bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of zirconium in microalloyed steels: A review
Authors: Baker T. N.
Published: April 2014

Recently there has been a renewed interest in the addition of zirconium to microalloyed steels. It has been used since the early 1920s, but has never been universally employed, as have niobium, titanium or vanadium. The functions of zirconium in steelmaking are associated with a strong chemical affinity, in decreasing order, for oxygen, nitrogen, sulphur and carbon. Historically, the main use of additions of zirconium to steel was for combination preferentially with sulphur, to avoid the formation of manganese sulphide, known to have a deleterious influence of the impact toughness of wrought and welded steel. Modern steelmaking techniques have also raised the possibility that zirconium additions can reduce the austenite grain size and increase dispersion strengthening, due to precipitation of zirconium carbonitrides, or in high nitrogen vanadium–zirconium steels, vanadium nitride. This review gathers information on the compounds of zirconium identified in steels together with crystallographic data and solubility equations. Also brief accounts of the role of sulphides and particles in general on austenite grain size control and toughness are included.
TFPI cofactor function of protein S: essential role of the protein S SHBG-like domain
Authors: Reglińska-Matveyev Natalia , Andersson Helena M. , Rezende Suely M. , Dahlbäck Björn , Crawley James T. B. , Lane David A. , Ahnström Josefin
Published: April 2014

Key Points

The protein S SHBG-like domain and, more specifically, its LG1 subunit are important for binding and enhancement of TFPI. TFPI binding to the protein S SHBG-like domain likely positions TFPI Kunitz domain 2 for optimal interaction with the active site of FXa.
Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis
Authors: Rampal Raajit , Al-Shahrour Fatima , Abdel-Wahab Omar , Patel Jay P. , Brunel Jean-Philippe , Mermel Craig H. , Bass Adam J. , Pretz Jennifer , Ahn Jihae , Hricik Todd , Kilpivaara Outi , Wadleigh Martha , Busque Lambert , Gilliland D. Gary , Golub Todd R. , Ebert Benjamin L. , Levine Ross L.
Published: April 2014

Key Points

A gene expression profile consistent with activated JAK2 signaling is seen in all MPN patients, including in patients with CALR mutations. Transcriptional profiling discriminates subsets of MPNs based on JAK2V617F allele burden and on the presence of CALR and TET2 mutations.
Expression of uPAR in tumor-associated stromal cells is associated with colorectal cancer patient prognosis: a TMA study
Authors: Boonstra Martin C , Verbeek Floris PR , Mazar Andrew P , Prevoo Hendrica AJM , Kuppen Peter JK , van de Velde Cornelis JH , Vahrmeijer Alexander L , Sier Cornelis FM
Published: April 2014

Background

The receptor for urokinase-type plasminogen activator (uPAR) is associated with cancer development and progression. Within the tumor microenvironment uPAR is expressed by malignant cells as well as tumor-associated stromal cells. However, the contribution of uPAR expression in these stromal cells to malignancy and patient survival in colorectal cancer is still unclear. This study compares the association of uPAR expression in both colorectal tumor-associated stromal cells and neoplastic cells with clinico-pathological characteristics and patient survival using tissue micro arrays (TMA).

Methods

Immunohistochemical staining of uPAR expression was performed on tumor tissue from 262 colorectal cancer patients. Kaplan-Meier, log rank, and uni- and multivariate Cox’s regression analyses were used to calculate associations between uPAR expression and patient survival.

Results

In the colorectal tumor-associated stromal microenvironment, uPAR is expressed in macrophages, (neoangiogenic) endothelial cells and myofibroblasts. uPAR expression in tumor-associated stromal cells and neoplastic cells (and both combined) were negatively associated with overall survival (OS) and Disease Free Survival (DFS). Uni- and multivariate Cox’s regression analysis for combined uPAR expression in tumor-associated stromal and neoplastic cells showed significant and independent negative associations with OS and DFS. Only uPAR expression in tumor-associated stromal cells showed independent significance in the uni- and multivariate analysis for DFS.

Conclusion

This study demonstrates a significant independent negative association between colorectal cancer patient survival and uPAR expression in especially tumor-associated stromal cells.
Inhibitory effect of kaolin minerals compound against hepatitis C virus in Huh-7 cell lines
Authors: Ali Liaqat , Idrees Muhammad , Ali Muhammad , Hussain Abrar , Rehman Irshad Ur , Ali Amjad , Iqbal Syed Abbas , Kamel Eyad Hassan
Published: April 2014

Background

Hepatitis C virus (HCV) is estimated to infect 200 million individuals in the globe, including approximately 10 million in Pakistan causing both acute and chronic hepatitis. The standard treatment against HCV is pegylated interferon therapy in combination with a nucleoside analogue ribavirin. In addition, several herbal extracts and phytochemicals derivatives are used traditionally in the treatment of liver diseases as well as HCV infection. The present study determines the inhibitory effect of kaolin minerals compound against hepatitis C virus in Huh-7 cell lines.

Methods

Huh-7 cell lines were used for the in vitro HCV replication by using HCV positive sera from different patients with known HCV genotypes and viral titer/load. Total RNA was extracted from these infected cells and was quantified by real-time polymerase chain reaction (Real-time PCR). The viral titer was compared with the control samples to determine the anti-HCV activity of kaolin derived compounds. Kaolin is a group of clay minerals, with the chemical composition Al2 Si2O5 (OH)4.

Results

The results showed promising effectiveness of local kaolin derived anti-HCV compounds by causing 28% to 77% decrease in the HCV titer, when applied to infected Huh-7 cell lines. This study provides the basis for future work on these compounds especially to determine the specific pathway and mechanism for inhibitory action in the replicon systems of viral hepatitis.

