bluuebunny/crossref_metadata_2025 huggingface dataset:
Presence of perforin in endomyocardial biopsies of patients with inflammatory cardiomyopathy predicts poor outcome
Authors: Escher Felicitas , Kühl Uwe , Lassner Dirk , Stroux Andrea , Westermann Dirk , Skurk Carsten , Tschöpe Carsten , Poller Wolfgang , Schultheiss Heinz‐Peter
Published: August 2014

Aims

Intramyocardial inflammation is considered an adverse prognostic factor in inflammatory cardiomyopathy (CMi). However, the precise nature of immune system factors relevant for the prediction of long‐term course remains elusive. The aim of this study was to analyse the prognostic relevance of perforin in a large cohort of patients with CMi.

Methods and results

We investigated 495 consecutive patients with suspected CMi, undergoing endomyocardial biopsies (EMBs), and examined haemodynamic measurements after a long follow‐up period (interquartile range 10.2–37.1 months). In EMBs, myocardial inflammation was assessed by histology and immunohistology. At follow‐up, 388 patients (Group I) showed stable mild dysfunction or significant improvement, with LVEF rising from 46.2 ± 14.8% to 64.3 ± 12.3% (P < 0.0001). Lack of improvement of LV function or significant deterioration of LVEF from 42.1 ± 14.2% to 32.3 ± 11.6% (P < 0.0001) was observed in 107 patients (Group II). Multivariable statistical analysis of LVEF and immunohistochemical parameters in all patients revealed that the single most important predictor of LVEF development was detection of perforin in EMBs, with an odds ratio (OR) of 7.922 [95% confidence interval (CI) 4.380–14.326; P < 0.001] for deteriorating LVEF. Importantly, baseline LVEF (OR 0.962), LV end‐diastolic diameter (OR 1.847), and other immmunohistochemical parameters (CD3, Mac‐1, CD45R0, LFA‐1, HLA‐1, and ICAM‐1) made minor or insignificant contributions to LVEF course in these 495 patients.

Conclusions

In this EMB‐based analysis of the long‐term course of CMi we identified, for the first time, that detection of perforin in the myocardium is a key predictor of LVEF course.
A detailed study of lid‐driven cavity flow at moderate Reynolds numbers using Incompressible SPH
Authors: Khorasanizade Shahab , Sousa Joao M. M.
Published: August 2014

Lid‐driven cavity flow at moderate Reynolds numbers is studied here, employing a mesh‐free method known as Smoothed Particle Hydrodynamics (SPH). In a detailed study of this benchmark, the incompressible SPH approach is applied together with a particle shifting algorithm. Additionally, a new treatment for no‐slip boundary conditions is developed and tested. The use of the aforementioned numerical treatment for solid walls leads to significant improvements in the results with respect to other SPH simulations carried out with similar spatial resolution. However, the effect of spatial resolution is not considered in the present study as the number of particles used in each case was kept constant, approximately reproducing the same resolutions employed in reference studies available in the literature as well. Altogether, the detailed comparisons of field variables at discreet points demonstrate the accuracy and robustness of the new SPH method. Copyright © 2014 John Wiley & Sons, Ltd.
Flux corrected remapping using piecewise parabolic reconstruction for 2D cell‐centered ALE methods
Authors: Velechovsky J. , Breil J. , Liska R.
Published: August 2014

A novel conservative interpolation (remapping) method, in the Arbitrary Lagrangian–Eulerian context for numerical solution of Euler equations on unstructured polygonal grids, is presented. Combination of a piecewise quadratic reconstruction and a flux corrected remapping approach provides a simple, symmetry‐preserving and bounds‐preserving method. The positivity of density and specific internal energy is guaranteed. The complete description of the method and both cyclic remapping and full hydrodynamic 2D numerical examples are given. Copyright © 2014 John Wiley & Sons, Ltd.
THE RELATIONSHIP OF PROBLEM‐SOLVING STYLES TO THE FACTOR COMPOSITION OF TESTS
Authors: French John W.
Published: August 2014

This study was undertaken to learn more about the way in which the characteristics being measured by a test vary with the kind of examinee taking the test or with the problem‐solving style he uses in approaching test problems.

Briefly, the procedure for this study included the following steps:

(1) The subjects took 15 tests which would later be examined by factor analysis. (2) In order to find out what problem‐solving styles the subjects used, they were required to fill out a questionnaire about their background and their approach to test problems, and were interviewed while they solved items similar to ones they had faced on the tests. In all, more than 100 items of information about each subject were gathered. (3) As an aid in recognizing the important problem‐solving styles in these data, the intercorrelations of the interview, questionnaire, and test variables were factor analyzed. (4) These variables, after being grouped and selected by the factor analysis, were used to divide the subjects into 17 different pairs of subsamples representing different problem‐solving styles or different background characteristics that might be expected to affect the way in which a person solves problems. (5) All subsamples in the 17 pairs and also the whole group were then used in performing separate factor analyses of the same 15 tests, in all of which five factors were extracted and rotated. (6) Factor loadings and factor intercorrelations were compared for the two subsamples in each pair.

