bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential Role of DNA Methyltransferase 1–mediated Transcription of Insulin-like Growth Factor 2 in Resistance to Histone Deacetylase Inhibitors
Authors: Min Hye-Young , Lee Su-Chan , Woo Jong Kyu , Jung Hyun Jin , Park Kwan Hee , Jeong Hae Min , Hyun Seung Yeob , Cho Jaebeom , Lee Wooin , Park Ji Eun , Kwon So Jung , Lee Hyo-Jong , Ni Xiao , Shin Young Kee , Johnson Faye M. , Duvic Madeleine , Lee Ho-Young
Published: September 2016

Purpose: Histone deacetylase inhibitors (HDI) are promising anticancer therapies; however, drug resistance limits their efficacy. Here, we investigated the molecular mechanisms underlying HDI resistance, focusing on the mechanism of HDI-mediated induction of insulin-like growth factor 2 (IGF2) based on our previous study.

Experimental Design: The methylation status of CCCTC-binding factor (CTCF)-binding sites in the IGF2/H19 imprinting control region (ICR) were determined by methylation-specific PCR and bisulfite sequencing. The effectiveness of single or combinatorial blockade of DNA methyltransferase 1 (DNMT1) and histone deacetylase (HDAC) was evaluated using cell viability assay and patient-derived tumor xenograft (PDX) model.

Results: HDAC inhibition by vorinostat increased acetylated STAT3 (K685), resulting in transcriptional upregulation of DNMT1. DNMT1-mediated hypermethylation of CTCF-binding sites in the IGF2/H19 ICR decreased CTCF insulator activity, leading to a transcriptional upregulation of IGF2 and activation of the insulin-like growth factor 1 receptor (IGF-1R) pathway in cells with acquired or de novo vorinostat resistance. Strategies targeting DNMT1 diminished the IGF2 expression and potentiated vorinostat sensitivity in preclinical models of lung cancer with hypermethylation in the H19/IGF2 ICR. The degree of ICR hypermethylation correlated with vorinostat resistance in patient-derived lung tumors and in patients with hematologic malignancies.

Conclusions: DNMT1-mediated transcriptional upregulation of IGF2 is a novel mechanism of resistance to HDIs, highlighting the role of epigenetic deregulation of IGF2 in HDI resistance and the potential value of the H19/IGF2 ICR hypermethylation and DNMT1 expression as predictive biomarkers in HDI-based anticancer therapies. Clin Cancer Res; 23(5); 1299–311. ©2016 AACR.
Targeted Sequencing Reveals Low-Frequency Variants in EPHA Genes as Markers of Paclitaxel-Induced Peripheral Neuropathy
Authors: Apellániz-Ruiz María , Tejero Héctor , Inglada-Pérez Lucía , Sánchez-Barroso Lara , Gutiérrez-Gutiérrez Gerardo , Calvo Isabel , Castelo Beatriz , Redondo Andrés , García-Donás Jesús , Romero-Laorden Nuria , Sereno María , Merino María , Currás-Freixes María , Montero-Conde Cristina , Mancikova Veronika , Åvall-Lundqvist Elisabeth , Green Henrik , Al-Shahrour Fátima , Cascón Alberto , Robledo Mercedes , Rodríguez-Antona Cristina
Published: September 2016

Purpose: Neuropathy is the dose-limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for interindividual differences remain unexplained. In this study, we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.

Experimental Design: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics, and 30 Charcot–Marie–Tooth genes, in 228 cancer patients with no/low neuropathy or high-grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/gene-based analyses were used to compare variant frequencies among neuropathy groups, and Cox regression models were used to analyze neuropathy along treatment.

Results: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low-frequency nonsynonymous variants in EPHA6 were present exclusively in patients with high neuropathy, and all affected the ligand-binding domain of the protein. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency nonsynonymous variant carriers [HR, 14.60; 95% confidence interval (CI), 2.33–91.62; P = 0.0042], and an independent cohort confirmed an increased neuropathy risk (HR, 2.07; 95% CI, 1.14–3.77; P = 0.017). Combining the series gave an estimated 2.5-fold higher risk of neuropathy (95% CI, 1.46–4.31; P = 9.1 × 10−4).

Conclusions: This first study sequencing EPHA genes revealed that low-frequency variants in EPHA6, EPHA5, and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHA's neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs. Clin Cancer Res; 23(5); 1227–35. ©2016 AACR.
Complementing T-cell Function: An Inhibitory Role of the Complement System in T-cell–Mediated Antitumor Immunity
Authors: Peng Weiyi , McKenzie Jodi A. , Hwu Patrick
Published: September 2016

Summary: New data from Wang and colleagues show that complement C3 suppresses the function of CD8+ tumor-infiltrating T cells by inhibiting IL10 production, and targeting the complement receptors C3aR and C5aR enhances the antitumor activity of immune checkpoint blockade. Their results not only define a new role of complement receptors as T-cell coinhibitory receptors, but also are useful in the development of novel strategies to improve the effectiveness of cancer immunotherapy. Cancer Discov; 6(9); 953–5. ©2016 AACR.