Conclusions

Kaolin mineral derivatives show promising inhibitory effects against HCV genotypes 3a and 1a infection, which suggests its possible use as complementary and alternative medicine for HCV viral infection.
CD4+CD25+/highCD127low/- regulatory T cells are enriched in rheumatoid arthritis and osteoarthritis joints—analysis of frequency and phenotype in synovial membrane, synovial fluid and peripheral blood
Authors: Moradi Babak , Schnatzer Philipp , Hagmann Sébastien , Rosshirt Nils , Gotterbarm Tobias , Kretzer Jan Philippe , Thomsen Marc , Lorenz Hanns-Martin , Zeifang Felix , Tretter Theresa
Published: April 2014

Introduction

CD4+CD25+/highCD127low/- regulatory T cells (Tregs) play a crucial role in maintaining peripheral tolerance. Data about the frequency of Tregs in rheumatoid arthritis (RA) are contradictory and based on the analysis of peripheral blood (PB) and synovial fluid (SF). Because Tregs exert their anti-inflammatory activity in a contact-dependent manner, the analysis of synovial membrane (SM) is crucial. Published reports regarding this matter are lacking, so we investigated the distribution and phenotype of Tregs in concurrent samples of SM, SF and PB of RA patients in comparison to those of osteoarthritis (OA) patients.

Methods

Treg frequency in a total of 40 patients (18 RA and 22 OA) matched for age and sex was assessed by flow cytometry. Functional status was assessed by analysis of cell surface markers representative of activation, memory and regulation.

Results

CD4+ T cells infiltrate the SM to higher frequencies in RA joints than in OA joints (P = 0.0336). In both groups, Tregs accumulate more within the SF and SM than concurrently in PB (P < 0.0001). Relative Treg frequencies were comparable in all compartments of RA and OA, but Treg concentration was significantly higher in the SM of RA patients (P = 0.025). Both PB and SM Tregs displayed a memory phenotype (CD45RO+RA-), but significantly differed in activation status (CD69 and CD62L) and markers associated with Treg function (CD152, CD154, CD274, CD279 and GITR) with only minor differences between RA and OA.

Conclusions

Treg enrichment into the joint compartment is not specific to inflammatory arthritis, as we found that it was similarly enriched in OA. RA pathophysiology might not be due to a Treg deficiency, because Treg concentration in SM was significantly higher in RA. Synovial Tregs represent a distinct phenotype and are activated effector memory cells (CD62L-CD69+), whereas peripheral Tregs are resting central memory cells (CD62L+CD69-).
Evidence That Diet-Induced Hyperleptinemia, but Not Hypothalamic Gliosis, Causes Ghrelin Resistance in NPY/AgRP Neurons of Male Mice
Authors: Briggs Dana I. , Lockie Sarah H. , Benzler Jonas , Wu Qunli , Stark Romana , Reichenbach Alex , Hoy Andrew J. , Lemus Moyra B. , Coleman Harold A. , Parkington Helena C. , Tups Alex , Andrews Zane B.
Published: April 2014

High-fat diet (HFD) feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/Agouti-related peptide neurons. In the current study, we investigated the time course over which this occurs and the mechanisms responsible for ghrelin resistance. After 3 weeks of HFD feeding, neither peripheral nor central ghrelin increased food intake and or activated NPY neurons as demonstrated by a lack of Fos immunoreactivity or whole-cell patch-clamp electrophysiology. Pair-feeding studies that matched HFD calorie intake with chow calorie intake show that HFD exposure does not cause ghrelin resistance independent of body weight gain. We observed increased plasma leptin in mice fed a HFD for 3 weeks and show that leptin-deficient obese ob/ob mice are still ghrelin sensitive but become ghrelin resistant when central leptin is coadministered. Moreover, ob/ob mice fed a HFD for 3 weeks remain ghrelin sensitive, and the ability of ghrelin to induce action potential firing in NPY neurons was blocked by leptin. We also examined hypothalamic gliosis in mice fed a chow diet or HFD, as well as in ob/ob mice fed a chow diet or HFD and lean controls. HFD-fed mice exhibited increased glial fibrillary acidic protein–positive cells compared with chow-fed mice, suggesting that hypothalamic gliosis may underlie ghrelin resistance. However, we also observed an increase in hypothalamic gliosis in ob/ob mice fed a HFD compared with chow-fed ob/ob and lean control mice. Because ob/ob mice fed a HFD remain ghrelin sensitive, our results suggest that hypothalamic gliosis does not underlie ghrelin resistance. Further, pair-feeding a HFD to match the calorie intake of chow-fed controls did not increase body weight gain or cause central ghrelin resistance; thus, our evidence suggests that diet-induced hyperleptinemia, rather than diet-induced hypothalamic gliosis or HFD exposure, causes ghrelin resistance.
Cadherin-11 regulates mesenchymal stem cell differentiation into smooth muscle cells and development of contractile function in vivo
Authors: Alimperti Stella , You Hui , George Teresa , Agarwal Sandeep K. , Andreadis Stelios T.
Published: April 2014

