelial cells, respectively, suggesting that Oatp1a4 and 1c1 are localized on the apical membrane and the basolateral membrane of the retinal pigment epithelial cells, respectively.

Conclusion

Oatp1a4 and 1c1 are present at the BRB and contribute to the transcellular transport of amphipathic organic anions across the BRB.
Predictive factors of successful microdissection testicular sperm extraction
Authors: Bernie Aaron M , Ramasamy Ranjith , Schlegel Peter N
Published: October 2013

Azoospermia in men requires microsurgical reconstruction or a procedure for sperm retrieval with assisted reproduction to allow fertility. While the chance of successful retrieval of sperm in men with obstructive azoospermia approaches >90%, the chances of sperm retrieval in men with non-obstructive azoospermia (NOA) are not as high. Conventional procedures such as fine needle aspiration of the testis, testicular biopsy and testicular sperm extraction are successful in 20-45% of men with NOA. With microdissection testicular sperm extraction (micro-TESE), the chance of successful retrieval can be up to 60%. Despite this increased success, the ability to counsel patients preoperatively on their probability of successful sperm retrieval has remained challenging. A combination of variables such as age, serum FSH and inhibin B levels, testicular size, genetic analysis, history of Klinefelter syndrome, history of cryptorchidism or varicocele and histopathology on diagnostic biopsy have provided some insight into the chance of successful sperm retrieval in men with NOA. The goal of this review was to evaluate the preoperative factors that are currently available to predict the outcome for success with micro-TESE.
Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients
Authors: Song Soken-Nakazawa J , Iwahashi Mitsuhiro , Tomosugi Naohisa , Uno Kazuko , Yamana Jiro , Yamana Seizou , Isobe Tomoyasu , Ito Hiroki , Kawabata Hiroshi , Yoshizaki Kazuyuki
Published: October 2013

Introduction

Anemia of inflammation (AI) is a common complication of rheumatoid arthritis (RA) and has a negative impact on RA symptoms and quality of life. Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In this study, we evaluated and compared the effects of IL-6 and TNF-α blocking therapies on anemia, disease activity, and iron-related parameters including serum hepcidin in RA patients.

Methods

Patients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-α inhibitors for 16 weeks. Major disease activity indicators and iron-related parameters including serum hepcidin-25 were monitored before and 2, 4, 8, and 16 weeks after the initiation of treatment. Effects of tocilizumab and infliximab (anti-TNF-α antibody) on cytokine-induced hepcidin expression in hepatoma cells were analyzed by quantitative real-time PCR.

Results

Anemia at base line was present in 66% of patients. Baseline serum hepcidin-25 levels were correlated positively with serum ferritin, C-reactive protein (CRP), vascular endothelial growth factor (VEGF) levels and Disease Activity Score 28 (DAS28). Significant improvements in anemia and disease activity, and reductions in serum hepcidin-25 levels were observed within 2 weeks in both groups, and these effects were more pronounced in the tocilizumab group than in the TNF-α inhibitors group. Serum hepcidin-25 reduction by the TNF-α inhibitor therapy was accompanied by a decrease in serum IL-6, suggesting that the effect of TNF-α on the induction of hepcidin-25 was indirect. In in vitro experiments, stimulation with the cytokine combination of IL-6+TNF-α induced weaker hepcidin expression than did with IL-6 alone, and this induction was completely suppressed by tocilizumab but not by infliximab.

Conclusions

Hepcidin-mediated iron metabolism may contribute to the pathogenesis of RA-related anemia. In our cohort, tocilizumab was more effective than TNF-α inhibitors for improving anemia and normalizing iron metabolism in RA patients by inhibiting hepcidin production.
Arterial hypertension assessed “out-of-office” in a contemporary cohort of rheumatoid arthritis patients free of cardiovascular disease is characterized by high prevalence, low awareness, poor control and increased vascular damage-associated “white coat” phenomenon
Authors: Protogerou Athanase D , Panagiotakos Demosthenis B , Zampeli Evangelia , Argyris Antonis A , Arida Katerina , Konstantonis Giorgos D , Pitsavos Christos , Kitas George D , Sfikakis Petros P
Published: October 2013

Introduction

Rheumatoid arthritis (RA) is associated with a high cardiovascular disease (CVD) risk, whereas arterial hypertension is a major modifiable CVD risk factor with still unclear prevalence in RA disease. We conducted a comprehensive study on hypertension characteristics evaluating for the first time out-of-office blood pressure (BP) in a typical contemporary RA cohort.