The problem‐solving approaches used for dividing many of the pairs of subsamples distinguished some kind of systematizing approach from a scanning approach. This is a distinction emphasized by Bloom and Broden and probably related to Gardner's Focusing vs. Scanning and Witkin's Analytic Attitude or Field‐Independence. While some of the divisions into pairs of subsamples revealed no substantial differences either in the loadings of the 15 tests on the five factors or in the intercorrelations of the factors, many interesting differences occurred. In particular the development of a systematic approach to solving the items of a test frequently reduced the loadings of that test on the factor which usually characterized it best. Also, for subjects using a systematic rather than an intuitive or scanning approach to test items, the space factor was usually found to be relatively less correlated with the verbal and mathematical factors and the verbal and mathematical factors were found to be more highly correlated with each other. An attempt is made to account for these findings psychologically by supposing that systematic persons develop specialized techniques for solving the visible, concrete spatial problems that are quite different from the symbolic techniques that they can use for solving problems in either of the symbolic areas, verbal and mathematics.
Uncovering Substance
Authors: Early Jessica Singer , Saidy Christina
Published: August 2014

This article shares the process and outcomes from a three‐day revision workshop designed and implemented in a diverse high school language arts classroom. The revision workshop included: direct instruction, self‐reflection, and peer feedback to provide struggling writers with opportunities to take part in substantive revision. The authors examine the impact of this instructional approach on student writing, the role of peer‐led feedback, and student self‐perceptions as writers. This article provides an accessible and adaptable workshop for teaching revision that may be used for teaching of writing across grade level, discipline, and genre.
Minimal Detection of Nuclear Mutations in XP‐V and Normal Cells Treated with Oxidative Stress Inducing Agents
Authors: Herman Kimberly N. , Toffton Shannon , McCulloch Scott D.
Published: August 2014

Elevated levels of reactive oxygen species (ROS) can be induced by exposure to various chemicals and radiation. One type of damage in DNA produced by ROS is modification of guanine to 7,8‐dihydro‐8‐oxoguanine (8‐oxoG). This particular alteration to the chemistry of the base can inhibit the replication fork and has been linked to mutagenesis, cancer, and aging. In vitro studies have shown that the translesion synthesis polymerase, DNA polymerase η (pol η), is able to efficiently bypass 8‐oxoG in DNA. In this study, we wanted to investigate the mutagenic effects of oxidative stress, and in particular 8‐oxoG, in the presence and absence of pol η. We quantified levels of oxidative stress, 8‐oxoG levels in DNA, and nuclear mutation rates. We found that most of the 8‐oxoG detected were localized to the mitochondrial DNA, opposed to the nuclear DNA. We also saw a corresponding lack of mutations in a nuclear‐encoded gene. This suggests that oxidative stress’ primary mutagenic effects are not predominantly on genomic DNA.
The Bone Marrow Endosteal Niche: How Far from the Surface?
Authors: Cordeiro‐Spinetti Eric , Taichman Russell S. , Balduino Alex
Published: August 2014

aaHematopoietic stem cells (HSC) self‐renewal takes place in the same microenvironment in which massive hematopoietic progenitor proliferation, commitment, and differentiation will occur. This is only made possible if the bone marrow microenvironment comprises different specific niches, composed by different stromal cells that work in harmony to regulate all the steps of the hematopoiesis cascade. Histological and functional assays indicated that HSC and multipotent progenitors preferentially colonize the endosteal and subendosteal regions, in close association with the bone surface. Conversely, committed progenitors and differentiated cells are distributed in the central and perisinusoidal regions, respectively. Over the last decade, many investigative teams sought to define which cell types regulate the HSC niche, how they are organized, and to what extent they interface with each other. System dynamics requires different stromal cells to operate distinct functions over similar HSC pools rather than a single stromal cell type controlling everything. Therefore, our focus herein is to depict the players in the endosteal and subendosteal regions, named the endosteal niche, a necessary step to better understand the interactions of the HSC within the niche and to identify potential targets to manipulate and/or modulate normal and malignant HSC behavior. J. Cell. Biochem. 116: 6–11, 2015. © 2014 Wiley Periodicals, Inc.
PTH Regulates β2‐Adrenergic Receptor Expression in Osteoblast‐Like MC3T3‐E1 Cells
Authors: Moriya Shuichi , Hayata Tadayoshi , Notomi Takuya , Aryal Smriti , Nakamaoto Testuya , Izu Yayoi , Kawasaki Makiri , Yamada Takayuki , Shirakawa Jumpei , Kaneko Kazuo , Ezura Yoichi , Noda Masaki
Published: August 2014

As the aged population is soaring, prevalence of osteoporosis is increasing. However, the molecular basis underlying the regulation of bone mass is still incompletely understood. Sympathetic tone acts via beta2 adrenergic receptors in bone and regulates the mass of bone which is the target organ of parathyroid hormone (PTH). However, whether beta2 adrenergic receptor is regulated by PTH in bone cells is not known. We therefore investigated the effects of PTH on beta2 adrenergic receptor gene expression in osteoblast‐like MC3T3‐E1 cells. PTH treatment immediately suppressed the expression levels of beta2 adrenergic receptor mRNA. This PTH effect was dose‐dependent starting as low as 1 nM. PTH action on beta2 adrenergic receptor gene expression was inhibited by a transcriptional inhibitor, DRB, but not by a protein synthesis inhibitor, cycloheximide suggesting direct transcription control. Knockdown of beta2 adrenergic receptor promoted PTH‐induced expression of c‐fos, an immediate early response gene. With respect to molecular basis for this phenomenon, knockdown of beta2 adrenergic receptor enhanced PTH‐induced transcriptional activity of cyclic AMP response element‐luciferase construct in osteoblasts. Knockdown of beta2 adrenergic receptors also enhanced forskolin‐induced luciferase expression, revealing that adenylate cyclase activity is influenced by beta2 adrenergic receptor. As for phosphorylation of transcription factor, knockdown of beta2 adrenergic receptor enhanced PTH‐induced phosphorylation of cyclic AMP response element binding protein (CREB). These data reveal that beta2 adrenergic receptor is one of the targets of PTH and acts as a suppressor of PTH action in osteoblasts. J. Cell. Biochem. 116: 142–148, 2015. © 2014 Wiley Periodicals, Inc.
Zfat‐Deficient CD4+CD8+ Double‐Positive Thymocytes Are Susceptible to Apoptosis With Deregulated Activation of p38 and JNK
Authors: Ishikura Shuhei , Ogawa Masahiro , Doi Keiko , Matsuzaki Hiroshi , Iwaihara Yuri , Tanaka Yoko , Tsunoda Toshiyuki , Hideshima Hiromasa , Okamura Tadashi , Shirasawa Senji
Published: August 2014