Although soluble factors (e.g. Transform Growth Factor beta 1 (TGF-β1)) induced mesenchymal stem cell (MSC) differentiation toward smooth muscle (SMC) lineage, the role of adherent junctions in this process is not well understood. We found that Cadherin-11 but not Cadherin-2 was necessary for MSC differentiation into SMC. Cadherin-11 regulated expression of TGF-β1 and affected SMC differentiation through a TGF-β receptor II (TGFβRII) dependent but Smad2/3 independent pathway. In addition, Cadherin-11 activated the serum response factor (SRF) and SMC proteins via the Rho-associated protein kinase (ROCK) pathway. Engagement of Cadherin-11 increased its own expression through SRF, suggesting the presence of an auto regulatory feedback loop that committed MSC to SMC fate. Notably, SMC-containing tissues such as aorta and bladder from Cadherin-11 null mice (Cdh11−/−) mice showed significantly reduced levels of SMC proteins and exhibited diminished contractility. This is the first report implicating Cadherin-11 in SMC differentiation and contractile function in vitro as well as in vivo.
Interphase phosphorylation of lamin A
Authors: Kochin Vitaly , Shimi Takeshi , Torvaldson Elin , Adam Stephen A. , Goldman Anne , Pack Chan-Gi , Melo-Cardenas Johanna , Imanishi Susumu Y. , Goldman Robert D. , Eriksson John E.
Published: April 2014

Nuclear lamins form the major structural elements comprising the nuclear lamina. While loss of nuclear structural integrity has been implicated as a key factor in the lamin A gene mutations causing laminopathies, the normal regulation of lamin A/C (LA/C) assembly and organization in interphase cells is still undefined. We assumed phosphorylation to be a major determinant, identifying 21 prime interphase phosphorylation sites, with 8 high turnover sites. The roles of these latter sites were examined by site-directed mutagenesis, followed by detailed microscopic analysis, including fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and nuclear extraction techniques. Results reveal three phosphorylation regions, each with dominant sites, together controlling LA/C structure and dynamics. Interestingly, two of these interphase sites are hyperphosphorylated in mitotic cells and one is within the sequence missing in progerin of the Hutchinson Gilford Progeria Syndrome. A model is presented where different phosphorylation combinations will yield markedly different effects on the assembly, subunit turnover, and mobility of LA/C between and within the lamina, the nucleoplasm, and the cytoplasm of interphase cells.
The dynamics of MAPK inactivation at fertilization in mouse eggs
Authors: Gonzalez-Garcia Jose Raul , Bradley Josephine , Nomikos Michail , Paul Laboni , Machaty Zoltan , Lai F. Anthony , Swann Karl
Published: April 2014

Egg activation at fertilization in mammals is initiated by prolonged Ca2+ oscillations that trigger the completion of meiosis and formation of pronuclei. A late fall in MAPK activity is essential for pronuclear formation, but the precise timing and mechanism of decline are unknown. Here, we have measured the dynamics of MAPK inactivation in fertilizing mouse eggs using novel chemiluminescent MAPK activity reporters. This reveals that the MAPK activity decrease begins during the Ca2+ oscillations, but MAPK does not completely inactivate until after pronuclear formation. MAPK in eggs consists of Mos, MEK and ERK1/2. Notably, the MAPK activity decline at fertilization is not explained by upstream destruction of Mos, because a decrease in Mos-luciferase signal is not associated with egg activation. Further, Mos over-expression does not affect the timing of MAPK inactivation or pronuclear formation. However, the late decrease in MAPK could be rapidly reversed by the protein phosphatase inhibitor, okadaic acid. These data suggest that the completion of meiosis in mouse zygotes is driven by an increased phosphatase activity and not by a decline in Mos levels, or MEK activity.
A unique mode of tissue oxygenation and the adaptive radiation of teleost fishes
Authors: Randall D. J. , Rummer J. L. , Wilson J. M. , Wang S. , Brauner C. J.
Published: April 2014

Teleost fishes constitute 95% of extant aquatic vertebrates, and we suggest that this is related in part to their unique mode of tissue oxygenation. We propose the following sequence of events in the evolution of their oxygen delivery system. First, loss of plasma-accessible carbonic anhydrase (CA) in the gill and venous circulations slowed the Jacobs–Stewart cycle and the transfer of acid between the plasma and the red blood cells (RBCs). This ameliorated the effects of a generalised acidosis (associated with an increased capacity for burst swimming) on haemoglobin (Hb)–O2 binding. Because RBC pH was uncoupled from plasma pH, the importance of Hb as a buffer was reduced. The decrease in buffering was mediated by a reduction in the number of histidine residues on the Hb molecule and resulted in enhanced coupling of O2 and CO2 transfer through the RBCs. In the absence of plasma CA, nearly all plasma bicarbonate ultimately dehydrated to CO2 occurred via the RBCs, and chloride/bicarbonate exchange was the rate-limiting step in CO2 excretion. This pattern of CO2 excretion across the gills resulted in disequilibrium states for CO2 hydration/dehydration reactions and thus elevated arterial and venous plasma bicarbonate levels. Plasma-accessible CA embedded in arterial endothelia was retained, which eliminated the localized bicarbonate disequilibrium forming CO2 that then moved into the RBCs. Consequently, RBC pH decreased which, in conjunction with pH-sensitive Bohr/Root Hbs, elevated arterial oxygen tensions and thus enhanced tissue oxygenation. Counter-current arrangement of capillaries (retia) at the eye and later the swim bladder evolved along with the gas gland at the swim bladder. Both arrangements enhanced and magnified CO2 and acid production and, therefore, oxygen secretion to those specialised tissues. The evolution of β-adrenergically stimulated RBC Na+/H+ exchange protected gill O2 uptake during stress and further augmented plasma disequilibrium states for CO2 hydration/dehydration. Finally, RBC organophosphates (e.g. NTP) could be reduced during hypoxia to further increase Hb–O2 affinity without compromising tissue O2 delivery because high-affinity Hbs could still adequately deliver O2 to the tissues via Bohr/Root shifts. We suggest that the evolution of this unique mode of tissue O2 transfer evolved in the Triassic/Jurassic Period, when O2 levels were low, ultimately giving rise to the most extensive adaptive radiation of extant vertebrates, the teleost fishes.
Formulating a New Express Minibus Service Design Problem as a Clustering Problem
Authors: Martínez L. Miguel , Viegas José Manuel , Eiró Tomás
Published: April 2014

