bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab initio Phonons in Kesterite and Stannite-Type Cu2ZnSnSe4
Authors: Postnikov Andrei , Amiri Narjes Beigom Mortazavi
Published: May 2011

On the basis of density functional calculations of electronic structure by the Siesta method in the local density approximation, the zone-center vibrational spectra for two crystallographic modifications of Cu2ZnSnSe4 are constructed. The difference of frequencies, between kesterite and stannite phases, of some characteristic modes is discussed. It is suggested to use some of these modes (notably the Zn-related one at 239–254 cm-1) as a vibrational signature of the kesterite structure, e.g., for samples characterization.
Effect of Rare Earth Element Codoping on the Mn Red Emission in Ca and Sr Thiogallates: Focusing on Its Mechanism through Electron Spin Resonance Study of Single Crystals
Authors: Takizawa Takeo , Obonai Toshimitsu , Nomura Shigetaka , Hidaka Chiharu
Published: May 2011

The weak Mn2+ involved red emission in CaGa2S4 can be greatly enhanced by codoping with a suitable rare earth element (REE). To clarify the involved physical mechanism, the actual Mn sites in the host crystal are investigated through electron spin resonance (ESR) measurements of single crystals. Three different patterns of ESR signals with different angular dependences are observed by rotating the magnetic field around the three crystal axes. As a result, three independent sites occupied by the Mn2+ ions are confirmed. Based on the experimental finding that the hyper fine constants (HFS) for the three sites are nearly the same, the Mn2+ ion sites may be ascribed to the Ca or Ga sites. To finally solve this ascription issue, ESR measurements of Eu2+ in CaGa2S4 are carried out, where the Eu2+ ions have been shown to exclusively substitute at Ca sites. From the similar angular variation of the ESR signals of Eu2+ and Mn2+, the Mn substitutional sites are finally determined to be the three Ca ones. A broad ESR signal appearing in the vicinity of the Lande g factor (g = 2.0) suggests the possible presence of Mn clusters. We have to investigate to see whether these may be the actual emission centers.
Luminescence Properties of Barium Thio- and Selenogallates Doped with Eu, Ce, and Eu+Ce
Authors: Yablonskii Gennadii P. , Zubialevich Vitaly Z. , Lutsenko Eugenii V. , Pashaev Arif M. , Tagiev Bahadir G. , Tagiev Oktay B. , Abushov Said A.
Published: May 2011

Photoluminescence properties of barium thio- and selenogallates doped with Eu2+, Ce3+ and co-doped with Eu2+ and Ce3+ were studied in a temperature range of 10–300 K and an optical excitation intensity interval of 3×10-4–1.25×106 W/cm2. Barium thiogallates doped with europium and co-doped by both rare-earth elements show a high thermal stability of the luminescence characteristics and significantly exceed the selenogallate analogues in respect of photoluminescence efficiency. Both thio- and selenogallates activated with the rare-earth elements demonstrate a considerable PL efficiency droop only at high excitation levels exceeding 20 and 10 kW/cm2, respectively. Possible reasons of the droop mechanisms are discussed.
Peculiarities of Current–Voltage Characteristics of Al–p-CdxHg1-xTe Tunnel Metal–Insulator–Semiconductor Structure
Authors: Huseynov Emil , Ismayilov Namig
Published: May 2011

The results of current–voltage (I–V) and capacity–voltage (C–V) characterization and study of kinetics of photocurrent relaxation in Al–p-Cd
x
Hg1-x
Te structures with tunnel thin insulating layer at 80 K are presented. All observed qualitative peculiarities are well explained by a simple model, taking into account the relative contribution of recombination of the photogenerated charge carriers and their tunneling through dielectric gap at reverse bias voltage. It is established that the studied structures are suitable for IR-system applications.
B-vitamin deficiency is protective against DSS-induced colitis in mice
Authors: Benight Nancy M. , Stoll Barbara , Chacko Shaji , da Silva Vanessa R. , Marini Juan C. , Gregory Jesse F. , Stabler Sally P. , Burrin Douglas G.
Published: May 2011

Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met), and its increase in patients with IBD indicates a disruption of Met metabolism; however, the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin-deficient diet would exacerbate experimental colitis. Mice were fed a B6-B12-deficient or control diet for 2 wk and then treated with dextran sodium sulfate (DSS) to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of inflammatory tissue injury and Met metabolites. We also quantified Met cycle activity by measurements of in vivo Met kinetics using [1-13C-methyl-2H3]methionine infusion in similarly treated mice. Unexpectedly, we found that mice given the B-vitamin-deficient diet had improved clinical outcomes, including increased survival, weight maintenance, and reduced disease scores. We also found lower histological disease activity and proinflammatory gene expression (TNF-α and inducible nitric oxide synthase) in the colon in deficient-diet mice. Metabolomic analysis showed evidence that these effects were associated with deficient B6, as markers of B12function were only mildly altered. In vivo methionine kinetics corroborated these results, showing that the deficient diet suppressed transsulfuration but increased remethylation. Our findings suggest that disrupted Met metabolism attributable to B6deficiency reduces the inflammatory response and disease activity in DSS-challenged mice. These results warrant further human clinical studies to determine whether B6deficiency and elevated Hcys in patients with IBD contribute to disease pathobiology.
Knockout of the neurokinin-1 receptor reduces cholangiocyte proliferation in bile duct-ligated mice
Authors: Glaser Shannon , Gaudio Eugenio , Renzi Anastasia , Mancinelli Romina , Ueno Yoshiyuki , Venter Julie , White Mellanie , Kopriva Shelley , Chiasson Valorie , DeMorrow Sharon , Francis Heather , Meng Fanyin , Marzioni Marco , Franchitto Antonio , Alvaro Domenico , Supowit Scott , DiPette Donald J. , Onori Paolo , Alpini Gianfranco
Published: May 2011

