bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous Glucagon-Like Peptide-1 as a Potential Mediator of the Resolution of Diabetic Kidney Disease following Roux en Y Gastric Bypass: Evidence and Perspectives
Authors: Docherty Neil G. , Le Roux Carel W.
Published: September 2014

Diabetic kidney disease in patients with type 2 diabetes strongly correlates with the incidence of major cardiovascular events and all-cause mortality. Pharmacological and lifestyle based management focusing on glycaemic, lipid, and blood pressure control is the mainstay of treatment but efficacy remains limited. Roux en Y gastric bypass is an efficacious intervention in diabetes. Emerging evidence also supports a role for bypass as an intervention for early diabetic kidney disease. This paper firstly presents level 1 evidence of the effects of bypass on hyperglycaemia and hypertension and then summarises emerging data on its effects on diabetic kidney disease. Glucagon-like peptide-1 is implicated as a central mediator of diabetes resolution following bypass through the incretin effect. It has been ascribed vasodilatory, pronatriuretic, and antioxidant properties and its exogenous administration or optimisation of its endogenous levels via dipeptidyl peptidase IV inhibition results in antioxidant and antiproteinuric effects in preclinical models of DKD. Some evidence is emerging of translation of coherent effects in the clinical setting. These findings raise the question of whether pharmacotherapy targeted at optimising circulating hormone levels may be capable of recapitulating some of the effects of bypass surgery on renal injury.
Tumor Suppression and Promotion by Autophagy
Authors: Ávalos Yenniffer , Canales Jimena , Bravo-Sagua Roberto , Criollo Alfredo , Lavandero Sergio , Quest Andrew F. G.
Published: September 2014

Autophagy is a highly regulated catabolic process that involves lysosomal degradation of proteins and organelles, mostly mitochondria, for the maintenance of cellular homeostasis and reduction of metabolic stress. Problems in the execution of this process are linked to different pathological conditions, such as neurodegeneration, aging, and cancer. Many of the proteins that regulate autophagy are either oncogenes or tumor suppressor proteins. Specifically, tumor suppressor genes that negatively regulate mTOR, such as PTEN, AMPK, LKB1, and TSC1/2 stimulate autophagy while, conversely, oncogenes that activate mTOR, such as class I PI3K, Ras, Rheb, and AKT, inhibit autophagy, suggesting that autophagy is a tumor suppressor mechanism. Consistent with this hypothesis, the inhibition of autophagy promotes oxidative stress, genomic instability, and tumorigenesis. Nevertheless, autophagy also functions as a cytoprotective mechanism under stress conditions, including hypoxia and nutrient starvation, that promotes tumor growth and resistance to chemotherapy in established tumors. Here, in this brief review, we will focus the discussion on this ambiguous role of autophagy in the development and progression of cancer.
Normoxic and Hyperoxic Cardiopulmonary Bypass in Congenital Heart Disease
Authors: Mokhtari Amir , Lewis Martin
Published: September 2014

Cyanotic congenital heart disease comprises a diverse spectrum of anatomical pathologies. Common to all, however, is chronic hypoxia before these lesions are operated upon when cardiopulmonary bypass is initiated. A range of functional and structural adaptations take place in the chronically hypoxic heart, which, whilst protective in the hypoxic state, are deleterious when the availability of oxygen to the myocardium is suddenly improved. Conventional cardiopulmonary bypass delivers hyperoxic perfusion to the myocardium and is associated with cardiac injury and systemic stress, whilst a normoxic perfusate protects against these insults.
Minimally Invasive Resection of an Extradural Far Lateral Lumbar Schwannoma with Zygapophyseal Joint Sparing: Surgical Nuances and Literature Review
Authors: Gonçalves Vítor M. , Santiago Bruno , Ferreira Vítor C. , Cunha e Sá Manuel
Published: September 2014

Introduction. Spinal schwannomas are benign nerve sheath tumors. Completely extradural schwannomas of the lumbar spine are extremely rare lesions, accounting for only 0,7–4,2% of all spinal NSTs. Standard open approaches have been used to treat these tumors, requiring extensive muscle dissection, laminectomy, radical foraminotomy, and facetectomy. In this paper the authors present the case of a minimally invasive resection of a completely extradural schwannoma. Operative technique literature review is presented.Material & Methods. A 50-year-old woman presented with progressive complains of chronic right leg pain and paresthesia. The magnetic resonance imaging revealed a giant well-encapsulated dumbbell-shaped extradural lesion at the L3-L4 level. The patient underwent a minimally invasive gross total resection of the tumor using a tubular expandable retractor system.Results. The patient had complete resolution of radiculopathy in the immediate postoperative period and she was discharged home, neurologically intact, on the second postoperative day. Postoperative MRI demonstrated no evidence of residual tumor. At latest follow-up (18 months) the patient remains asymptomatic.Conclusion. Although challenging, this minimally invasive procedure is safe and effective, being an appropriate alternative, with many potential advantages, to the open approach.
Gender-Dependent Effect of GSTM1 Genotype on Childhood Asthma Associated with Prenatal Tobacco Smoke Exposure
Authors: Wu Chih-Chiang , Ou Chia-Yu , Chang Jen-Chieh , Hsu Te-Yao , Kuo Ho-Chang , Liu Chieh-An , Wang Chih-Lu , Chuang Chia-Ju , Chuang Hau , Liang Hsiu-Mei , Yang Kuender D.
Published: September 2014

