bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose selection method for pharmacokinetic study in hemodialysis patients using a subpharmacological dose: oseltamivir as a model drug
Authors: Kim Dong Ki , Lee Jay Wook , Shin Kwang-Hee , Kim Sejoong , Oh Kook-Hwan , Kim Myounghee , Yu Kyung-Sang , Lee Jung Pyo , Lim Chun-Soo , Kim Yon Su , Joo Kwon Wook
Published: March 2014

Background

Dose selection is an important step in pharmacokinetic (PK) studies of hemodialysis patients. We propose a simulation-based dose-selection method for PK studies of hemodialysis patients using a subpharmacological dose of oseltamivir as a model drug.

Methods

The concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were measured by liquid chromatography-tandem mass spectrometry. To determine a low oseltamivir dose exhibiting PK linearity, a pilot low dose determination investigation (n = 4) was performed using a single administration dose-escalation study. After the dose was determined, a low dose study (n = 10) was performed, and the optimal dose required to reach the hypothetical target OC exposure (area under the concentration-time curve [AUC] of 60,000 ng · hr/mL) was simulated using a nonparametric superposition method. Finally, observed PKs at the optimal dose were compared to the simulated PKs to verify PK predictability.

Results

In the pilot low dose determination study, 2.5 mg of oseltamivir was determined to be the low dose. Subsequently, we performed a single-dose PK study with the low oseltamivir dose in an additional group of 10 hemodialysis patients. The predicted AUClast of OC following continuous oseltamivir doses was simulated, and 35 mg of oseltamivir corresponded to the hypothetical target AUClast of OC. The observed PK profiles of OC at a 35-mg oseltamivir dose and the simulated data based on the low dose study were in close alignment.

Conclusion

The results indicate that the proposed method provides a rational approach to determine the proper PK dose in hemodialysis patients.
Molecular beam epitaxy and properties of GaAsBi/GaAs quantum wells grown by molecular beam epitaxy: effect of thermal annealing
Authors: Makhloufi Hajer , Boonpeng Poonyasiri , Mazzucato Simone , Nicolai Julien , Arnoult Alexandre , Hungria Teresa , Lacoste Guy , Gatel Christophe , Ponchet Anne , Carrère Hélène , Marie Xavier , Fontaine Chantal
Published: March 2014

We have grown GaAsBi quantum wells by molecular beam epitaxy. We have studied the properties of a 7% Bi GaAsBi quantum well and their variation with thermal annealing. High-resolution X-ray diffraction, secondary ion mass spectrometry, and transmission electron microscopy have been employed to get some insight into its structural properties. Stationary and time-resolved photoluminescence shows that the quantum well emission, peaking at 1.23 μm at room temperature, can be improved by a rapid annealing at 650°C, while the use of a higher annealing temperature leads to emission degradation and blue-shifting due to the activation of non-radiative centers and bismuth diffusion from the quantum well.
Enhanced resistive switching memory characteristics and mechanism using a Ti nanolayer at the W/TaO
x
interface
Authors: Prakash Amit , Maikap Siddheswar , Chiu Hsien-Chin , Tien Ta-Chang , Lai Chao-Sung
Published: March 2014

Enhanced resistive memory characteristics with 10,000 consecutive direct current switching cycles, long read pulse endurance of >105 cycles, and good data retention of >104 s with a good resistance ratio of >102 at 85°C are obtained using a Ti nanolayer to form a W/TiO
x
/TaO
x
/W structure under a low current operation of 80 μA, while few switching cycles are observed for W/TaO
x
/W structure under a higher current compliance >300 μA. The low resistance state decreases with increasing current compliances from 10 to 100 μA, and the device could be operated at a low RESET current of 23 μA. A small device size of 150 × 150 nm2 is observed by transmission electron microscopy. The presence of oxygen-deficient TaO
x
nanofilament in a W/TiO
x
/TaO
x
/W structure after switching is investigated by Auger electron spectroscopy. Oxygen ion (negative charge) migration is found to lead to filament formation/rupture, and it is controlled by Ti nanolayer at the W/TaO
x
interface. Conducting nanofilament diameter is estimated to be 3 nm by a new method, indicating a high memory density of approximately equal to 100 Tbit/in.2.
Correlation between the suppressor of cytokine signaling-1 and 3 and hepatitis B virus: possible roles in the resistance to interferon treatment
Authors: Du Ling-yao , Cui Yao-li , Chen En-qiang , Cheng Xing , Liu Li , Tang Hong
Published: March 2014

Background

The suppressor of cytokine signaling family (SOCS) is an important negative regulator in the JAK-STAT signaling pathway. This study was designed to explore the correlation between SOCS-1, 2 and 3, Hepatitis B Virus (HBV) and interferon (IFN), and the relationship between SOCS and IFN therapeutic efficacy.

Methods

Four types of mouse models were established. Mice were administered with HBV replicative plasmid pHBV4.1 and IFN inducer Poly IC (Group A), pHBV4.1 (Group B), Poly IC (Group C) and saline (Group D), respectively. Liver tissues were harvested from the mice and SOCS expression was determined. Meanwhile, patients with chronic hepatitis B (CHB) were treated with pegylated interferon α-2b for 24-48 weeks. Liver biopsy was collected and the baseline SOCS expression was determined. Serum assay was performed for efficacy evaluation and correlation analysis.