See related article by Wang et al., p. 1022.
Endoscopic Approach for Superficial Colorectal Neoplasms
Authors: Xu Jun-feng , Yang Lang , Jin Peng , Sheng Jian-qiu
Published: September 2016

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, with an estimated 1.4 million cases and 693,900 deaths in 2012. Colonoscopy is the cornerstone for the detection and prevention of CRC. In addition, endoscopic treatment for CRC at an early stage can effectively improve patients' quality of life and cure rate. Summary: This review focuses on endoscopic approaches, including white light endoscopy, chromoendoscopy, magnifying endoscopy and therapeutic endoscopy, for the evaluation and treatment of superficial colorectal neoplasms. Key Message: Understanding the preoperative evaluation, indications and techniques of endoscopic mucosal resection/endoscopic submucosal dissection as well as postoperative surveillance for superficial colorectal neoplasms is critical for providing appropriate management to the patients. Practical Implications: Endoscopic therapy, a method preserving organ function and improving quality of life, is a widely applied microinvasive treatment for superficial colorectal neoplasms. This review describes the basics and developments of endoscopic approaches and may facilitate daily practice for superficial colorectal neoplasms.
Safety and Efficacy of Chitosan-Dextran Hydrogel in the Middle Ear in an Animal Model
Authors: Ünsaler Selin , Başaran Bora , Öztürk Sarı Şule , Kara Eyüp , Değer Kemal , Wormald Peter John
Published: September 2016

Objectives: To investigate the efficacy of chitosan-dextran hydrogel (CDH) in preventing postoperative adhesions between the tympanic membrane (TM) and intratympanic structures, and to evaluate its ototoxicity in an animal study. Methods: In the first step, ototoxicity was evaluated with 7 male albino guinea pigs (GPs) via auditory brainstem responses (ABR) before and 4 weeks after unilateral intratympanic injection of CDH and saline solution contralaterally. In the second step, 12 GPs underwent bilateral ear surgery. The middle ear (ME) mucosa was abraded, and the cavity was filled with CDH on one side and packed with Gelfoam on the contralateral side. A control group of 6 GPs underwent the same procedure except that no material was applied in the ME. The animals were euthanized at the end of the 7th week, and otomicroscopic findings were noted and the temporal bones harvested for the histologic examination. The findings were scored and compared. Results: There was no statistically significant difference between the pre- and postoperative ABR thresholds. In the otomicroscopic findings, the most prominent difference between the two groups was the presence of retraction of the TM in the Gelfoam group. The histopathologic findings revealed a higher degree of inflammation in the Gelfoam group compared with the CDH group. Conclusion: This study demonstrated that CDH has no ototoxic effects in GPs. Its use as an ME packing material revealed significantly less TM retraction and inflammatory reaction compared with Gelfoam.
Stratum Corneum Tape Stripping: Monitoring of Inflammatory Mediators in Atopic Dermatitis Patients Using Topical Therapy
Authors: Koppes Sjors A. , Brans Richard , Ljubojevic Hadzavdic Suzana , Frings-Dresen Monique H.W. , Rustemeyer Thomas , Kezic Sanja
Published: September 2016

Objective: The aim of this study was to explore the tape strip sampling technique in the assessment of stratum corneum levels of inflammatory mediators in a clinical trial setting. Methods: Thirty-eight inflammatory mediators were analyzed by a multiplex-assay in the stratum corneum, collected by adhesive tapes before and after 6 weeks of therapy, in mild and moderate atopic dermatitis (AD) patients (n = 90). Treatment was a ceramide- and magnesium-containing emollient. Results: Twenty-four mediators could quantitatively be determined. The Th2 mediators interleukin (IL)-4, IL-13, CCL2 (monocyte chemotactic protein-1), CCL22 (macrophage-derived chemokine), and CCL17 [thymus and activation-regulated chemokine (TARC)] were significantly decreased after therapy as well as IL-1β, IL-2, IL-8 (CXCL8), IL-10, acute-phase protein serum amyloid A, C-reactive protein, and vascular adhesion molecule-1. The decrease of CCL17 and IL-8 was correlated with the decrease in disease severity in a subgroup of moderate AD individuals. Conclusion: Stratum corneum tape stripping offers a minimally invasive approach for studying local levels of immunomodulatory molecules in the skin. CCL17 (TARC) and IL-8 were found to be the most promising biomarkers of AD and might be useful for investigating the course of skin diseases and the effect of local therapy.
Early Caries Predicts Low Oral Health-Related Quality of Life at a Later Age
Authors: Kragt Lea , van der Tas Justin T. , Moll Henriëtte A. , Elfrink Marlies E.C. , Jaddoe Vincent W.V. , Wolvius Eppo B. , Ongkosuwito Edwin M.
Published: September 2016

Oral health-related quality of life (OHRQOL) is the perceived impact of one's own oral health on daily life. Oral diseases influence children's OHRQOL directly, but OHRQOL might also be related to oral health experiences from the past. We investigate the relation between dental caries at the age of 6 with OHRQOL assessed at the age of 10. This study was conducted within the Generation R Study, a population-based prospective cohort study. Caries experience was assessed with the decayed, missing, and filled teeth index (dmft) at a median age of 6.09 years (90% range: 5.73-6.80). OHRQOL was assessed with a short form of the Child Oral Health Impact Profile at the children's age of 9.79 years (9.49-10.44). In total, 2,833 children participated in this study, of whom 472 (16.6%) had mild caries (dmft 1-3) and 228 (8.0%) had severe caries (dmft >3). The higher the dmft score at the age of 6, the lower the OHRQOL at the age of 10 (p < 0.001). The children with severe caries at the age of 6 had significantly higher odds of being in the lowest OHRQOL quartile at the age of 10 (OR = 1.69; 95% CI: 1.17-2.45). Our study highlights the importance of oral health during childhood, because those who get a compromised start to oral health are much more likely to follow a trajectory which will lead to poor oral health (-related QOL) later. OHRQOL is not only related to current oral health experiences but also to oral health experiences from the past.
Language Profile in Congenital Hypothyroid Children Receiving Replacement Therapy
Authors: Soliman Hend , Abdel Hady Aisha Fawzy , Abdel Hamid Asmaa , Mahmoud Heba
Published: September 2016

