bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergist ablation induces rapid tendon growth through the synthesis of a neotendon matrix
Authors: Gumucio Jonathan P. , Phan Anthony C. , Ruehlmann David G. , Noah Andrew C. , Mendias Christopher L.
Published: October 2014

Mechanical loading can increase tendon cross-sectional area (CSA), but the mechanisms by which this occurs are largely unknown. To gain a greater understanding of the cellular mechanisms of adult tendon growth in response to mechanical loading, we used a synergist ablation model whereby a tenectomy of the Achilles tendon was performed to induce growth of the synergist plantaris tendon. We hypothesized that after synergist ablation progenitor cells in the epitenon would proliferate and increase the size of the existing tendon matrix. Adult male mice were subjected to a bilateral Achilles tenectomy, and plantaris tendons were isolated from mice at 0, 2, 7, 14, and 28 days after surgery. Tendons were sectioned stained with either fast green and hematoxylin, prepared for fluorescent microscopy, or prepared for gene expression of scleraxis and type I collagen. After overload, there was a dramatic increase in total CSA of tendons, whereas the size of the original tendon matrix was not changed. Growth primarily occurred through the formation of a neotendon matrix between the original tendon and the epitenon, and contained cells that were proliferative and scleraxis positive. Additionally, an initial expansion of fibroblast cells occurred before the synthesis of new extracellular matrix. Fibroblasts in the original tendon did not re-enter the cell cycle. The results from this study provide new insight into the mechanisms of tendon growth, indicate tendon consists mostly of postmitotic cells, and that growth of tendon primarily occurs from the most superficial layers outward.
The Polyamine Catabolic Enzyme SAT1 Modulates Tumorigenesis and Radiation Response in GBM
Authors: Brett-Morris Adina , Wright Bradley M. , Seo Yuji , Pasupuleti Vinay , Zhang Junran , Lu Jun , Spina Raffaella , Bar Eli E. , Gujrati Maneesh , Schur Rebecca , Lu Zheng-Rong , Welford Scott M.
Published: October 2014

Glioblastoma multiforme (GBM) is the most common and severe form of brain cancer. The median survival time of patients is approximately 12 months due to poor responses to surgery and chemoradiation. To understand the mechanisms involved in radioresistance, we conducted a genetic screen using an shRNA library to identify genes in which inhibition would sensitize cells to radiation. The results were cross-referenced with the Oncomine and Rembrandt databases to focus on genes that are highly expressed in GBM tumors and associated with poor patient outcomes. Spermidine/spermine-N1-acetyltransferase 1 (SAT1), an enzyme involved in polyamine catabolism, was identified as a gene that promotes resistance to ionizing radiation (IR), is overexpressed in brain tumors, and correlates with poor outcomes. Knockdown of SAT1 using shRNA and siRNA approaches in multiple cell and neurosphere lines resulted in sensitization of GBM cells to radiation in colony formation assays and tumors, and decreased tumorigenesis in vivo. Radiosensitization occurred specifically in G2–M and S phases, suggesting a role for SAT1 in homologous recombination (HR) that was confirmed in a DR-GFP reporter system. Mechanistically, we found that SAT1 promotes acetylation of histone H3, suggesting a new role of SAT1 in chromatin remodeling and regulation of gene expression. In particular, SAT1 depletion led to a dramatic reduction in BRCA1 expression, explaining decreased HR capacity. Our findings suggest that the biologic significance of elevated SAT1 expression in GBM lies in its contribution to cell radioresistance and that SAT1 may potentially be a therapeutic target to sensitize GBM to cancer therapies. Cancer Res; 74(23); 6925–34. ©2014 AACR.
UGT1A and UGT2B Genetic Variation Alters Nicotine and Nitrosamine Glucuronidation in European and African American Smokers
Authors: Wassenaar Catherine A. , Conti David V. , Das Soma , Chen Peixian , Cook Edwin H. , Ratain Mark J. , Benowitz Neal L. , Tyndale Rachel F.
Published: October 2014

Background: Identifying sources of variation in the nicotine and nitrosamine metabolic inactivation pathways is important to understanding the relationship between smoking and cancer risk. Numerous UGT1A and UGT2B enzymes are implicated in nicotine and nitrosamine metabolism in vitro; however, little is known about their roles in vivo.

Methods: Within UGT1A1, UGT1A4, UGT1A9, UGT2B7, UGT2B10, and UGT2B17, 47 variants were genotyped, including UGT2B10*2 and UGT2B17*2. The association between variation in these UGTs and glucuronidation activity within European and African American current smokers (n = 128), quantified as urinary ratios of the glucuronide over unconjugated compound for nicotine, cotinine, trans-3′-hydroxycotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), was investigated in regression models assuming a dominant effect of variant alleles.

Results: Correcting for multiple testing, three UGT2B10 variants were associated with cotinine glucuronidation, rs2331559 and rs11726322 in European Americans and rs835309 in African Americans (P ≤ 0.0002). Additional variants predominantly in UGT2B10 were nominally associated with nicotine (P = 0.008–0.04) and cotinine (P = <0.001–0.02) glucuronidation in both ethnicities in addition to UGT2B10*2 in European Americans (P = 0.01, P < 0.001). UGT2B17*2 (P = 0.03) in European Americans and UGT2B7 variants (P = 0.02–0.04) in African Americans were nominally associated with 3HC glucuronidation. UGT1A (P = 0.007–0.01), UGT2B10 (P = 0.02), and UGT2B7 (P = 0.02–0.03) variants in African Americans were nominally associated with NNAL glucuronidation.