In bile duct-ligated (BDL) rats, cholangiocyte proliferation is regulated by neuroendocrine factors such as α-calcitonin gene-related peptide (α-CGRP). There is no evidence that the sensory neuropeptide substance P (SP) regulates cholangiocyte hyperplasia. Wild-type (WT,+/+) and NK-1 receptor (NK-1R) knockout (NK-1R−/−) mice underwent sham or BDL for 1 wk. Then we evaluated 1) NK-1R expression, transaminases, and bilirubin serum levels; 2) necrosis, hepatocyte apoptosis and steatosis, and the number of cholangiocytes positive by CK-19 and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling in liver sections; 3) mRNA expression for collagen 1α and α-smooth muscle (α-SMA) actin in total liver samples; and 4) PCNA expression and PKA phosphorylation in cholangiocytes. In cholangiocyte lines, we determined the effects of SP on cAMP and d-myo-inositol 1,4,5-trisphosphate levels, proliferation, and PKA phosphorylation. Cholangiocytes express NK-1R with expression being upregulated following BDL. In normal NK-1R−/−mice, there was higher hepatocyte apoptosis and scattered hepatocyte steatosis compared with controls. In NK-1R−/−BDL mice, there was a decrease in serum transaminases and bilirubin levels and the number of CK-19-positive cholangiocytes and enhanced biliary apoptosis compared with controls. In total liver samples, the expression of collagen 1α and α-SMA increased in BDL compared with normal mice and decreased in BDL NK-1R−/−compared with BDL mice. In cholangiocytes from BDL NK-1R−/−mice there was decreased PCNA expression and PKA phosphorylation. In vitro, SP increased cAMP levels, proliferation, and PKA phosphorylation of cholangiocytes. Targeting of NK-1R may be important in the inhibition of biliary hyperplasia in cholangiopathies.
Aortic stiffness in vivo in hypertensive rat via echo-tracking: analysis of the pulsatile distension waveform
Authors: Vayssettes-Courchay Christine , Ragonnet Christophe , Isabelle Marc , Verbeuren Tony J.
Published: May 2011

Large-artery stiffening is a major risk factor in aging and hypertension. Elevated blood pressure (BP) and vascular wall properties participate in arterial stiffening; we aimed to evaluate their respective role by combining echo-tracking and the spontaneously hypertensive rats (SHR) treated with low doses of a nitric oxide synthase inhibitor, shown to have arterial stiffening. Normotensive [Wistar-Kyoto (WKY)], SHR, and SHR treated for 2 wk with NG-nitro-l-arginine methyl ester (SHRLN) were anesthetized; BP and distension (pulsatile displacement) of the aortic walls with the ArtLab echo-tracking device were measured. Stiffness index increased in SHRLN vs. SHR; compliance, distensibility, and the slopes and area of the distension-pressure loop curve decreased. The pulsatile distension and pressure waveforms were strongly altered in SHRLN. Maximal values were decreased and increased, respectively, and the waveform kinetics also differed. Thus the area under the curve adjusted to heart rate (AUC/ms) was calculated. Acute BP reductions were induced by diltiazem in SHR and SHRLN, to levels similar to those of WKY. In SHR, compliance, distensibility, stiffness index, and the ascending slope of the distension-pressure loop reached the values of WKY, whereas they were only partially improved in SHRLN. Aortic distension (maximal value and AUC/ms) and the area of the distension-pressure loop were improved in SHR, but not in SHRLN. These data confirm the aortic stiffening induced by nitric oxide reduction in SHR. They show that the ArtLab system analyzes aortic stiffness in rats, and that the aortic pulsatile distension waveform is a parameter strongly dependent on the vascular wall properties.
Prior exposure to oxidized low-density lipoprotein limits apoptosis in subsequent generations of endothelial cells by altering promoter methylation
Authors: Mitra Sona , Khaidakov Magomed , Lu Jingjun , Ayyadevara Srinivas , Szwedo Jackob , Wang Xian Wei , Chen Chien , Khaidakov Said , Kasula Srikanth Reddy , Stone Annjanette , Pogribny Igor , Mehta Jawahar L.
Published: May 2011

