bluuebunny/crossref_metadata_2025 huggingface dataset:
Djulis (Chenopodium formosanum Koidz.) Water Extract and Its Bioactive Components Ameliorate Dermal Damage in UVB-Irradiated Skin Models
Authors: Hong Yong-Han , Huang Ya-Ling , Liu Yao-Cheng , Tsai Pi-Jen
Published: October 2016

Dermal photoaging is a condition of skin suffering inappropriate ultraviolet (UV) exposure and exerts inflammation, tissue alterations, redness, swelling, and uncomfortable feelings. Djulis (Chenopodium formosanum Koidz.) is a cereal food and its antioxidant and pigment constituents may provide skin protection from photoaging, but it still lacks proved experiments. In this study, protective effects of djulis extract (CFE) on UVB-irradiated skin were explored. The results showed that HaCaT cells with 150 μg/mL CFE treatment had higher survival and less production of interleukin- (IL-) 6, matrix metalloprotease- (MMP-) 1, and reactive oxygen species (ROS) in UVB-irradiated conditions. Subsequently, in animal studies, mice supplemented with CFE (100 mg/kg BW) were under UVB irradiation and had thinner epidermis and lower IL-6 levels in skin layer. These data demonstrate that bioactive compounds possessing the potency of antiphotoaging exist in CFE. Following that, we found rutin and chlorogenic acid (10–100 μM) could significantly increase cell viability and decrease the production of IL-6 in UVB models. Additionally, djulis pigment-betanin has no effect of increasing cell viability in this study. Our findings suggest CFE can protect skin against UV-induced damage and this protection is mainly from contributions of rutin and chlorogenic acid.
Effects of Reynolds and Womersley Numbers on the Hemodynamics of Intracranial Aneurysms
Authors: Asgharzadeh Hafez , Borazjani Iman
Published: October 2016

The effects of Reynolds and Womersley numbers on the hemodynamics of two simplified intracranial aneurysms (IAs), that is, sidewall and bifurcation IAs, and a patient-specific IA are investigated using computational fluid dynamics. For this purpose, we carried out three numerical experiments for each IA with various Reynolds (Re=145.45to378.79) and Womersley (Wo=7.4to9.96) numbers. Although the dominant flow feature, which is the vortex ring formation, is similar for all test cases here, the propagation of the vortex ring is controlled by bothReandWoin both simplified IAs (bifurcation and sidewall) and the patient-specific IA. The location of the vortex ring in all tested IAs is shown to be proportional toRe/Wo2which is in agreement with empirical formulations for the location of a vortex ring in a tank. In sidewall IAs, the oscillatory shear index is shown to increase withWoand1/Rebecause the vortex reached the distal wall later in the cycle (higher resident time). However, this trend was not observed in the bifurcation IA because the stresses were dominated by particle trapping structures, which were absent at lowRe=151.51in contrast to higherRe=378.79.
Active Vibration Control and Coupled Vibration Analysis of a Parallel Manipulator with Multiple Flexible Links
Authors: Zhang Quan , Li Chaodong , Zhang Jiantao , Jin Jiamei
Published: October 2016

This paper addresses the active vibration control and coupled vibration analysis of a planar parallel manipulator (PPM) with three flexible links. Multiple piezoelectric ceramic transducers are integrated with the flexible links to constitute the smart beam structures, and hence the vibration of the flexible link can be self-sensed and self-controlled. To prevent the spillover phenomena and improve the vibration control efficiency, the independent modal space control combined with an input shaper is developed to suppress both the structural and the residual vibration of the flexible links. The coupled vibration features between rigid and elastic motions and the interaction effects among three flexible links are theoretically analyzed based on the one-pass rigid-flexible dynamic models. Numerical simulation and experiment results show that the vibration of the three flexible links is coupled through the moving platform and the vibration suppression efficiency is getting improved with the number of controlled flexible links increased.
Jacobi Stability Analysis of Scalar Field Models with Minimal Coupling to Gravity in a Cosmological Background
Authors: Dănilă Bogdan , Harko Tiberiu , Mak Man Kwong , Pantaragphong Praiboon , Sabau Sorin V.
Published: October 2016