Objective: The aim of this work was to evaluate receptive and expressive language skills in children with congenital hypothyroidism receiving early hormonal replacement treatment before the age of 3 months and to identify any subtle areas of weaknesses in their language development to check the necessity for future language intervention. Patients and Methods: The study was conducted on 30 hypothyroid children receiving hormonal replacement. They were subdivided into group I (5-8 years 11 months; 12 cases) and group II (9-12 years 11 months; 18 cases). All patients were subjected to a protocol of assessment applied in the Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU) and evaluation of language skills by the REAL scale. Results: The younger group reached average Arabic language scores, while the older group showed moderate language delay. Conclusion: Early replacement therapy supports language development in young children. However, longitudinal and follow-up studies are required to identify difficulties presenting at older ages that may affect children in the academic settings.
PARK2 Microduplication: Clinical and Molecular Characterization of a Further Case and Review of the Literature
Authors: Palumbo Orazio , Palumbo Pietro , Leone Maria P. , Stallone Raffaella , Palladino Teresa , Vendemiale Marcella , Palladino Stefano , Papadia Francesco , Carella Massimo , Fischetto Rira
Published: September 2016

We report on a patient with psychomotor deficits, language delay, dyspraxia, skeletal anomalies, and facial dysmorphisms (hirsutism, right palpebral ptosis, a bulbous nasal tip with enlarged and anteverted nares, and a mild prominent antihelix stem). Using high-resolution SNP array analysis, we identified a 0.49-Mb microduplication in chromosome 6q26 inherited from the mother involving the PARK2 gene: arr[hg19] 6q26(162,672,821-163,163,143)×3 mat. To the best of our knowledge, this is the third patient to date described in whom a 6q26 microduplication encompassing only the PARK2 gene has been reported in medical literature. The PARK2 gene is a neurodevelopmental gene that was initially discovered as one of the causes of autosomal recessive juvenile Parkinson disease and subsequently reported to be linked to autism spectrum disorders and attention-deficit hyperactivity disorders. We provide an overview of the literature on PARK2 microduplications and further delineate the associated phenotype. Taken together, our findings confirm the involvement of this gene in neurodevelopmental disorders and are useful to strengthen the hypothesis that, although with variable expressivity and incomplete penetrance, the PARK2 microduplication is associated with a new emerging neurodevelopmental delay syndrome. However, clinical and molecular evaluations of more patients with the microduplication are needed for full delineation of this syndrome.
Longitudinal Executive Changes in Drivers with Parkinson's Disease: Study Using Neuropsychological and Driving Simulator Tasks
Authors: Ranchet Maud , Broussolle Emmanuel , Paire-Ficout Laurence
Published: September 2016

Background/Aims: (1) To investigate how specific executive functions change over 2 years in drivers with Parkinson's disease (PD) compared to controls, using both neuropsychological and driving simulator tasks; and (2) to explore the association between the decline of specific executive functions and changes in driving habits in PD. Methods: Sixteen PD patients and 21 controls underwent neuropsychological testing twice and performed tasks on a driving simulator, with an interval of approximately 2 years. Questions on participants' self-perception of their driving ability were administered. Results: A significant decline was observed in shift cost over time (Plus Minus Test) in patients (p = 0.008). This decline was greater in patients than in controls (p = 0.008). No significant change emerged over time in the flexibility cost of PD patients on a simulator (p = 0.158). Significant correlations were found between the decline in shift cost over time and driving question outcomes (p < 0.05). Conclusion: This study reveals a differential course of executive functions in PD. Over time, patients displayed significant decline in flexibility associated with modifications in their driving. Flexibility seems to be affected as the disease progresses. This research opens new avenues in cognitive and driving rehabilitation.
Clinical presentation and course of bleeding events in patients with venous thromboembolism, treated with apixaban or enoxaparin and warfarin
Authors: Cohen Alexander T. , Büller Harry R. , Agnelli Giancarlo , Gallus Alexander S. , Raskob Gary E. , Weitz Jeffrey I. , Curto Madelyn , Sisson Melanie , Middeldorp Saskia , Bleker Suzanne M.
Published: September 2016

Apixaban, a direct acting oral anticoagulant (DOAC), was found to be non-inferior to and safer as enoxaparin followed by warfarin for treatment of venous thromboembolism (VTE) in the AMPLIFY trial. Information is needed on how bleeding events with DOACs present and develop. In this post-hoc analysis, the clinical presentation and course of all major and clinically relevant non major (CRNM) bleeding events in the AMPLIFY trial were blindly classified by three investigators, using predesigned classification schemes containing four categories. Odds ratios (OR) for classifying as category three or four (representing a more severe clinical presentation and course) were calculated between apixaban and enoxaparin/warfarin. In total, 63 major and 311 CRNM bleeding events were classified. Of the major bleeds, a more severe clinical presentation occurred in 28.5% of apixaban versus 44.9% of enoxaparin/warfarin related recipients (OR 0.49, 95% confidence interval [CI] 0.14–1.78). A severe clinical course was observed in 14.3% and in 12.2%, respectively (OR 1.19, 95%CI 0.21–6.69). Of the CRNM bleeding events, a more severe clinical presentation and extent of clinical care was found in 25% of apixaban recipients compared to 22.7% in the enoxaparin/warfarin group (OR 1.13, 95%CI 0.65–1.97). The clinical presentation and course of major and CRNM bleeds were similar in apixaban and enoxaparin/warfarin treated patients. This finding should reassure physicians and patients that even in the absence of a specific reversal agent, apixaban is a convenient and safe choice for VTE.
Risk of myocardial infarction and death in patients with atrial fibrillation treated with dabigatran or vitamin K antagonists
Authors: Darwiche Walid , Bejan-Angoulvant Theodora , Angoulvant Denis , Babuty Dominique , Fauchier Laurent
Published: September 2016