This paper presents the formulation of a new optimization problem designated as the express minibus problem, which intends to form small groups of clients with compatible boarding/exiting points in time and space for a new type of urban mobility service. This new transport option, as a competitive alternative to the private car, aims to provide almost direct services between dispersed demand poles in places where high-capacity and efficient public transport options are scarce, thus combining the major strengths of both public transport and private vehicles. Conventional public transport systems can present efficient space and energy consumption, whereas private vehicles have high levels of flexibility, are fast, and are always available.

The proposed algorithm aims at assessing the potential demand of this new service by developing a clustering algorithm in which the groups of clients formed for each minibus route should present the following characteristics: there is a small number of boarding and exiting points, where in each point there is only boarding or alighting; boarding points should be close to each other, as well as the exiting points; there must be a reasonable distance between the last boarding point and the first exiting point; the average load factor must be high; and for all clients the overall detour time relative to the direct service should be small.

This paper presents the rationale and structure of the clustering algorithm, followed by an application for the Lisbon metropolitan area during the morning peak, which could be adapted to the afternoon peak with some slight modifications.
Composite Flooring Quality of Combined Wood Species Using Adhesive from Merbau Wood Extract
Authors: Santoso Adi , Hadi Yusuf Sudo , Malik Jamaludin
Published: April 2014

Polyphenol chemical components extracted from merbau (Intsia spp.) wood exhibit a strong affinity for resorcinol and formaldehyde in alkaline conditions, forming a copolymer that could serve as an adhesive. A liquid extract of merbau wood (M) was allowed to copolymerize with resorcinol (R) and formaldehyde (F) under alkaline conditions, with an M:R:F weight ratio of 100:5:10. The course of the reaction and potential mechanisms of copolymerization were scrutinized using Fourier transform infrared spectroscopy, X-ray diffraction, and differential thermal analysis. The adhesive was used to manufacture three-ply composite flooring consisting of a back layer of rubberwood (Hevea brasiliensis), a core layer from sengon (Paraserianthes falcataria) wood, and a face layer with one of seven wood species, namely, sengon, sungkai (Peronema canescens), mangium (Acacia mangium), rubberwood, mahogany (Swietenia spp.), kempas (Koompassia malaccensis), and merbau. The adhesive was spread on the face and back layers of 170 g/m2 single glue line, which was followed by pressing at 11 kg/cm2 for 3 hours at room temperature. After conditioning for 10 days, the resulting composite flooring was examined to assess its physical and mechanical properties, shear strength, and formaldehyde emission. Results revealed that the bioadhesive exhibited crystallinity of 23.32 percent and a melting glass transition of 115.31°C. IV-meter intrinsic viscosity tools were used to determine the product's molecular weight of 49,658. Physical–mechanical properties and shear quality of the composite flooring were similar to products that use synthetic phenolic adhesive and belong to the exterior quality type with E0 or F**** types of low formaldehyde emission.
Productivity and Cost of Industrial Firewood Processing Operations
Authors: Lombardini Carolina , Magagnotti Natascia , Spinelli Raffaele
Published: April 2014

The study determined the performance of industrial firewood processing operations under the typical work conditions of Southern Europe. In particular, we surveyed five commercial operations processing 1-m-long oak logs from coppice forests. Mean log volume was very small, in the range of 0.01 to 0.02 m3 solid. Machine utilization was quite high, ranging from 70 to 80 percent. Mechanical availability was excellent, always exceeding 90 percent of the total worksite time. Productivity varied between 1.4 and 4.9 m3 per scheduled machine hour (SMH), inclusive of all delays. Processing cost ranged from 26 to 44 €/m3. The largest machine in the group offered significant productivity and cost benefits over all the others. Owing to their multiple log handling capacity, firewood processors designed for Southern Europe may be less sensitive to log volume, compared with Nordic machines. The energy balance was always very favorable. The ratio between output and input was never smaller than 220 and peaked at 327. That was much higher than recorded for small-scale firewood processors, and it may depend on the use of more efficient electric motors compared with diesel engines. However, the main advantage of industrial firewood processors is production capacity and operator comfort and safety. This allows business growth, in the face of a very large market and a decreasing availability of skilled labor. Cost reduction is a secondary advantage, which becomes dramatic only when adopting machines at the higher end of the range.
Maternal Plasma RNA Sequencing for Genome-Wide Transcriptomic Profiling and Identification of Pregnancy-Associated Transcripts
Authors: Tsui Nancy B Y , Jiang Peiyong , Wong Yuen Fei , Leung Tak Y , Chan K C Allen , Chiu Rossa W K , Sun Hao , Lo Y M Dennis
Published: April 2014

BACKGROUND

Analysis of circulating RNA in the plasma of pregnant women has the potential to serve as a powerful tool for noninvasive prenatal testing and research. However, detection of circulating RNA in the plasma in an unbiased and high-throughput manner has been technically challenging. Therefore, only a limited number of circulating RNA species in maternal plasma have been validated as pregnancy- and placenta-specific biomarkers.