Conclusions: Findings from this initial in vivo study support a role for multiple UGTs in the glucuronidation of tobacco-related compounds in vivo, in particular UGT2B10 and cotinine glucuronidation.

Impact: Findings also provide insight into ethnic differences in glucuronidation activity, which could be contributing to ethnic disparities in the risk for smoking-related cancers. Cancer Epidemiol Biomarkers Prev; 24(1); 94–104. ©2014 AACR.
iNOS Expression in CD4+ T Cells Limits Treg Induction by Repressing TGFβ1: Combined iNOS Inhibition and Treg Depletion Unmask Endogenous Antitumor Immunity
Authors: Jayaraman Padmini , Alfarano Matthew G. , Svider Peter F. , Parikh Falguni , Lu Geming , Kidwai Sarah , Xiong Huabao , Sikora Andrew G.
Published: October 2014

Purpose: Expression of inducible nitric oxide synthase (iNOS) in different cellular compartments may have divergent effects on immune function. We used a syngeneic tumor model to functionally characterize the role of iNOS in regulation of CD4+FOXP3+ regulatory T cells (Treg), and optimize the beneficial effects of iNOS inhibition on antitumor immunity.

Experimental Design: Wild-type (WT) or iNOS knockout mice bearing established MT-RET-1 melanoma were treated with the small-molecule iNOS inhibitor L-NIL and/or cyclophosphamide alone or in combination. The effect of iNOS inhibition or knockout on induction of Treg from mouse and human CD4+ T cells in ex vivo culture was determined in parallel in the presence or absence of TGFβ1-depleting antibodies, and TGFβ1 levels were assessed by ELISA.

Results: Whereas intratumoral myeloid-derived suppressor cells (MDSC) were suppressed by iNOS inhibition or knockout, systemic and intratumoral FOXP3+ Treg levels increased in tumor-bearing mice. iNOS inhibition or knockout similarly enhanced induction of Treg from activated cultured mouse splenocytes or purified human or mouse CD4+ T cells in a TGFβ1-dependent manner. Although either iNOS inhibition or Treg depletion with low-dose cyclophosphamide alone had little effect on growth of established MT-RET1 melanoma, combination treatment potently inhibited MDSC and Treg, boosted tumor-infiltrating CD8+ T-cell levels, and arrested tumor growth in an immune-dependent fashion.

Conclusions: iNOS expression in CD4+ T cells suppresses Treg induction by inhibiting TGFβ1 production. Our data suggest that iNOS expression has divergent effects on induction of myeloid and lymphoid-derived regulatory populations, and strongly support development of combinatorial treatment approaches that target these populations simultaneously. Clin Cancer Res; 20(24); 6439–51. ©2014 AACR.
HPV Infection–Associated Cancers: Next-Generation Technology for Diagnosis and Treatment
Authors: Trimble Cornelia L.
Published: October 2014

Disease caused by human papillomavirus (HPV) remains common, despite preventive vaccines and screening strategies. Globally, HPVs cause one third of infection-associated cancers. The indolent clinical course of the precursor intraepithelial lesions provides an opportunity to understand immunologic obstacles posed by the microenvironment of incipient disease, and how they might be overcome. Results from recent therapeutic HPV vaccine clinical trials suggest that relevant immune responses may be sequestered at the lesion site and are difficult to detect in the circulation. In this Cancer Immunology at the Crossroads article, we outline the current understanding of the risk, diagnosis, and treatment of HPV infection–associated cancers and suggest that quantitative tissue–based endpoints should be included whenever possible in the evaluation of immune-based therapies. Cancer Immunol Res; 2(10); 937–42. ©2014 AACR.
Mutational Screening of EFNA5 in Chinese Age-Related Cataract Patients
Authors: Lin Qinghong , Zhou Nan , Zhang Na , Qi Yanhua
Published: October 2014

Background/Aim: In the past few years, Ephrin-A5 (EFNA5) had been identified to be associated with lens development, but so far no sequence variation in EFNA5 has been reported in humans. Therefore, we conduct this study to investigate the EFNA5 genetic variations in Chinese age-related cataract (ARC) patients. Methods: Sequencing of EFNA5 was performed in 140 sporadic ARC patients and 142 random unrelated healthy subjects. Genomic DNA was extracted from peripheral blood leukocytes. All exons of EFNA5 were sequenced after being amplified by polymerase chain reaction. The functional consequences of the variations were analyzed using PolyPhen2. Results: Three single nucleotide polymorphisms in EFNA5, c.668C>T (rs201008479), c.102C>T (rs199980747) and c.-27C>G (rs200187971), were found in the patients, and none of them presented in the normal controls. Using PolyPhen2, c.668C>T in EFNA5 is predicted to be possibly damaging. Conclusions: The genetic variations c.668C>T (rs201008479), c.102C>T (rs199980747) and c.-27C>G (rs200187971) may present an additional genetic risk factor for ARC in the Chinese population. This study shows the first cases of these genetic variations in EFNA5 in human beings.
VEGF mRNA Assessment in Human Pterygium: A New ‘Scope' for a Future Hope
Authors: Poenaru Sava Mihai G. , Raica Marius L. , Cimpean Anca Maria G.
Published: October 2014