Results

In animal studies, the expression level of SOCS-1 and 3 was found in the descending order of B, A, C and D. The difference between Group B and D suggested that HBV could induce SOCS. The difference between Group A and C suggested that HBV could still induce SOCS with up-regulated endogenous IFN. The difference between Group C and D suggested that ploy IC could induce SOCS, while the difference between Group B and A suggested that Poly IC might have a stronger inhibition effect for SOCS. There was no difference in SOCS-2 expression. In clinical studies, eight of twenty-four enrolled patients achieved either complete or partial therapeutic response. The expression of both SOCS-1 and 3 was higher in CHB patients than in normal controls. The baseline HBV-DNA level was positively correlated with SOCS-1 and 3. The age, viral genotype, HBVDNA, SOCS-1 and SOCS-3 were found to be related to IFN efficacy.

Conclusion

HBV could induce both SOCS-1 and 3 expression regardless of endogenous IFN level. Elevated IFN could directly up-regulate SOCS-1 and 3 expression, but it could also indirectly down-regulate SOCS-1 and 3 expression by inhibiting HBV replication. HBV might play a more important role in the SOCS up-regulation than IFN, a possible reason why patients with high HBV viral load encounter poor efficacy of IFN treatment.
Using a large-scale knowledge database on reactions and regulations to propose key upstream regulators of various sets of molecules participating in cell metabolism
Authors: Blavy Pierre , Gondret Florence , Lagarrigue Sandrine , van Milgen Jaap , Siegel Anne
Published: March 2014

Background

Most of the existing methods to analyze high-throughput data are based on gene ontology principles, providing information on the main functions and biological processes. However, these methods do not indicate the regulations behind the biological pathways. A critical point in this context is the extraction of information from many possible relationships between the regulated genes, and its combination with biochemical regulations. This study aimed at developing an automatic method to propose a reasonable number of upstream regulatory candidates from lists of various regulated molecules by confronting experimental data with encyclopedic information.

Results

A new formalism of regulated reactions combining biochemical transformations and regulatory effects was proposed to unify the different mechanisms contained in knowledge libraries. Based on a related causality graph, an algorithm was developed to propose a reasonable set of upstream regulators from lists of target molecules. Scores were added to candidates according to their ability to explain the greatest number of targets or only few specific ones. By testing 250 lists of target genes as inputs, each with a known solution, the success of the method to provide the expected transcription factor among 50 or 100 proposed regulatory candidates, was evaluated to 62.6% and 72.5% of the situations, respectively. An additional prioritization among candidates might be further realized by adding functional ontology information. The benefit of this strategy was proved by identifying PPAR isotypes and their partners as the upstream regulators of a list of experimentally-identified targets of PPARA, a pivotal transcriptional factor in lipid oxidation. The proposed candidates participated in various biological functions that further enriched the original information. The efficiency of the method in merging reactions and regulations was also illustrated by identifying gene candidates participating in glucose homeostasis from an input list of metabolites involved in cell glycolysis.

Conclusion

This method proposes a reasonable number of regulatory candidates for lists of input molecules that may include transcripts of genes and metabolites. The proposed upstream regulators are the transcription factors themselves and protein complexes, so that a multi-level description of how cell metabolism is regulated is obtained.
Acute kidney injury associated with rhabdomyolysis after coronary artery bypass graft: a case report and review of the literatures
Authors: Sudarsanan Suraj , Omar Amr S , Pattath Rasheed A , Al Mulla Abdulwahid
Published: March 2014

Background

Post-operative rhabdomyolysis is a well-known complication, especially after bariatric and orthopaedic surgeries. There are few published reports of rhabdomyolysis following cardiac surgery. Acute kidney injury had been distinguished as a serious complication of cardiac surgery. We report a case of 55-years-old male patient who developed rhabdomyolysis precipitated acute kidney injury after coronary artery bypass graft.

Case presentation

The patient underwent urgent coronary artery bypass graft surgery, with a long duration of surgery due to technical difficulty during grafting. He developed rhabdomyolysis induced acute kidney injury necessitating hemodialysis. The patient in turn developed heart failure, which along with acute kidney injury lead to prolonged ventilation. There was supervening sepsis with prolonged intensive care unity stay and eventually prolonged hospitalization. The peak creatine kinase level was 39000 IU/mL and peak myoglobin was 40000 ng/ml. Reviewing the patient, surgery was prolonged due to technical difficulties encountered during grafting, leading to rhabdomyolysis induced acute kidney injury. The pre-operative use of statins by the patient could also have contributed to the development of rhabdomyolysis. He developed post-operative right heart failure and sepsis. The patient’s renal function gradually improved over 4 week’s duration. Favorable outcome could be achieved but after prolonged course of renal replacement therapy in the form of hemodialysis.