METHODS

We explored the use of massively parallel sequencing for plasma transcriptome profiling in first-, second-, and third-trimester pregnant women. Genotyping was performed for amniotic fluid, placental tissues, and maternal blood cells, with exome-enriched sequencing.

RESULTS

In the early pregnancy group comprising 1 first- and 1 second-trimester pregnancy cases, the fetal contribution to the RNA pool in maternal plasma was 3.70%. The relative proportion of fetal contribution was increased to 11.28% in the late pregnancy group comprising 2 third-trimester pregnancy cases. The placental biallelic expression pattern of PAPPA (pregnancy-associated plasma protein A, pappalysin 1), a known pregnancy-specific gene, and the monoallelic expression pattern of H19 [H19, imprinted maternally expressed transcript (non-protein coding)], an imprinted maternally expressed gene, were also detected in the maternal plasma. Furthermore, by direct examination of the maternal plasma transcriptomic profiles before and after delivery, we identified a panel of pregnancy-associated genes.

CONCLUSIONS

Plasma RNA sequencing provides a holistic view of the maternal plasma transcriptomic repertoire. This technology is potentially valuable for using circulating plasma nucleic acids for prenatal testing and research.
Recurrent Carotico-Cavernous Fistula after Internal Carotid Artery Ligation: A Case with Embolization of the Fistula via Contralateral Internal Carotid Artery Approach
Authors: Dang Nguyen Vu , Hai Nguyen Thanh , Cuong Tran Chi
Published: April 2014

We are reporting a 51-year-old female patient having a history of direct carotid cavernous fistula (CCF) which was treated by internal carotid artery (ICA) ligation 17 year ago. She presented to Ho Chi Minh City University Medical Center with symptoms of recurrent CCF. The recurred CCF was supplied by multiple feeders coming from anterior, posterior communicating artery and the recanalized left ICA. Her CCF was not plausible for another surgical ligation and was referred for endovascular treatment. The fistula was eventually occluded by percutaneous embolization via the right ICA approach. Through this case, we would like to discuss about the treatment strategies of those having recurrent CCF with preexisted ICA ligation.

In Vietnam, previously carotico-cavernous fistula was mainly treated with muscle occlusion, carotid artery ligation or combinations of these methods. There were reported good outcomes for treatment of CCF surgically. However, surgical repairs had carried, not only complication, but a risk of recurrence due to recanalization of the previously ligated ICA.

Since the emergence of endovascular intervention, the treatment of direct CCF has evolved from surgical ligation to angiographic embolization using balloon or coils via artery route or venous access. This endovascular method currently is the treatment of choice for traumatic CCF due to its ability to preserve the carotid artery and flexibility in treatment strategy with various approaches to the fisutla.
Treatment of Ruptured Vertebral Artery Dissecting Aneurysms
Authors: Hamasaki Osamu , Ikawa Fusao , Hidaka Toshikazu , Kurokawa Yasuharu , Yonezawa Ushio
Published: April 2014

We evaluated the outcomes of endovascular or surgical treatment of ruptured vertebral artery dissecting aneurysms (VADAs), and investigated the relations between treatment complications and the development and location of the posterior inferior cerebellar artery (PICA).

We treated 14 patients (12 men, two women; mean age, 56.2 years) with ruptured VADAs between March 1999 and June 2012 at our hospital. Six and eight patients had Hunt and Hess grades 1–3 and 4–5, respectively.

Twelve patients underwent internal endovascular trapping, one underwent proximal endovascular occlusion alone, and one underwent proximal endovascular occlusion in the acute stage and occipital artery (OA)-PICA anastomosis and surgical trapping in the chronic stage. The types of VADA based on their location relative to the ipsilateral PICA were distal, PICA-involved, and non-PICA in nine, two, and three patients, respectively. The types of PICA based on their development and location were bilateral anterior inferior cerebellar artery (AICA)-PICA, ipsilateral AICA-PICA, extradural, and intradural type in one, two, two, and nine patients, respectively. Two patients with high anatomical risk developed medullary infarction, but their midterm outcomes were better than in previous reports. The modified Rankin scale indicated grades 0–2, 3–5, and 6 in eight, three, and three patients, respectively.

A good outcome is often obtained in the treatment of ruptured VADA using internal endovascular trapping, except in the PICA-involved type, even with high-grade subarachnoid hemorrhage. Treatment of the PICA-involved type is controversial. The anatomical location and development of PICA may be predicted by complications with postoperative medullary infarction.
Intra-Arterial Treatment in a Child with Embolic Stroke Due to Atrial Myxoma
Authors: van den Wijngaard IDO , Wermer Marieke , van Walderveen Marianne , Wiendels Natalie , Peeters-Scholte Cacha , Nijeholt Geert Lycklama à
Published: April 2014

Arterial ischaemic stroke is an important cause of morbidity in children. Timely diagnosis is necessary for acute stroke treatment but can be challenging in clinical practice. Due to a paucity of data there are no specific recommendations regarding the use of mechanical thrombectomy devices in current paediatric stroke guidelines. A 14-year-old boy presented with a severe acute left hemisphere stroke due to a proximal middle cerebral artery occlusion caused by emboli from an atrial myxoma. No clinical improvement was seen after administration of intravenous thrombolysis. Subsequent mechanical thrombectomy with a second-generation stent-based thrombectomy device resulted in successful recanalization and clinical improvement. To our knowledge, this is the first report of mechanical thrombectomy in a child with acute embolic stroke caused by atrial myxoma.
Cerebral Arterial Fenestrations
Authors: Cooke Daniel L. , Stout Charles E. , Kim Warren T. , Kansagra Akash P. , Yu John Paul , Gu Amy , Jewell Nicholas P. , Hetts Steven W. , Higashida Randall T. , Dowd Christopher F. , Halbach Van V.
Published: April 2014

Arterial fenestrations are an anatomic variant with indeterminate significance. Given the controversy surrounding fenestrations we sought their prevalence within our practice along with their association with other cerebrovascular anomalies.