We study the stability of the cosmological scalar field models by using the Jacobi stability analysis, or the Kosambi-Cartan-Chern (KCC) theory. In this approach, we describe the time evolution of the scalar field cosmologies in geometric terms, by performing a “second geometrization” and considering them as paths of a semispray. By introducing a nonlinear connection and a Berwald-type connection associated with the Friedmann and Klein-Gordon equations, five geometrical invariants can be constructed, with the second invariant giving the Jacobi stability of the cosmological model. We obtain all the relevant geometric quantities, and we formulate the condition for Jacobi stability in scalar field cosmologies. We consider the Jacobi stability properties of the scalar fields with exponential and Higgs type potential. The Universe dominated by a scalar field exponential potential is in Jacobi unstable state, while the cosmological evolution in the presence of Higgs fields has alternating stable and unstable phases. We also investigate the stability of the phantom quintessence and tachyonic scalar field models, by lifting the first-order system to the tangent bundle. It turns out that in the presence of a power law potential both of these models are Jacobi unstable during the entire cosmological evolution.
Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2‐Mediated Oxidative Stress and NLRP3 Inflammatory Pathway
Authors: Dong Zhaojun , Shang Haixiao , Chen Yong Q. , Pan Li-Long , Bhatia Madhav , Sun Jia
Published: October 2016

Acute pancreatitis (AP) is characterized by early activation of intra‐acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP. We found that SFN administration attenuated pancreatic injury as evidenced by serum amylase, pancreatic edema, and myeloperoxidase, as well as by histological examination. SFN administration reverted AP‐associated dysregulation of oxidative stress markers including pancreatic malondialdehyde and redox enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In acinar cells, SFN treatment upregulated nuclear factor erythroid 2‐related factor 2 (Nrf2) expression and Nrf2‐regulated redox genes including quinoneoxidoreductase‐1, heme oxidase‐1, SOD1, and GPx1. In addition, SFN selectively suppressed cerulein‐induced activation of the nucleotide‐binding domain leucine‐rich repeat containing family, pyrin domain‐containing 3 (NLRP3) inflammasome, in parallel with reduced nuclear factor‐ (NF‐) κB activation and modulated NF‐κB‐responsive cytokine expression. Together, our data suggested that SFN modulates Nrf2‐mediated oxidative stress and NLRP3/NF‐κB inflammatory pathways in acinar cells, thereby protecting against AP.
Climate Change Is Increasing the Risk of the Reemergence of Malaria in Romania
Authors: Ivanescu Larisa , Bodale Ilie , Florescu Simin-Aysel , Roman Constantin , Acatrinei Dumitru , Miron Liviu
Published: October 2016

The climatic modifications lead to global warming; favouring the risk of the appearance and development of diseases are considered until now tropical diseases. Another important factor is the workers’ immigration, the economic crisis favouring the passive transmission of new species of culicidae from different areas. Malaria is the disease with the widest distribution in the globe. Millions of people are infected every year in Africa, India, South-East Asia, Middle East, and Central and South America, with more than 41% of the global population under the risk of infestation with malaria. The increase of the number of local cases reported in 2007–2011 indicates that the conditions can favour the high local transmission in the affected areas. In the situation presented, the establishment of the level of risk concerning the reemergence of malaria in Romania becomes a priority.
Digital Rectal Examination and Balloon Expulsion Test in the Study of Defecatory Disorders: Are They Suitable as Screening or Excluding Tests?
Authors: Caetano Ana C. , Santa-Cruz André , Rolanda Carla
Published: October 2016