Methods

Assessment of office and out-of-office BP (when office systolic/diastolic BP was >129/79) and vascular studies including evaluation of aortic stiffness, carotid hypertrophy/plaques and ankle-brachial index, were performed in 214 consecutive, consenting RA patients free of CVD (aged 58.4 ± 12.3 years, 82% women). As comparators regarding office hypertension measurements, data from 214 subjects (1:1 matched for age and gender with the RA patients) derived from a cohort designed to assess the prevalence of hypertension in the general population were used.

Results

The prevalence of declared known hypertension in the RA population was 44%. Of the remaining RA patients, 2 in every 5 individuals had abnormal office BP (systolic/diastolic >139/89 mmHg), contributing to almost double the prevalence of declared/office hypertension compared to the general matched population (67% vs. 34%). Out-of-office (home or ambulatory 24 hour) BP measurements revealed that: (i) a 54% prevalence of actual hypertension in RA, in other words almost 10% of the patients were unaware of having hypertension and (ii) 29% of the RA patients with known hypertension were not well controlled. Actual hypertension was positively associated with age and body mass index, and inversely with the use of biologic drugs. Overall, almost 1 out of 5 presented the 'white coat’ phenomenon. An intermediately compromised vascular phenotype was evident in this “white coat” subgroup (lying between patients with sustained normotension and sustained hypertension) in terms of aortic stiffness, carotid hypertrophy and ankle-brachial index, even after adjustment for confounders.

Conclusion

Beyond any doubt on the basis of out-of-office evaluation, arterial hypertension in RA has a high prevalence, low awareness and poor control, as well as substantial and vascular damage-associated “white coat” phenomenon. Thus, correct diagnosis and effective treatment of hypertension is of key importance in RA for CVD risk reduction.
Early treatment with IgM-enriched intravenous immunoglobulin does not mitigate critical illness polyneuropathy and/or myopathy in patients with multiple organ failure and SIRS/sepsis: a prospective, randomized, placebo-controlled, double-blinded trial
Authors: Brunner Richard , Rinner Walter , Haberler Christine , Kitzberger Reinhard , Sycha Thomas , Herkner Harald , Warszawska Joanna , Madl Christian , Holzinger Ulrike
Published: October 2013

Introduction

Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical illness. Retrospective data suggest that early application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting.

Methods

In this prospective, randomized, double-blinded and placebo-controlled trial, 38 critically ill patients with multiple organ failure (MOF), systemic inflammatory response syndrome (SIRS)/sepsis, and early clinical signs of CIPNM were included. Patients were randomly assigned to be treated either with IgM-enriched IVIG or placebo over a period of three days. CIPNM was measured by the CIPNM severity sum score based on electrophysiological stimulation of the median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8 (very severe CIPNM).

Results

A total of 38 critically ill patients were included and randomized to receive either IgM-enriched IVIG (n = 19) or placebo (n = 19). Baseline characteristics were similar between the two groups. CIPNM could not be improved by IVIG treatment, represented by similar CIPNM severity sum scores on day 14 (IVIG vs. placebo: 4.8 ± 2.0 vs. 4.5 ± 1.8; P = 0.70). CIPNM severity sum score significantly increased from baseline to day 14 (3.5 ± 1.6 vs. 4.6 ± 1.9; P = 0.002). After an interim analysis the study was terminated early due to futility in reaching the primary endpoint.

Conclusions

Early treatment with IVIG did not mitigate CIPNM in critically ill patients with MOF and SIRS/sepsis.