Purpose: The lack of powerful evidence to support the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in human pterygium can be attributed to incomplete VEGF expression assessment by restrictive use of immunohistochemistry only and failure to use the molecular methods able to confirm immunohistochemical findings. By adding at least one more sensitive method to assess human pterygium VEGF expression, a more accurate selection of patients for bevacizumab therapy could be done and this would improve the efficacy of anti-VEGF therapy in human pterygium. Methods: We assessed VEGF mRNA amplification on paraffin-embedded specimens by applying the RNAscope method for the first time in human pterygium, an in situ hybridization-based technique able to detect VEGF mRNA as a single gene copy on paraffin-embedded samples. Results: Heterogeneous VEGF mRNA distribution and amplification inside the epithelial compartment of human pterygium were observed. Despite previous reports concerning the immunohistochemical expression of VEGF in the human pterygium fibrovascular compartment, no stromal components were characterized by VEGF mRNA amplification assessed by in situ hybridization in our study. A higher amplification score was observed in epithelium from recurrent pterygium, especially located in the basal and suprabasal epithelial cells. Conclusions: Based on our findings we consider that in situ hybridization assessment of VEGF for human pterygium specimens can be a useful tool for reconsidering the selection of pterygium patients to be enrolled in anti-VEGF therapy.
How Is Our Self Altered in Psychiatric Disorders? A Neurophenomenal Approach to Psychopathological Symptoms
Authors: Northoff Georg
Published: October 2014

The self is central in our experience and has often been assumed to be necessary for any kind of consciousness in philosophy. Recent investigations in neuroscience demonstrate a particular set of regions such as the cortical midline regions to be associated with the processing of stimuli specifically related to the self as distinguished from those remaining unrelated to the self. Furthermore, findings show a close overlap between self-related activity and high levels of resting state activity in especially anterior midline regions. Interestingly, recent findings in psychiatric disorders such as depression and schizophrenia show resting state abnormalities in exactly these regions, that is in the cortical midline structures. Based on phenomenal and neural observations, I here suggest a neurophenomenal approach that directly links neuronal and phenomenal features (without sandwiching cognitive or sensorimotor functions) to psychopathological symptoms of self in depression and schizophrenia.
Women Are Designed to Deliver Vaginally and Not by Cesarean Section: An Obstetrician's View
Authors: Visser Gerard H.A.
Published: October 2014

Worldwide, there is a rapid increase in deliveries by cesarean section. The large differences among countries, from about 16% to more than 60%, suggest that the cesarean delivery (CD) rate has little to do with evidence-based medicine. In this review, the background for the increasing CD rate is discussed as well as the limited positive effects on neonatal outcome in both term and preterm neonates. Negative effects of CD, including direct maternal morbidity, complications of subsequent pregnancies and iatrogenic early delivery resulting in increased neonatal morbidity, are discussed in addition to long-term implications for the offspring involving altered development of the immune system. The ‘battle' to lower the CD rate will be difficult, but we should not forget that women are designed to deliver vaginally and not by cesarean section.
Characterization of Human Influenza Viruses in Lebanon during 2010-2011 and 2011-2012 Post-Pandemic Seasons
Authors: Zaraket Hassan , Dapat Clyde , Ghanem Soha , Ali Zainab , Lteif Mireille , Kondo Hiroki , Dapat Isolde C. , Saito Kousuke , Kayali Ghazi , Suzuki Hiroshi , Dbaibo Ghassan , Saito Reiko
Published: October 2014

Objective: To genetically characterize human influenza viruses and their susceptibilities to antivirals during two post-pandemic seasons in Lebanon. Methods: Influenza virus was isolated from nasopharyngeal swabs that were obtained from patients with influenza-like illness during 2010-2012 and further analyzed both phenotypically and genotypically. Results: During the 2010-2011 season, both 2009 pandemic H1N1 (H1N1p) and B viruses co-circulated with equal prevalence, while the H3N2 virus predominated during the 2011-2012 season. All H3N2 and H1N1 viruses were resistant to amantadine. Importantly, all viruses of the influenza A and B types were susceptible to the neuraminidase (NA) inhibitors oseltamivir, zanamivir, peramivir, and laninamivir. Nonetheless, all 2011-2012 H1N1p isolates had three mutations (V241I, N369K, and N386S) in the NA gene that were suggested to be permissive of the H275Y mutation, which confers resistance to oseltamivir. We also detected one H1N1p virus during the 2010-2011 season with a 4-fold decrease in susceptibility to oseltamivir due to an NA-S247N mutation. This isolate was phylogenetically distinct from other H1N1p viruses that were isolated in other regions. Conclusions: Influenza A viruses with reduced susceptibility to oseltamivir and mutations permissive for acquiring NA resistance-conferring mutation with minimal burden on their fitness were isolated in Lebanon.
Conservative Management of an Iatrogenic Arteriovenous Fistula
Authors: Miller Robert J.H. , MacRae Jennifer M. , Mustata Stefan
Published: October 2014

Background: Arteriovenous fistula is an uncommon complication of central venous catheterization that often requires invasive repair. Case Report: We report the case of an arteriovenous fistula that presented as ongoing pain following removal of a tunneled central venous catheter. The fistula resolved spontaneously following a period of compression and observation. Conclusion: Our study highlights the etiology of this uncommon complication as well as suggesting a role for conservative management.
Serum Adiponectin Is Associated with Worsened Overall Survival in a Prospective Cohort of Hepatocellular Carcinoma Patients
Authors: Siegel Abby B. , Goyal Abhishek , Salomao Marcela , Wang Shuang , Lee Valerie , Hsu Christine , Rodriguez Rosa , Hershman Dawn L. , Brown Jr. Robert S. , Neugut Alfred I. , Emond Jean , Kato Tomoaki , Samstein Benjamin , Faleck David , Karagozian Raffi
Published: October 2014