Background. Rome III criteria add physiological criteria to symptom-based criteria of chronic constipation (CC) for the diagnosis of defecatory disorders (DD). However, a gold-standard test is still lacking and physiological examination is expensive and time-consuming. Aim. Evaluate the usefulness of two low-cost tests—digital rectal examination (DRE) and balloon expulsion test (BET)—as screening or excluding tests of DD. Methods. We performed a systematic search in PUBMED and MEDLINE. We selected studies where constipated patients were evaluated by DRE or BET. Heterogeneity was assessed and random effect models were used to calculate the sensitivity, specificity, and negative predictive value (NPV) of the DRE and the BET. Results. Thirteen studies evaluating BET and four studies evaluating DRE (2329 patients) were selected. High heterogeneity (I2>80%) among studies was demonstrated. The studies evaluating the BET showed a sensitivity and specificity of 67% and 80%, respectively. Regarding the DRE, a sensitivity of 80% and specificity of 84% were calculated. NPV of 72% for the BET and NPV of 64% for the DRE were estimated. The sensitivity and specificity were similar when we restrict the analysis to studies using Rome criteria to define CC. The BET seems to perform better when a cut-off time of 2 minutes is used and when it is compared with a combination of physiological tests. Considering the DRE, strict criteria seem to improve the sensitivity but not the specificity of the test. Conclusion. Neither of the low-cost tests seems suitable for screening or excluding DD.
Cost Analysis of Precast and Cast-in-Place Concrete Construction for Selected Public Buildings in Ghana
Authors: Asamoah Richard Oduro , Ankrah John Solomon , Offei-Nyako Kofi , Tutu Ernest Osei
Published: October 2016

The construction industry in Ghana is becoming efficient in the area of cost and achieving advance technologies. The effective management of cost enables clients, developers, and facilitators to achieve value for money. Concrete is a major component in every construction project. The use of precast concrete technology has been embraced by the construction industry in Ghana. This study seeks to analyze cost estimating of the structural frame (column and slab) by considering cast-in-place and precast concrete slabs and columns, respectively. Relative importance and Kendall’s concordance agreement were used to determine the rankings and agreement of advantages of using precast concrete. The study established that precast concrete slabs were on average 23.22% cheaper than the cast-in-place concrete elements and precast columns were averagely 21.4% less than cast-in-place concrete columns. The study established that professionals prefer the use of precast concrete products because of the life cycle cost.
Novel Approach for Enterocutaneous Fistula Treatment with the Use of Viable Cryopreserved Placental Membrane
Authors: Nichols Frederick , Overly Aaron
Published: October 2016

Enterocutaneous fistulas (ECF) are a difficult and costly surgical complication to manage. The standard treatment ofnil per os(NPO) and total paraenteral nutrition (TPN) is not well tolerated by patients. TPN is also known for complications associated with long term central venous catheterization and for high cost of prolonged hospital stay. We present two low output ECF cases successfully treated with viable cryopreserved placental membrane (vCPM) placed into the fistula tracts. One patient is a 59-year-old male with a low output ECF from a jejunostomy tube site four weeks after the surgery. The second patient is an 87-year-old male with a low output ECF following a small bowel resection secondary to a strangulated inguinal hernia. He was evaluated on day 41 after surgery. NPO and TPN for several weeks did not resolute the ECF. The fistulae were closed postoperatively in both patients with zero output on the same day after one vCPM application. On day 3 postoperatively both patients were started on clear liquid diets and subsequently advanced to regular diets. The ECF have remained resolved for over 2 months. The use of vCPM is a novel promising approach for treatment of ECF.
Assessing Availability in Wireless Visual Sensor Networks Based on Targets’ Perimeters Coverage
Authors: Costa Daniel G. , Duran-Faundez Cristian
Published: October 2016

Availability in wireless visual sensor networks is a major design issue that is directly related to applications monitoring quality. For targets monitoring, visual sensors may be deployed to cover most or all of targets, and monitoring quality may be focused on how well a set of targets are being covered. However, targets may have different dimensions and it is expected that large targets may be only partially viewed by source nodes, which may affect coverage quality and lead to a state of unavailability. In this context, this article analyzes the effect of target’s size on effective coverage in wireless visual sensor networks. A new coverage metric, the Effective Target Viewing (ETV), is proposed to measure monitoring quality over a set of targets, which is exploited as a fundamental parameter for availability assessment. Results show that ETV can be used as a practical coverage metric when assessing availability in wireless visual sensor networks.
Convolutional Deep Belief Networks for Single-Cell/Object Tracking in Computational Biology and Computer Vision
Authors: Zhong Bineng , Pan Shengnan , Zhang Hongbo , Wang Tian , Du Jixiang , Chen Duansheng , Cao Liujuan
Published: October 2016