Trial registration

Clinicaltrials.gov: NCT01867645
Continuous regional arterial infusion for acute pancreatitis: a propensity score analysis using a nationwide administrative database
Authors: Hamada Tsuyoshi , Yasunaga Hideo , Nakai Yousuke , Isayama Hiroyuki , Horiguchi Hiromasa , Matsuda Shinya , Fushimi Kiyohide , Koike Kazuhiko
Published: October 2013

Introduction

Although continuous regional arterial infusion (CRAI) of a protease inhibitor and an antibiotic may be effective in patients with severe acute pancreatitis, CRAI has not yet been validated in large patient populations. We therefore evaluated the effectiveness of CRAI based on data from a national administrative database covering 1,032 Japanese hospitals.

Methods

In-hospital mortality, length of stay and costs were compared in the CRAI and non-CRAI groups, using propensity score analysis to adjust for treatment selection bias.

Results

A total of 17,415 eligible patients with acute pancreatitis were identified between 1 July and 30 September 2011, including 287 (1.6%) patients who underwent CRAI. One-to-one propensity-score matching generated 207 pairs with well-balanced baseline characteristics. In-hospital mortality rates were similar in the CRAI and non-CRAI groups (7.7% vs. 8.7%; odds ratio, 0.88; 95% confidence interval, 0.44–1.78, P = 0.720). CRAI was associated with significantly longer median hospital stay (29 vs. 18 days, P < 0.001), significantly higher median total cost (21,800 vs. 12,600 United States dollars, P < 0.001), and a higher rate of interventions for infectious complications, such as endoscopic/surgical necrosectomy or percutaneous drainage (2.9% vs. 0.5%, P = 0.061).

Conclusions

CRAI was not effective in reducing in-hospital mortality rate in patients with acute pancreatitis, but was associated with longer hospital stay and higher costs. Randomized controlled trials in large numbers of patients are required to further evaluate CRAI for this indication.
A Tris-fused Tetrathiafulvalene Extended with Cyclohexene-1,4-diylidene: A New Positive Electrode Material for Organic Rechargeable Batteries
Authors: Kato Minami , Ogi Daisuke , Yao Masaru , Misaki Yohji
Published: October 2013

Derivatives of tris-fused TTF donors 3 extended with cyclohexene-1,4-diylidene were synthesized. Cyclic voltammetry revealed that the tetrakis(hexylthio)-3 (3c) exhibited three stages of a two-electron redox process to afford the hexacation. The rechargeable battery incorporating tetrakis(methylsulfanyl)-3 (3b) as the positive electrode material exhibited a high cycle performance in spite of utilizing the highest oxidation state of +6.
Adsorption of Vanillin Using Macroporous Resin H103
Authors: Samah Rozaimi Abu , Zainol Norazwina , Yee Phang Lai , Pawing Christine Michael , Abd-Aziz Suraini
Published: October 2013

Six resins (Amberlite XAD-16, Amberlite XAD-2, Sepabeads SP207, DIAION HP-20, DM11 and H103) were tested for vanillin adsorption in aqueous solution. All of the resins gave more than 95% adsorption rate except for Amberlite XAD-2 and DM11. Resin H103 was selected for the subsequent work due to its high adsorption capacity and low cost. A kinetic analysis revealed that the adsorption process followed pseudo-second-order kinetic model and occurred rapidly. The equilibrium point was reached after 90 minutes of reaction. Adsorption isotherm was also determined at 25 °C and it was fitted to Langmuir and Freundlich equations using linear regression and non-linear regression (sum of squares) methods. The regression shows that the adsorption of vanillin onto resin H103 followed Langmuir model (R2 = 0.9984) with a maximum capacity of 73.015 mg/g.
Removal of Cu2+ and Zn2+ Ions from Aqueous Solution Using Sodium Alginate and Attapulgite Composite Hydrogels
Authors: Huang Dajian , Wang Wenbo , Wang Aiqin
Published: October 2013