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The rise in metabolic syndrome has contributed to this trend. Adipokines, such as adiponectin, are associated with prognosis in several cancers, but have not been well studied in HCC. Methods: We prospectively enrolled 140 patients with newly diagnosed or recurrent HCC with Child-Pugh (CP) class A or B cirrhosis. We examined associations between serum adipokines, clinicopathological features of HCC, and time to death. We also examined a subset of tumors with available pathology for tissue adiponectin receptor (AR) expression by immunohistochemistry. Results: The median age of subjects was 62 years; 79% were men, 59% had underlying hepatitis C, and 36% were diabetic. Adiponectin remained a significant predictor of time to death (hazard ratio 1.90; 95% confidence interval 1.05-3.45; p = 0.03) in a multivariable adjusted model that included age, alcohol history, CP class, stage, and serum E-fetoprotein level. Cytoplasmic AR expression (AR1 and AR2) in tumors trended higher in those with higher serum adiponectin levels and in those with diabetes mellitus, but the association was not statistically significant. Conclusions: In this hypothesis-generating study, we found the serum adiponectin level to be an independent predictor of overall survival in a diverse cohort of HCC patients. Impact: Understanding how adipokines affect the HCC outcome may help develop novel treatment and prevention strategies. i 2014 S. Karger AG, Basel
Hepatogastric Fistula following Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma
Authors: Grover Inderpreet , Ahmad Naveed , Googe Amber B.
Published: October 2014

Hepatogastric fistula (HGF) formation following transcatheter arterial chemoembolization (TACE) leads to increased morbidity and mortality. A 51-year-old Caucasian male with chronic hepatitis B virus-associated cirrhosis and unresectable hepatocellular carcinoma (HCC) presented to the Interventional Radiology Unit for TACE to achieve tumor necrosis. Following the procedure, the patient was admitted with symptoms of fever, epigastric and right upper quadrant pain secondary to the development of an abscess. The abscess was drained; however, an exceedingly rare HGF resulted that was favored to represent a direct invasion of HCC. HGF, the rare complication following TACE, leads to grave consequences and vigilant monitoring, for the development of this entity is recommended to reduce patient mortality. We present a case and literature review of HGF development following TACE for HCC.
Canonical and Noncanonical Vascular Endothelial Growth Factor Pathways
Authors: Domigan Courtney K. , Ziyad Safiyyah , Iruela-Arispe M. Luisa
Published: October 2014

The past 5 years have witnessed a significant expansion in our understanding of vascular endothelial growth factor (VEGF) signaling. In particular, the process of canonical activation of VEGF receptor tyrosine kinases by homodimeric VEGF molecules has now been broadened by the realization that heterodimeric ligands and receptors are also active participants in the signaling process. Although heterodimer receptors were described 2 decades ago, their impact, along with the effect of additional cell surface partners and novel autocrine VEGF signaling pathways, are only now starting to be clarified. Furthermore, ligand-independent signaling (noncanonical) has been identified through galectin and gremlin binding and upon rise of intracellular levels of reactive oxygen species. Activation of the VEGF receptors in the absence of ligand holds immediate implications for therapeutic approaches that exclusively target VEGF. The present review provides a concise summary of the recent developments in both canonical and noncanonical VEGF signaling and places these findings in perspective to their potential clinical and biological ramifications.
Identification of Small Proline-Rich Repeat Protein 3 as a Novel Atheroprotective Factor That Promotes Adaptive Akt Signaling in Vascular Smooth Muscle Cells
Authors: Segedy Amanda K. , Pyle Amy L. , Li Bin , Zhang Youmin , Babaev Vladimir R. , Jat Parmjit , Fazio Sergio , Atkinson James B. , Linton MacRae F. , Young Pampee P.
Published: October 2014

Objective—

Atherosclerosis is the primary driver of cardiovascular disease, the leading cause of death worldwide. Identification of naturally occurring atheroprotective genes has become a major goal for the development of interventions that will limit atheroma progression and associated adverse events. To this end, we have identified small proline-rich repeat protein (SPRR3) as selectively upregulated in vascular smooth muscle cells (VSMCs) of atheroma-bearing arterial tissue versus healthy arterial tissue. In this study, we sought to determine the role of SPRR3 in atheroma pathophysiology.

Approach and Results—

We found that atheroprone apolipoprotein E-null mice lacking SPRR3 developed significantly greater atheroma burden. To determine the cellular driver(s) of this increase, we evaluated SPRR3-dependent changes in bone marrow–derived cells, endothelial cells, and VSMCs. Bone marrow transplant of SPRR3-expressing cells into SPRR3
−/−
apolipoprotein E–deficient recipients failed to rescue atheroma burden. Similarly, endothelial cells did not exhibit a response to SPRR3 loss. However, atheromas from SPRR3-deficient mice exhibited increased TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive VSMCs compared with control. Cell death in SPRR3-deficient VSMCs was significantly increased in vitro. Conversely, SPRR3-overexpressing VSMCs exhibited reduced apoptosis compared with control. We also observed a PI3K (phosphatidylinositol 3-kinase)/Akt-dependent positive association between SPRR3 expression and levels of active Akt in VSMCs. The survival advantage seen in SPRR3-overexpressing VSMCs was abrogated after the addition of a PI3K/Akt pathway inhibitor.

Conclusions—

These results indicate that SPRR3 protects the lesion from VSMC loss by promoting survival signaling in plaque VSMCs, thereby significantly decreasing atherosclerosis progression. As the first identified atheroma-specific VSMC prosurvival factor, SPRR3 represents a potential target for lesion-specific modulation of VSMC survival.
PCSK9 R46L, Lower LDL, and Cardiovascular Disease Risk in Familial Hypercholesterolemia
Authors: Luna Saavedra Yascara Grisel , Dufour Robert , Davignon Jean , Baass Alexis
Published: October 2014

Objective—

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a downregulator of the low density lipoprotein receptor. The aims of this cross-sectional cohort-study were to examine whether the PCSK9 R46L loss of function variant found in a cohort of familial hypercholesterolemia (FH) patients was associated with lower low density lipoprotein cholesterol, lower frequency of xanthomata, and cardiovascular risk.