It remains unclear whether the GSTM1 genotype interacts with tobacco smoke exposure (TSE) in asthma development. This study aimed to investigate the interactions among GSTM1 genotype, gender, and prenatal TSE with regard to childhood asthma development. In a longitudinal birth cohort in Taiwan, 756 newborns completed a 6-year follow-up, and 591 children with DNA samples available for GSTM1 genotyping were included in the study,and the interactive influences of gender-GSTM1 genotyping-prenatal TSE on childhood asthma development were analyzed. Among these 591 children, 138 (23.4%) hadphysician-diagnosed asthmaat 6 years of age, and 347 (58.7%) werenull-GSTM1. Prenatal TSE significantly increased the prevalence of childhood asthma innull-GSTM1children relative to those withpositiveGSTM1. Further analysis showed that prenatal TSE significantly increased the risk of childhood asthma in girls withnull-GSTM1. Furthermore, among the children without prenatal TSE, girls withnull-GSTM1had a significantly lower risk of developing childhood asthma and a lower total IgE level at 6 years of age than those withpositiveGSTM1. This study demonstrates that the GSTM1 null genotype presents a protective effect against asthma development in girls, but the risk of asthma development increases significantly under prenatal TSE.
CBCT Evaluation of Bony Nasal Pyramid Dimensions in Iranian Population: A Comparative Study with Ethnic Groups
Authors: Zamani Naser Asieh , Panahi Boroujeni Mariyya
Published: September 2014

Background. The aim of the present study was to have normative data of nasal bone thickness for use before reconstructive surgery and nasal augmentation through radiography analysis. Methods and Materials. In this descriptive-analytical study, 74 patients were selected from people referred to Radiology Department of Isfahan University for CBCT examination in 2012. Patients with a history of nasal surgery or facial trauma and known congenital anomaly were excluded from the study. Height of nasal bone and width of pyriform aperture and nasal bone thickness in lateral and medial osteotomy line were measured. All these measurements were repeated by two radiologists; finally one sample t-test was performed. Results. The mean thickness of nasal bone on the lateral osteotomy line was 1.92 ± 0.29 mm in females and 1.73 ± 0.32 mm in males (P value = 0.39). The mean thickness of medial osteotomy line was 1.63 ± 0.47 mm in females and 1.94 ± 0.19 mm in males (P value = 0.31). The mean length of nasal bone was 23.5 ± 3.34 mm in females and 25.7 ± 2.96 mm in males (P value = 0.11). The mean width of pyriform aperture was 23.77 ± 2.58 mm in females and 25.67 ± 1.79 mm in males (P value = 0.25). Conclusions. The dimensions of nasal pyramid are known to be significant in choosing suitable osteotome size for reducing surgery side effect. Our results can be used for preoperative estimation of nasal bone dimension of people undergoing reconstructive surgery and augmentation.
Synthesis of an Anion-Exchange Membrane Based on Imidazolium-Type Ionic Liquids for a Capacitive Energy Extraction Donnan Potential Device
Authors: Kim Young-Seok , Choi Seong-Ho
Published: September 2014

Polymeric anion-exchange membranes (AEMs) were synthesized via the photocopolymerization of a vinyl imidazolium ionic liquid, with 1-butyl-3-(4-vinylbenzyl)imidazolium chloride ([BVBI][Cl]) as the anion-exchange group and styrene, acrylonitrile, and divinylbenzene as cross-linked agents. The physical, mechanical, and electrochemical properties of the prepared AEMs such as water uptake (%), swelling degree (%), ion-exchange capacity (mmol/g), thermal stability, tensile strength (Mpa), tensile modulus (Mpa), elongation (%), and ionic conductivity (S/cm) were evaluated. The synthesized AEMs were shown to have good physical, mechanical, and electrochemical properties for application of a capacitive energy extraction Donnan potential (CDP) device membrane. The CDP device was fabricated by using the synthesized AEM. The specific capacitance of the CDP device with AEM was determined as 2.53 F/g and 3.44 F/g by galvanostatic charge/discharge and cyclic voltammetry, respectively. The synthesized AEM with imidazolium ionic liquid can be applied as the CDP device membrane.
Biomarker Analysis Revealed Distinct Profiles of Innate and Adaptive Immunity in Infants with Ocular Lesions of Congenital Toxoplasmosis
Authors: Machado Anderson Silva , Carneiro Ana Carolina Aguiar Vasconcelos , Béla Samantha Ribeiro , Andrade Gláucia Manzan Queiroz , Vasconcelos-Santos Daniel Vitor , Januário José Nélio , Coelho-dos-Reis Jordana G. , Ferro Eloisa Amália Vieira , Teixeira-Carvalho Andréa , Vitor Ricardo Wagner Almeida , Martins-Filho Olindo Assis , Brazilian —UFMG-CTBG UFMG Congenital Toxoplasmosis Group
Published: September 2014

Toxoplasma gondiiis the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14+CD16+HLA-DRhighmonocytes andCD56dimcytotoxic NK-cells in ARL. Moreover, augmented TCRγδ+and CD8+T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8+T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis.
Frequency in Usage ofTerminologia AnatomicaTerms by Clinical Anatomists
Authors: Martin Bradford D. , Thorpe Donna , DeLuna Vanessa , Howard Trish , Hagemeyer Josh , Wilkins Nicholas
Published: September 2014