Oxidized LDL (ox-LDL) plays a critical role in atherogenesis, including apoptosis. As hypercholesterolemia causes epigenetic changes resulting in long-term phenotypic consequences, we hypothesized that repeated and continuous exposure to ox-LDL may alter the pattern of apoptosis in human umbilical vein endothelial cells (HUVECs). We also analyzed global and promoter-specific methylation of apoptosis-related genes. As expected, ox-LDL evoked a dose-dependent increase in apoptosis in the first passage HUVECs that was completely abrogated by lectin-like ox-LDL receptor (LOX-1)-neutralizing antibody. Ox-LDL-induced apoptosis was associated with upregulation of proapoptotic LOX-1, ANXA5, BAX, and CASP3 and inhibition of antiapoptotic BCL2 and cIAP-1 genes accompanied with reciprocal changes in the methylation of promoter regions of these genes. Subsequent passages of cells displayed attenuated apoptotic response to repeat ox-LDL challenge with blunted gene expression and exaggerated methylation of LOX-1, BAX, ANXA5, and CASP3 genes (all P < 0.05 vs. first exposure to ox-LDL). Treatment of cells with LOX-1 antibody before initial ox-LDL treatment prevented both gene-specific promoter methylation and expression changes and reduction of apoptotic response to repeat ox-LDL challenge. Based on these data, we conclude that exposure of HUVECs to ox-LDL induces epigenetic changes leading to resistance to apoptosis in subsequent generations and that this effect may be related to the LOX-1-mediated increase in DNA methylation.
Silencing of sodium/hydrogen exchanger in the heart by direct injection of naked siRNA
Authors: Morgan Patricio E. , Correa María V. , Ennis Irene L. , Diez Ariel A. , Pérez Néstor G. , Cingolani Horacio E.
Published: May 2011

Cardiac Na+/H+exchanger (NHE1) hyperactivity is a central factor in cardiac remodeling following hypertension, myocardial infarction, ischemia-reperfusion injury, and heart failure. Treatment of these pathologies by inhibiting NHE1 is challenging because specific drugs that have been beneficial in experimental models were associated with undesired side effects in clinical practice. In the present work, small interference RNA (siRNA) produced in vitro to specifically silence NHE1 (siRNANHE1) was injected once in vivo into the apex of the left ventricular wall of mouse myocardium. After 48 h, left ventricular NHE1 protein expression was reduced in siRNANHE1-injected mice compared with scrambled siRNA by 33.2 ± 3.4% ( n = 5; P < 0.05). Similarly, NHE1 mRNA levels were reduced by 20 ± 2.0% ( n = 4). At 72 h, siRNANHE1spreading was evident from the decrease in NHE1 expression in three portions of the myocardium (apex, medium, base). NHE1 function was assessed based on maximal velocity of intracellular pH (pHi) recovery (dpHi/d t) after an ammonium prepulse-induced acidic load. Maximal dpHi/d t was reduced to 14% in siRNANHE1-isolated left ventricular papillary muscles compared with scrambled siRNA. In conclusion, only one injection of naked siRNANHE1successfully reduced NHE1 expression and activity in the left ventricle. As has been previously suggested, extensive NHE1 expression reduction may indicate myocardial spread of siRNA molecules from the injection site through gap junctions, providing a valid technique not only for further research into NHE1 function, but also for consideration as a potential therapeutic strategy.
Influence of juvenile housing conditions on the ventilatory, thermoregulatory, and endocrine responses to hypoxia of adult male rats
Authors: Fournier Sébastien , Joseph Vincent , Kinkead Richard
Published: May 2011

“Extreme” housing conditions, such as isolation (single housing) or crowding, are stressful for rats, and their deleterious impact on behavior is well documented. To determine whether more subtle variations in housing can affect animal physiology, the present study tested the hypothesis that the hypoxic ventilatory response (HVR) of adult male rats housed in pairs during the juvenile period (postnatal day 21 to adulthood) does not differ from that of animals housed in triads. Because neonatal stress augments the neuroendocrine responsiveness to stress and HVR, experiments were performed both on “control” (undisturbed) animals and rats subjected to neonatal maternal separation (NMS; 3 h/day, postnatal days 3–12). At adulthood, ventilatory activity was measured by whole body plethysmography under normoxic and hypoxic conditions (inspired fraction of O2= 0.12; 20 min). The ventilatory and body temperature responses to hypoxia of rats raised in triads were less than those of rats housed in pairs. For the HVR, however, the attenuation induced by triad housing was more important in NMS rats. Triad housing decreased “basal” plasma corticosterone, but increased estradiol and testosterone levels. Much like the HVR, housing-related decrease in corticosterone level was greater in NMS than control rats. We conclude that modest changes in housing conditions (pairs vs. triads) during the juvenile period can influence basic homeostatic functions, such as temperature, endocrine, and respiratory regulation. Housing conditions can influence (even eliminate) the manifestations of respiratory plasticity subsequent to deleterious neonatal treatments. Differences in neuroendocrine function likely contribute to these effects.
Anaplastic Thyroid Cancers Harbor Novel Oncogenic Mutations of the ALK Gene
Authors: Murugan Avaniyapuram Kannan , Xing Mingzhao
Published: May 2011

Thyroid cancer is the most common endocrine cancer, and targeted approaches to treat it pose considerable interest. In this study, we report the discovery of ALK gene mutations in thyroid cancer that may rationalize clinical evaluation of anaplastic lymphoma kinase (ALK) inhibitors in this setting. In undifferentiated anaplastic thyroid cancer (ATC), we identified two novel point mutations, C3592T and G3602A, in exon 23 of the ALK gene, with a prevalence of 11.11%, but found no mutations in the matched normal tissues or in well-differentiated thyroid cancers. These two mutations, resulting in L1198F and G1201E amino acid changes, respectively, both reside within the ALK tyrosine kinase domain where they dramatically increased tyrosine kinase activities. Similarly, these mutations heightened the ability of ALK to activate the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein (MAP) kinase pathways in established mouse cells. Further investigations showed that these two ALK mutants strongly promoted cell focus formation, anchorage-independent growth, and cell invasion. Similar oncogenic properties were observed in the neuroblastoma-associated ALK mutants K1062M and F1174L but not in wild-type ALK. Overall, our results reveal two novel gain-of-function mutations of ALK in certain ATCs, and they suggest efforts to clinically evaluate the use of ALK kinase inhibitors to treat patients who harbor ATCs with these mutations. Cancer Res; 71(13); 4403–11. ©2011 AACR.
Cryogenic Transmission Electron Microscopy Study of Amelogenin Self-Assembly at Different pH
Authors: Fang Ping-An , Margolis Henry C. , Conway James F. , Simmer James P. , Dickinson Gary H. , Beniash Elia
Published: May 2011