The safety of dabigatran versus adjusted-dose vitamin K antagonist (VKA) treatment is the subject of debate. We evaluated the risk of myocardial infarction (MI) or mortality in patients with atrial fibrillation (AF) treated in clinical practice with dabigatran or a VKA. We performed a meta-analysis of observational studies that included an adjusted or matched analysis and reported MI, or death in AF patients treated with dabigatran or a VKA. Ten published analyses met the inclusion criteria. Of the 539,559 patients, 17,365 (3%) patients were on dabigatran 110 mg twice daily (bid), 150,948 (28%) were on dabigatran 150 mg bid, and 371,246 (69%) were on VKA. Adjusted risk for MI versus VKA was 0.71 (0.47–1.07; p=0.10) in patients starting oral anticoagulant (OAC) treatment with dabigatran 110 mg, 0.82 (0.71–0.96; p=0.01) in patients starting dabigatran 150 mg, 1.40 (1.04–1.88; p=0.03) in patients switching OAC treatment to dabigatran 110 mg, and 1.28 (0.88–1.87; p=0.19) in patients switching OAC treatment to dabigatran 150 mg, with statistical homogeneity in each subgroup. Risk of death was consistently lower in patients treated with dabigatran 110 mg (HR 0.79; 0.65–0.96; p=0.02) or 150 mg (HR 0.65; 0.57–0.73; p<0.00001) versus VKA. In conclusion, dabigatran use, as currently prescribed in routine practice for AF patients, was associated with a lower risk of MI in OAC-naïve patients treated with dabigatran 150 mg compared with VKA, and a higher risk of MI in patients switching from VKA to dabigatran 110 mg. Risk of death was lower in AF patients treated with either dose of dabigatran versus VKA.
“Unreal world” or “real world” data in oral anticoagulant treatment of atrial fibrillation
Authors: Lip Gregory Y. H. , Freedman Ben
Published: September 2016

Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.
Grupos minoritários, grupos vulneráveis e o problema da (in)tolerância: uma relação linguístico-discursiva e ideológica entre o desrespeito e a manifestação do ódio no contexto brasileiro
Authors: Carmo Cláudio Márcio do
Published: September 2016

O presente artigo consiste numa reflexão que parte do domínio conceitual do que se pode compreender por grupos minori­tários (ou minorias) e grupos vulneráveis, no que tange a duas problemáticas: a primeira diz respeito ao que se entende por (in)tolerância, e a outra, às questões ideológicas que perpassam um discurso que tem se tornado cada vez mais comum no Brasil, o discurso de ódio, com des­dobramentos na esfera comportamental que não condizem nem com os ideais democráti­cos nem com o respeito à dignidade humana.
Cartas e ficção, um capítulo da obra alencariana
Authors: Pereira Patrícia Regina Cavaleiro
Published: September 2016

Lendo a correspondência de José Martiniano de Alencar (1829-1877), deparamo-nos com um conjunto de quase trezentas missi­vas de naturezas e finalidades distintas: cartas reais e fictícias. Tais textos epistolares passa­ram pelas mãos de muitos receptores – desti­natários primordiais ou leitores secundários –, para quem o epistológrafo reservava diferentes formas de pronunciar-se, adequando o discur­so aos objetivos almejados em cada carta. Com este artigo, pretendemos trazer uma reflexão a respeito da persona epistolar alencariana e pensar de que forma José de Alencar utilizou a habilidade de escritor de cartas também na construção de suas tramas romanescas.
As cartas também constroem a história: potencialidades em uma conversa vinda do passado
Authors: Munhós Fernando
Published: September 2016

A carta, enquanto gênero discursivo oferecido aos pesquisadores como fonte documental de outros tempos e espaços, cumpre papel de relevo nas ciências humanas. As diversas áreas do conhecimento preocupadas com o passado, distante ou próximo, terão nas missivas ricos vestígios, a partir dos quais se pode investigar um tempo que não é o nosso. O estudo da carta vem ganhando relevo nos estudos universitários nas últimas décadas. Como gênero pouco louvável, como escrita não ficcional – secundária na mentalidade editorial –, ou como portador da máxima maleabilidade que lhe é atribuível –, pode caminhar do estilo mais complexo e rebuscado ao mais simples e desleixado, sem nenhum entrave –, esse, que é dentre os dispositivos discursivos o mais comum e corriqueiro, foi também o mais subestimado. Não é como a poesia, que possui um valor “estético” em si, ou como o documento oficial, o despacho, produzido pelos poderes estatais e nacionais, de valor histórico inquestionável.
Arqueologia da paisagem urbana: lógicas, ritmos e atores na construção do centro histórico de São Paulo (1809-1942)
Authors: Bueno Beatriz Piccolotto Siqueira
Published: September 2016