In this paper, we propose deep architecture to dynamically learn the most discriminative features from data for both single-cell and object tracking in computational biology and computer vision. Firstly, the discriminative features are automatically learned via a convolutional deep belief network (CDBN). Secondly, we design a simple yet effective method to transfer features learned from CDBNs on the source tasks for generic purpose to the object tracking tasks using only limited amount of training data. Finally, to alleviate the tracker drifting problem caused by model updating, we jointly consider three different types of positive samples. Extensive experiments validate the robustness and effectiveness of the proposed method.
Diagnosis and Treatment of Neurological and Ischemic Disorders Employing Carbon Nanotube Technology
Authors: Komane Patrick P. , Choonara Yahya E. , du Toit Lisa C. , Kumar Pradeep , Kondiah Pierre P. D. , Modi Girish , Pillay Viness
Published: October 2016

Extensive research on carbon nanotubes has been conducted due to their excellent physicochemical properties. Based on their outstanding physicochemical properties, carbon nanotubes have the potential to be employed as theranostic tools for neurological pathologies such as Alzheimer’s disease and Parkinson’s disease including ischemic stroke diagnosis and treatment. Stroke is currently regarded as the third root cause of death and the leading source of immobility around the globe. The development and improvement of efficient and effective procedures for central nervous system disease diagnosis and treatment is necessitated. The main aim of this review is to discuss the application of nanotechnology, specifically carbon nanotubes, to the diagnosis and treatment of neurological disorders with an emphasis on ischemic stroke. Areas covered include the conventional current diagnosis and treatment of neurological disorders, as well as a critical review of the application of carbon nanotubes in the diagnosis and treatment of ischemic stroke, covering areas such as functionalization of carbon nanotubes and carbon nanotube-based biosensors. A broad perspective on carbon nanotube stimuli-responsiveness, carbon nanotube toxicity, and commercially available carbon nanotubes is provided. Potential future studies employing carbon nanotubes have been discussed, evaluating their extent of advancement in the diagnosis and treatment of neurological and ischemic disorders.
Effect of Interleukin-15 on CD11b, CD54, and CD62L Expression on Natural Killer Cell and Natural Killer T-Like Cells in Systemic Lupus Erythematosus
Authors: Lin Syh-Jae , Chen Ji-Yih , Kuo Ming-Ling , Hsiao Hsiu-Shan , Lee Pei-Tzu , Huang Jing-Long
Published: October 2016

Adhesion molecules may play an important role in systemic lupus erythematosus (SLE) pathogenesis. We investigated the effect of interleukin- (IL-) 15 on CD11b, CD54, and CD62L expression on natural killer (NK) cells, T cells, and CD56+CD3+NKT-like cells from SLE subjects and healthy controls. SLE patients had decreased circulating NK cells and NKT-like cells compared to controls. NK cells from SLE patients showed higher CD11b and CD62L expression compared to controls. IL-15 enhanced CD11b and CD54 but downregulated CD62L expression on NK cells from SLE patients. Similar observations were found for T cells and NKT-like cells. NK cells from SLE patients expressed higher CD56 than controls; both could be further enhanced by IL-15. IL-15 also enhanced CD56 expression of NKT-like cells from SLE patients. A greater degree of IL-15 induced downregulation of CD62L on NKT-like cells noted in SLE patients compared to controls. The percentage of CD11b expressing NK cells and the % inhibition of CD62L expression on NKT-like cells by IL-15 correlated with serum anti-dsDNA levels in SLE patients, respectively. Taken together, we demonstrated the dysfunctional NK and NKT-like cells in SLE patients with regard to CD11b and CD62L expression and their response to IL-15.
Spontaneous Regression of Choroidal Neovascularization in a Patient with Pattern Dystrophy
Authors: Anastasakis Anastasios , Goleni Flamur , Livir-Rallatos Gerasimos , Livir-Rallatos Charalampos , Zafirakis Panagiotis , Allen Fishman Gerald
Published: October 2016