Cryogenic transmission electron microscopy (cryo-EM) was used to explore the self-assembly of recombinant murine amelogenin (rM179) in vitro.Our cryo-EM data showed that amelogenin self-assembly is a strongly pH-dependent process. At pH 4.4 the main fraction of the protein exists in a monomeric form, although some peculiar structures consisting of chains of monomers were also observed. At pH 5.8 large nanospheres comprising ring-like structures ∼50 nm in diameter were the most abundant particle class. Similarly, at pH 8.0 amelogenins self-assembled into ring-like oligomers of different sizes, which subsequently assembled into nanospheres 15–20 nm in diameter. Furthermore, at pH 7.2, which is close to a physiological pH, branched chains of nanospheres were observed. Our results show that amelogenin assembly is a multistep hierarchical process and provides new insight into the control of enamel mineralization.
The Nature and Role of Periosteum in Bone and Cartilage Regeneration
Authors: Matsushima Seika , Isogai Noritaka , Jacquet Robin , Lowder Elizabeth , Tokui Taku , Landis William J.
Published: May 2011

This study was undertaken to determine whether periosteum from different bone sources in a donor results in the same formation of bone and cartilage. In this case, periosteum obtained from the cranium and mandible (examples of tissue supporting intramembranous ossification) and the radius and ilium (examples of tissues supporting endochondral ossification) of individual calves was used to produce tissue-engineered constructs that were implanted in nude mice and then retrieved after 10 and 20 weeks. Specimens were compared in terms of their osteogenic and chondrogenic potential by radiography, histology, and gene expression levels. By 10 weeks of implantation and more so by 20 weeks, constructs with cranial periosteum had developed to the greatest extent, followed in order by ilium, radius, and mandible periosteum. All constructs, particularly with cranial tissue although minimally with mandibular periosteum, had mineralized by 10 weeks on radiography and stained for proteoglycans with safranin-O red (cranial tissue most intensely and mandibular tissue least intensely). Gene expression of type I collagen, type II collagen, runx2, and bone sialoprotein (BSP) was detectable on QRT-PCR for all specimens at 10 and 20 weeks. By 20 weeks, the relative gene levels were: type I collagen, ilium >> radial ≧ cranial ≧ mandibular; type II collagen, radial > ilium > cranial ≧ mandibular; runx2, cranial >>> radial > mandibular ≧ ilium; and BSP, ilium ≧ radial > cranial > mandibular. These data demonstrate that the osteogenic and chondrogenic capacity of the various constructs is not identical and depends on the periosteal source regardless of intramembranous or endochondral ossification. Based on these results, cranial and mandibular periosteal tissues appear to enhance bone formation most and least prominently, respectively. The appropriate periosteal choice for bone and cartilage tissue engineering and regeneration should be a function of its immediate application as well as other factors besides growth rate.
Cerebral Ischemia Related to Globus Pallidus Internus Stimulation for Cervical Dystonia
Authors: Kang Dong Wan , Kim Hae Yu , Chang Jin Woo
Published: May 2011

Background: Deep brain stimulation (DBS) is generally a safe and effective method to treat intractable movement disorders. However, complications of surgery have been reported, such as hemorrhage, infection and hardware failure. Objectives and Methods: We describe an unusual complication associated with DBS of the globus pallidus internus (GPi). The patient was a 34-year-old man with a 5-year history of progressive cervical dystonia that was unresponsive to medical treatment. He underwent bilateral DBS of the posteroventral GPi. After test stimulation, the patient developed left facial weakness, as well as dysarthria and hemiparesis of the left side. Magnetic resonance imaging showed a small infarct in the right posterior internal capsule. There was no misplacement of the microelectrode. Results and Conclusion: The authors present this unique case of cerebral infarction as a complication of DBS. The mechanism of ischemia is unclear. However, in this case, we had performed microstimulation with high amplitude in order to determine the adverse effects. This magnitude of electrical stimulation may have led to small-vessel vasospasm, which may have induced ischemia. Although ischemia after DBS surgery is seldom reported, cerebral ischemia may be a surgical complication after DBS implantation.
Bilateral Globus Pallidus Internus Deep Brain Stimulation for DYT1+ Generalized Dystonia with Previously Received Bilateral Thalamotomy and Unilateral Pallidotomy
Authors: Kim Joo Pyung , Chang Won Seok , Park Young Seok , Chang Jin Woo
Published: May 2011