Conclusion

Prolonged duration of surgery is a well-recognized risk factor in the development of rhabdomyolysis. Early recognition of rhabdomyolysis induced acute kidney injury is important in reducing the post-operative morbidity and mortality in patients. A protocol based approach could be applied for early recognition and management.
Inhibition of ABA-induced stomatal closure by fusicoccin is associated with cytosolic acidification-mediated hydrogen peroxide removal
Authors: Huang Ai-Xia , She Xiao-Ping , Zhao Jin-Liang , Zhang Yun-Ying
Published: March 2014

Background

Fusicoccin (FC), a fungal phytotoxin produced by Fusicoccum amygdale, causes the inhibition of ABA-induced stomatal closure. The mechanism of inhibition is remaining unclear. We analyzed the role of hydrogen peroxide (H2O2) and relationship between H2O2 removal and cytosolic pH changes during inhibition of ABA-induced stomatal closure by FC.

Results

According to the results, ABA treatment induced H2O2 production and stomatal closure, but FC inhibited the effects of ABA on these two parameters. Treatment with catalase (CAT) and NADPH oxidase inhibitor diphenylene iodonium (DPI) mimicked the effect of FC. These data suggest that inhibition of ABA effect by FC is related to the decrease of H2O2 levels in guard cells. Furthermore, similar to CAT, FC not only suppressed stomatal closure and H2O2 levels in guard cells treated with exogenous H2O2, but also reopened the stomata which had been closed by ABA and reduced the level of H2O2 that had been produced by ABA, indicating that FC causes H2O2 removal in guard cells. The butyric acid treatment simulated the effects of FC on the stomatal aperture and H2O2 levels in guard cells treated with exogenous H2O2 and had been closed by ABA, and both FC and butyric acid reduced cytosolic pH in guard cells of stomata treated with H2O2 and had been closed by ABA, which demonstrate that cytosolic acidification mediates FC-induced H2O2 removal.

Conclusion

These results suggest that FC causes cytosolic acidification in guard cells, then induces H2O2 removal and reduces H2O2 levels in guard cells, finally inhibits stomatal closure induced by ABA.
Proper paraffin slide storage is crucial for translational research projects involving immunohistochemistry stains
Authors: Economou Mary , Schöni Liliane , Hammer Caroline , Galván José A , Mueller Dominique‐Elisabeth , Zlobec Inti
Published: March 2014

The use of paraffin slides and tissue microarrays (TMA) is indispensable for translational research. However, storage of paraffin slides over time has a substantial detrimental effect on the quality and reliability of immunohistochemistry stains. Particularly affected by this issue may be any collaborative efforts where paraffin slides or TMAs are shipped to central laboratories and then ‘biobanked’ for some time until use. This article summarizes some of the key issues affecting loss of antigenicity on paraffin slides and some simple storage solutions to help maintain high quality immunohistochemistry results when paraffin slides must be stored for a certain time prior to use.
Study of materials and techniques in painted ceiling panels from a palace in Cremona (Italy, 15thcentury)
Authors: Malagodi Marco , Rovetta Tommaso , Licchelli Maurizio
Published: March 2014

Background

This study concerns the analysis of four painted wooden panels from the second half of the 15th century which embellish the ceiling of a palace situated in Cremona (Northern Italy). This type of painting was generally used to decorate the top of the walls and the ceilings of the rooms in aristocratic palaces and they usually portray the owner’s ancestors, family members or important visitors. The paintings are of historical importance since they enable us to study the clothing and hair styles which were in fashionable in Italy during the Renaissance. These panels were heavily damaged and required a lot of restoration including the cleaning of the paint layers. This enabled us to carry out a thorough examination of the materials and techniques used for creating these paintings.

Results

Various micro-samples were taken in order to distinguish the materials and, in particular: (i) to analyze the ground layer and study its function; (ii) to typify the organic binders and the pigments of the polychrome films. The stratigraphic sequence of micro-samples was analyzed using optical microscopy, the elemental composition was determined by means of the SEM-EDX technique while the organic binders were analyzed by means of μFT-IR spectroscopy. The main component of ground layer proved to be clay. The organic binder was probably composed of a protein-based material such as animal glue. This type of ground layer is similar to the traditional 15th century Flemish formula and seems to confirm the strong influence of that artistic technique in Northern Italy. Cross-section investigation showed a primer layer over the ground layer made of white lead pigment. In fact, a white primer was used to cover the ground layer of yellowish clay common in Central Europe. The importance of this research is also confirmed by the study of paint films, for which pigments such as azurite or cinnabar were used. Red lake pigment for painting the subjects’ complexions was emphasized.

Conclusions

The analyses provide new detailed information concerning the materials used for painting the ceiling panels, the layer sequence of the paints and Northern Italian 15th century painting techniques.
Initial impacts of the Ticket to Work program: estimates based on exogenous variation in Ticket mail months
Authors: Stapleton David , Mamun Arif , Page Jeremy
Published: March 2014

This paper presents results from an impact analysis of the Ticket to Work (TTW) program, as implemented by the Social Security Administration (SSA) from 2002 through 2007. For new, young Social Security Disability beneficiaries, we use exogenous variation in the month of Ticket mailing to rigorously estimate impacts of TTW on beneficiary outcomes over a 48-month period following the start of Ticket mailings in the beneficiary’s state. We find substantial impacts on enrollment for employment services with TTW-qualified providers, but no consistent evidence of impacts on the number of months in which beneficiaries did not receive benefits because of work, or on other outcomes.