Almost 16 years since the publishing ofTerminologia Anatomica(TA) by the Federative Committee on Anatomical Terminology (FCAT), there has yet to be a unified adoption of TA-recommended anatomical terms by anatomists. A survey was sent to members of the American Association of Clinical Anatomists (AACA) to determine the frequency of TA term usage. Most respondents (70.3%) received their terminal degrees in anatomy, with 23.4% in clinical and anthropological areas. Academically ranked, most respondents were professors (38.4%) and most were from North America (81.1%). Almost 40% of respondents were textbook authors. Overall results indicate that the TA preferred term had the highest frequency of usage in only 53% of the anatomical structures/features surveyed. Compliance with TA preferred terms ranged from 98.2% to 3.6% usage. Almost 25% of AACA anatomists were not familiar with the FCAT and over 75% were concerned about synonymity in anatomical terminology. Data demonstrates that clinical anatomists of the AACA are not consistent in how they use anatomical terminology, as well as how they conform to TA terminology.
Calreticulin Promotes Migration and Invasion of Esophageal Cancer Cells by Upregulating Neuropilin-1 Expression via STAT5A
Authors: Shi Feng , Shang Li , Pan Bei-Qing , Wang Xiao-Min , Jiang Yan-Yi , Hao Jia-Jie , Zhang Yu , Cai Yan , Xu Xin , Zhan Qi-Min , Wang Ming-Rong
Published: September 2014

Purpose: We previously revealed that the calreticulin (CRT) gene is a candidate oncogene promoting cell migration and invasion and that neuropilin-1 (NRP1) is a possible effector downstream of CRT in esophageal squamous carcinoma cells. This study aims to explore the mechanisms underlying the migration and invasion of esophageal cancer cells regulated by CRT through NRP1.

Experimental Design: Quantitative reverse-transcription polymerase chain reaction, Western blot analysis, chromatin immunoprecipitation, and reporter gene assays were used to investigate the relationship between CRT and NRP1. In vitro and in vivo assays were carried out to evaluate the effects of NRP1 on malignant phenotypes of ESCC cells and tumor metastasis in NOD/SCID mice. Immunohistochemistry was performed to analyze the expression of CRT and NRP1 in esophageal squamous cell carcinomas (ESCC).

Results: Knockdown of CRT decreased the expression of NRP1. Inhibition of NRP1 reduced ESCC cell motility in vitro and experimental metastasis in vivo. Ectopic expression of NRP1 rescued the defects of cell migration and invasion in CRT-shRNA cells. CRT depletion inhibited STAT5A phosphorylation at the Y694 site via a CaMKII-independent pathway. Moreover, STAT5A directly regulated NRP1 transcription. Knockdown of CRT or NRP1 led to a downregulation of MMP2, MMP9, and FAK. Notably, positive correlation was found between CRT and NRP1 expression in ESCC tissues (P = 5.87 × 10−5). CRT and NRP1 coexpression was significantly associated with lymph node metastasis (P = 0.025).

Conclusions: Our findings suggest that NRP1 is a critical downstream effector of CRT in promoting cell migration and invasion, which might contribute to the metastasis of ESCC. Clin Cancer Res; 20(23); 6153–62. ©2014 AACR.
A Phase I, Dose-Finding Study in Patients with Advanced Solid Malignancies of the Oral γ-Secretase Inhibitor PF-03084014
Authors: Messersmith Wells A. , Shapiro Geoffrey I. , Cleary James M. , Jimeno Antonio , Dasari Arvind , Huang Bo , Shaik M. Naveed , Cesari Rossano , Zheng Xianxian , Reynolds Jennifer M. , English Patricia A. , McLachlan Karen R. , Kern Kenneth A. , LoRusso Patricia M.
Published: September 2014

Purpose: To estimate the maximum tolerated dose (MTD) for continuous oral administration of the γ-secretase inhibitor PF-03084014, determine the recommended phase II dose (RP2D), and evaluate safety and preliminary activity in patients with advanced solid tumors.

Experimental Design: This open-label, phase I study consisted of a dose-finding portion based on a 3+3 design, followed by an expansion cohort. PF-03084014 was administered orally, twice daily (BID) for 21 continuous days. Tested doses ranged from 20 to 330 mg BID. In the expansion cohort, patients were to receive the estimated MTD or a lower dose of PF-03084014.

Results: A total of 64 patients received treatment. The MTD was estimated to be 220 mg BID. The RP2D was determined to be 150 mg BID, based on the better safety profile versus the 220-mg BID dose, given comparable NOTCH-related target inhibition. The most common treatment-related adverse events were diarrhea, nausea, fatigue, hypophosphatemia, vomiting, rash, and decreased appetite, which were generally mild to moderate in severity. One patient with advanced thyroid cancer had a complete response, and five of seven response-evaluable patients with desmoid tumor achieved a partial response (71.4% objective response rate). Tumor responses were mostly durable, ranging from 1.74+ to 24+ months. PF-03084014 demonstrated a generally dose-dependent pharmacokinetic profile at doses ranging from 20 to 330 mg BID. Consistent downmodulation of NOTCH-related HES4 gene expression was observed in peripheral blood from all evaluable patients.