We retrospectively reviewed 10,927 patients undergoing digital subtraction angiography between 1992 and 2011. Dictated reports were searched for the terms “fenestration” or “fenestrated” with images reviewed for relevance, yielding 228 unique cases. A Medline database search from February 1964 to January 2013 generated 304 citations, 127 cases of which were selected for analysis.

Cerebral arterial fenestrations were identified in 228 patients (2.1%). At least one aneurysm was noted in 60.5% of patients, with an aneurysm arising from the fenestration in 19.6% of patients. Aneurysmal subarachnoid hemorrhage or non-aneurysmal subarachnoid hemorrhage were present in 60.1% and 15.8%, respectively. For the subset of patients with an aneurysm arising directly from a fenestration relative to those patients with an aneurysm not immediately associated with a fenestration, the prevalence of aneurysmal subarachnoid hemorrhage was 66.7% vs. 58.6% (p = 0.58). Fenestrations were more often within the posterior circulation (73.2%) than the anterior circulation (24.6%), though there was no difference in the prevalence of aneurysms within these groups (61.1% vs. 60.7%, p = 1.0).

Cerebral arterial fenestrations are an anatomic variant more often manifesting at the anterior communicating arterial complex and basilar artery and with no definite pathological relationship with aneurysms.
Ocular Thrombosis after Stent-Assisted Coiling of a C7 (Paraclinoid) Internal Carotid Artery Aneurysm
Authors: Namba Katsunari , Higaki Ayuho , Nemoto Shigeru
Published: April 2014

Stent-assisted coiling of paraclinoid aneurysms is widely performed in neurointerventional surgery. The most common adverse event related to this procedure is cerebral thromboembolism. However, reports on ocular thromboembolism are scarce.

We report our experience with two patients who developed ocular thromboembolism following Enterprise stent-assisted coiling of paraclinoid aneurysms. We then review the available literature for the possible pathomechanism of ocular thrombosis.

Ocular thromboembolism may be a risk of stent-assisted coiling when the stent traverses the orifice of the ophthalmic artery or the stent is placed in the C3 internal carotid artery. Further study is needed to clarify how to avoid this disabling complication.
Multiple Intracranial Aneurysms: Endovascular Treatment and Complications
Authors: Shen Xun , Xu Tao , Ding Xuan , Wang Wenlei , Liu Zhi , Qin Huaihai
Published: April 2014

This study evaluated the results of endovascular embolization of multiple intracranial aneurysms. A retrospective hospital chart and radiograph review were made of all patients with multiple intracranial aneurysms seen between March 2010 and January 2011.

Ten patients presented with subarachnoid hemorrhage, four with mass effect, two with brain ischemia and twenty were incidental. These 36 patients harbored 84 aneurysms, 63 of which were treated with endovascular techniques, two by surgical clipping, and 19 were left untreated. Of the coil-treated lesions, a complete endovascular occlusion was achieved in 54 aneurysms (85.7%), and eight (12.7%) presented neck remnants with one (1.6%) stented only. Twenty-six patients (72.2%) underwent coil embolization of more than one aneurysm in the first session. Follow-up angiographic studies in 31 patients demonstrated an unchanged or improved result in 93.0% of the aneurysms (53 lesions) and coil compaction in 7.0% (four lesions). The overall clinical outcome was excellent in 33 patients (91.7%), good in one (2.8%) and fair in two (5.5%).

Endovascular techniques may be a particularly suitable method for treating multiple intracranial aneurysms.
Radiation-Induced Cerebral Aneurysm Treated with Endovascular Coil Embolization
Authors: Matsumoto Hiroaki , Minami Hiroaki , Yamaura Ikuya , Yoshida Yasuhisa
Published: April 2014

Radiation-induced cerebral aneurysms are rare. We describe a case of radiation-induced cerebral aneurysm successfully treated with endovascular coil embolization. A 39-year-old man received 60 Gy of radiation to a pineal germinoma at eight years old. The left internal carotid artery (ICA) aneurysm which developed within the irradiated field and stenotic change in the left ICA due to radiation-induced vasculopathy were detected incidentally. Because these aneurysms show a high risk of rupture and mortality, and even small aneurysms are prone to rupture, any such suspected aneurysm should be treated with surgical or endovascular procedures. Endovascular treatment is probably useful if the aneurysm is inaccessible to direct surgery. Special attention must be paid to treatment because of stenotic changes in cerebral vessels within the irradiated field.
Effect of Body Habitus on Radiation Dose during CT Fluoroscopy-Guided Spine Injections
Authors: Viola Ronald J. , Nguyen Giao B. , Yoshizumi Terry T. , Stinnett Sandra S. , Hoang Jenny K. , Kranz Peter G.
Published: April 2014

This study investigated the degree to which body habitus influences radiation dose during CT fluoroscopy (CTF)-guided lumbar epidural steroid injections (ESI).

An anthropomorphic phantom containing metal oxide semiconductor field effect transistor (MOSFET) detectors was scanned at two transverse levels to simulate upper and lower lumbar CTF-guided ESI. Circumferential layers of adipose-equivalent material were sequentially added to model patients of three sizes: small (cross-sectional dimensions 25×30 cm), average (34×39 cm), and oversize (43×48 cm). Point dose rates to skin and internal organs within the CTF beam were measured. Scattered point dose rates 5 cm from the radiation beam were also measured.