A series of sodium alginate-g-sodium acrylate/attapulgite (NaAlg-g-PNaA/APT) composite hydrogels were used as adsorbents to adsorb Cu2+ and Zn2+ from aqueous solutions. The effect of common variables including the content of APT, pH value, contact time and initial concentration of metal ions on the adsorption properties of the composite hydrogels for the adsorption of Cu2+ and Zn2+ ions was investigated using a batch adsorption technique. The results show that the composites evaluated have an excellent adsorption capacity and fast adsorption rate for both Cu2+ and Zn2+ ions. Repeated adsorption–desorption experimental results show that the composite hydrogels have a good reusability and stability, and 50% of the original adsorption capacity can be retained after being reused five times. The pseudo-second-order equation and the Langmuir equation best describe the adsorption kinetics and isotherms, respectively.
Performance of Poly(Styrene—Divinylbenzene) Magnetic Porous Microspheres Prepared by Suspension Polymerization for the Adsorption of 2, 4-Dichlorophenol and 2, 6-Dichlorophenol from Aqueous Solutions
Authors: Yu Ping , Sun Qilong , Pan Jianming , Tan Zhenjiang , Dai Jiangdong , Yan Yongsheng , Cheng Feng
Published: October 2013

Poly(styrene–divinylbenzene)/Fe3O4 (Fe3O4@St–DVB) magnetic porous polymer microspheres based on suspension polymerization were prepared for adsorption of 2, 4-dichlorophenol (2, 4-DCP) and 2, 6-dichlorophenol (2, 6-DCP) from aqueous solution. The as-prepared product was characterized by Fourier transform infrared spectroscopy, Raman, X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, differential thermal analysis and elemental analysis. The results showed that the composite material has both porous and magnetic characteristics, which aid in faster separation and increase in adsorption capacity. The adsorption performance of the Fe3O4@(St–DVB) magnetic porous microspheres was manifested by batch mode adsorption experiments with respect to pH, initial concentration, contact time and temperature. The adsorbent was found to be sensitive to changes in pH, and the adsorption capacity of 2, 4-DCP is higher than that of 2, 6-DCP. The kinetics experimental data fitted well with the pseudo-second-order model, as three steps belonged to the pseudo-second-order adsorption process. The adsorption isotherms were also described by the Langmuir and Freundlich isotherm models, respectively. It was found that the Langmuir isotherm model fitted the equilibrium data superior to the Freundlich model. Thermodynamic parameters were calculated by the Gibbs free energy function, confirming that adsorption process was spontaneous and endothermic. In addition, the reusability performance of the Fe3O4@(St–DVB) magnetic porous microspheres was demonstrated by four repeated cycles.
Investigating Room Acoustics by Simulations and Measurements
Authors: Christensen Claus Lynge
Published: October 2013

Measurements in room acoustics are often used as the true reference of reality, while simulations are considered to be only a crude representation of it. However, both approaches have their own challenges and limitations, so measuring an impulse response and deriving room acoustic parameters correctly may be more difficult than it appears at first glance. In this article we present the comparison between measurements and simulations for two real-case rooms: an auditorium and a cathedral. The comparison is made in the ODEON Room Acoustics Software version 121 and shows that careful postprocessing of the measured data can lead to high agreement with advanced room acoustics simulations. For a complete room acoustics study both measurements and simulations seem to be equivalently necessary.
Interaction of Sonic Booms with Isolated and Multiple Buildings
Authors: Remillieux Marcel C. , Pasareanu Stephanie M.
Published: October 2013

The sonic boom an aircraft generates when it travels faster than the speed of sound is the last environmental obstacle to the economic viability and widespread development of a commercial supersonic transport. One important aspect to consider in this problem is the impact of sonic booms at the ground level, and in particular their interactions with buildings. With this objective in mind, acoustic data was collected at Virginia Tech around and on the exterior surfaces of a simplified building structure exposed to simulated sonic booms, where an explosive technique was used to generate the desired pressure waveforms. These experiments were simulated with a three-dimensional numerical model by combining the image-source method for the reflected field with an extension of the Biot-Tolstoy-Medwin method for the diffracted field. This numerical model is verified against a boundary element solution and validated against experimental data. The key advantages of this modeling approach are pointed out such as the ability to model large three-dimensional domains over a wide frequency range and also to decompose the sound field into direct, reflected, and diffracted components, thus allowing a better understanding of the physical mechanisms involved in the sound propagation. This validated numerical model is also used to study the sound propagation around a cluster of six rectangular buildings, for a range of elevated source positions.