Conclusion: Further development of PF-03084014 for the treatment of patients with advanced solid tumors is warranted and currently under evaluation. Clin Cancer Res; 21(1); 60–67. ©2014 AACR.

See related commentary by Hughes et al., p. 7
Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers
Authors: Oberthuer André , Juraeva Dilafruz , Hero Barbara , Volland Ruth , Sterz Carolina , Schmidt Rene , Faldum Andreas , Kahlert Yvonne , Engesser Anne , Asgharzadeh Shahab , Seeger Robert , Ohira Miki , Nakagawara Akira , Scaruffi Paola , Tonini Gian Paolo , Janoueix-Lerosey Isabelle , Delattre Olivier , Schleiermacher Gudrun , Vandesompele Jo , Speleman Frank , Noguera Rosa , Piqueras Marta , Bénard Jean , Valent Alexander , Avigad Smadar , Yaniv Isaac , Grundy Richard G. , Ortmann Monika , Shao Chunxuan , Schwab Manfred , Eils Roland , Simon Thorsten , Theissen Jessica , Berthold Frank , Westermann Frank , Brors Benedikt , Fischer Matthias
Published: September 2014

Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression–based classification and established prognostic markers.

Experimental Design: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4 × 44 K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n = 634) by Kaplan–Meier estimates and Cox regression analyses.

Results: The best-performing classifier predicted patient outcome with an accuracy of 0.95 (sensitivity, 0.93; specificity, 0.97) in the validation cohort. The highest potential clinical value of this predictor was observed for current low-risk patients [5-year event-free survival (EFS), 0.84 ± 0.02 vs. 0.29 ± 0.10; 5-year overall survival (OS), 0.99 ± 0.01 vs. 0.76 ± 0.11; both P < 0.001] and intermediate-risk patients (5-year EFS, 0.88 ± 0.06 vs. 0.41 ± 0.10; 5-year OS, 1.0 vs. 0.70 ± 0.09; both P < 0.001). In multivariate Cox regression models for low-risk/intermediate-risk patients, the classifier outperformed risk assessment of the current German trial NB2004 [EFS: hazard ratio (HR), 5.07; 95% confidence interval (CI), 3.20–8.02; OS: HR, 25.54; 95% CI, 8.40–77.66; both P < 0.001]. On the basis of these findings, we propose to integrate the classifier into a revised risk stratification system for low-risk/intermediate-risk patients. According to this system, we identified novel subgroups with poor outcome (5-year EFS, 0.19 ± 0.08; 5-year OS, 0.59 ± 0.1), for whom we propose intensified treatment, and with beneficial outcome (5-year EFS, 0.87 ± 0.05; 5-year OS, 1.0), who may benefit from treatment de-escalation.

Conclusions: Combination of gene expression–based classification and established prognostic markers improves risk estimation of patients with low-risk/intermediate-risk neuroblastoma. We propose to implement our revised treatment stratification system in a prospective clinical trial. Clin Cancer Res; 21(8); 1904–15. ©2014 AACR.

See related commentary by Attiyeh and Maris, p. 1782
First-in-Human Study of CH5132799, an Oral Class I PI3K Inhibitor, Studying Toxicity, Pharmacokinetics, and Pharmacodynamics, in Patients with Metastatic Cancer
Authors: Blagden Sarah , Olmin Aurelius , Josephs Debra , Stavraka Chara , Zivi Andrea , Pinato David J. , Anthoney Alan , Decordova Shaun , Swales Karen , Riisnaes Ruth , Pope Lorna , Noguchi Kohei , Shiokawa Rie , Inatani Michiyasu , Prince Jenny , Jones Keith , Twelves Chris , Spicer James , Banerji Udai
Published: September 2014

Purpose: This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CH5132799.

Experimental Design: Patients with metastatic solid tumors were eligible for the study. CH5132799 was administered orally once daily or twice daily in 28-day cycles.

Results: Thirty-eight patients with solid tumors received CH5132799 at 2 to 96 mg once daily or 48 to 72 mg twice daily. The MTD was 48 mg on the twice-daily schedule but was not reached on the once daily schedule. DLTs were grade 3 elevated liver function tests (LFT), grade 3 fatigue, grade 3 encephalopathy, grade 3 diarrhea, and grade 3 diarrhea with grade 3 stomatitis; all DLTs were reversible. Most drug-related adverse events were grade 1/2. Diarrhea (34%) and nausea (32%) were the most common events. Mean Cmax and AUC0-24 in steady state at MTD were 175 ng/mL and 1,550 ng·h/mL, respectively, consistent with efficacious exposure based on preclinical modeling. Reduction in SUVmax with [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) was observed in 5 of 7 patients at MTD. A patient with PIK3CA-mutated clear cell carcinoma of the ovary achieved a partial response by GCIG CA125 criteria and further, a heavily pretreated patient with triple-negative breast cancer had marked improvement in her cutaneous skin lesions lasting six cycles.