Direct point dose rates to the internal organs ranged from 0.05–0.11 mGy/10mAs in the oversized phantom, and from 0.18–0.43 mGy/10mAs in the small phantom. Skin direct point dose rates ranged from 0.69–0.71 mGy/10mAs in the oversized phantom and 0.88–0.94 mGy/10mAs in the small phantom. This represents a 180–310% increase in organ point dose rates and 24–36% increase in skin point dose rates in the small habitus compared with the oversize habitus. Scatter point dose rates increased by 83–117% for the small compared to the oversize phantom.

Decreasing body habitus results in substantial increases in direct organ and skin point doses as well as scattered dose during simulated CTF-guided procedures. Failure to account for individual variations in body habitus will result in inaccurate dose estimation and inappropriate choice of tube current in CTF-guided procedures.
Frequent EPAS1/HIF2α exons 9 and 12 mutations in non-familial pheochromocytoma
Authors: Welander Jenny , Andreasson Adam , Brauckhoff Michael , Bäckdahl Martin , Larsson Catharina , Gimm Oliver , Söderkvist Peter
Published: April 2014

Pheochromocytomas are neuroendocrine tumors arising from the adrenal medulla. While heritable mutations are frequently described, less is known about the genetics of sporadic pheochromocytoma. Mutations in genes involved in the cellular hypoxia response have been identified in tumors, and recentlyEPAS1, encoding HIF2α, has been revealed to be a new gene involved in the pathogenesis of pheochromocytoma and abdominal paraganglioma. The aim of this study was to further characterizeEPAS1alterations in non-familial pheochromocytomas. Tumor DNA from 42 adrenal pheochromocytoma cases with apparently sporadic presentation, without known hereditary mutations in predisposing genes, were analyzed for mutations inEPAS1by sequencing of exons 9 and 12, which contain the two hydroxylation sites involved in HIF2α degradation, and also exon 2. In addition, the copy number at theEPAS1locus as well as transcriptome-wide gene expression were studied by DNA and RNA microarray analyses, respectively. We identified six missenseEPAS1mutations, three in exon 9 and three in exon 12, in five of 42 pheochromocytomas (12%). The mutations were both somatic and constitutional, and had no overlap in 11 cases (26%) with somatic mutations inNF1orRET. One sample had two differentEPAS1mutations, shown by cloning to occur incis, possibly indicating a novel mechanism of HIF2α stabilization through inactivation of both hydroxylation sites. One of the tumors with anEPAS1mutation also had a gain in DNA copy number at theEPAS1locus. AllEPAS1-mutated tumors displayed a pseudo-hypoxic gene expression pattern, indicating an oncogenic role of the identified mutations.
Revising the role of the androgen receptor in breast cancer
Authors: Fioretti F M , Sita-Lumsden A , Bevan C L , Brooke G N
Published: April 2014

Breast cancer (BC) is traditionally viewed as an oestrogen-dependent disease in which the androgen receptor (AR) is inhibitory, counteracting the oncogenic activity of oestrogen receptor α (ERα (ESR1)). Most probably as a result of this crosstalk, the AR has prognostic value in ER-positive disease, with AR positivity reported to correlate with a better prognosis. Activation of the AR pathway has been previously used as a therapeutic strategy to treat BC, but its usage declined following the introduction of the anti-oestrogen tamoxifen. More recently, it has been demonstrated that a subset of triple-negative BCs (molecular apocrine) are dependent upon androgen signalling for growth and therapies that inhibit androgen signalling, currently used for the treatment of prostate cancer, e.g. the antiandrogen bicalutamide and the CYP17 inhibitor abiraterone acetate are undergoing clinical trials to investigate their efficacy in this BC subtype. This review summarises the current knowledge of AR activity in BC.
Development of mammalian ovary
Authors: Smith Peter , Wilhelm Dagmar , Rodgers Raymond J
Published: April 2014

Pre-natal and early post-natal ovarian development has become a field of increasing importance over recent years. The full effects of perturbations of ovarian development on adult fertility, through environmental changes or genetic anomalies, are only now being truly appreciated. Mitigation of these perturbations requires an understanding of the processes involved in the development of the ovary. Herein, we review some recent findings from mice, sheep, and cattle on the key events involved in ovarian development. We discuss the key process of germ cell migration, ovigerous cord formation, meiosis, and follicle formation and activation. We also review the key contributions of mesonephric cells to ovarian development and propose roles for these cells. Finally, we discuss polycystic ovary syndrome, premature ovarian failure, and pre-natal undernutrition; three key areas in which perturbations to ovarian development appear to have major effects on post-natal fertility.
Mex3c mutation reduces adiposity partially through increasing physical activity
Authors: Han Changjie , Jiao Yan , Zhao Qingguo , Lu Baisong
Published: April 2014

MEX3C is an RNA-binding protein with unknown physiological function. We have recently reported that aMex3cmutation in mice causes growth retardation and reduced adiposity, but how adiposity is reduced remains unclear. Herein, we show that homozygousMex3cgene trap mice have increased physical activity. TheMex3cmutation consistently conferred full protection from diet-induced obesity, hyperglycemia, insulin resistance, hyperlipidemia, and hepatic steatosis. Inob/obmice with leptin deficiency, theMex3cmutation also increased physical activity and improved glucose and lipid profiles. Expressing cre in the neurons ofMex3cgene trap mice, an attempt to partially restoring neuronalMex3cexpression, significantly increased white adipose tissue deposition, but had no effects on body length. Our data suggest that one way in whichMex3cregulates adiposity is through controlling physical activity, and that neuronalMex3cexpression could play an important role in this process.
A Nutritional Conditional Lethal Mutant Due to Pyridoxine 5′-Phosphate Oxidase Deficiency inDrosophila melanogaster
Authors: Chi Wanhao , Zhang Li , Du Wei , Zhuang Xiaoxi
Published: April 2014