Zfat, which is a nuclear protein harboring an AT‐hook domain and 18‐repeats of C2H2 zinc‐finger motif, is highly expressed in immune‐related tissues, including the thymus and spleen. T cell specific deletion of the Zfat gene by crossing Zfatf/f mice with LckCre mice yields a significant reduction in the number of CD4+CD8+ double‐positive (DP) thymocytes. However, physiological role for Zfat in T cell development in the thymus remains unknown. Here, we found that Zfat‐deficient DP thymocytes in Zfatf/f‐LckCre mice were susceptible to apoptosis both at an unstimulated state and in response to T cell receptor (TCR)‐stimulation. The phosphorylation levels of p38 and JNK were elevated in Zfat‐deficient thymocytes at an unstimulated state with an enhanced phosphorylation of ATF2 and with an over‐expression of Gadd45α⋅ On the other hand, the activation of JNK in the Zfat‐deficient thymocytes, but not p38, was strengthened and prolonged in response to TCR‐stimulation. All these results demonstrate that Zfat critically participates in the development of DP thymocytes through regulating the activities of p38 and JNK. J. Cell. Biochem. 116: 149–157, 2015. © 2014 Wiley Periodicals, Inc.
14‐3‐3ζ Reduces DNA Damage by Interacting With and Stabilizing Proliferating Cell Nuclear Antigen
Authors: Gao Xuejuan , Dan Songsong , Xie Yingying , Qin Huanhuan , Tang Donge , Liu Xiaohui , He Qing‐Yu , Liu Langxia
Published: August 2014

Proliferating cell nuclear antigen (PCNA) is a processivity factor of DNA replication which plays critical roles in the regulation of DNA replication and repair. In this study, we show that PCNA interacts directly in vitro and in cells with 14‐3‐3ζ, an adaptor protein that regulates cell growth and response to DNA damage in eukaryotes. The interaction is mediated by at least two PCNA‐binding sites on 14‐3‐3ζ, one of which is a novel non‐canonical PIP (PCNA interacting protein) box. We find that DNA damages induced by UVC irradiation and MMS (methyl methanesulfonate) can enhance both the interaction of these two proteins and their co‐localization with chromatin. Functional analyses suggest that 14‐3‐3ζ stabilizes PCNA possibly by regulating its ubiquitination, which impacts on DNA damage repair and cell viability. J. Cell. Biochem. 116: 158–169, 2015. © 2014 Wiley Periodicals, Inc.
Inhibitory Effect of Hsa‐miR‐590‐5p on Cardiosphere‐derived Stem Cells Differentiation Through Downregulation of TGFB Signaling
Authors: Ekhteraei‐Tousi Samaneh , Mohammad‐Soltani Bahram , Sadeghizadeh Majid , Mowla Seyed Javad , Parsi Sepideh , Soleimani Masoud
Published: August 2014

The cardiac cells generation via stem cells differentiation is a promising approach to restore the myocardial infarction. Promoted by our primary bioinformatics analysis as well as some previously published data on potential role of hsa‐miR‐590‐3p in cardiogenesis, we have tried to decipher the role of miR‐590‐5p during the course of differentiation of cardiosphere‐derived cells (CDCs). The differentiation induction of CDCs by TGFB1 was confirmed by real‐time PCR, ICC, and flow cytometry. The expression pattern of hsa‐miR‐590‐5p and some related genes were examined during the differentiation process. In order to study the role of miR‐590‐5p in cardiac differentiation, the effect of miR‐590 overexpression in CDCs was studied. Evaluating the expression patterns of miR‐590 and its potential targets (TGFBRs) during the course of differentiation, demonstrated a significant downregulation of miR‐590 and an upregulation of TGFBR2, following the treatment of CDCs with TGFB1. Therefore, we proposed a model in which TGFB1 exerts its differentiation induction via downregulation of miR‐590, and hence the higher transcriptional expression level of TGFBR2. In accordance with our proposed model, transfection of CDCs by a pLenti‐III‐hsa‐mir‐590‐GFP expression vector before or after the first TGFB1 treatment caused a significant alteration in the expression levels of TGFBRs. Moreover, our data revealed that overexpression of miR‐590 before TGFB1 induction was able to attenuate the CDCs differentiation probably via the reduction of TGFBR2 expression level. Altogether, our data suggest an inhibitory role of miR‐590 during the cardiac differentiation of CDCs which its suppression might elevate the rate of differentiation. J. Cell. Biochem. 116: 179–191, 2015. © 2014 Wiley Periodicals, Inc.
Palmitate Induces ER Stress and Autophagy in H9c2 Cells: Implications for Apoptosis and Adiponectin Resistance
Authors: Park Min , Sabetski Anna , Kwan Chan Yee , Turdi Subat , Sweeney Gary
Published: August 2014