JEL classification

H55; I38
Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank
Authors: Pardo Ivanesa , Lillemoe Heather A , Blosser Rachel J , Choi MiRan , Sauder Candice A M , Doxey Diane K , Mathieson Theresa , Hancock Bradley A , Baptiste Dadrie , Atale Rutuja , Hickenbotham Matthew , Zhu Jin , Glasscock Jarret , Storniolo Anna Maria V , Zheng Faye , Doerge RW , Liu Yunlong , Badve Sunil , Radovich Milan , Clare Susan E
Published: March 2014

Introduction

Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established. The KTB is, to our knowledge, the only biorepository in the world prospectively established to collect normal, healthy breast tissue from volunteer donors. As a first initiative toward a molecular understanding of the biology and developmental genetics of the normal mammary gland, the effect of the menstrual cycle and hormonal contraceptives on DNA expression in the normal breast epithelium was examined.

Methods

Using normal breast tissue from 20 premenopausal donors to KTB, the changes in the mRNA of the normal breast epithelium as a function of phase of the menstrual cycle and hormonal contraception were assayed using next-generation whole transcriptome sequencing (RNA-Seq).

Results

In total, 255 genes representing 1.4% of all genes were deemed to have statistically significant differential expression between the two phases of the menstrual cycle. The overwhelming majority (221; 87%) of the genes have higher expression during the luteal phase. These data provide important insights into the processes occurring during each phase of the menstrual cycle. There was only a single gene significantly differentially expressed when comparing the epithelium of women using hormonal contraception to those in the luteal phase.

Conclusions

We have taken advantage of a unique research resource, the KTB, to complete the first-ever next-generation transcriptome sequencing of the epithelial compartment of 20 normal human breast specimens. This work has produced a comprehensive catalog of the differences in the expression of protein-coding genes as a function of the phase of the menstrual cycle. These data constitute the beginning of a reference data set of the normal mammary gland, which can be consulted for comparison with data developed from malignant specimens, or to mine the effects of the hormonal flux that occurs during the menstrual cycle.
Another brick in the wall of needs for invasive ventilation?
Authors: Quintel Michael , Moerer Onnen
Published: March 2014

Ventilator-induced lung injury and ventilator-induced diaphragmatic dysfunction are major complications in mechanically ventilated patients with acute respiratory failure. Invasive ventilation adds a further burden by increasing the risk of infections. An approach that protects both lung and diaphragm is pivotal. Mirabella and colleagues compared conventional controlled ventilation with a mode that combines several potentially lung-protective properties - non-invasively applied neurally adjusted ventilatory assist - in an animal experiment. This approach seemed to be as effective but potentially more lung-protective. Although the experimental setup and results cannot be translated directly to the clinical setting, they should motivate us to further study this innovative approach.
Functional differentiation of midbrain neurons from human cord blood-derived induced pluripotent stem cells
Authors: Stanslowsky Nancy , Haase Alexandra , Martin Ulrich , Naujock Maximilian , Leffler Andreas , Dengler Reinhard , Wegner Florian
Published: March 2014

Introduction

Human induced pluripotent stem cells (hiPSCs) offer great promise for regenerative therapies or in vitro modelling of neurodegenerative disorders like Parkinson’s disease. Currently, widely used cell sources for the generation of hiPSCs are somatic cells obtained from aged individuals. However, a critical issue concerning the potential clinical use of these iPSCs is mutations that accumulate over lifetime and are transferred onto iPSCs during reprogramming which may influence the functionality of cells differentiated from them. The aim of our study was to establish a differentiation strategy to efficiently generate neurons including dopaminergic cells from human cord blood-derived iPSCs (hCBiPSCs) as a juvenescent cell source and prove their functional maturation in vitro.

Methods

The differentiation of hCBiPSCs was initiated by inhibition of transforming growth factor-β and bone morphogenetic protein signaling using the small molecules dorsomorphin and SB 431542 before final maturation was carried out. hCBiPSCs and differentiated neurons were characterized by immunocytochemistry and quantitative real time-polymerase chain reaction. Since functional investigations of hCBiPSC-derived neurons are indispensable prior to clinical applications, we performed detailed analysis of essential ion channel properties using whole-cell patch-clamp recordings and calcium imaging.

Results

A Sox1 and Pax6 positive neuronal progenitor cell population was efficiently induced from hCBiPSCs using a newly established differentiation protocol. Neuronal progenitor cells could be further maturated into dopaminergic neurons expressing tyrosine hydroxylase, the dopamine transporter and engrailed 1. Differentiated hCBiPSCs exhibited voltage-gated ion currents, were able to fire action potentials and displayed synaptic activity indicating synapse formation. Application of the neurotransmitters GABA, glutamate and acetylcholine induced depolarizing calcium signal changes in neuronal cells providing evidence for the excitatory effects of these ligand-gated ion channels during maturation in vitro.