Approach and Results—

We studied FH patients attending the IRCM (Institut de Recherches Cliniques de Montréal) Lipid Clinic and whose DNA genotyping was positive for a low density lipoprotein receptor mutation. The presence of the PCSK9 loss of function R46L missense variant was determined among a cohort of 582 FH patients by genotyping. Frequency of the R46L variant was 3%. Carriers had significantly lower low density lipoprotein cholesterol (11%,
P
=0.002), total cholesterol (9%,
P
=0.007), apolipoprotein B (10%,
P
=0.037), and non-high density lipoprotein (12%,
P
<0.001) concentrations compared with noncarriers. Furthermore, R46L carriers showed a decreased average number of xanthoma per individual compared with noncarriers (0.33 and 0.76, respectively;
P
<0.001). Importantly, the R46L genetic variant was associated with a significant 86% lower odd of presenting a cardiovascular event (odds ratio, 0.14; 95% confidence interval, 0.032–0.63;
P
=0.001).

Conclusions—

Even though the R46L variant was present in 3% of our FH population, carriers of this polymorphism showed attenuated effect of the low density lipoprotein receptor mutation on parameters, such as low density lipoprotein cholesterol, apolipoprotein B, total cholesterol, and non-high density lipoprotein. More importantly, this mutation is associated with a significant lower risk of cardiovascular disease compared with noncarriers. It is therefore likely that targeting PCSK9 in FH patients with novel anti-PCSK9 therapies will be useful in reducing cardiovascular risk in affected subjects.
Elevation in High-Sensitivity Troponin T in Heart Failure and Preserved Ejection Fraction and Influence of Treatment With the Angiotensin Receptor Neprilysin Inhibitor LCZ696
Authors: Jhund Pardeep S. , Claggett Brian L. , Voors Adriaan A. , Zile Michael R. , Packer Milton , Pieske Burkert M. , Kraigher-Krainer Elisabeth , Shah Amil M. , Prescott Margaret F. , Shi Victor , Lefkowitz Marty , McMurray John J.V. , Solomon Scott D.
Published: October 2014

Background—

Elevated high-sensitivity troponin is associated with increasing disease severity in patients with stable heart failure with reduced ejection fraction, but less is known about the association in heart failure with preserved ejection fraction.

Methods and Results—

We examined the prevalence of elevated high-sensitivity troponin T (hs-TnT) in 298 patients with heart failure with preserved ejection fraction enrolled in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial, in which the angiotensin receptor neprilysin inhibitor LCZ696 reduced markers of heart failure severity compared with valsartan. We assessed the association between hs-TnT and cardiac structure and function, and the effect of LCZ696, compared with valsartan, on hs-TnT over 36 weeks. Elevated hs-TnT in the myocardial injury range (>0.014 μg/L) was found in 55% of patients and was associated with older age, history of diabetes mellitus, higher N-terminal pro-brain natriuretic peptide, lower estimated glomerular filtration rate, and larger left atrial size, left ventricular volume, and mass. LCZ696 treatment reduced hs-TnT to a greater extent at 12 weeks (12% reduction;
P
=0.05) and at 36 weeks (14% reduction;
P
=0.03) compared with valsartan.

Conclusions—

Troponin T was elevated in a substantial number of patients enrolled in a heart failure with preserved ejection fraction clinical trial and was associated with abnormalities of cardiac structure, function, and elevated baseline N-terminal pro-brain natriuretic peptide. Decreases in hs-TnT with LCZ696 in parallel with improvement in N-terminal pro-brain natriuretic peptide and left atrial size suggest that the angiotensin receptor neprilysin inhibitor LCZ696 may reduce this measure of myocardial injury in heart failure with preserved ejection fraction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00887588.
Quantitative T2′-Mapping in Acute Ischemic Stroke
Authors: Bauer Sonja , Wagner Marlies , Seiler Alexander , Hattingen Elke , Deichmann Ralf , Nöth Ulrike , Singer Oliver C.
Published: October 2014

Background and Purpose—

Quantitative T2′-mapping detects regional changes in the relation of oxygenated and deoxygenated haemoglobine and might reflect areas with increased oxygen extraction. T2′-mapping in conjunction with an elaborate algorithm for motion correction was performed in patients with acute large-vessel stroke, and quantitative T2′-values were determined within the diffusion-weighted imaging lesion and perfusion-restricted tissue.

Methods—

Eleven patients (median age, 71 years) with acute middle cerebral or internal carotid artery occlusion underwent MRI before scheduled endovascular treatment. MR-examination included diffusion- and perfusion-weighted imaging and quantitative, motion-corrected mapping of T2′. Time-to-peak maps were thresholded for different degrees of perfusion delays (eg, ≥0 s, ≥ 2s) when compared with a reference time-to-peak value from healthy contralateral tissue. Mean T2′-values in areas with reduced apparent diffusion coefficient and in areas with impaired perfusion were compared with T2′-values in corresponding contralateral areas.

Results—

Median time between symptom onset and MRI was 238 minutes. T2′-values were significantly reduced within the apparent diffusion coefficient -lesion when compared with contralateral healthy tissue (83 ms [67, 97] versus 97 ms [91, 111];
P
<0.003). In perfusion-restricted tissue, T2′-values were also significantly lower when compared with contralateral healthy tissue (ie, for time to peak, ≥0 s 93 ms [86, 102] versus 104 [90, 110];
P
=0.008) but were significantly higher than within the apparent diffusion coefficient lesion. The severity of the perfusion impairment had no influence on median T2′-values.