The association between obesity and heart failure is well documented and recent studies have indicated that understanding the physiological role of autophagy will be of great significance. Cardiomyocyte apoptosis is one component of cardiac remodeling which leads to heart failure and in this study we used palmitate‐treated H9c2 cells as an in vitro model of lipotoxicity to investigate the role of autophagy in cell death. Temporal analysis revealed that palmitate (100 μM) treatment induced a gradual increase of intracellular lipid accumulation as well as apoptotic cell death. Palmitate induced autophagic flux, determined via increased LC3‐II formation and p62 degradation as well as by detecting reduced colocalization of GFP with RFP in cells overexpressing tandem fluorescent GFP/RFP‐LC3. The increased level of autophagy indicated by these measures were confirmed using transmission electron microscopy (TEM). Upon inhibiting autophagy using bafilomycin we observed an increased level of palmitate‐induced cell death assessed by Annexin V/PI staining, detection of active caspase‐3 and MTT cell viability assay. Interestingly, using TEM and p‐PERK or p‐eIF2α detection we observed increased endoplasmic reticulum (ER) stress in response to palmitate. Autophagy was induced as an adaptive response against ER stress since it was sensitive to ER stress inhibition. Palmitate‐induced ER stress also induced adiponectin resistance, assessed via AMPK phosphorylation, via reducing APPL1 expression. This effect was independent of palmitate‐induced autophagy. In summary, our data indicate that palmitate induces autophagy subsequent to ER stress and that this confers a prosurvival effect against lipotoxicity‐induced cell death. Palmitate‐induced ER stress also led to adiponecin resistance. J. Cell. Physiol. 230: 630–639, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Perspectives on low voltage transmission electron microscopy as applied to cell biology
Authors: Bendayan Moise , Paransky Eugene
Published: August 2014

Low voltage transmission electron microscopy (LVTEM) with accelerating voltages as low as 5 kV was applied to cell biology. To take advantage of the increased contrast given by LVTEM, tissue preparation was modified omitting all heavy metals such as osmium, uranium, and lead from the fixation, on block staining and counterstaining. Nonstained ultra‐thin tissue sections (40 nm thick) generated highly contrasted images. While the aspect of the cells remains similar to that obtained by conventional TEM, some new substructures were revealed. The pancreatic acinar cells granules present a heterogeneous matrix with partitions corresponding to segregation of their different secretory proteins. Microvilli display their core of microfilaments anchored to the dense top membrane. Mitochondria revealed the presence of distinct particles along their cristea membranes that may correspond to the ATP synthase complexes or oxysomes. The dense nuclear chromatin displays a honey‐comb appearance while distinct beads aligned along thin threads were seen in the dispersed chromatin. These new features revealed by LVTEM correlate with structures described or predicted through other approaches. Masking effects due to thickness of the tissue sections and to the presence of heavy metals must have prevented their observation by conventional TEM. Furthermore, the immunogold was adapted to LVTEM revealing nuclear lamin‐A at the edge of the dense chromatin ribbons. Combining cytochemistry with LVTEM brings additional advantages to this new approach in cell biology. Microsc. Res. Tech. 77:999–1004, 2014. © 2014 Wiley Periodicals, Inc.
Characteristic time courses of cortical and medullary sodium signals measured by noninvasive 23Na‐MRI in rat kidney induced by furosemide
Authors: Liu Haiying , Zhou Dan , Garcia Maria L. , Kohler Martin G. , Shen Xiaolan , Williams Donald S. , Klimas Michael T. , Hargreaves Richard J. , Kaczorowski Gregory J.
Published: August 2014

Background

To characterize regional kidney sodium response by MRI following NKCC2 inhibition.

Methods

Regional renal sodium signals were monitored noninvasively using 23Na‐MRI at 9.4T with a temporal resolution of 1.5 min in anesthetized rats (N = 14). A mild NKCC2 inhibition was induced using a slow intravenous furosemide infusion. Time course of sodium signal was modeled as an exponential transient with a single characteristic time constant.

Results

Under normal physiological conditions, the renal sodium signals in medullary and cortical regions were stable and found to respond differently to furosemide challenge. Furosemide infusion at 1.2 mg/kg/h (N = 7) increased sodium signal in the cortex by 40 ± 6% (P < 7 × 10−5) whereas decreased in the medulla by 29 ± 2% (P < 3 × 10−6) with different temporal kinetics. The characteristic time constants of the change were determined to be: 8 ± 2 and 70 ± 10 min for medulla and cortex. Also, the medullary change occurred 9(±3) times faster than cortical independent of furosemide infusion rate up to 35 mg/kg/h.