Ablation of the globus pallidus internus (GPi) and thalamotomy have been extensively used in the past. Posteroventral GPi deep brain stimulation has been considered as a treatment for dystonia. However, to date, there is no report in the literature of any dystonia patient who underwent GPi deep brain stimulation who had previously undergone staged bilateral thalamotomy and unilateral pallidotomy. The authors of the present study have acquired relatively good clinical results, even in patients who previously received bilateral thalamotomy and unilateral pallidotomy for DYT1+ primary generalized dystonia.
Treatment of Homocystinuria-Related Dystonia with Deep Brain Stimulation: A Case Report
Authors: Aydin Sabri , Abuzayed Bashar , Varlibas Figen , Apaydin Hulya , Mengi Murat , Kucukyuruk Baris , Hanimoglu Hakan , Yagci Selin , Kizilkilic Osman , Hanci Murat
Published: May 2011

A 23-year-old woman with the medical history of homocystinuria that had been diagnosed at the age of 14 has been non-responsive to treatment. The patient presented with the symptoms of dysphonia, dysarthria and severe dystonia of the neck and left extremities. Blood and urine biochemistry revealed high levels of homocystine. Brain magnetic resonance imaging was normal with no detectable pathologies. Medical treatment strategies were used and repeated injections of botulinum toxin A were administered, but the symptoms showed no significant improvement. The patient was then operated, and deep brain stimulators targeting the bilateral globus pallidus internus were implanted. After the activation of the electrodes, dystonia symptoms showed a remarkable improvement. Good outcome was documented during the follow-up period of 7 months. To our best knowledge, this is the first reported case of homocystinuria-related dystonia symptoms that were successfully treated with deep brain stimulation.
UK National COPD Resources and Outcomes Project 2008: Patients with Chronic Obstructive Pulmonary Disease Exacerbations Who Present with Radiological Pneumonia Have Worse Outcome Compared to Those with Non-Pneumonic Chronic Obstructive Pulmonary Disease Exacerbations
Authors: Myint Phyo Kyaw , Lowe Derek , Stone Robert A. , Buckingham Rhona J. , Roberts C. Michael ,   British Thoracic Society and the Royal College of Physicians Clinical Effectiveness Evaluation Unit (CEEu)
Published: May 2011

Background: Limited comparative data exist on the outcomes of patients presenting with chronic obstructive pulmonary disease (COPD) exacerbations with or without radiological pneumonia. Objective: To examine the outcome differences amongst these patients. Methods: We analysed 2008 UK National COPD audit data to examine the characteristics, management and outcomes, inpatient- and 90-day mortality and length of stay of patients admitted with COPD exacerbations. Results: Of 9,338 admissions, 16% (1,505) had changes consistent with pneumonia indicated on the admission chest X-ray. They tended to be older (mean ages 75 vs. 72 years), male (53 vs. 50%), more likely to come from care homes, with more disability, higher BMI and co-morbidity, lower albumin but higher urea levels, and less likely to be current smokers. COPD exacerbations with pneumonia were associated with worse outcomes: inpatient mortality was 11 and 7% and 90-day mortality was 17 and 13% for pneumonia and non-pneumonia patients, respectively (p < 0.001). After adjusting for factors that are significantly different between the 2 groups, including age, sex, place of residence, level of disability, co-morbidity, albumin and urea levels, estimated risk ratios for inpatient and 90-day mortality for pneumonia compared to non-pneumonia cases in this series were 1.19 (1.01,1.42) and 1.09 (0.96,1.23), respectively. The adjusted risk ratio of a prolonged acute hospital stay of more than 7 days was 1.15 (1.07, 1.23). Conclusions: Patients who present with radiological pneumonia have worse outcomes compared to those admitted without pneumonia in exacerbation of COPD.
Rapamycin-Induced Impaired Wound Healing Is Associated with Compromised Tissue Lactate Accumulation and Extracellular Matrix Remodeling
Authors: Weinreich J. , Löb S. , Löffler M. , Königsrainer I. , Zieker D. , Königsrainer A. , Coerper S. , Beckert S.
Published: May 2011

Introduction: Extracellular matrix (ECM) remodeling involving matrix metalloproteinases (MMPs) and wound lactate accumulation are essential elements of tissue repair. The aim of this study was to investigate whether rapamycin-induced impaired healing is associated with compromised wound fluid lactate accumulation and altered ECM remodeling. Methods: Polyvinyl alcohol sponges were subcutaneously implanted in male C57/BL6 mice. Animals were randomized to daily intraperitoneal treatment with either vehicle or 1.5 mg/kg rapamycin. After 7 or 14 days, sponges were harvested to collect wound fluid for subsequent analyses. Wounds were excised for assessment of tensile strength. Results: After 7 days, wound hydroxyproline content was significantly decreased due to rapamycin therapy, whereas the observed difference in tensile strength marginally failed to show statistical significance. In addition, rapamycin reduced wound lactate accumulation and enhanced MMP-2 protein expression, and both MMP-2 and MMP-9 activity. At day 14, wound tensile strength and hydroxyproline content were significantly lower along with an increase in MMP-2 and MMP-9 activity in rapamycin-treated mice. Similarly, wound fluid lactate concentration and MMP-2 protein expression were found to be persistently decreased and increased, respectively. Conclusions: Rapamycin affects tissue repair by interfering with fundamental mechanisms involved in healing, namely lactate accumulation and ECM remodeling.
An Increased Burden of Common and Rare Lipid-Associated Risk Alleles Contributes to the Phenotypic Spectrum of Hypertriglyceridemia
Authors: Johansen Christopher T. , Wang Jian , Lanktree Matthew B. , McIntyre Adam D. , Ban Matthew R. , Martins Rebecca A. , Kennedy Brooke A. , Hassell Reina G. , Visser Maartje E. , Schwartz Stephen M. , Voight Benjamin F. , Elosua Roberto , Salomaa Veikko , O'Donnell Christopher J. , Dallinga-Thie Geesje M. , Anand Sonia S. , Yusuf Salim , Huff Murray W. , Kathiresan Sekar , Cao Henian , Hegele Robert A.
Published: May 2011

Objective—

Earlier studies have suggested that a common genetic architecture underlies the clinically heterogeneous polygenic Fredrickson hyperlipoproteinemia (HLP) phenotypes defined by hypertriglyceridemia (HTG). Here, we comprehensively analyzed 504 HLP-HTG patients and 1213 normotriglyceridemic controls and confirmed that a spectrum of common and rare lipid-associated variants underlies this heterogeneity.