Conclusion: CH5132799 is well tolerated at the MTD dose of 48 mg twice daily. At this dose, the drug had a favorable PK and PD profile and preliminary evidence of clinical activity. Clin Cancer Res; 20(23); 5908–17. ©2014 AACR.
Comparison of Brainstem Auditory Evoked Response at Different Click Rates between Preterm Babies after Neonatal Necrotizing Enterocolitis and Healthy Preterm Babies
Authors: Ping Li L. , Jiang Ze D.
Published: September 2014

Background: Neonatal necrotizing enterocolitis (NEC) is associated with an increased incidence of poor neurodevelopment. The knowledge of underlying neurophysiology is very limited, and the influence of NEC on the preterm brainstem is very poorly understood. Objective: To assess the effect of NEC on the immature auditory brainstem by excluding any possible confounding effect of preterm birth. Methods: We recorded and analyzed brainstem auditory evoked response (BAER) at different click rates in preterm babies (30-34 weeks gestation) after NEC. The results were compared with those in age-matched healthy preterm babies who had no NEC. Results: At click rate 21/s, the latencies of BAER waves I and III in the preterm NEC babies were similar to those babies without NEC. However, wave V latency was longer in the NEC babies than in those without NEC. The I-V interpeak interval was also longer in the NEC babies than in those without NEC. These abnormalities were persistent at higher click rates 51 and 91/s. Wave I amplitude in the preterm NEC babies did not differ significantly from that in those without NEC, but wave III and V amplitudes were smaller than in those without NEC at all 21-91/s clicks. Conclusions: Compared with healthy preterm babies, preterm babies after NEC showed a major increase in wave V latency and I-V interval at all 21-91/s clicks. Brainstem auditory function is impaired in preterm NEC babies after excluding the possible confounding effect of preterm birth. Neonatal NEC and associated perinatal conditions adversely affect the premature brainstem.
Pleomorphic Xanthoastrocytoma Arising from Olfactory Groove: A Rare Location for a Rare Tumor
Authors: Kaku Mayur V. , Bhat Dhananjaya I. , Shukla Dhaval , Mahadevan Anita , Devi B. Indira
Published: September 2014

Pleomorphic xanthoastrocytomas (PXAs) are a rare variety of WHO grade II gliomas in children and young adults. The common site of location of PXAs is temporal or cortical. We present a rare case of PXA presenting as anterior cranial fossa (ACF) base lesion. A 7-year-old male presented with a history of a single episode of generalized tonic-clonic seizures and anosmia of 1 year's duration. An MRI of the brain revealed a large solid and cystic tumor in the ACF base with leptomeningeal involvement. The origin of the tumor could not be made out. The patient underwent parasagittal frontal craniotomy and gross total resection of the tumor. The tumor was parenchymal, involving both frontal lobes. It seemed to have been arising from the olfactory groove region. The solid portion of the tumor was also adherent to the falx and basal dura. He recovered completely following surgery. The postoperative period was uneventful. Histopathology was suggestive of PXA with high mitotic index. There was no recurrence of tumor at 6 months' follow-up. He is under close follow-up and will be offered radiotherapy if the tumor recurs. No PXAs arising from this location have been reported previously, and it is important to be aware of this possibility in children presenting with seizures and MRI which shows a solid cystic lesion superficially located in the ACF base region.
Evaluation of Tumor Progression and Detection of New Tumors during Repeat Gamma Knife® Stereotactic Radiosurgery Utilizing the Co-Registration Tool in Leksell Gamma Plan®: Technical Note
Authors: Monaco III Edward A. , Bhatnagar Jagdish P. , Xu Yuanguang , Arai Yoshio , Niranjan Ajay , Huq M. Saiful , Lunsford L. Dade
Published: September 2014

Background: Repeat Gamma Knife stereotactic radiosurgery (GKSR) procedures are becoming common, especially for brain metastases. It is important to identify tumors requiring treatment at repeat GKSR and it can be challenging to distinguish treated tumors, tumor progression and new tumors. Using the image co-registration tool within the Leksell Gamma Plan software, we developed a technique to aid in the identification of tumors needing treatment. Objectives: The objective was to explore a new co-registration technique to identify tumors requiring treatment at repeat GKSR procedures. Methods: Ten patients who underwent repeat GKSR for brain metastases were identified. Contrast-enhanced volumetric T1 magnetic resonance images (MRI) from the previous GKSR were co-registered with the new images and the resulting two-color format image was used to evaluate tumor status. Results: Using the co-registered images, tumors were characterized as: resolved, regressed, stable, larger or new. Overall, 13.6% of tumors completely resolved, 26.2% regressed, 13.1% remained stable, while 7.9% progressed. Thirty-nine percent of tumors were new. Conclusions: The co-registration technique makes clinically relevant changes conspicuous on MRI. It distinguishes between tumors potentially requiring treatment and those that have been treated successfully. It can be used with tumors other than metastases and for evaluating tumor response at follow-up.
Age-Related Changes in Visceral Patterns Associated with Anxiety Disorders or Depression according to Traditional Chinese Medicine
Authors: Kondo Tetsuya , Yoshimasu Kouichi , Tokunaga Shoji , Sugahara Hideyo , Kanemitsu Yoshio , Kubo Chiharu
Published: September 2014