Conclusions

This study demonstrates for the first time that hCBiPSCs can be used as a juvenescent cell source to generate a large number of functional neurons including dopaminergic cells which may serve for the development of novel regenerative treatment strategies.
Thrombin promotes fibronectin secretion by bone marrow mesenchymal stem cells via the protease-activated receptor mediated signalling pathways
Authors: Chen Jin , Ma Yujie , Wang Zi , Wang Hengxiang , Wang Lisheng , Xiao Fengjun , Wang Hua , Tan Jianming , Guo Zikuan
Published: March 2014

Introduction

Fibronectin (FN) is commonly used in the development of serum-free media for the expansion of mesenchymal stem cells (MSCs). This study was aimed to observe if thrombin could stimulate FN secretion by human bone marrow MSCs and investigate the potential underlying mechanisms.

Methods

PCR was performed to detect the expression of the protease-activated receptors (PARs) in MSCs. After thrombin treatment, the expression level and secretion of FN were observed by RT-PCR, immunofluorescence staining and ELISA, respectively, and the activation of ERK1/2 and NF kappa B pathways was revealed by Western blotting, with or without pre-treatment of small-molecule blockers specific for PAR-1 and –2. The phenotypic and functional activities of thrombin-treated MSCs were also observed.

Results

PCR analysis showed that human bone marrow MSCs expressed two subtypes of PARs, PAR-1 and PAR-2. Thrombin treatment enhanced MSCs to express FN at mRNA and protein levels and promoted FN secretion by MSCs, accompanied by potent adherence to the culture plastic. Thrombin induced prompt phosphorylation of ERK 1/2 and NF kappa B p65 and the stimulatory effects of thrombin on FN secretion were blunted by specific inhibitors of these signaling molecules. Blockage to PAR-1 and PAR-2 partially abrogated thrombin-elicited FN secretion by MSCs and ERK 1/2 phosphorylation, whereas that of NF kappa B p65 was unaffected. Moreover, thrombin-treated MSCs maintained the phenotypic features, in vitro osteogenesis and adipogenesis capacities, and inhibitory activity on Phytohemagglutinin-induced allogeneic lymphocyte proliferation.

Conclusions

Thrombin could promote FN secretion by MSCs via PAR-mediated ERK 1/2 activation, while NF kappa B might be also involved in an undefined manner.
Mesenchymal stem cells with overexpression of midkine enhance cell survival and attenuate cardiac dysfunction in a rat model of myocardial infarction
Authors: Zhao Shu-Li , Zhang Yao-Jun , Li Ming-Hui , Zhang Xin-Lei , Chen Shao-Liang
Published: March 2014

Introduction

Elevated midkine (MK) expression may contribute to ventricular remodeling and ameliorate cardiac dysfunction after myocardial infarction (MI). Ex vivo modification of signaling mechanisms in mesenchymal stem cells (MSCs) with MK overexpression may improve the efficacy of cell-based therapy. This study sought to assess the safety and efficacy of MSCs with MK overexpression transplantation in a rat model of MI.

Methods

A pLenO-DCE vector lentivirus encoding MK was constructed and infected in MSCs. MSC migration activity and cytoprotection was examined in hypoxia-induced H9C2 cells using transwell insert in vitro. Rats were randomized into five groups: sham, MI plus injection of phosphate buffered saline (PBS), MSCs, MSCs-green fluorescent protein (MSCs-GFP) and MSCs-MK, respectively. Survival rates were compared among groups using log-rank test and left ventricular function was measured by echocardiography at baseline, 4, 8 and 12 weeks.

Results

Overexpression of MK partially prevented hypoxia-induced MSC apoptosis and exerted MSC cytoprotection to anoxia induced H9C2 cells. The underlying mechanisms may be associated with the increased mRNA and protein levels of vascular endothelial growth factor (VEGF), transformation growth factor-β (TGF-β), insulin-like growth factor 1 (IGF-1) and stromal cell-derived factor 1 (SDF-1a) in MSCs-MK compared with isolated MSCs and MSCs-GFP. Consistent with the qPCR results, the culture supernatant of MSCs-MK had more SDF-1a (9.23 ng/ml), VEGF (8.34 ng/ml) and TGF-β1 (17.88 ng/ml) expression. In vivo, a greater proportion of cell survival was observed in the MSCs-MK group than in the MSCs-GFP group. Moreover, MSCs-MK administration was related to a significant improvement of cardiac function compared with other control groups at 12 weeks.