Conclusion

The pharmacological effects in terms of regional kidney sodium signal changes induced by NKCC2 inhibition are region‐specific and highly predictable. Using noninvasive sodium MRI, we obtained regional renal sodium kinetics data sets in response to a low dose furosemide infusion in normal rats. J. Magn. Reson. Imaging 2015;41:1622–1628. © 2014 Wiley Periodicals, Inc.
Mutations associated with occult hepatitis B in HIV‐positive South Africans
Authors: Powell Eleanor A. , Gededzha Maemu P. , Rentz Michael , Rakgole Nare J. , Selabe Selokela G. , Seleise Tebogo A. , Mphahlele M. Jeffrey , Blackard Jason T.
Published: August 2014

Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV‐positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult‐associated mutations—those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references—were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult‐associated mutations were identified. Ten occult‐associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult‐associated mutations at the same residue. Occult‐associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro. J. Med. Virol. 87:388–400, 2015. © 2014 Wiley Periodicals, Inc.
Seroprevalence of hepatitis E virus among pregnant women and control subjects in China
Authors: Cong Wei , Sui Jian‐Chao , Zhang Xiang‐Yan , Qian Ai‐Dong , Chen Jia , Zhu Xing‐Quan
Published: August 2014

Hepatitis E infection, caused by the hepatitis E virus (HEV), is an important global public health concern, with particularly high mortality in pregnant women. China is generally judged to be an HEV‐endemic area, but epidemiological data for HEV among pregnant women are limited. Between June 2011 and July 2013, a case‐control study was conducted to estimate the seroprevalence and potential risk factors associated with the acquisition of HEV infection by pregnant women in China. Nine‐hundred and ninety pregnant women who visited hospitals for antenatal follow‐up or medication in Qingdao and Weihai and 965 control subjects matched by age, gender and residence were examined for the presence of anti‐HEV IgG and IgM antibodies by enzyme immunoassays. Socio‐demographic and behavioral characteristics from the study subjects were obtained. The overall prevalence of anti‐HEV IgG in all 1,955 samples was 20.7%. In pregnant women, 16.2% of samples were anti‐HEV IgG positive whereas, in control subjects 25.3% of samples were anti‐HEV IgG positive, (P < 0.01). For anti‐HEV IgM detection, 62 (3.2%) of the 1,955 serum samples were positive and the seroprevalence in pregnant women and control subjects was 2.6% and 3.6%, respectively. Age, contact with cats, contact with pigs and exposure to soil were found to be associated with HEV infection. These findings demonstrated the high prevalence of HEV and the considerable potential for the transmission of HEV infection in pregnant women in China. J. Med. Virol. 87:446–450, 2015. © 2014 Wiley Periodicals, Inc.
Complete coding regions of the prototypes enterovirus B93 and C95: Phylogenetic analyses of the P1 and P3 regions of EV‐B and EV‐C strains
Authors: Junttila N. , Lévêque N. , Magnius L.O. , Kabue J.P. , Muyembe‐Tamfum J. J. , Maslin J. , Lina B. , Norder H.
Published: August 2014

Complete coding regions were sequenced for two new enterovirus genomes: EV‐B93 previously identified by VP1 sequencing, derived from a child with acute flaccid paralysis in the Democratic Republic of Congo; and EV‐C95 from a French soldier with acute gastroenteritis in Djibouti. The EV‐B93 P1 had more than 30% nucleotide divergence from other EV‐B types, with highest similarity to E‐15 and EV‐B80. The P1 nucleotide sequence of EV‐C95 was most similar, 71%, to CV‐A21. Complete coding regions for the new enteroviruses were compared with those of 135 EV‐B and 176 EV‐C strains representing all types available in GenBank. When strains from the same outbreak or strains isolated during the same year in the same geographical region were excluded, 27 of the 58 EV‐B, and 16 of the 23 EV‐C types were represented by more than one sequence. However, for EV‐B the P3 sequences formed three clades mainly according to origin or time of isolation, irrespective of type, while for EV‐C the P3 sequences segregated mainly according to disease manifestation, with most strains causing paralysis, including polioviruses, forming one clade, and strains causing respiratory illness forming another. There was no intermixing of types between these two clades, apart from two EV‐C96 strains. The EV‐B P3 sequences had lower inter‐clade and higher intra‐clade variability as compared to the EV‐C sequences, which may explain why inter‐clade recombinations are more frequent in EV‐B. Further analysis of more isolates may shed light on the role of recombinations in the evolution of EV‐B in geographical context. J. Med. Virol. 87:485–497, 2015. © 2014 Wiley Periodicals, Inc.
Prevalence of HBV and HCV among outpatients in the plovdiv region of Bulgaria, 2010–2011
Authors: Kevorkyan Ani , Teoharov Pavel , Lernout Tinne , Petrova Nedyalka , Raycheva Ralitsa , Ivanov Ivailo , van Damme Pierre , Kojouharova Mira
Published: August 2014

Viral hepatitis, particularly hepatitis B and C, are diseases with worldwide distribution that present a significant public health problem. Seroprevalence studies allow assessment of the extent of the disease burden, the identification of populations at risk and the monitoring trends over time. A multi‐center seroprevalence study, carried out in Bulgaria (covering the five largest cities – Sofia, Plovdiv, Varna, Pleven, and Stara Zagora) in 1999–2000 estimated a crude seroprevalence rate of 3.9% for HBsAg and 1.3% for anti‐HCV. A decade later, comparable rates were observed in a study including 865 outpatients consulting a clinical laboratory in Plovdiv, the second largest administrative region in Bulgaria. The crude seroprevalence rate measured for hepatitis B (HBsAg) was 3.9%. The HBsAg prevalence rate in individuals ≤19 years of age (targeted by vaccination) was significantly lower compared to the rate in adults ≥20 years of age –1% versus 4.8%. The lack of dynamics in the overall level of HBsAg carriers is likely related to the excessively low hepatitis B vaccine coverage in individuals, born before the introduction of the universal vaccination of newborns in August 1991. Anti‐HCV antibodies were detected in 0.7% of the subjects. J. Med. Virol. 87:401–406, 2015. © 2014 Wiley Periodicals, Inc.
Outcomes with cytoreductive surgery and HIPEC for peritoneal metastasis
Authors: Ahmed Shuja , Stewart John H. , Shen Perry , Votanopoulos Konstantinos I. , Levine Edward A.
Published: August 2014