Purpose. To present a case of a patient with pattern dystrophy (PD) associated choroidal neovascularization (CNV) that resolved spontaneously without treatment.Methods. A 69-year-old male patient was referred to our unit, for evaluation of a recent visual loss (metamorphopsias) in his left eye. Fundus examination, fundus autofluorescence imaging, and fluorescein angiography showed a choroidal neovascular membrane in his left eye. Since visual acuity was satisfactory the patient elected observation. Clinical examination and OCT testing were repeated at 6 and 12 months after presentation.Results. Visual acuity remained stable at the level of 0.9 (baseline BCVA) during the follow-up period (12 months). Repeat OCT testing showed complete spontaneous regression of the choroidal neovascular membrane without evidence of intra- or subretinal fluid in both follow-up visits.Conclusions. Spontaneous regression of choroidal neovascularization can occur in patients with retinal dystrophies and associated choroidal neovascular membranes. The decision to treat or observe these patients relies strongly on the presenting visual acuity, since, in isolated instances, spontaneous resolution of choroidal neovascularization may occur.
KLF6 Suppresses Metastasis of Clear Cell Renal Cell Carcinoma via Transcriptional Repression of E2F1
Authors: Gao Yu , Li Hongzhao , Ma Xin , Fan Yang , Ni Dong , Zhang Yu , Huang Qingbo , Liu Kan , Li Xintao , Wang Lei , Gu Liangyou , Yao Yuanxin , Ai Qing , Du Qingshan , Song Erlin , Zhang Xu
Published: October 2016

The transcription factor KLF6 has an essential role in the development and metastasis of multiple human cancers. Paradoxically, KLF6 expression was found to be attenuated in primary metastatic clear cell renal cell carcinoma (ccRCC), such that it is unclear how KLF6 affects malignant progression in this setting. In this study, we demonstrate that KLF6 attenuation in renal cells is sufficient to promote E2F1-mediated epithelial–mesenchymal transition and metastatic prowess. In a mouse xenograft model of human ccRCC, silencing KLF6 increased tumor cell proliferation and malignant character, whereas E2F1 silencing reversed these properties. These effects were corroborated in a metastatic model system, where we observed a greater number of pulmonary metastatic lesions formed by ccRCC cells where KLF6 was silenced and E2F1 enforced. Analysis of clinical specimens of ccRCC revealed that low levels of KLF6 and high levels of E2F1 correlated closely with ccRCC development. Overall, our results established the significance of activating the KLF6–E2F1 axis in aggressive ccRCC, defining a novel critical signaling mechanism that drives human ccRCC invasion and metastasis. Cancer Res; 77(2); 330–42. ©2016 AACR.
Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms
Authors: Babic Ana , Bao Ying , Qian Zhi Rong , Yuan Chen , Giovannucci Edward L. , Aschard Hugues , Kraft Peter , Amundadottir Laufey T. , Stolzenberg-Solomon Rachael , Morales-Oyarvide Vicente , Ng Kimmie , Stampfer Meir J. , Ogino Shuji , Buring Julie E. , Sesso Howard D. , Gaziano John Michael , Rifai Nader , Pollak Michael N. , Anderson Matthew L. , Cochrane Barbara B. , Luo Juhua , Manson JoAnn E. , Fuchs Charles S. , Wolpin Brian M.
Published: October 2016

Leptin is an adipokine involved in regulating energy balance, which has been identified as a potential biologic link in the development of obesity-associated cancers, such as pancreatic cancer. In this prospective, nested case–control study of 470 cases and 1,094 controls from five U.S. cohorts, we used conditional logistic regression to evaluate pancreatic cancer risk by prediagnostic plasma leptin, adjusting for race/ethnicity, diabetes, body mass index, physical activity, plasma C-peptide, adiponectin, and 25-hydroxyvitamin D. Because of known differences in leptin levels by gender, analyses were conducted separately for men and women. We also evaluated associations between 32 tagging SNPs in the leptin receptor (LEPR) gene and pancreatic cancer risk. Leptin levels were higher in female versus male control participants (median, 20.8 vs. 6.7 ng/mL; P < 0.0001). Among men, plasma leptin was positively associated with pancreatic cancer risk and those in the top quintile had a multivariable-adjusted OR of 3.02 [95% confidence interval (CI), 1.27–7.16; Ptrend = 0.02] compared with men in the bottom quintile. Among women, circulating leptin was not associated with pancreatic cancer risk (Ptrend = 0.21). Results were similar across cohorts (Pheterogeneity = 0.88 for two male cohorts and 0.35 for three female cohorts). In genetic analyses, rs10493380 in LEPR was associated with increased pancreatic cancer risk among women, with an OR per minor allele of 1.54 (95% CI, 1.18–2.02; multiple hypothesis-corrected P = 0.03). No SNPs were significantly associated with risk in men. In conclusion, higher prediagnostic levels of plasma leptin were associated with an elevated risk of pancreatic cancer among men, but not among women. Cancer Res; 76(24); 7160–7. ©2016 AACR.
T-cell Receptor Signaling Activates an ITK/NF-κB/GATA-3 axis in T-cell Lymphomas Facilitating Resistance to Chemotherapy
Authors: Wang Tianjiao , Lu Ye , Polk Avery , Chowdhury Pinki , Zamalloa Carlos Murga , Fujiwara Hiroshi , Suemori Koichiro , Beyersdorf Niklas , Hristov Alexandra C. , Lim Megan S. , Bailey Nathanael G. , Wilcox Ryan A.
Published: October 2016