Conclusions

Therapies employing MSCs with MK overexpression may represent an effective treatment for improving cardiac dysfunction and survival rate after MI.
The 5′-Deiodinases Are Not Essential for the Fasting-Induced Decrease in Circulating Thyroid Hormone Levels in Male Mice: Possible Roles for the Type 3 Deiodinase and Tissue Sequestration of Hormone
Authors: Galton Valerie Anne , Hernandez Arturo , St. Germain Donald L.
Published: March 2014

Fasting in rodents is characterized by decreases in serum T4 and T3 levels but no compensatory increase in serum TSH level. The types 1 and 2 deiodinases (D1 and D2) are postulated to play key roles in mediating these changes. However, serum T4 and T3 levels in fasted 5′-deiodinase-deficient mice decreased by at least the same percentage as that observed in wild-type mice, whereas serum TSH level was unaffected. D3 activity was increased in kidney, muscle, and liver up to 4-fold during fasting, and the mean serum rT3 level was increased 3-fold in fasted D1-deficient mice, compared with fed animals. In wild-type mice, the tissue contents of T4 and T3 in liver, kidney, and muscle were unchanged or increased in fasted animals, and after the administration of [125I]T4 or [125I]T3, the radioactive content in the majority of tissues from fasted mice was increased 2- or 4-fold, respectively. These findings suggest that the observed fasting-induced reductions in the circulating T3 and T4 levels are mediated in part by increased D3 activity and by the sequestration of thyroid hormone and their metabolites in tissues. Studies performed in D3-deficient mice demonstrating a blunting of the fasting-induced decrease in serum T4 and T3 levels were consistent with this thesis. Thus, the systemic changes in thyroid hormone economy as a result of acute food deprivation are not dependent on the D1 or D2 but are mediated in part by sequestration of T4 and T3 in tissues and their enhanced metabolism by the D3.
Anti-Mullerian Hormone Deficiency in Girls With Congenital Multiple Pituitary Hormone Deficiency
Authors: Deubzer Beate , Weber Karin , Lawrenz Barbara , Schweizer Roland , Binder Gerhard
Published: March 2014

Context:

Anti-Mullerian hormone (AMH) is believed to validly reflect the ovarian reserve. We wanted to test whether congenital absence of gonadotropin stimulation of the ovaries affects AMH production.

Objective:

The objective of the study was to test the validity of AMH as a marker for the ovarian reserve in females with congenital multiple pituitary hormone deficiency (MPHD; deficiency of three or more axes).

Design:

This was a retrospective laboratory study.

Setting:

The study was conducted in the Department of Pediatric Endocrinology in a tertiary center.

Patients:

The AMH serum levels were assessed in females with congenital (n = 16; median age 12.5 y, range 0.7–31 y) or acquired (n = 20; 18.5 y, range 2–33 y) MPHD and in controls with short stature (n = 100; 9.7 y, range 2–17 y).

Main Outcome Measure:

AMH was measured by AMH Gen II ELISA from Beckmann Coulter.

Results:

In the controls, AMH ranged between 1.8 (P3) and 67.8 pmol/L (P97). Three patients with a severe form of congenital MPHD were AMH deficient, whereas the other 33 patients with MPHD had normal AMH levels. There was significantly more AMH deficiency in congenital than in acquired MPHD (P < .05).

Conclusions:

Most girls with MPHD have normal serum AMH levels. However, some females with severe congenital MPHD are AMH deficient. This deficiency might be the result of the total absence of gonadotropins. In these females, AMH is unlikely to be an accurate prognostic parameter of the efficacy of fertility treatment.
Fractionation in Radiotherapy: A View from the Clinic
Authors: Saunders M I , Dische S
Published: March 2014

A century of the evolution of the fractionation of radiotherapy has brought clinical oncologists to the testing of protocols in randomized controlled clinical trials. The British Institute of Radiology's pioneering trials, together with more recent studies, are described and future developments suggested.
Target Volume Definition in Radiation Therapy
Authors: Van Kampen M , Levegrün S , Wannenmacher M
Published: March 2014

Target volume definition in radiation therapy is a broad field of interdisciplinary research. We give a brief history of clinical research in this field and outline some remarkable steps which led to the well-defined target volume concepts. The challenges in target volume definition for high-precision conformal radiation therapy are discussed, and possibilities of improving target volume definition, such as the integration of modern imaging modalities and the use of computer-based systems to support the radiation oncologist are indicated, as well as novel techniques for increasing the accuracy of patient positioning. All these tools should be evaluated with regard to their potential for increasing the therapeutic ratio and, as appropriate, should be implemented in clinical practice. However, target volume definition is a complex process influenced by many factors, currently under investigation. While questions remain in this field, and the impact of the influencing factors is not defined, the process of target volume definition should remain the subject of clinical research.
The Volume Effect in Radiotherapy—Its Biological Significance
Authors: Hopewell J W
Published: March 2014

Volume-related effects are an important consideration in clinical radiotherapy. The early rationale for the need to consider treatment volume has become clouded by the lack of clarity and a misinterpretation of some early clinical findings. In particular, there is a need to separate our understanding of biologically iso-effective radiation responses from the clinical concept of normal tissue tolerance, as they relate to changes in treatment volume. Animal data, including those for large animals, are reviewed. These animal studies indicate the need for caution in extrapolating retrospective clinical data to new treatment situations, since the conclusions reached may have been dictated by dogma and not by careful consideration of different factors that may have been involved. These include anatomical and physiological factors, and variations in the dose distribution pattern to a specific organ or tissue. These biological factors could limit the general applicability of simple approaches based on mathematical models to the volume effect relationship in radiotherapy.
MRI Developments in Perspective
Authors: Redpath T W
Published: March 2014