Conclusions—

Motion-corrected T2′-mapping reveals significant and gradually declining values from healthy to perfusion-disturbed to apparent diffusion coefficient-restricted tissue. Current T2′-mapping can differentiate between the ischemic core and the perfusion-impaired areas but not on its own between penumbral and oligemic tissue.
Translating Ottoman Justice: Ragusan Dragomans As Interpreters of Ottoman Law
Authors: Zecevic Selma
Published: October 2014

This article focuses on strategies of legal translation and interpretation adopted by dragomans of the Ottoman tributary state of the Republic of Ragusa. Based on hüccets, iʿlāms and draft-documents (minute) from the Turkish Chancellery of the Republic of Ragusa that shed light on the multiple roles played by Ragusan dragomans in Ottoman-Ragusan legal exchanges, I argue that these Ragusan expert-linguists were not disinterested parties in these legal communications; rather, they actively shaped and controlled the content of information in Ottoman-Ragusan legal interchanges, thereby influencing the outcomes of legal cases involving Ragusan litigants.
E-typing for nematodes: an assessment of type specimen use by nematode taxonomists with a summary of types deposited in the Smithsonian Nematode Collection
Authors: Abebe Eyualem , Mekete Tesfamariam , Decraemer Wilfrida
Published: October 2014

We assessed 301 taxonomic papers published in nine journals between 1999-2011 to determine the use of type specimens and to evaluate the habitat focus and the number of new species described per year. A total of ca 100 new nematode species were described every year, primarily from terrestrial habitats. Two-thirds were terrestrial, 16% were aquatic and the remaining 9% were animal-parasitic nematodes. Only 2.5% of the taxonomic literature reported a comparative study of type material for making a decision on the identity of the target taxon. The overwhelming majority (i.e., 97.5%) relied only on literature comparisons. Our closer scrutiny of the 61 papers revealed a number of shared problems: a third stated that inadequacy of original descriptions, or unavailability/inaccessibility of type specimens had hindered them from unequivocally determining the identity of their species. Fourteen percent reported a discrepancy between the text descriptions and the illustrations, and a tenth revealed the absence of designated types for taxa relevant to their work. A similar number indicated deterioration of types to be a reason for either making wrong conclusions in previous descriptions, or for rendering their descriptions incomplete. We argue for E-typing of nematodes as a solution to enhance the future accessibility of type specimens. We stress the need for a concerted effort between museum curators, nematological journals and nematological societies to address the problem and thereby to forge a brighter future for the science.
Anatomy and the Body in Renaissance Protestant Psychology
Authors: Cellamare Davide
Published: October 2014

This article addresses the use of anatomical knowledge in Renaissance works on the soul produced at northern European universities, as well as the notions of ‘body’ and ‘soul’ that emerge from them. It examines specifically Philip Melanchthon’s and Rudolph Snell van Royen’s treatises on the soul. This analysis shows that a number of Protestant professors of arts and medicine generally considered the anatomical study of the body – which they conceived of as a teleologically organised machina (machine) – to be instrumental in studying the human soul. This article will, however, also document that the reasons motivating this conception were not uniform.
Nine new species of Timonius (Rubiaceae) from Kinabalu Park, Borneo
Authors: Chen Junhao , Wong Khoon Meng , Van der Ent Antony , Tan Hugh Tiang Wah
Published: October 2014

Nine new species of Timonius (Rubiaceae) from Kinabalu Park are described: T. abanii, T. beamanii, T. bullatus, T. kinabaluensis, T. leopoldii, T. ophioliticus, T. pannosus, T. stenolobus, and T. tambuyukonensis. Of the nine species, six are likely to be endemic to the Kinabalu massif, and four appear to occur exclusively on ultramafic soils.
A new species of Lepidium (Brassicaceae) in the Cook Islands
Authors: SYKES W. R.
Published: October 2014

Lepidium makateanum is a small, erect, densely bushy shrublet confined to areas of makatea (raised coral) on Miti‘aro in the Ngaputoru Group north-east of Rarotonga.  It is closely related to L. bidentatum, a common coastal species throughout East Polynesia.  On some other islands of East Polynesia, other taxa are also said to be closely related to L. bidentatum, but none represent the Miti‘aro plant.
Typification of two Stereocaulon names (Lecanorales, Ascomycota)
Authors: Oset Magdalena , Kukwa Martin
Published: October 2014

The nomenclature, bibliographic citations and typifications of the names Stereocaulon botryosum and S. condensatum are discussed. A neotype is designated for S. condensatum and the lectotypification of S. botryosum is clarified. In addition, the morphological and chemical characteristics of both species and information on exsiccates examined are presented.
Taxonomic notes on some species of Euselasia Hübner, [1819] from the "Uriiformes" group, with the description of the immature stages of Euselasia satyroides Lathy, 1926, stat. rev. (Lepidoptera: Riodinidae: Euselasiinae)
Authors: SANTOS FABIO LUIS DOS , Dias Fernando Maia Silva , LEITE LUIS ANDERSON RIBEIRO , Dolibaina Diego Rodrigo , Casagrande Mirna Martins , Mielke Olaf Hermann Hendrik
Published: October 2014