Background: Since, to our knowledge, there is no report on age-related changes in the patterns associated with anxiety and mood disorders, a large-size case-control study was conducted. Methods: A total of 914 new cases were assessed at a psychosomatic clinic of a tertiary medical care center. The severity of visceral patterns was analyzed according to the main symptoms described and a comprehensive questionnaire. Patterns of the liver (three), heart (four), and kidney (one) as well as dual deficiency of the heart and spleen were assessed. Results: In females under 40 years of age, liver qi depression and phlegm fire harassing the heart were associated with generalized anxiety disorder. Liver fire flaming upward was associated with all forms of anxiety disorders in this group. Phlegm fire harassing the heart was associated with depression and all forms of mood disorders in females over 40 years of age, while it was inversely associated in males over 40 years of age. Conclusion: The order of the traditional Chinese patterns resulting in anxiety or mood disorders was consistent with the development of liver qi depression into liver fire flaming upward or phlegm fire harassing the heart according to the traditional Chinese theory. The patterns associated with depression and all forms of mood disorders vary according to age and sex.
Clinical Research in Surgery: Threats and Opportunities
Authors: Ceelen Wim P.
Published: September 2014

Surgery is a discipline which profoundly affects human integrity. Therefore, there is an ethical and scientific imperative that surgical practice depends on the best possible trial-based evidence. Traditionally, the quality and quantity of clinical research have been lagging behind other disciplines in clinical medicine. However, recent collaborative initiatives, such as the IDEAL framework which tests surgical innovation, international registries, and quality assurance platforms, the development of modified randomized controlled trials and alternative trial designs as well as the impending reforms of the regulatory framework surrounding nonpharmaceutical interventions and devices offer significant and timely opportunities to enhance the relevance of clinical research in surgery. Here, we provide an overview of the current state of clinical research in surgery, identify possible obstacles, and discuss realistic and emerging solutions that have the potential to change the way surgical research is organized, funded, and translated to the patient's benefit.
Differential impact of unrecognised brain infarction on stroke outcome in non-valvular atrial fibrillation
Authors: Song Tae-Jin , Kim Jinkwon , Lee Hye Sun , Nam Chung Mo , Nam Hyo Seok , Kim Eun Hye , Lee Ki Jeong , Song Dongbeom , Heo Ji Hoe , Kim Young Dae
Published: September 2014

There has been little information regarding the impact of unrecognised brain infarctions (UBIs) on stroke outcome in patients with nonvalvular atrial fibrillation (NVAF). By using volumetric analysis of ischaemic lesions, we evaluated the potential impact of UBIs on clinical outcome according to their presence and categorised type. This study enrolled 631 patients with NVAF having no clinical stroke history. UBIs were categorised into three types as territorial, lacunar, or subcortical. We collected stroke severity, functional outcome at three months, and the total volume of UBIs and acute infarction lesions. We investigated the association between clinical outcome and the type or volume of UBI, using a linear mixed model and logistic regression analysis. UBIs were detected in 285 (45.2 %) patients; territorial UBIs were observed in 24.4 % of patients (154/631), lacunar UBIs in 25 % (158/631), and subcortical UBIs in 15.7 % (99/631). Although initial stroke severity was not different between patients with UBIs and those without, those with UBIs had less improvement during hospitalisation, leading to poorer outcome at three months. Among the three types of UBIs, only territorial UBIs were associated with poor outcome, especially in patients with relatively smaller acute infarction volume. UBIs, in particular, territorial UBIs, may be considered as predictors for poor outcome after ischaemic stroke in patients with NVAF. Our results suggest that the impact of UBIs on clinical outcome differs according to the type of UBIs and the acute stroke severity.
How to improve the concept of individualised antiplatelet therapy with P2Y12 receptor inhibitors – is an algorithm the answer?
Authors: Trenk Dietmar , Schrör Karsten , Gawaz Meinrad , Kristensen Steen D. , Storey Robert F. , Huber Kurt , Siller-Matula Jolanta M. ,   for the European Platelet Academy
Published: September 2014

Within the past decade, high on-treatment platelet reactivity (HTPR) on clopidogrel and its clinical implications have been frequently discussed. Although it has been previously assumed that HTPR is a phenomenon occurring only in patients treated with clopidogrel, recent data show that HTPR might also occur during treatment with prasugrel or ticagrelor in the acute phase of ST-elevation myocardial infarction. Moreover, it has been postulated that there is a therapeutic window for P2Y12 receptor blockers, thus indicating that HTPR is associated with thrombotic events whereas low on-treatment platelet reactivity (LTPR) is associated with bleeding events. The current paper focuses on tools to identify risk factors for HTPR (pharmacogenomic testing, clinical scoring and drug-drug interactions) and on the use of platelet function testing in order to identify patients who might not respond adequately to clopidogrel. The majority of recent clinical randomised trials have not supported the hypothesis that platelet function testing and tailored antiplatelet therapy are providing a favourable clinical outcome. These trials, mainly performed in low-to-moderate risk patients, will be reviewed and discussed. Finally, an algorithm based on current knowledge is suggested, which might be of use for design of clinical trials.
Selected CD133
+
Progenitor Cells to Promote Angiogenesis in Patients With Refractory Angina
Authors: Jimenez-Quevedo Pilar , Gonzalez-Ferrer Juan Jose , Sabate Manel , Garcia-Moll Xavier , Delgado-Bolton Roberto , Llorente Leopoldo , Bernardo Esther , Ortega-Pozzi Aranzazu , Hernandez-Antolin Rosana , Alfonso Fernando , Gonzalo Nieves , Escaned Javier , Bañuelos Camino , Regueiro Ander , Marin Pedro , Fernandez-Ortiz Antonio , Neves Barbara Das , del Trigo Maria , Fernandez Cristina , Tejerina Teresa , Redondo Santiago , Garcia Eulogio , Macaya Carlos
Published: September 2014

Rationale:

Refractory angina constitutes a clinical problem.