Peritoneal metastasis (PM) has traditionally been approached with therapeutic nihilism. The evolution of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) over the last two decades, however, has caused a paradigm shift in treatment for PM. This modality is rapidly gaining acceptance as standard of care for PM from various cancers. This article reviews the current literature regarding the use of CRS/HIPEC for PM from the most common intra‐abdominal malignancies. J. Surg. Oncol. 2014 110:575–584. © 2014 Wiley Periodicals, Inc.
Effect of laser generated shockwaves 1 on ex‐vivo pigskin
Authors: Ramaprasad Vidyunmala , Navarro Artemio , Patel Shahzad , Patel Vikash , Nowroozi Bryan N. , Taylor Zach D. , Yong William , Gupta Vijay , Grundfest Warren S.
Published: August 2014

Introduction

Persistent bacterial infection prolongs hospitalizations, leading to increased healthcare costs. Treatment of these infections costs several billion dollars annually. Biofilm production is one mechanism by which bacteria become resistant. With the help of biofilms, bacteria withstand the host immune response and are much less susceptible to antibiotics. Currently, there is interest in the use of laser‐generated shockwaves (LGS) to delaminate biofilm from infected wound surfaces; however, the safety of such an approach has not yet been established. Of particular concern are the thermal and mechanical effects of the shockwave treatment on the epidermis and the underlying collagen structure of the dermis. The present study is a preliminary investigation of the effect of LGS on freshly harvested ex vivo porcine skin tissue samples.

Materials and Methods

Tissue samples for investigation were harvested immediately post‐mortem and treated with LGS within 30 minutes. Previous studies have shown that laser fluences between 100 and 500 mJ/pulse are capable of delaminating biofilms off a variety of surfaces, thus our preliminary investigation focused on this range of laser energy. For each sample, LGS were produced via laser irradiation of a thin layer (0.5 µm) of titanium sandwiched between a 50 and 100 µm thick layer of water glass and a 0.1 mm thick sheet of Mylar. The rapid thermal expansion of the irradiated titanium film generates a transient compressive wave that is coupled through a liquid layer to the surface of the ex vivo pigskin sample. Shocked samples were immediately fixed in formalin and prepared for histological analysis. A blinded pathologist evaluated and scored each section on the basis of its overall appearance (O) and presence of linear/slit‐like spaces roughly parallel to the surface of the skin (S). The scores were given on a scale of 0–3.

Results

The present investigation revealed no visible difference between the tissue sections of the control sample and those that were subjected to laser‐generated shockwaves. There was no relationship between the scores received by the samples and the energy with which they were shocked.

Conclusion

Preliminary investigation into the safety of the LGS treatment for biofilm delamination appears promising. Additional investigation will continue on ex vivo porcine samples, followed by an in vivo animal trial to better understand the physiological response to LGS treatment. Lasers Surg. Med. 46:620–627, 2014. © 2014 Wiley Periodicals, Inc.
Photoactive dye‐enhanced tissue ablation for endoscopic laser prostatectomy
Authors: Ahn Minwoo , Hau Nguyen Trung , Van Phuc Nguyen , Oh Junghwan , Kang Hyun Wook
Published: August 2014

Background and Objective

Laser light has been widely used as a surgical tool to treat benign prostate hyperplasia (BPH) over 20 years. Recently, application of high laser power up to 200 W was often reported to swiftly remove a large amount of prostatic tissue. The purpose of this study was to validate the feasibility of photoactive dye injection to enhance light absorption and eventually to facilitate tissue vaporization with low laser power.

Materials and Methods

Chicken breast tissue was selected as a target tissue due to minimal optical absorption at the visible wavelength. Four biocompatible photoactive dyes, including amaranth (AR), black dye (BD), hemoglobin powder (HP), and endoscopic marker (EM), were selected and tested in vitro with a customized 532 nm laser system with radiant exposure ranging from 0.9 to 3.9 J/cm2. Light absorbance and ablation threshold were measured with UV–Vis spectrometer and Probit analysis, respectively, and compared to feature the function of the injected dyes. Ablation performance with dye‐injection was evaluated in light of radiant exposure, dye concentration, and number of injection.

Results

Higher light absorption by injected dyes led to lower ablation threshold as well as more efficient tissue removal in the order of AR, BD, HP, and EM. Regardless of the injected dyes, ablation efficiency principally increased with radiant exposure, dye concentration, and number of injection. Among the dyes, AR created the highest ablation rate of 44.2 ± 0.2 µm/pulse due to higher absorbance and lower ablation threshold. High aspect ratios up to 7.1 ± 0.4 entailed saturation behavior in the tissue ablation injected with AR and BD, possibly resulting from plume shielding and increased scattering due to coagulation. Preliminary tests on canine prostate with a hydraulic injection system demonstrated that 80 W with dye injection yielded comparable ablation efficiency to 120 W with no injection, indicating 33% reduced laser power with almost equivalent performance.