The specific status of Euselasia satyroides Lathy, 1926, stat. rev., currently recognized as a synonym of Eurygona modesta Hewitson, 1856, is reinstated, and its immature stages, reared on Pouteria salicifolia (Sapotaceae), are thoroughly described and illustrated. The identity of some species of the genus Euselasia Hübner, [1819] belonging to the "Uriiformes" species group is clarified: lectotypes are designated to Eurygona eugeon Hewitson, 1856, Eurygona modesta Bates, 1868, Euselasia geon Seitz, 1913, and Euselasia satyroides Lathy, 1926, stat. rev.; Euselasia geon Seitz, 1913, syn. rev. is considered a synonym of Eurygona eugeon Hewitson, 1856. Additionally, a taxonomic dichotomous key for the species belonging to the "Uriiformes" group is provided.
A taxonomic revision of two local endemic Radix spp. (Gastropoda: Lymnaeidae) from Khodutka geothermal area, Kamchatka, Russian Far East
Authors: BOLOTOV IVAN , BESPALAYA YULIA , AKSENOVA OLGA , AKSENOV ANDREY , BOLOTOV NIKITA , GOFAROV MIKHAIL , KONDAKOV ALEXANDER , PALTSER INGA , VIKHREV ILYA
Published: October 2014

Khodutka geothermal area is located near Khodutka and Priemysh volcanoes and is one of the largest geothermal areas of the Kamchatka Peninsula. Vakin (2003) described geological, geochemical and geothermic conditions of this geothermal area in detail. The main thermal water sources have temperatures up to 87°C and a discharge of approximately 150 l×sec.-1 are flows out into the warm lake with dimensions of ca. 250 m length and 80 m width. This warm river is ca. 20 m in width beginning from the lake and flows to the Bolshaya Khodutka River basin. Two local endemic Radix species were described from this geothermal area, especially Lymnaea (Radix) hadutkae Kruglov & Starobogatov, 1989 and L. (R.) thermokamtschatica Kruglov & Starobogatov, 1989 (Kruglov & Starobogatov 1989, 1993; Kruglov 2005). These species were separated using proportions of shell and reproductive system (Kruglov & Starobogatov 1989, 1993; Starobogatov et al. 2004). According to the diagnosis, L. (R.) hadutkae differs in the ear-shape shell, a form of the provaginal duct with cylindrical distal part and conical proximal part, and larger value of the index of the copulatory apparatus (ICA: proportion of the preputium to phallotheca is 1.27) from other species within the section Thermoradix Kruglov & Starobogatov, 1989. The last whorl is large, 0.86–0.89 of the shell height; an excess of the last whorl over upper margin of the aperture is 0.15–0.16 of the aperture height. L. (R.) thermokamtschatica has the cylindrical provaginal duct, relatively short bursa duct (1.5X longer than the bursa copulatrix diameter) and very long phallotheca (ICA is 0.77). The last whorl is large, 0.85–0.87 of the shell height; an excess of the last whorl over upper margin of the aperture is 0.2–0.25 of the aperture height. In accordance with an identification key (Starobogatov et al. 2004), the main diagnostic feature is an excess of the last whorl over the shell aperture, which has ≤0.78 and ≥0.80 of the penultimate whorl width in the first and second species, respectively. In the present paper, we revised these taxa using newly collected topotypes and additional Radix spp. specimens from other areas of the Russian Far East.
Moistening Processes before the Convective Initiation of Madden–Julian Oscillation Events during the CINDY2011/DYNAMO Period
Authors: Nasuno Tomoe , Li Tim , Kikuchi Kazuyoshi
Published: October 2014

Convective initiation processes in the Madden–Julian oscillation (MJO) events that occurred during the Cooperative Indian Ocean Experiment on Intraseasonal Variability in the Year 2011 (CINDY2011)/Dynamics of the Madden–Julian Oscillation (DYNAMO) intensive observation period (IOP) were investigated. Two episodes that were initiated in mid-October (MJO1) and mid-November (MJO2) 2011 were analyzed using European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and satellite data. Moisture budgets in the equatorial Indian Ocean (IO) domain (10°S–10°N, 60°–90°E) were analyzed in detail by separating each variable into basic-state (>80 day), intraseasonal (20–80 day), and high-frequency (<20 day) variations. The quality of the ECMWF reanalysis was also evaluated against the sounding data collected during the field campaign.

In both MJO events, the increase in precipitable water started 8–9 days prior to the convective initiation. Moisture advection decomposition revealed that advection of basic moisture by intraseasonal easterly anomalies and of intraseasonal moisture anomalies by the basic zonal wind were pronounced in these two events. The nonlinear high-frequency terms in the meridional moisture advection were the same order of magnitude as the primary term in the middle troposphere, implying systematic upscale transport of moisture. As a possible mechanism of the acceleration of easterly anomalies, amplification of off-equatorial Rossby wave trains that intruded into the equatorial zone was detected during the preconditioning periods in both MJO events.
Disagreements in Low-Level Moisture between (Re)Analyses over Summertime West Africa
Authors: Roberts Alexander J. , Marsham John H. , Knippertz Peter
Published: October 2014