Sistemas de Informações Geográfi­cas (SIGs) permitem reconstituir paisagens ur­banas na longa duração. Os SIGs Históricos são fundamentais na espacialização de banco de dados complexos, viabilizando a elaboração de cartografias regressivas e temáticas – quadra a quadra, rua a rua, lote a lote –, cruzando infor­mações textuais e visuais. Propomo-nos a de­monstrar nossa metodologia e a linha teórica que a alicerça, bem como evidenciar os resulta­dos adquiridos, desenvolvendo novas pistas de pesquisa e contribuindo para uma melhor com­preensão do processo, das dinâmicas e ritmos de produção social da cidade do ponto de vista da sua dimensão material.
Efficacy of Intravenous Magnesium in Facilitating Cardioversion of Atrial Fibrillation
Authors: Rajagopalan Bharath , Shah Zubair , Narasimha Deepika , Bhatia Ashish , Kim Chee H. , Switzer Donald F. , Gudleski Gregory H. , Curtis Anne B.
Published: September 2016

Background—

Low serum magnesium (Mg) levels are associated with an increased risk of atrial fibrillation. Some studies have shown a benefit of Mg in facilitating pharmacological cardioversion. The role of an intravenous infusion of Mg alone in facilitating electric cardioversion is not clear.

Methods and Results—

In a prospective, randomized, double-blind, placebo-controlled trial, we enrolled patients with atrial fibrillation who were scheduled for electric cardioversion. Patients were randomized to receive Mg or placebo before cardioversion using a step-up protocol with 75, 100, 150, and 200 J biphasic shocks. Patients with hypokalemia, hypermagnesemia, or postcardiac surgery atrial fibrillation were excluded. Patients on antiarrhythmic drugs were included as long as they were at steady state. All patients were monitored for 1 hour post procedure for the maintenance of sinus rhythm. A total of 261 patients (69% male, mean age 65.5±11.1 years) were randomized (132 and 129 patients receiving Mg and placebo, respectively). Baseline characteristics were similar between both the groups. There was no statistically significant difference in the success rate of cardioversion between the 2 groups (86.4% versus 86.0%;
P
=0.94), cumulative amount of energy required for successful cardioversion (123.3±55.5 versus 129.5±52.6 J;
P
=0.40), or the number of shocks required to convert to sinus rhythm (2.25±1.24 versus 2.41±1.22,
P
=0.31). No adverse events were noted in either group.

Conclusions—

In patients undergoing electric cardioversion for persistent atrial fibrillation, Mg infusion does not increase the rate of successful cardioversion.

Clinical Trial Information—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT01597557.
Long-Term Outcomes of Carotid Artery Stenting in Clinical Practice
Authors: Mudra Harald , Staubach Stephan , Hein-Rothweiler Ralph , Segerer Manuela , Strohm Henning , Weber Hannes , Ledwoch Jakob
Published: September 2016

Background—

There is a lack of long-term data and data outside of controlled clinical trials in carotid artery stenting. Thus, we sought to evaluate the long-term effectiveness in stroke prevention by carotid artery stenting in a large number of patients in a real-world setting.

Methods and Results—

The present work represents an all-comer registry with a strict, prospectively designed, follow-up protocol, including an independent pre- and postprocedural neurological assessment. Between November 1999 and March 2015, 1000 procedures in 901 patients were consecutively performed in a single center. Mean age was 71±9 years, and symptomatic stenosis was present in 262 patients (29.1%). The population was also characterized by a high comorbidity: 289 patients (32.1%) would have been excluded according to the CREST protocol (Carotid Revascularization Endarterectomy Versus Stent Trial). The median length of follow-up was 5.5 (interquartile range, 2.6–7.9) years and complete in 93% of the patients. The rate of the primary end point (composite of stroke, death, and myocardial infarction [major adverse cardiac or cerebrovascular event] by day 30 plus ipsilateral stroke beyond 30 days) was 6.9% (9.9% in symptomatic versus 5.7% in asymptomatic patients;
P
=0.03). The rate was higher in CREST ineligible than in CREST eligible patients (11.4% versus 4.9%;
P
=0.001).

Conclusions—

Long-term stroke prevention by carotid artery stenting is effective in experienced centers. A high percentage of patients who would have been excluded from controlled clinical trials undergoes carotid artery stenting in daily clinical practice. However, these patients have a substantially higher risk for an acute major adverse cardiac or cerebrovascular event.
Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications
Authors: Ranque Brigitte , Menet Aymeric , Boutouyrie Pierre , Diop Ibrahima Bara , Kingue Samuel , Diarra Mamadou , N’Guetta Roland , Diallo Dapa , Diop Saliou , Diagne Ibrahima , Sanogo Ibrahima , Tolo Aissata , Chelo David , Wamba Guillaume , Gonzalez Jean Paul , Abough’elie Cochise , Diakite Cheick Oumar , Traore Youssouf , Legueun Gaëlle , Deme-Ly Indou , Faye Blaise Felix , Seck Moussa , Kouakou Boidy , Kamara Ismael , Le Jeune Sylvain , Jouven Xavier
Published: September 2016

Background:

Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We assessed arterial stiffness in SCD patients and looked for associations between arterial stiffness and SCD-related vascular complications.

Methods:

The CADRE (Coeur Artères et Drepanocytose, ie, Heart Arteries and Sickle Cell Disease) study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali, and Senegal. Patients underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumin/creatinine ratio measure, and a measure of carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AI) at a steady state. The clinical and biological correlates of cf-PWV and AI were investigated by using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries.