The concept of auxotrophic complementation has been proposed as an approach to identify genes in essential metabolic pathways in Drosophila melanogaster. However, it has achieved limited success to date, possibly due to the low probability of finding mutations fit with the chemically defined profile. Instead of using the chemically defined culture media lacking specific nutrients, we used bare minimum culture medium, i.e., 4% sucrose, for adult Drosophila. We identified a nutritional conditional lethal mutant and localized a c.95C > A mutation in the Drosophila pyridoxine 5′-phosphate oxidase gene [dPNPO or sugarlethal (sgll)] using meiotic recombination mapping, deficiency mapping, and whole genome sequencing. PNPO converts dietary vitamin B6 such as pyridoxine to its active form pyridoxal 5′-phosphate (PLP). The missense mutation (sgll95) results in the substitution of alanine to aspartate (p.Ala32Asp). The sgll95 flies survive well on complete medium but all die within 6 d on 4% sucrose only diet, which can be rescued by pyridoxine or PLP supplement, suggesting that the mutation does not cause the complete loss of PNPO activity. The sgll knockdown further confirms its function as the Drosophila PNPO. Because better tools for positional cloning and cheaper whole genome sequencing have made the identification of point mutations much easier than before, alleviating the necessity to pinpoint specific metabolic pathways before gene identification, we propose that nutritional conditional screens based on bare minimum growth media like ours represent promising approaches for discovering important genes and mutations in metabolic pathways, thereby accelerating the establishment of in vivo models that recapitulate human metabolic diseases.
Aspectos eletrencefalográficos das malformações vasculares intracranianas
Authors: Pupo Paulo Pinto
Published: April 2014

Analisando os casos publicados sôbre o assunto, e apresentando um material próprio constituído de 5 casos de aneurismas arteriovenosos, um de aneurisma da artéria silviana e 3 de malformação de Sturge-Weber-Dimitri, estudados clínica, eletrencefalográfica e radiològicamente (craniograma simples e arteriografia cerebral), o autor procura mostrar a importância dos resultados eletrencefalográficos para o diagnóstico exato e para orientação da terapêutica etiológica. Com os elementos assim coligidos conclui: 1) Nos casos de aneurismas arteriovenosos, o EEG deu sinais de diagnóstico focai decisivo em 4, sendo que em 2 levou à arteriografia pacientes que tinham tido uma e duas crises convulsivas, respectivamente, possibilitando, assim, diagnóstico etiológico e terapêutica cirúrgica; em um caso orientou o diagnóstico exato de um paciente de 55 anos, que há 25 anos era tido como epilético; em um caso sòmente não deu sinais de anormalidades, tratando-se de pequeno aneurisma arteriovenoso situado entre circunvoluções parietais. 2) No caso de aneurisma da artéria silviana, situado na base do cérebro, o EEG mostrou somente os distúrbios difusos e bilaterais conseqüentes à hemorragia meníngea. 3) Nos 3 casos de malformação de Sturge-Weber-Dimitri, o EEG demonstrou alterações de tipo depressão de atividade elétrica cerebral correspondente à malformação calcificada; em um dêstes casos mostrou ní- tido foco epileptógeno frontal, explicando perfeitamente sintomatologia de convulsões de tipo bravais-jacksoniano e hemiparesia, independentemente da calcificação tipo angiomatosa, de situação occipital.
Complicações neurológicas no decurso de tratamento pelo ACTH: A propósito de um caso de agnosia visual
Authors: Julião O. Freitas , Assis Licio M. , Gomes Julio Pereira
Published: April 2014

Os autores relatam a observação de um menino de 8 anos de idade, portador de síndrome nefrótica tratada pelo ACTH e que apresentou uma série de graves distúrbios neurológicos conseqüentes a uma crise hipertensiva (a pressão arterial elevou-se a 220-130 mm Hg), ocorrida por ocasião desse tratamento. Manifestando-se inicialmente por cefaléia intensa, depois por crise convulsiva generalizada, à qual se seguiu estado comatoso e posteriormente síndrome confusional, a encefalopatía hipertensiva condicionou, como seqüelas neurológicas mais importantes, distúrbios visuais. Êstes, que se apresentaram, a princípio, sob a forma de amaurose total, assumiram depois o aspecto de distúrbios da percepção, tipo agnóstico, persistentes ainda hoje. A agnosia visual refere-se aos objetos, pessoas, figuras simbólicas e côres.
Síndrome de Guillain-Barré: a propósito de 5 casos tratados com ACTH e cortisona
Authors: Assis José Lamartine de , França Netto A. Spina
Published: April 2014

São registrados 5. casos de síndrome de Guillain-Barré (polirradiculoneurite) tratados com ACTH ou cortisona. Foi observada melhora rápida em todos êles, em tempo variável de um para outro caso, mas menor que o tempo médio de evolução da moléstia quando tais hormônios não são empregados. Em vista da evolução observada é discutida a teoria da patogenia alérgica da doença e sua inclusão no grupo das doenças desmielinizantes do sistema nervoso.