Objective:

The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133
+
cells to foster angiogenesis in patients with refractory angina.

Methods and Results:

In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133
+
cells or no treatment. The primary end point was the safety of transendocardial injection of CD133
+
cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, −8.5 [95% confidence interval, −15.0 to −4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, −1.0 [95% confidence interval, −1.9 to −0.1]) but not in the control arm.

Conclusions:

Our findings support feasibility and safety of transendocardial injection of CD133
+
cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.
Miyazakia, a new aphid genus from Japan (Hemiptera: Aphididae: Macrosiphini)
Authors: Stekolshchikov Andrey V.
Published: September 2014

Miyazakia gen. nov. with type species Miyazakia ranunculi (Miyazaki, 1971) comb. nov. is described. The species is illustrated and biometric data are provided for all morphs, except the fundatrix. This aphid genus is closely related to Sappaphis Matsumura, 1919. M. ranunculi is a heteroecious species; its primary host is probably Photinia villosa (Thunb.) DC and its secondary host is Ranunculus.
First record of the velvet ants (Hymenoptera: Mutillidae) reared from puparia of the ber fruit fly Carpomya vesuviana Costa (Diptera: Tephritidae) in Iran
Authors: AMINI ALIEH , LELEJ ARKADY S. , SADEGHI HUSSEIN , KARIMI JAVAD
Published: September 2014

Two species of mutillids, Smicromyrme (Astomyrme) nikolskajae Lelej, 1985 and S. (Eremotilla) tekensis Skorikov, 1935, reared from puparia of ber fruit fly, Carpomya vesuviana Costa, in South Khorasan, Iran are recorded. Both mutillids are newly recorded from Iran. An overview of eight species of mutillids associated with six species of flies is given in the appendix.
Two new endemic species of Lygaeinae from Baja California, Mexico (Hemiptera: Heteroptera: Lygaeidae)
Authors: PEREDO LUIS CERVANTES , Brailovsky Harry
Published: September 2014

Two new species of Lygaeinae endemic to the Peninsula of Baja California, Mexico, are described. Dalmochrimnus insularis sp. nov. endemic to San Ildefonso Island in the Gulf of California and Melacoryphus lagunensis sp. nov. endemic to the Reserve area of Sierra La Laguna in the South of the Peninsula. A discussion about their relationships within their genera and their endemic status is also provided.
Gentrification and Violent Crime in New York City
Authors: Barton Michael S.
Published: September 2014

Research has frequently referenced the influence of gentrification on crime, but only a few studies empirically assessed this relationship. Recent research has utilized innovative measures of gentrification and advanced statistical techniques, but many questions remain unanswered. One such question is whether and to what extent gentrification influenced crime in New York City. The current study used a quantitative operationalization of gentrification that was grounded in qualitative information and hybrid fixed-effects regression to assess whether changes in violent crime rates in New York City were associated with gentrification. Results indicate that sub-boroughs that experienced greater rates of gentrification featured significantly larger declines in assault, homicide, and robbery and that this relationship did not vary significantly over time.
A petition-like application? Rhetoric and rationing documents in wartime Delhi, 1941–45
Authors: Sriraman Tarangini
Published: September 2014

This article looks at rhetorical devices employed by certain classes of claimants in applications for rationed commodities in wartime Delhi in the last decade of colonial rule. In the face of a war-driven colonial frenzy to regulate and constrict all essential and non-essential commodities, rhetoric in application-writing flourished. The covering letters accompanying application forms for rations resembled petitions in their appeals to sovereignty, their affinity to rhetorical parlance, the scope they extended to applicants to exploit colonial structures of bureaucratic authority and their role in shaping the formation of cultural subjectivities. This turn to rhetoric was equally implicit in colonial responses to requests for supplementary rations which were phrased in turgid and caustic prose that drew out the various rationalities of the war and colonial rule while taking cognizance of the encumbrances and cultural imperatives of the everyday. Rhetorical thrusts were not confined to the written requests accompanying the application form. The forms for rationed commodities like motor spirit, electricity, tyres and tubes were themselves peppered with persuasive graphic signs and artifacts that enacted certain relationships between the document and the rule, between intermediate and higher authorities, between applicants and rationed commodities.
The Dark Period: Myth or reality?
Authors: Gillet Valérie
Published: September 2014