Results:

Included were 3627 patients with SCD and 943 controls. Mean cf-PWV was lower in SCD patients (7.5±2.0 m/s) than in controls (9.1±2.4 m/s,
P
<0.0001), and lower in SS-Sβ
0
than in SC-Sβ
+
phenotypes. AI, corrected for heart rate, increased more rapidly with age in SCD patients and was higher in SCD than in control adults. cf-PWV and AI were independently associated with age, sex, height, heart rate, mean blood pressure, hemoglobin level, country, and hemoglobin phenotype. After adjustment for these correlates, cf-PWV and AI were associated with the glomerular filtration rate and osteonecrosis. AI was also associated with stroke, pulmonary hypertension, and priapism, and cf-PWV was associated with microalbuminuria.

Conclusions:

PWV and AI are deeply modified in SCD patients in comparison with healthy controls. These changes are independently associated with a lower blood pressure and a higher heart rate but also with the hemoglobin phenotype. Moreover, PWV and AI are associated with several SCD clinical complications. Their prognostic value will be assessed at follow-up of the patients.
Information Technology and Lifestyle: A Systematic Evaluation of Internet and Mobile Interventions for Improving Diet, Physical Activity, Obesity, Tobacco, and Alcohol Use
Authors: Afshin Ashkan , Babalola Damilola , Mclean Mireille , Yu Zhi , Ma Wenjie , Chen Cheng‐Yu , Arabi Mandana , Mozaffarian Dariush
Published: September 2016

Background

Novel interventions are needed to improve lifestyle and prevent noncommunicable diseases, the leading cause of death and disability globally. This study aimed to systematically review, synthesize, and grade scientific evidence on effectiveness of novel information and communication technology to reduce
noncommunicable disease
risk.

Methods and Results

We systematically searched PubMed for studies evaluating the effect of Internet, mobile phone, personal sensors, or stand‐alone computer software on diet, physical activity, adiposity, tobacco, or alcohol use. We included all interventional and prospective observational studies conducted among generally healthy adults published between January 1990 and November 2013. American Heart Association criteria were used to evaluate and grade the strength of evidence. From 8654 abstracts, 224 relevant reports were identified. Internet and mobile interventions were most common. Internet interventions improved diet (N=20 studies) (Class
II
a A), physical activity (N=33), adiposity (N=35), tobacco (N=22), and excess alcohol (N=47) (Class I A each). Mobile interventions improved physical activity (N=6) and adiposity (N=3) (Class I A each). Evidence limitations included relatively brief durations (generally <6 months, nearly always <1 year), heterogeneity in intervention content and intensity, and limited representation from middle/low‐income countries.

Conclusions

Internet and mobile interventions improve important lifestyle behaviors up to 1 year. This systematic review supports the need for long‐term interventions to evaluate sustainability.
Effective Breeding Size and the Adaptive Significance of color Polymorphism in the Cricket Frog (Acris crepitans) in Illinois, U. S. A.
Authors: Gray Robert H.
Published: September 2016

A three year field study was conducted to investigate the adaptive significance of color polymorphism in the cricket frog, Acris crepitans, in Illinois, U. S. A. Effective population breeding sizes were determined at seven different locations. Population characteristics in Illinois were compared with those from Texas. The three color morphs appear to be of equal survival value for cricket frogs in Illinois. Although strong selection may occur in Texas, small effective breeding sizes suggest that chance plays a major role in determining color morph frequencies in Illinois.
Tail Regeneration in the Scincid Lizard, Mabuya carinata, related to Breeding Seasons and Thyroid Activity
Authors: Ramachandran A. V. , Swamy M. S. , Shah R. V.
Published: September 2016

The influence of two different seasons as well as of thyroid hormone on tail regeneration in Mabuya carinata has been evaluated by measuring the rate of growth of the regenerate at various time intervals. The analysis has revealed no apparent seasonal alteration in the final length attained at the end of 60 days. However, the average per day rate of growth indicates some difference between the late non-breeding and the early breeding phases. A better growth rate was noticeable in the non-breeding phase during the first 25 days (blastemic and differentiation phases) while it was better in the early breeding phase during the last 20 days of tail regeneration (late differentiation and growth phases). These observations correlate with the differential physiological and endocrine status characteristic of the two seasons. Hypothyroidic animals showed a 71% retardation of regenerative ability as compared to euthyroidic animals, which was however rectified by thyroxine replacement. Modes of action of thyroxine on lizard tail regeneration are discussed.
A New Species of Montane Rain Frog, Genus Eleutherodactylus (Leptodactylus), from Guerrero, Mexico
Authors: Savage Jay M.
Published: September 2016

Eleutherodactylus uno n. sp . is described from the oak-pine zone of the Sierra Madre del Sur, in the Mexican state of Guerrero . The new species cannot be associated with any currently recognized supraspecific division within the genus and demonstrates the unsatisfactory nature of attempts to cluster the approximately 400 known species into groups.
Bastardierung von Testudo horsfieldii (Gray) und Testudo h. h erman ni Gmelin.
Authors: Kirsche W.
Published: September 2016

Abstract. The egglaying (4 eggs) of a Testudo horsfieldii (1570g), which lives in a large outdoor enclosure since 1968, was observed. In a special breeding apparatus two hybrids hatched, the two other ones died in the shell. The parent's mating had not been observed. Fertile males of Testudo h. hermanni (7), Testudo horsfieldii (2) and Testudo graeca ibera (1) are living together in the enclosure with female tortoises. An analysis of the phenotype demonstrated the two hatchlings to be hybrids between T. horsfieldii and T. hermanni. The inauguration of a separate genus Agrionemys is critically discussed.