Purpose: T-cell lymphomas are a molecularly heterogeneous group of non-Hodgkin lymphomas (NHL) that account for a disproportionate number of NHL disease-related deaths due to their inherent and acquired resistance to standard multiagent chemotherapy regimens. Despite their molecular heterogeneity and frequent loss of various T cell–specific receptors, the T-cell antigen receptor is retained in the majority of these lymphomas. As T-cell receptor (TCR) engagement activates a number of signaling pathways and transcription factors that regulate T-cell growth and survival, we examined the TCR's role in mediating resistance to chemotherapy.

Experimental Design: Genetic and pharmacologic strategies were utilized to determine the contribution of tyrosine kinases and transcription factors activated in conventional T cells following TCR engagement in acquired chemotherapy resistance in primary T-cell lymphoma cells and patient-derived cell lines.

Results: Here, we report that TCR signaling activates a signaling axis that includes ITK, NF-κB, and GATA-3 and promotes chemotherapy resistance.

Conclusions: These observations have significant therapeutic implications, as pharmacologic inhibition of ITK prevented the activation of this signaling axis and overcame chemotherapy resistance. Clin Cancer Res; 23(10); 2506–15. ©2016 AACR.
Deep Brain Stimulation of the Caudal Zona Incerta: Tremor Control in Relation to the Location of Stimulation Fields
Authors: Fytagoridis Anders , Åström Mattias , Samuelsson Jennifer , Blomstedt Patric
Published: October 2016

Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.
Review on Factors Affecting Targeting Accuracy of Deep Brain Stimulation Electrode Implantation between 2001 and 2015
Authors: Li Zhe , Zhang Jian-Guo , Ye Yan , Li Xiaoping
Published: October 2016

Background: Accurate implantation of a depth electrode into the brain is of the greatest importance in deep brain stimulation (DBS), and various stereotactic systems have been developed for electrode implantation. However, an updated analysis of depth electrode implantation in the modern era of DBS is lacking. Objective: This study aims at providing an updated review on targeting accuracy of DBS electrode implantation by analyzing contemporary DBS electrode implantation operations from the perspective of precision engineering. Methods: Eligible articles with information on targeting accuracy of DBS electrode implantation were searched in the PubMed database. Results: An average targeting error of DBS electrode implantation is reported to decrease toward 1 mm; the standard deviation of targeting error is decreasing toward 0.5 mm. Targeting accuracy is not only found to be affected by individual surgical steps, but also systematically affected by the architecture of the implantation operation. Conclusion: A systematic strategy should be adopted to further improve the targeting accuracy of depth electrode implantation. Attention should be paid to optimizing the whole electrode implantation operation, which can help minimize error accumulation or amplification throughout the serially connected procedures for DBS electrode implantation.
Clinical Application of Biomarkers in Heart Failure with a Preserved Ejection Fraction: A Review
Authors: Garg Aakash , Virmani Deepti , Agrawal Sahil , Agarwal Chirag , Sharma Abhishek , Stefanini Giulio , Kostis John B.
Published: October 2016