Methods and Results—

First, we demonstrated that genetic determinants of plasma lipids and lipoproteins, including common variants associated with plasma triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from the Global Lipids Genetics Consortium were associated with multiple HLP-HTG phenotypes. Second, we demonstrated that weighted risk scores composed of common TG-associated variants were distinctly increased across all HLP-HTG phenotypes compared with controls; weighted HDL-C and LDL-C risk scores were also increased, although to a less pronounced degree with some HLP-HTG phenotypes. Interestingly, decomposition of HDL-C and LDL-C risk scores revealed that pleiotropic variants (those jointly associated with TG) accounted for the greatest difference in HDL-C and LDL-C risk scores. The
APOE
E2/E2 genotype was significantly overrepresented in HLP type 3 versus other phenotypes. Finally, rare variants in 4 genes accumulated equally across HLP-HTG phenotypes.

Conclusion—

HTG susceptibility and phenotypic heterogeneity are both influenced by accumulation of common and rare TG-associated variants.
Microbleeds Are Associated With Subsequent Hemorrhagic and Ischemic Stroke in Healthy Elderly Individuals
Authors: Bokura Hirokazu , Saika Reiko , Yamaguchi Takuya , Nagai Atsushi , Oguro Hiroaki , Kobayashi Shotai , Yamaguchi Shuhei
Published: May 2011

Background and Purpose—

Cerebral microbleeds (MBs) are frequently detected in patients with stroke, especially those who experience intracerebral hemorrhage. However, the clinical significance of MBs in subjects without cerebrovascular disease is still unclear. We performed a prospective study to determine whether the presence of MBs provides useful prognostic information in healthy elderly individuals.

Methods—

We tracked 2102 subjects (mean age, 62.1 years) over a mean interval of 3.6 years after they voluntarily participated in the brain checkup system at the Shimane Institute of Health Science. An initial assessment was performed to document the presence of MBs and silent ischemic brain lesions and to map the location of the MBs. During the follow-up period, we obtained information about stroke events that occurred in each subject.

Results—

MBs were detected in 93 of the 2102 subjects (4.4%). Strokes occurred in 44 subjects (2.1%) during the follow-up period. They were significantly more common among subjects with MBs. Age and hypertension were independent risk factors for MBs. The presence of MBs was more strongly associated with a deep brain hemorrhage (hazard ratio, 50.2; 95% CI, 16.7 to 150.9) than ischemic stroke (hazard ratio, 4.48; 95% CI, 2.20 to 12.2). All hemorrhagic strokes occurred in deep brain regions, and they were associated with MBs located in the deep brain region.

Conclusions—

This longitudinal study demonstrated that the presence of MBs can be used to predict hemorrhagic and ischemic stroke, even in healthy elderly individuals.
Geographical Information Systems and the Study of History
Authors: Martí-Henneberg Jordi
Published: May 2011

The articles in this special issue are unique in their use of historical geographical information systems (hgis) to explore a common theme—transport infrastructure and its effects on population distribution in nineteenth- and twentieth-century Europe. Collectively and individually, they demonstrate how to integrate spatial analysis into historical research and how to bring a historical dimension to geographical analyses.
Characteristics and Changes of Extreme Precipitation in the Yellow–Huaihe and Yangtze–Huaihe Rivers Basins, China
Authors: Dong Quan , Chen Xing , Chen Tiexi
Published: May 2011

Many works suggest that the intensity of extreme precipitation might be changing under the background of global warming. Because of the importance of extreme precipitation in the Yellow–Huaihe and Yangtze–Huaihe River basins of China and to compare the spatial difference, the generalized Pareto distribution (GPD) function is used to fit the daily precipitation series in these basins and an estimate of the extreme precipitation spatial distribution is presented. At the same time, its long-term trends are estimated for the period between 1951 and 2004 by using a generalized linear model (GLM), which is based on GPD. High quality daily precipitation data from 215 observation stations over the area are used in this study. The statistical significance of the trend fields is tested with a Monte Carlo experiment based on a two-dimensional Hurst coefficient, H2.