Conclusion

Due to efficient coupling of optical energy, pre‐injection of photoactive dyes promoted the degree of tissue removal during laser irradiation. Further studies will investigate spatial distribution of dyes and optimal injecting pressure to govern the extent of dye‐assisted ablation in a predictable manner. In‐depth comprehension on photoactive dye‐enhanced tissue ablation can help accomplish efficient and safe laser vaporization for BPH with low power application. Lasers Surg. Med. 46:703–711, 2014. © 2014 Wiley Periodicals, Inc.
Evaluation of two quantitative analysis methods of optical coherence tomography for detection of enamel demineralization and comparison with microhardness
Authors: Cara Ana C.B. , Zezell Denise M. , Ana Patricia A. , Maldonado Edison P. , Freitas Anderson Z.
Published: August 2014

Background and Objective

We aimed to evaluate in the same study two quantitative methods for quantification of incipient caries in human dental enamel by using optical coherence tomography (OCT): the optical attenuation coefficient and the area under the A‐scan signal, and to compare their results with those obtained from microhardness analysis.

Study Design/Materials and Methods

One hundred and sixty samples were obtained from 40 sound human third molars, which had their crowns sectioned. Simulated caries were created by a pH cycling method. OCT measurements were performed on the samples, before and after the induced demineralization. We determined the total optical attenuation coefficient from the OCT signal in each site and evaluated the sensitivity and specificity of this approach to the detection of the demineralization. Also, the areas under the OCT curves (AUC‐OCT) and those from sectional microhardness tests (AUC‐MH) were compared.

Results

Both the analysis of the optical attenuation coefficient and the AUC‐OCT were adequate to efficiently distinguish sound and demineralized samples with sensitivity of 0.93 and specificity of 0.96. The AUC‐MH and the AUC‐OCT data presented linear relationship and correlation of 0.99.

Conclusion

Both methods for signal analysis from OCT allowed detection of demineralization with good performance. The AUC‐OCT approach enables obtaining a linear relation with the microhardness results, for a quantitative assessment of mineral loss in human teeth. Lasers Surg. Med. 46:666–671, 2014. © 2014 Wiley Periodicals, Inc.
Investigation of passivation and galvanic corrosion of Ti–Nb alloys and pure titanium
Authors: Hwang M.‐J. , Choi H.‐R. , Kook M.‐S. , Song H.‐J. , Park Y.‐J.
Published: August 2014

The aim of this study was to investigate the role of the passive layers in galvanic corrosion of Ti–Nb alloys and commercially pure titanium (cp‐Ti). Ti–Nb alloys with 5, 10, 15, and 20 wt% niobium (Nb) content were prepared using an arc‐melting technique under high purity Ar gas. The cp‐Ti was used as a control. The electrochemical corrosion behaviors were investigated by A.C. impedance, potentiodynamic polarization, and galvanic corrosion tests. According to the results of impedance analysis, the passivation layer on Ti–Nb alloys consisted of outer, intermediate, inner, and metal defect layers, while the passivation layer on cp‐Ti consisted of outer, intermediate, and inner layers. According to the results of anodic polarization tests, Ti–Nb alloys exhibited better zero potentials and reduced zero current densities. The outer layer and the inner layer of Ti–Nb alloys and cp‐Ti had an effect mainly on the values of the initial galvanic current density and the sign of galvanic current density, respectively. Ti–10Nb alloy exhibited a relatively high initial galvanic current density compared to the other Ti–Nb alloys. Unlike Ti–5Nb, Ti–10Nb, and Ti–15Nb, which exhibited galvanic current densities with a minus sign, Ti–20Nb exhibited a galvanic current density with a plus sign due to its weaker inner layer than that of Ti.
Ribosomal Proteins and Human Diseases: Pathogenesis, Molecular Mechanisms, and Therapeutic Implications
Authors: Wang Wei , Nag Subhasree , Zhang Xu , Wang Ming‐Hai , Wang Hui , Zhou Jianwei , Zhang Ruiwen
Published: August 2014

Ribosomes are essential components of the protein synthesis machinery. The process of ribosome biogenesis is well organized and tightly regulated. Recent studies have shown that ribosomal proteins (RPs) have extraribosomal functions that are involved in cell proliferation, differentiation, apoptosis, DNA repair, and other cellular processes. The dysfunction of RPs has been linked to the development and progression of hematological, metabolic, and cardiovascular diseases and cancer. Perturbation of ribosome biogenesis results in ribosomal stress, which triggers activation of the p53 signaling pathway through RPs–MDM2 interactions, resulting in p53‐dependent cell cycle arrest and apoptosis. RPs also regulate cellular functions through p53‐independent mechanisms. We herein review the recent advances in several forefronts of RP research, including the understanding of their biological features and roles in regulating cellular functions, maintaining cell homeostasis, and their involvement in the pathogenesis of human diseases. We also highlight the translational potential of this research for the identification of molecular biomarkers, and in the discovery and development of novel treatments for human diseases.
A critical evaluation of heteronuclear TOCSY (HEHAHA) experiments for 1H,6Li spin pairs
Authors: Bergander Klaus , Hüls Dietmar , Glaser Steffen J. , Günther Harald , Luy Burkhard
Published: August 2014

Heteronuclear TOCSY (HEHAHA) experiments for 1H,6Li spin pairs in organolithium compounds with adjacent strongly coupled 1H,1H spin systems showed unexpected cross peak behaviour: for n‐butyllithium 1H,6Li cross peaks were completely missing, whereas for the dimer of (Z)‐2‐lithio‐1‐(o‐lithiophenyl)ethane, a cross peak for remote protons was observed even at very short mixing times. It was assumed that strong magnetization transfer within the proton spin systems was responsible for these results, which prevented unambiguous chemical shift assignments. Selective experiments with the 6Li,1H‐HET‐PLUSH‐TACSY sequence then showed the expected 6Li,1H cross peaks for the transfer via the directly coupled 1H and 6Li nuclei. For n‐butyllithium transfer to H(Cα) via an unresolved heteronuclear coupling constant below 0.1 Hz is unambiguously observed. Cross peaks in the 2D 6Li,1H‐HET‐PLUSH‐TACSY spectra for the dimer of (Z)‐2‐lithio‐1‐(o‐lithiophenyl)ethane are readily explained by the measured coupling network and the corresponding active mixing conditions. Copyright © 2014 John Wiley & Sons, Ltd.
Relaxation and exchange dynamics of hyperpolarized 129Xe in human blood
Authors: Norquay Graham , Leung General , Stewart Neil J. , Tozer Gillian M. , Wolber Jan , Wild Jim M.
Published: August 2014

Purpose

129Xe‐blood NMR was performed over the full blood oxygenation range to evaluate 129Xe relaxation and exchange dynamics in human blood.