Heart failure with a preserved ejection fraction (HFpEF) is increasingly prevalent and a leading cause of morbidity and mortality worldwide. HFpEF has a complex pathophysiology, with recent evidence suggesting that an interaction of cardiovascular and noncardiovascular comorbidities (e.g. obesity, hypertension, diabetes, coronary artery disease, and chronic kidney disease) induces an inflammatory state that eventually leads to myocardial structural and functional alterations. Current ACCF/AHA guidelines suggest incorporation of biomarkers along with clinical and imaging tools to establish the diagnosis and disease severity in heart failure (HF). However, the majority of data on biomarkers relating to their levels, or their role in accurate diagnosis, prognostication, and disease activity, has been derived from studies in undifferentiated HF or HF with a reduced EF (HFrEF). As the understanding of the mechanisms underlying HFpEF continues to evolve, biomarkers reflecting different pathways including neurohormonal activation, myocardial injury, inflammation, and fibrosis have a clinical utility beyond the diagnostic scope. Accordingly, in this review article we describe the various established and novel plasma biomarkers and their emerging value in diagnosis, prognosis, response, and guiding of targeted therapy in patients with HFpEF.
Safety, Tolerability and Clinical Effects of a Rapid Dose Titration of Subcutaneous Treprostinil Therapy in Pulmonary Arterial Hypertension: A Prospective Multi-Centre Trial
Authors: Grünig Ekkehard , Benjamin Nicola , Lange Tobias J. , Krueger Ulrich , Klose Hans , Neurohr Claus , Wilkens Heinrike , Halank Michael , Seyfarth Hans-Jürgen , Held Matthias , Traube Andrew , Pernow Michelle , Grover E. Robert , Egenlauf Benjamin , Gerhardt Felix , Viethen Thomas , Rosenkranz Stephan
Published: October 2016

Background: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. Objectives: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. Methods: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study. Results: Thirty-nine patients with idiopathic or heritable pulmonary arterial hypertension on stable treatment with oral pulmonary arterial hypertension-approved drugs (90% on dual combination therapy) were included. Patients achieved a median treprostinil dosage of 35.7 ng/kg/min after 16 weeks. A good overall safety profile was demonstrated with 3 patients (8%) withdrawing due to infusion site pain, which occurred in 97% of patients. After 16 weeks, median 6-min walking distance, cardiac index, pulmonary vascular resistance, and tricuspid annular plane systolic excursion improved. Conclusions: Rapid up-titration of subcutaneous treprostinil was well tolerated, achieving a clinically effective dose associated with improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may improve the handling of this therapy and contribute to better treatment outcome.
Patiromer Decreases Serum Potassium and Phosphate Levels in Patients on Hemodialysis
Authors: Bushinsky David A. , Rossignol Patrick , Spiegel David M. , Benton Wade W. , Yuan Jinwei , Block Geoffrey A. , Wilcox Christopher S. , Agarwal Rajiv
Published: October 2016

Background: Persistent hyperkalemia (serum potassium (K) ≥5.5 mEq/l) is a common condition in hemodialysis (HD) patients, is associated with increased mortality, and treatment options are limited. The effect of patiromer, a gastrointestinal K binder, on serum K was examined in HD patients. Methods: Six hyperkalemic HD patients (5 anuric) were admitted to clinical research units for 15 days (1 pretreatment week and 1 patiromer treatment week) and they received a controlled diet with identical meals on corresponding days of pretreatment and treatment weeks. Phosphate (P) binders were discontinued on admission. Patiromer, 12.6 g daily (divided 4.2 g TID with meals), was started on the Monday morning following the last pretreatment week blood sampling. Serum and 24-hour stool samples were collected daily. Results: Mean ± SE serum K decreased (maximum change per corresponding day, 0.6 ± 0.2 mEq/l, p = 0.009) and fecal K increased 58% on patiromer compared with the pretreatment week. During the pretreatment week, 69.0, 47.6, and 11.9% of patients' serum K values were ≥5.5, ≥6.0, and ≥6.5 mEq/l, respectively. This was reduced to 38.1% (p = 0.009), 11.9% (p < 0.001), and 2.4% (p = 0.2) on patiromer. Following P binder discontinuation, the long interdialytic interval mean ± SE serum P numerically increased from 5.8 ± 0.4 to 7.0 ± 0.5 mg/dl (p = 0.06). On patiromer, P decreased from 7.0 ± 0.5 to 6.2 ± 0.5 mg/dl (p = 0.04). While on patiromer, fecal P numerically increased by 112 ± 72 mg/day (17%; p = 0.1792; range -148 to 344 mg/day). No patient discontinued patiromer because of adverse events (AEs); none had serious AEs. Conclusions: In 6 hyperkalemic HD patients, patiromer decreased serum K and P levels and increased fecal K.
“Road-Dividing Line”-Like Pigmentation of Hair as a Diagnostic Clue for Griscelli Syndrome
Authors: Katoulis Alexandros C. , Daskari Dimitra , Liakou Aikaterini I. , Bozi Evangelia , Lianou Dimitra , Rigopoulos Dimitris
Published: October 2016