The spatial distribution of the shape parameter of GPD indicates that the upper reaches of the Huaihe River (HuR) basin have the largest probability of extreme rainfall events, which is consistent with most historical flood records in this region. Spatial variations in extreme precipitation trends are found and show significant positive trends in the upper reaches of Poyang Lake in the Yangtze River (YaR) basin and a significant negative trend in the mid- to lower reaches of the Yellow River (YeR) and Haihe River (HaR) basins. The trends in the HuR basin and the lower reaches of Poyang Lake in the YaR basin are nearly neutral. All trend fields are significant at the 5% level of significance from the Monte Carlo experiments.
Altimetry Combined with Hydrography for Ocean Transport Estimation
Authors: Gourcuff Claire , Lherminier Pascale , Mercier Herlé , Le Traon Pierre Yves
Published: May 2011

A method to estimate mass and heat transports across hydrographic sections using hydrography together with altimetry data in a geostrophic inverse box model is presented. Absolute surface velocities computed from Archiving, Validation, and Interpretation of Satellite Oceanographic data (AVISO) altimetry products made up of a combination of sea surface height measurements and geoid estimate are first compared to ship acoustic Doppler current profiler (S-ADCP) measurements of the Observatoire de la Variabilité Interannuelle et Décennale (OVIDE) project along hydrographic sections repeated every 2 yr in summer from Portugal to Greenland. The RMS difference between S-ADCP and altimetry velocities averaged on distances of about 100 km accounts for 3.3 cm s−1. Considering that the uncertainty of S-ADCP velocities is found at 1.5 cm s−1, altimetry errors are estimated at 3 cm s−1. Transports across OVIDE sections previously obtained using S-ADCP data to constrain the geostrophic inverse box model are used as a reference. The new method is found useful to estimate absolute transports across the sections, as well as part of their variability. Despite associated uncertainties that are about 50% larger than when S-ADCP is used, the results for the North Atlantic Current and heat transports, with uncertainties of 10%–15%, reproduce the already observed variability. The largest uncertainties are found in the estimates of the East Greenland Irminger Current (EGIC) transport (30%), induced by larger uncertainties associated with altimetry data at the western boundary.
The Meteorological Global Model GLOBO at the ISAC-CNR of Italy Assessment of 1.5 Yr of Experimental Use for Medium-Range Weather Forecasts
Authors: Malguzzi Piero , Buzzi Andrea , Drofa Oxana
Published: May 2011

Since August 2009, the GLOBO atmospheric general circulation model has been running experimentally at the Institute of Atmospheric Sciences and Climate (ISAC) of the National Council of Research of Italy. GLOBO is derived from the Bologna Limited Area Model (BOLAM), a gridpoint limited-area meteorological model that was developed at the same institute and that has been extended to the entire earth atmosphere. The main dynamical features and physical parameterizations of GLOBO are presented. Starting from initial conditions obtained from the analysis of the NCEP Global Forecast System (GFS) model valid at 0000 UTC, 6-day forecasts with average horizontal resolution of 32 km were performed on a daily basis and in real time. The assessment of the forecast skill during the 1.5-yr period included the calculation of the monthly averaged root-mean-square errors (model prediction versus gridded analyses) of geopotential height at 500 hPa and mean sea level pressure for the northern and southern extratropics, performed accordingly to WMO Commission for Basic Systems (CBS) standards. The verification results are compared with models from other global data processing and forecasting system centers, as are available in the literature. The GLOBO skill for medium-range forecasts turns out to be comparable to that of the above models. The lack of analyses based on model forecasts and data assimilation is likely to penalize the scores for shorter-term forecasts.
Anatomic Single- and Double-Bundle Anterior Cruciate Ligament Reconstruction, Part 1
Authors: Yasuda Kazunori , van Eck Carola F. , Hoshino Yuichi , Fu Freddie H. , Tashman Scott
Published: May 2011

Anterior cruciate ligament reconstruction is a frequently performed orthopaedic procedure. Although short-term results are generally good, long-term outcomes are less favorable. Thus, there is renewed interest in improving surgical techniques. Recent studies of anterior cruciate ligament anatomy and function have characterized the 2-bundle structure of the native ligament. During non-weightbearing conditions, the anteromedial (AM) and posterolateral (PL) bundles display reciprocal tension patterns. However, during weightbearing, both the AM and PL bundles are maximally elongated at low flexion angles and shorten significantly with increasing knee flexion. Conventional single-bundle reconstruction techniques often result in nonanatomic tunnel placement, with a tibial PL to a femoral “high AM” tunnel position. In vitro studies have demonstrated that these nonanatomic single-bundle reconstructions cannot completely restore normal anterior-posterior or rotatory laxity. Cadaveric studies suggest that anatomic single-bundle and anatomic double-bundle reconstruction may better restore knee stability. Although many cadaver studies suggest that double-bundle reconstruction techniques result in superior stability when compared with single-bundle techniques, others failed to demonstrate a clear benefit of this more complex procedure. Cadaver studies generally do not apply physiologically relevant loads and provide only a “time-zero” assessment that ignores effects of healing and remodeling after anterior cruciate ligament reconstruction. In vivo, dynamic studies offer the most comprehensive assessment of knee function after injury or reconstruction, as they can evaluate dynamic stability during functional joint loading. Studies of knee kinematics during activities such as gait and running suggest that nonanatomic single-bundle anterior cruciate ligament reconstruction fails to restore preinjury knee function under functional loading conditions. Similar studies of more anatomic single- and double-bundle surgical approaches are in progress, and preliminary results suggest that these anatomic techniques may be more effective for restoring preinjury knee function. However, more extensive, well-designed studies of both kinematics and long-term outcomes are warranted to characterize the potential benefits of more anatomic reconstruction techniques for improving long-term outcomes after anterior cruciate ligament reconstruction.
Second-Generation Autologous Chondrocyte Implantation
Authors: Kon Elizaveta , Filardo Giuseppe , Condello Vincenzo , Collarile Marco , Di Martino Alessandro , Zorzi Claudio , Marcacci Maurilio
Published: May 2011

Background

Aging is responsible for degenerative changes in all cartilage elements, thus impairing its properties and healing potential. Most studies on surgical procedures for cartilage focus on young patients because these procedures are generally not considered suitable for older patients.