Following Paul Lauterbur's seminal 1973 paper in Nature, considerable work was needed to overcome a number of physical, engineering and technical problems before the new technique of magnetic resonance imaging (MRI) could be applied clinically. Much of that pioneering work was done in the UK. Since the first head and whole-body images were obtained in the late 1970s, MRI has become a widely used clinical imaging modality capable of yielding tomographic images of excellent spatial resolution and tissue contrast. This review outlines the historical development of MRI in the context both of the technical problems which had to be overcome, and of the clinical uses of MRI. Current areas of research, such as the use of MRI to map brain function, the measurement of physiological parameters such as tissue perfusion, and the use of open-access realtime MRI to guide interventional procedures, are briefly discussed.
The Interventional Magnetic Resonance Unit—The Minimal Access Operating Theatre of the Future?
Authors: Gould S W T , Darzi A
Published: March 2014

Interventional magnetic resonance units give the surgeon the potential to use intraoperative imaging to guide the surgical procedure. The advantages of magnetic resonance (MR) over other intraoperative imaging modalities include excellent soft tissue resolution, lack of ionizing radiation and the ability to reconstruct images in any desired plane. Postulated advantages include the ability to confirm adequate tumour resection, reduction in procedure magnitude and complication rate, shortened inpatient stay and the development of novel minimally invasive techniques including the use of thermal energy to destroy lesions. Fully MR compatible anaesthetic and patient monitoring equipment is available. However, before the MR-guided minimally invasive surgery can become a reality, much work is required in the assessment and development of MR compatible surgical instrumentation and equipment. This review describes the testing and development of instruments and equipment for MR image-guided surgery that we have undertaken. We describe the techniques we employ for open and minimal access surgery within this unique environment. The difficulties of operating within such an environment and the safety issues that this engenders are discussed. The current applications of intraoperative MR in the main surgical specialities are reviewed, and possible future areas of development for MR-guided minimally invasive surgery described.
Radionuclide Developments
Authors: Medley C M T , Vivian G C
Published: March 2014

This review considers a number of recent important developments in nuclear medicine, and possible future introductions, priority being given to those products which are most likely to find a place in clinical practice. This includes both novel radiopharmaceuticals and progress with new types of imaging equipment. Three areas are chosen as being of particular importance: brain imaging, heart imaging, and diagnosis and therapy of cancer. In the brain, the clinical value of imaging regional cerebral blood flow and certain aspects of the neuroreceptor/neurotransmitter system are discussed. Cardiac imaging is considered in the light of recent work on diagnosis and risk assessment, investigating the hibernating myocardium, and the possible place of fatty acid imaging. Both diagnosis and therapy of cancer are increasingly important, and the use of radionuclides in these areas is considered.
The Future of Digital Imaging
Authors: Kamm K F
Published: March 2014

For most applications, conventional film based methods may be replaced by digital imaging. This trend is influenced technically by the advent of more efficient detectors, improved image processing methods, faster computers, brighter and sharper displays and larger systems for image storage and archiving. The evolution of digital imaging reflects the fast development of information technology. Work in radiology departments will change. Information systems will organize the registration and administration of patient data, the scheduling of examinations, management of work flow and the generation of reports. Images will be taken without film cassettes and will be directly displayed on monitors for reporting. Digital imaging provides greater flexibility in processing, transmitting and displaying images. A larger dynamic range and improved contrast resolution lead to a consistently high image quality. This must lead to new rules of diagnosing images and quality assurance. Interfaces are interrelating imaging modalities, displays, the administration and the archive system to each other. The resulting net has to be safe, stable and fault-tolerant. Digital imaging systems will depend much more on the proper function of the interrelated systems in the network.
Thoracic Imaging—Then and Now
Authors: Hansell D M
Published: March 2014

The chest radiograph has proved a robust diagnostic aid over the last century. The accumulation of knowledge about chest disease by radiography has been gained slowly during the last 90 years. New impetus has been given by the development of computed tomography and the recent refinements of high resolution and spiral computed tomography. The pathophysiological insights provided by these new techniques have been obtained in a remarkably short period, with the promise of more to come.
Cardiac Imaging: Present Status and Future Trends
Authors: Rees M
Published: March 2014

Cardiac imaging has developed rapidly in a number of different areas, to the extent that the clinical practice of cardiology is highly image dependent. Advances in cross-sectional and three-dimensional imaging using computed tomography and magnetic resonance imaging have now found a significant role in demonstrating cardiac anatomy and function alongside the more traditional role of ultrasound which with its intravascular use is becoming a part of intravascular cardiac therapy. The imaging of myocardial perfusion by nuclear medicine techniques including single photon emission tomography and positron emission tomography has grown to add substantial clinical and academic information on cardiac blood flow and metabolism.
The Future of Arteriography and Vascular Interventional Radiology
Authors: Belli A-M
Published: March 2014

Non-invasive vascular imaging techniques threaten to diminish the catheter skills which radiology trainees currently acquire during diagnostic angiography. This, coupled with the desire of some vascular surgeons to perform minimally invasive “endovascular surgery”, may threaten the future of this radiological subspecialty, or perhaps it will help to create a new discipline incorporating surgical, medical and radiological skills.
The Future of Barium Radiology
Authors: Ott D J , Gelfand D W
Published: March 2014