Zusammenfassung. Von einer beobachteten Eiablage (4 Eier) einer Testudo horsfieldii (1570g), die seit 1968 in einer grossen Freiland-Anlage lebt, schlüpften in einem speziellen Brutapparat zwei Bastarde, während 2 Embryonen abstarben. Die vorangegangene Paarung konnte nicht beobachtet werden. In der Anlage Ieben fertile ♂♂ von Testudo h. hermanni (7), Testudo horsfieldii (2) und Testudo graeca ibera (1) . Durch Merkmalsanalyse der Bas tarde konnte eine Kreuzung zwischen Testudo horsfieldii und Testudo h. hermanni nachgewiesen werden . Die Berechtigung einer eigenen Gattung Agrionemys fiir die Art h orsfieldii wird kritisch diskutiert.
Three new species of Oedura (Reptilia: Gekkonidae) from the Mitchell Plateau of North Western Australia
Authors: King Max
Published: September 2016

Three new species of the gekkonid genus Oedura, collected in the Mitchell plateau area of North Western Australia are described. These very distinctive animals are sympatric in their distribution, but differ markedly in size and morphology. They probably utilize different microhabitats.
Local Litigation Requirements in International Investment Agreements: Their Characteristics and Potential in Times of Reform in Latin America
Authors: Pérez Aznar Facundo
Published: September 2016

A number of international investment agreements (IIAs) set out a ‘local litigation requirement’, i.e. specify that recourse to investor-State arbitration becomes possible only after a certain period of time spent litigating in domestic courts. Numerous tribunals have dealt with this type of provision but they have followed different approaches as to its nature, function and scope, or as to whether non-compliance with it can be excused. This article focuses on the different aspects of local litigation requirement clauses in search of an interpretation that gives effectiveness to the provision, paying particular attention to the experience of Latin American countries and arbitral decisions discussing this topic, which in most cases involve countries from this region. It is argued that this precondition has an enormous potential to foster good governance and could serve to achieve a better coexistence between investor-State dispute settlement (ISDS) and local tribunals.
Acellular Dermal Matrix from Different Ages for Tissue Engineering Scaffold: Aged Prior to Young
Authors: Zhang Aijun , Chen Feifei , Jiang Tao , Tao Changbo , Li Xueyang , Jin Peisheng , Li Qiang
Published: September 2016

Acellular dermal matrix (ADM) scaffolds have been used in a series of tissue engineered products. However, due to the undesirable recellularization and vascularization, the use of ADM has been frequently linked to significant complications. In the present study, we prepared ADM from
different ages and examined the in vitro biological behavior and in vivo recellularization and vascularization. We compared the porosity of the ADM made from young and aged skin and found that aged ADM was more loose and porous than the young, the pore size was also more appropriate.
The in vitro coculture test of ADM and fibroblast showed that cells extended into the inside of ADM from the dermis surface and aged ADM was more able to support cell migration than the young. In a subcutaneously transplantation, aged ADM exhibited advantage over young ADM in cell penetration
depth of fibroblast, the inflammation reaction was also milder than the young. Moreover, immunofluorescence staining of vimentin and CD31 showed that aged ADM recellularized rapidly by vimentin and CD31 positive cells, the extent of cell penetration and capillary regeneration in old group
was higher than the young. Overall, this study highlights that aged ADM is more porous, the recellularization, revascularization and immunogenicity properties are superior to the young, it may be a more favorable tissue engineering scaffold than the young.
Biomolecule Modification of Scaffolds in Vascular Regeneration
Authors: Yao Yuan , Fan Jiabing , Sung Im Choong , Liu Haifeng , Fan Yubo
Published: September 2016

Vascular regeneration is thought to be crucial in the repair of damaged vessels as well as nonvascular tissues. A healthy endothelial layer provides homeostasis and prevents thrombosis in blood vessels. The variety of cells such as hematopoietic stem cells (HSCs), endothelial progenitor
cells (EPCs), and mature endothelial cells (ECs), are revealed to play an important role in forming an endothelial layer. There are a number of biomolecules that have been identified to be capable of attacting these cells to participate in vascular repair. In terms of these findings, alternative
strategies through the biomolecule modification of scaffold have been recently established to enhance in situ endothelialization for vascular regeneration. This article mainly reviews current and developing biomolecules that can be immobilized onto biomaterial surfaces to accelerate
in situ endothelialization for vascular repair, providing potentials in further discovering novel tissue engineering therapeutics for the treatment of human vascular diseases.
Tanshinone IIA Prevent Tendon Adhesion in the Rat Achilles Tendon Model
Authors: Lu Hui , Chen Qiang , Yang Hu , Shen Hui , Lin Xiang-Jin
Published: September 2016