Methods

Hyperpolarized 129Xe was equilibrated with blood and isolated plasma, and NMR was performed at 1.5 T.

Results

The 129Xe relaxation rate was found to increase nonlinearly with decreasing blood oxygenation. Three constants were extrapolated:
 =  11.1, a “relaxivity index” characterizing the rate of change of 129Xe relaxation as a function of blood oxygenation, and
  =  0.13 s−1 and
 = 0.42 s−1, the 129Xe relaxation rates in oxygenated blood and deoxygenated blood, respectively. In addition, rate constants,
0.022 ms−1 and
 =  0.062 ms−1, were determined for xenon diffusing between red blood cells (RBCs) and plasma (hematocrit  =  48%). The 129Xe‐O2 relaxivity in plasma,
 = 0.075 s−1 mM−1, and the 129Xe relaxation rate in isolated plasma (without dissolved O2),
 = 0.046 s−1, were also calculated. Finally, intrinsic 129Xe‐RBC relaxation rates,
 = 0.19 s−1 and
 = 0.84 s−1, in oxygenated blood and deoxygenated blood, respectively, were calculated.

Conclusion

The relaxation and exchange analysis performed in this study should provide a sound experimental basis upon which to design future MR experiments for dissolved xenon transport from the lungs to distal tissues. Magn Reson Med 74:303–311, 2015. © 2014 Wiley Periodicals, Inc.
Quantitative contrast‐enhanced MRI with superparamagnetic nanoparticles using ultrashort time‐to‐echo pulse sequences
Authors: Gharagouzloo Codi Amir , McMahon Patrick N. , Sridhar Srinivas
Published: August 2014

Purpose

Conventional MRI using contrast agents is semiquantitative because it is inherently sensitive to extravoxular susceptibility artifacts, field inhomogeneity, partial voluming, perivascular effects, and motion/flow artifacts. Herein we demonstrate a quantitative contrast‐enhanced MRI technique using ultrashort time‐to‐echo pulse sequences for measuring clinically relevant concentrations of ferumoxytol, a superparamagnetic iron oxide nanoparticle contrast agent with high sensitivity and precision in vitro and in vivo.

Methods

The method achieves robust, reproducible results by using rapid signal acquisition at ultrashort time‐to‐echo (UTE) to produce positive contrast images with pure T1 weighting and little T2* decay. The spoiled gradient echo equation is used to transform UTE intensities directly into concentration using experimentally determined relaxivity constants and image acquisition parameters.

Results

A multiparametric optimization of acquisition parameters revealed an optimal zone capable of producing high‐fidelity measurements. Clinically relevant intravascular concentrations of ferumoxytol were measured longitudinally in mice with high sensitivity and precision (∼7.1% error). MRI measurements were independently validated by elemental iron analysis of sequential blood draws. Automated segmentation of ferumoxytol concentration yielded high quality three‐dimensional images for visualization of perfusion.

Conclusions

This ability to longitudinally quantify blood pool CA concentration is unique to quantitative UTE contrast‐enhanced (QUTE‐CE) MRI and makes QUTE‐CE MRI competitive with nuclear imaging. Magn Reson Med 74:431–441, 2015. © 2014 Wiley Periodicals, Inc.
Fast group matching for MR fingerprinting reconstruction
Authors: Cauley Stephen F. , Setsompop Kawin , Ma Dan , Jiang Yun , Ye Huihui , Adalsteinsson Elfar , Griswold Mark A. , Wald Lawrence L.
Published: August 2014

Purpose

MR fingerprinting (MRF) is a technique for quantitative tissue mapping using pseudorandom measurements. To estimate tissue properties such as T1, T2, proton density, and B0, the rapidly acquired data are compared against a large dictionary of Bloch simulations. This matching process can be a very computationally demanding portion of MRF reconstruction.

Theory and Methods

We introduce a fast group matching algorithm (GRM) that exploits inherent correlation within MRF dictionaries to create highly clustered groupings of the elements. During matching, a group specific signature is first used to remove poor matching possibilities. Group principal component analysis (PCA) is used to evaluate all remaining tissue types. In vivo 3 Tesla brain data were used to validate the accuracy of our approach.

Results

For a trueFISP sequence with over 196,000 dictionary elements, 1000 MRF samples, and image matrix of 128 × 128, GRM was able to map MR parameters within 2s using standard vendor computational resources. This is an order of magnitude faster than global PCA and nearly two orders of magnitude faster than direct matching, with comparable accuracy (1–2% relative error).

Conclusion

The proposed GRM method is a highly efficient model reduction technique for MRF matching and should enable clinically relevant reconstruction accuracy and time on standard vendor computational resources. Magn Reson Med 74:523–528, 2015. © 2014 Wiley Periodicals, Inc.