Barium radiology of the gastrointestinal tract has had a long history but its survival into the next century will be a challenge. The numbers of barium studies performed has declined in recent decades due to several factors; also, health care reforms in the United States will further impact on the use of barium examinations. The future status of these radiological procedures will change depending on these factors and the organ system being examined; an increased emphasis on functional evaluation of the gastrointestinal tract will also have an effect on the evolving role of barium radiology. We provide a brief historical review of the evolution of barium radiology in the twentieth century, discuss the present and changing status of the various gastrointestinal examinations, and offer our thoughts concerning the potential future of this specialty.
The Future for Radiography Practice
Authors: Carr D , Fell K
Published: March 2014

In evaluating the future face of radiography practice, a historical review of developments to date has been undertaken, together with a look at the changes which will face the profession into the new millennium. This article focuses on changing healthcare provision, changing radiographic practice, the changing face of the healthcare professions and the changing focus of education and training. The opportunities for further development of the profession are explored along with an overview of some of the possible barriers to progress. Our contention is that radiographers are more than adequately prepared for a rapidly changing future. To ensure that they are prepared, however, it is essential for the profession to adopt an appropriate vision, formulate an achievable strategy, and promote a culture of professional practice which is able to respond adequately to the problems facing its continued existence.
Electrical Impedance Tomography
Authors: Kotre C J
Published: March 2014

Electrical impedance tomography (EIT) is a technique which allows cross-sectional images related to the local electrical impedance within an object to be reconstructed from sets of measurements made on its surface. The main drive behind the development of EIT has been its possible application in medical imaging, as biological tissues are known to exhibit a wide range of electrical impedance and many physiological events are accompanied by electrical impedance changes. This article reviews the technical aspects of EIT as a medical imaging modality, and considers the range of applications over which it might be employed. Existing technical limitations and future developments are discussed. It is concluded that the future of EIT as a clinical diagnostic tool is likely to lie in the area of functional monitoring, where the capability of performing image-guided localized electrical impedance measurements with high acquisition speed, good sensitivity and no hazard can be exploited.
On Terminology: are the Concepts of «Pedagogical Technology» and «Educational Technology» Identical?
Authors: Ахриева  , Akhrieva Anna
Published: March 2014

Specifics of technological approach, underpinning current

educational paradigm, are discussed. Also highlighted are

terminological issues related to the notion of «technology», and

an effort is made to distinguish and demarcate the concepts of «pedagogical

» and «educational» as applied to the term «technology».
Towards Socio-Pedagogical Foundations of Victimization Prevention in Children and Adolescents in Russia
Authors: Юлин  , Yulin B. , Юлина  , Yulina Galina
Published: March 2014

The effort is undertaken to articulate the concept of victimology, with the emphasis to the children’s victimity, and also social and pedagogic foundations of victimity prevention in children and adolescents.
Civil Identity and Social Values
Authors: Персиянцева  , Persiyantseva S.
Published: March 2014

The paper considers the concept of «civil identity», its

structural elements, civil identity forming factors, interrelations

between civil identity, social values and accepted standards of

public conduct; the role of family in cultivating social values and

civil identity.
Trends of Budgetary Federalism in Ukraine
Authors: Бредихин  , Bredikhin A.
Published: March 2014

The regionalism trend in modern Ukraine favors changes in interaction along the «сenter—periphery» axis, and thus encourages the regions to expand the range of their rights. Budgetary federalism is one of the dynamics, conducive to such changes, and the issue of more than 20 years’ debate among Ukrainian political quarters. The ups and downs of these discussions is directly related to the geopolitical vector of the country’s development and to the model of its coming future.
Current Technologies of Public Relations: Timely Trends
Authors: Моисеева  , Moiseeva Olga
Published: March 2014

Swift progress in all kinds of communications, seen in

the recent years, prompts to seek out new ways of communicating

in the social sphere. The most demanded are communications in

the youth environment, which is known to be the most active and

aggressive. The paper explores current trends in the field of public

relations. Various aspects of target audience are considered,

recent changes in conditions and grounds for communications

are analyzed.
A Capacitated Facility Location Model with Bidirectional Flows
Authors: Zhang Zhi-Hai , Berenguer Gemma , Shen Zuo-Jun (Max)
Published: March 2014

Supply chains with returned products are receiving increasing attention in the operations management community. The present paper studies a capacitated facility location model with bidirectional flows and a marginal value of time for returned products. The distribution system consists of a single supplier that provides one new product to a set of distribution centers (DCs), which then ships to the final retailers. While at the retailers' site, products can be shipped back to the supplier for reprocessing. Each DC is capacitated and handles stocks of new and/or returned products. The model is a nonlinear mixed-integer program that optimizes DC location and allocation between retailers and DCs. We show that it can be converted to a conic quadratic program that can be efficiently solved. Some valid inequalities are added to the program to improve computational efficiency. We conclude by reporting numerical experiments that reveal some interesting properties of the model.