Background: Tendon adhesion between the sheath and tendon surface is a common clinical problem. Orthopedist makes the improvement of repair techniques and rehabilitation to treat tendon adhesion, but it fails to cure completely. TSA was one of the major active phytochemicals
because of its anti-inflammatory activity. We used tanshinone IIA (TSA) for the prevention of tendon adhesion in the rat Achilles tendon model and investigated the possible mechanisms, including microRNAs (miRNAs) and protein expression via TGF-β/Smad signaling pathway. Method:
Sprague-Dawley (SD) rat Achilles tendons were half partial lacerated and sutured by a modified Kessler's technique, with TSA and normal saline for control. Macroscopic and histological evaluations were applied to examine the injured tendon six weeks after surgery. We evaluated the degree of
adhesion in Gross observation and the remodeling of collagen fibers by observing microscopically and determining the amount of scar formation. The expression of microRNAs (miRNAs) was quantified by real-time PCR detection and protein expression were quantified by western blotting detection.
Results: In gross evaluation of tendon adhesion, the TSA group had less adhesion appeared. No evidences of tendon rupture or local infection were observed. The content of collagen fibers in tendon tissue was decreased in TSA group compared with the control group, it indicated a significant
difference from the control group, P = 0.0004. The expression of miRNAs including miR-155, miR-29b, miR21, miR-133b and let7 were detected in the repaired tendon tissue, and only miR-29b treated with TSA was observed significantly higher than control group, P <0.0001. The
protein expression of TGF-β1 and p-Smad3 treated with TSA was lower than control group. Conclusions: The usage of TSA may be an efficient approach for preventing tendon adhesion.
Testing Atmospheric Oxidation in an Alabama Forest
Authors: Feiner Philip A. , Brune William H. , Miller David O. , Zhang Li , Cohen Ronald C. , Romer Paul S. , Goldstein Allen H. , Keutsch Frank N. , Skog Kate M. , Wennberg Paul O. , Nguyen Tran B. , Teng Alex P. , DeGouw Joost , Koss Abigail , Wild Robert J. , Brown Steven S. , Guenther Alex , Edgerton Eric , Baumann Karsten , Fry Juliane L.
Published: September 2016

The chemical species emitted by forests create complex atmospheric oxidation chemistry and influence global atmospheric oxidation capacity and climate. The Southern Oxidant and Aerosol Study (SOAS) provided an opportunity to test the oxidation chemistry in a forest where isoprene is the dominant biogenic volatile organic compound. Hydroxyl (OH) and hydroperoxyl (HO2) radicals were two of the hundreds of atmospheric chemical species measured, as was OH reactivity (the inverse of the OH lifetime). OH was measured by laser-induced fluorescence (LIF) and by taking the difference in signals without and with an OH scavenger that was added just outside the instrument’s pinhole inlet. To test whether the chemistry at SOAS can be simulated by current model mechanisms, OH and HO2 were evaluated with a box model using two chemical mechanisms: Master Chemical Mechanism, version 3.2 (MCMv3.2), augmented with explicit isoprene chemistry and MCMv3.3.1. Measured and modeled OH peak at about 106 cm−3 and agree well within combined uncertainties. Measured and modeled HO2 peak at about 27 pptv and also agree well within combined uncertainties. Median OH reactivity cycled between about 11 s−1 at dawn and about 26 s−1 during midafternoon. A good test of the oxidation chemistry is the balance between OH production and loss rates using measurements; this balance was observed to within uncertainties. These SOAS results provide strong evidence that the current isoprene mechanisms are consistent with measured OH and HO2 and, thus, capture significant aspects of the atmospheric oxidation chemistry in this isoprene-rich forest.
The Influence of Wind Direction on Campbell Scientific CSAT3 and Gill R3-50 Sonic Anemometer Measurements
Authors: Grare Laurent , Lenain Luc , Melville W. Kendall
Published: September 2016

Measurements from the Campbell CSAT3 and Gill R3-50 anemometers were conducted in four different experiments, in laboratory and field environments. Consistent differences between these two sonic anemometers were observed. The data have revealed that the differences were strongly correlated with the wind direction. According to the datasets used, the CSAT3 was the anemometer whose measurements were more sensitive to the instrument’s orientation relative to the wind direction. While the mean wind speed and direction remained within the manufacturers’ specifications (a few percent for the wind speed and a few degrees for the wind direction), the estimates of the friction velocity from the CSAT3 differed from the R3-50 by up to 20%.
The Role of Topographically Induced Vortices in Tropical Cyclone Formation over the Indian Ocean
Authors: Fine Caitlin M. , Johnson Richard H. , Ciesielski Paul E. , Taft Richard K.
Published: September 2016

The role of Sumatra and adjacent topographic features in tropical cyclone (TC) formation over the Indian Ocean (IO) is investigated. Sumatra, as well as the Malay Peninsula and Java, have mountainous terrain that partially blocks low-level flow under typical environmental stratification. For easterly low-level flow, these terrain features often produce lee vortices, some of which subsequently shed and move westward from the northern and southern tips of Sumatra and thence downstream over the IO. Since Sumatra straddles the equator, extending in a northwest–southeast direction from approximately 6°N to 6°S, the lee vortices, while counter-rotating, are both cyclonic. Hence, they can serve as initial disturbances that eventually contribute to TC formation over the IO. In addition, low-level, equatorial westerly flow impinging on Sumatra is also typically blocked and diverges, at times contributing to cyclonic circulations over the IO, primarily near the southern end of the island.

Data from two recent tropical campaigns, the 2008–10 Year of Tropical Convection (YOTC) and the 2011 Dynamics of the Madden–Julian Oscillation (DYNAMO), are used to study these phenomena. These datasets reveal the frequent occurrence of shed and nonshed terrain-induced cyclonic circulations over the IO, the majority of which occur during boreal fall and winter. During the 2.5 yr of the two campaigns, 13 wake vortices (13% of the shed circulations identified) were tracked and observed to subsequently develop into TCs over the northern and southern IO, accounting for 25% of the total TCs forming in the IO during that period.