Purpose

To analyze the clinical outcome of cartilage lesion treatment using second-generation autologous chondrocyte implantation (ACI) techniques in patients more than 40 years old with no clear signs of osteoarthritis, to understand their real potential in relation to aging, the failure rate, and complications in older patients.

Study Design

Case series; Level of evidence, 4.

Methods

Sixty-one patients with grade III to IV cartilaginous lesions of the condyles with no clear signs of osteoarthritis and a minimum age of 40 years were treated with second-generation ACI and prospectively evaluated at 5 years’ follow-up. Twenty-two patients were treated with arthroscopic Hyalograft C implantation, and 39 underwent the open Chondro-Gide MACI procedure.

Results

A significant improvement in both subjective and objective evaluations was observed. The International Knee Documentation Committee (IKDC) subjective score improved from 36.8 ± 8.4 to 68.1 ± 21.8 at the final evaluation. The failure rate was 20%. A faster improvement was observed in the group treated with the arthroscopic Hyalograft C technique, whereas similar scores were found at the 24-month follow-up and final evaluation.

Conclusion

A clinical improvement was found in patients more than 40 years old, who in most cases benefited from second-generation ACI with good results lasting at medium-term follow-up. However, the results were inferior with respect to those previously found for younger populations, and the failure rate at medium-term follow-up was also higher. These findings were consistent in the 2 treatment groups. The only difference was the faster recovery when the arthroscopic approach was used.
Precocious Puberty in Two Girls With PEHO Syndrome: A Clinical Feature Not Previously Described
Authors: Alfadhel Majid , Yong Siu Li , Lillquist Yolanda , Langlois Sylvie
Published: May 2011

The authors present 2 girls with progressive encephalopathy, hypsarrhythmia, and optic atrophy syndrome. They describe a novel finding, precocious puberty, a feature not previously reported in this syndrome. The authors also present their clinical features and the results of investigations, including radiological findings, and compare the patients of this report to previously reported cases.
Brain Diffusivity in Infants With Hypoxic–Ischemic Encephalopathy Following Whole Body Hypothermia
Authors: Artzi Moran , Sira Liat Ben , Bassan Haim , Gross-Tsur Varda , Berger Irit , Marom Ronella , Leitner Yael , Bental Yoram , Shiff Yakov , Geva Ronny , Weinstein Maya , Bashat Dafna Ben
Published: May 2011

Hypoxic–ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic–ischemic encephalopathy: cooled; (2) three infants with hypoxic–ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic–ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.
Bilateral Ptosis in a Child Following Massive Attack by a Swarm of Wasps
Authors: Mondal Nivedita , Krishnamurthy Sriram , Narayanan Parameswaran , Srinivasan Sadagopan
Published: May 2011

Neurological manifestations of wasp sting are rare and the etiopathogenesis is not completely understood. We report a 2-year-old girl who developed bilateral ptosis after multiple wasp stings, which responded partially to pyridostigmine. This is the first reported case of wasp venom-induced ptosis in a child. We discuss the possible pathogenetic mechanisms behind this phenomenon.
Differences in Methylphenidate Use Between Immigrants and Spaniards in the Child Population of Aragon, Spain
Authors: Macipe-Costa Rosa M. , García-Campayo Javier , Gimeno-Feliu Luis A. , Magallón-Botaya Rosa , Armesto-Gomez Javier
Published: May 2011

The aim of this research is to study the differences in methylphenidate use in children from different ethnic groups in the region of Aragon, Spain. Differences in the use of methylphenidate between both groups of children, immigrants and Spanish nationals, were assessed based on the total number of methylphenidate prescriptions made out for all children in Aragon in 2008 (N = 98 837). We have used defined daily doses and the defined daily doses per 1000 inhabitants per day. Defined daily doses per 1000 inhabitants per day of methylphenidate use was 18.49 in Spanish boys compared with 2.70 in immigrant boys, and 5.48 in Spanish girls versus 0.83 in immigrant girls. All differences between groups were statistically significant ( P < .001). This study confirms that methylphenidate use is higher in a local population than in an immigrant population. Western European and North American children show the highest use, followed by Latin Americans and Eastern Europeans.
Impaired Mandibular Function in Spinal Muscular Atrophy Type II
Authors: van Bruggen H. Willemijn , van den Engel-Hoek Lenie , van der Pol W. Ludo , de Wijer Anton , de Groot Imelda J. M. , Steenks Michel H.
Published: May 2011

The aim of the study is to assess mandibular function in young patients with spinal muscular atrophy type II. A total of 12 children and young adults with spinal muscular atrophy type II and 12 healthy matched controls participated. The mandibular function impairment was moderate to severe in 50% of patients. A limited mouth opening (≤30 mm) was observed in 75% of the patients. In patients with a severe reduction of the mandibular range of motion the temporomandibular joint mainly rotated during mouth opening instead of the usual combination of rotation and sliding. The severity of the limited active mouth opening correlated with the severity of the disease (motor function measure scores). This study shows that mandibular dysfunction is common among young patients with spinal muscular atrophy type II. Early recognition of mandibular dysfunction may help to prevent complications such as aspiration as a result of chewing problems.