This article is an attempt to reconsider the widespread concept of a Dark Period in the Tamil-speaking South between the third and sixth centuries of the Common Era. Archaeological, epigraphical and literary evidence from the first few centuries before the common era to the seventh century are gathered here and carefully analysed, showing no actual interruption. A decrease in the amount of data may easily be explained as the result of a change of practices—such as the use of perishable materials for buildings, for example. An important part of this article focuses on the Kaḷabhra dynasty, often thought to have been responsible for this so-called Dark Period. However, in the light of an accurate reading of peculiar passage of the Paṇḍyan copper-plates of Vēḷvikuṭi on which K.A. Nilakantha Sastri elaborated, probably for the first time, the concept of a Kaḷabhra interregnum responsible for the Dark Period, and after recontextualising this passage in the eighth-century South Indian history, it appears that the notion of a ‘break’ in the history of South India, as well as the three-century rule of an obscure dynasty, does not withstand a fact based investigation.
Book Review: Neeti Nair, Changing Homelands: Hindu Politics and the Partition of India
Authors: Kamtekar Indivar
Published: September 2014

NEETI NAIR, Changing Homelands: Hindu Politics and the Partition of India, Ranikhet: Permanent Black, 2011, pp. 343.
Identification and Performance Management
Authors: Campbell Jesse W.
Published: September 2014

This study develops a theoretical framework linking performance management (PM) to change-oriented organizational citizenship behavior, an extra-role employee activity aimed at improving organizational functioning by introducing micro-level change. The role of organizational identification as a mediating mechanism linking PM to change-oriented behavior is also explored. Using survey data gathered from employees of central government ministries in South Korea, structural equation modeling and bias-corrected bootstrap confidence intervals are used to test a number of empirical hypotheses related to the constructs mentioned above. The results of the analysis suggest that PM has a positive effect on change-oriented behavior, but that its effect is primarily due to its positive relationship with identification. Following a presentation of the results of the analysis, the theoretical and practical implications of this study are discussed.
Vacuum-assisted breast biopsy with 7-gauge, 8-gauge, 9-gauge, 10-gauge, and 11-gauge needles: how many specimens are necessary?
Authors: Preibsch Heike , Baur Astrid , Wietek Beate M , Krämer Bernhard , Staebler Annette , Claussen Claus D , Siegmann-Luz Katja C
Published: September 2014

Background

Published national and international guidelines and consensus meetings on the use of vacuum-assisted biopsy (VAB) give different recommendations regarding the required numbers of tissue specimens depending on needle size and imaging method.

Purpose

To evaluate the weights of specimens obtained with different VAB needles to facilitate the translation of the required number of specimens between different breast biopsy systems and needle sizes, respectively.

Material and Methods

Five different VAB systems and seven different needle sizes were used: Mammotome® (11-gauge (G), 8-G), Vacora® (10-G), ATEC Sapphire™ (9-G), 8-G Mammotome® Revolve™, and EnCor Enspire® (10-G, 7-G). We took 24 (11-G) or 20 (7–10-G) tissue cores from a turkey breast phantom. The mean weight of a single tissue core was calculated for each needle size. A matrix, which allows the translation of the required number of tissue cores for different needle sizes, was generated. Results were compared to the true cumulative tissue weights of consecutively harvested tissue cores.

Results

The mean tissue weights obtained with the 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G Revolve™ / 7-G needles were 0.084 g / 0.142 g / 0.221 g / 0.121 g / 0.192 g / 0.334 g / 0.363 g, respectively. The calculated required numbers of VAB tissue cores for each needle size build the matrix. For example, the minimum calculated number of required cores according to the current German S3 guideline is 20 / 12 / 8 / 14 / 9 / 5 / 5 for needles of 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G Revolve™ / 7-G size. These numbers agree with the true cumulative tissue weights.

Conclusion

The presented matrix facilitates the translation of the required number of VAB specimens between different needle sizes and thereby eases the implementation of current guidelines and consensus recommendations into clinical practice.
Polycystic Kidneys and GM2 Gangliosidosis-Like Disease in Neonatal Springboks (Antidorcas marsupialis)
Authors: Herder V. , Kummrow M. , Leeb T. , Sewell A. C. , Hansmann F. , Lehmbecker A. , Wohlsein P. , Baumgärtner W.
Published: September 2014

Clinical, gross, histopathologic, electron microscopic findings and enzymatic analysis of 4 captive, juvenile springboks ( Antidorcas marsupialis) showing both polycystic kidneys and a storage disease are described. Springbok offspring (4 of 34; 12%) were affected by either one or both disorders in a German zoo within a period of 5 years (2008–2013). Macroscopic findings included bilaterally severely enlarged kidneys displaying numerous cysts in 4 animals and superior brachygnathism in 2 animals. Histopathologically, kidneys of 4 animals displayed cystic dilation of the renal tubules. In addition, abundant cytoplasmic vacuoles with a diameter ranging from 2 to 10 μm in neurons of the central and peripheral nervous system, hepatocytes, thyroid follicular epithelial cells, pancreatic islets of Langerhans and renal tubular cells were found in 2 springbok neonates indicative of an additional storage disease. Ultrastructurally, round electron-lucent vacuoles, up to 4 μm in diameter, were present in neurons. Enzymatic analysis of liver and kidney tissue of 1 affected springbok revealed a reduced activity of total hexosaminidase (Hex) with relatively increased HexA activity at the same level of total Hex, suggesting a hexosaminidase defect. Pedigree analysis suggested a monogenic autosomal recessive inheritance for both diseases. In summary, related springboks showed 2 different changes resembling both polycystic kidney and a GM2 gangliosidosis similar to the human Sandhoff disease. Whether the simultaneous occurrence of these 2 entities represents an incidental finding or has a genetic link needs to be investigated in future studies.