Reanalysis and operational analysis products are routinely used as the best estimates of the atmospheric state for operational and research purposes. However, different models, assimilation techniques, and assimilated datasets lead to differences between products. Here, such differences in the distribution of low-level water vapor over summertime West Africa are analyzed, as reflected in the zonal mean position of the leading edge of the West African monsoon [the intertropical discontinuity (ITD)] using five reanalyses [NCEP–NCAR, NCEP–Department of Energy (DOE), the Modern-Era Retrospective Analysis for Research and Applications (MERRA), the Climate Forecast System Reanalysis (CFSR), and the Interim ECMWF Re-Analysis (ERA-Interim)] and two operational analyses [Global Forecast System (GFS) and ECMWF] during the 11 monsoon seasons (April–September) from 2000 to 2010. Specific humidity differences regularly reach 50% of the mean value over areas spanning hundreds of kilometers and often coincide with northward excursions of the ITD that last several days and bring unusual rainfall to the Sahel and Sahara. The largest disagreements occur during the southward retreat of the ITD and are connected with anomalously high values of aerosol optical depth, consistent with the production of haboob dust storms. The results suggest that known errors in the representation of moist convection and cold pools may contribute to the identified disagreements. A large reduction in disagreement occurs in 2006, when upper-air observations were enhanced during the African Monsoon Multidisciplinary Analysis (AMMA) campaign, pointing to an insufficient observational constraint of the (re)analyses in other years. It is hoped that this work will raise awareness of the limited reliability of (re)analysis products over West Africa during the summer, particularly during northward surges of the ITD, and will instigate further work to improve their quality.
Drawing Trauma
Authors: Farley Lisa , Mishra Tarc Aparna
Published: October 2014

Countertransference plays an often neglected role in witnessing children’s testimony of war and trauma. A dual notion of countertransference, based on the work of Winnicott and Klein, is offered that involves both internal conflict related to early life experience and socially mediated notions of childhood, war, and trauma circulating in a given time and place. A drawing by a thirteen-year-old boy living in the refugee camps in Darfur is used to show how countertransference affects our interpretation of the image, even while its symbolization in language establishes the conditions for a potentially therapeutic response. It is argued that a psychoanalytic reading can supplement the “legal-conscious terminology” in which the Darfur archive has been predominantly framed (Felman 2002, p. 5). This expanded view of witnessing involves reading the child’s testimony both for the history of violence it conveys and for the social and emotional histories it calls up in the witness as the ground and possibility of justice.
Resistant Bacteria in Middle Ear Fluid at the Time of Tympanotomy Tube Surgery
Authors: Sutton Darin V. , Derkay Craig S. , Darrow David H. , Strasnick Barry
Published: October 2014

This study was performed to determine the prevalence of resistant Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolated from middle ear fluid of children undergoing placement of ventilation tubes. The extent of resistance to commonly prescribed antibiotics and the risk factors associated with this resistance were also examined. Children who had fluid present in their middle ears at the time of ventilation tube placement from May 1996 to May 1997 were included in the study. Middle ear fluid was plated onto culture media in the operating room, and antimicrobial resistance of cultured organisms was ascertained. Risk factors for this resistance were determined from the medical history and analyzed. Cultures of 244 patients (355 ears) were positive for organisms in 29.6%. Penicillin resistance was found in 38.2% of S pneumoniae cultures. β-Lactamase production was found in 65.1% and 100% of H influenzae and M catarrhalis specimens, respectively. Risk factor analysis revealed young age, day care attendance, and number of antibiotic courses to most reliably predict the presence of resistant microorganisms.
Giant Cell Tumor of the Larynx
Authors: Hinni Michael L.
Published: October 2014

Giant cell tumors are benign tumors generally found in the long bones. Very rarely, they can occur in the larynx and may present with dysphonia, dysphagia, or dyspnea. A case of giant cell tumor of the larynx was recently identified and successfully treated by a partial laryngectomy. A literature review has revealed 18 case reports of giant cell tumor of the larynx. All cases occurred in men. These 19 cases are reviewed, and follow-up data presented where available. There have been no reports of recurrence regardless of treatment, and an excellent prognosis can be expected when one encounters this unusual laryngeal neoplasm.
Morphometric and Histochemical Study of the Human Vocal Muscle
Authors: Guida Heraldo Lorena , Zorzetto Neivo Luiz
Published: October 2014

The present study was conducted on vocal muscles removed at autopsy from adult individuals (10 men and 8 women, ages ranging from 48 to 78 years) with no laryngeal disease. Histologic analysis was performed with hematoxylin and eosin staining, and histochemical analysis was performed by nicotinamide-adenine-dinucleotide tetrazolium reductase, succinate dehydrogenase, and acid and alkaline myofibrillar adenosine triphosphatase reactions. The histochemical reactions showed that the muscle consists of slow-twitch oxidative (SO), fast-twitch glycolytic (FG), and fast-twitch glycolytic oxidative (FOG) fibers distributed in mosaic form. The frequencies of SO, FOG, and FG fibers were 40.50%, 54.75%, and 4.75%, respectively. The higher frequency of SO and FOG oxidative fibers characterizes the muscle as having aerobic metabolism, resistance to fatigue, and fast contraction. The mean minimum diameters were 31.37 μm for SO fibers and 36.46 μm for FOG and FG fibers.
Videoendoscopic Laryngeal Surgery
Authors: Omori Koichi , Tsuji Tomoko , Shinohara Kaoru , Kojima Hisayoshi
Published: October 2014

This paper introduces videoendoscope-assisted laryngeal surgery with office-based equipment. With this technique, a patient is seated and the nose, pharynx, and larynx are topically anesthetized. A flexible videoendoscope with a light-sensitive charge-coupled device chip built into the tip is transnasally inserted by an assistant. Specially designed fine-tipped forceps and scalpels were developed for removal of laryngeal lesions. Videoendoscopic laryngeal surgery was undertaken in 114 cases of laryngeal lesions such as polyps, granuloma, and cancer. For benign vocal fold lesions, postoperative vocal function was shown to be improved on aerodynamic and perceptual analyses. For laryngeal tumors, biopsy of the lesion was easily undertaken. Videoendoscopic laryngeal surgery presents the following advantages. It is applicable to outpatients not requiring general anesthesia, it enables functional monitoring of the patient's voice and vocal fold during phonation, it allows for delicate manipulations with both hands, and it gives high-resolution images in comparison to conventional fiberscopy.