We report a case of a 5-year-old girl with physical and psychomotor retardation, acquired microcephaly, and history of recurrent infections. Dermoscopic and microscopic hair examination revealed a “road-dividing line”-like pigmentation of hair shafts. The combination of history, clinical findings, and hair examination led to the diagnosis of Griscelli syndrome type II. The picture of “road-dividing line” on hair microscopic and dermoscopic examination is highly characteristic for Griscelli syndrome, and in this framework, dermatologic examination may be of high importance for the diagnosis.
Migratory Pallas’s Gull Larus ichthyaetus (Pallas, 1773): a new record from Sikkim, the eastern Himalaya, India
Authors: Sharma Santosh , Bhatt Dinesh
Published: October 2016

The present study documents the first sightings of the migratory Pallas’s Gull at two different locations (Cholamu Lake and Singtam Valley) in the eastern Himalayan state of Sikkim in India.  We recommend that long term surveys are required to determine and establish the distribution and status of the species in the state.
An inventory of herpetofauna from Wadi Sayq, Dhofar, Oman
Authors: Ball Lawrence Derek , Borrell James Stefan
Published: October 2016

Two research expeditions surveyed the herpetofauna within the monsoon-influenced zone of Wadi Sayq, a coastal wadi system 31.5km in length, situated in the southwestern Jabal Qamar mountain range, Dhofar, Oman.  Surveys were undertaken from 02 to 29 February 2012, and from 06 February to 07 March 2013.  Ninety-three individuals belonging to 15 species were recorded.  Morphological data was collected for 10 species.  An elevation gradient in habitat preference is observed for the genus Hemidactylus, and the discovery of four Coluber thomasi individuals significantly increases the total global records for this species.
Range extension of the endangered Salim Ali’s Fruit Bat Latidens salimalii (Chiroptera: Pteropodidae) in the Anamalai Hills, Tamil Nadu, India
Authors: Wordley Claire F.R. , Foui Eleni K. , Mudappa Divya , Sankaran Mahesh , Altringham John D.
Published: October 2016

Salim Ali’s Fruit Bat Latidens salimalii is an IUCN Red listed Endangered species known only from a few locations in southern India.  Here we report three records of Latidens salimalii from the Valparai plateau and Anamalai Tiger Reserve in Tamil Nadu where this species has not been previously recorded.  This bat was caught in riparian habitats close to or inside intact tropical wet forest in the Western Ghats.
Recent records of the Pale Jezebel Delias sanaca sanaca (Moore, 1857) (Lepidoptera: Pieridae) from Mussoorie hills, western Himalaya, India
Authors: Singh Arun P.
Published: October 2016

The  west Himalayan sub-species, ‘sanaca’ of the pale jezebel, Delias sanaca sanaca, which is  intermediate between the pale form flavalba, dark fromconfusa, was recently recorded, in  the oak forests adjoining Mussoorie hills of Garhwal  after a gap of  about 8 decades. Observations are presented on the  past records, specimens, morphological features and sexual dimorphism, ecology, seasonality  of the intermediate or normal form of this sub-species sanaca, that is generally overlooked.
Camera trapping the Palawan Pangolin Manis culionensis (Mammalia: Pholidota: Manidae) in the wild
Authors: Marler Paris N.
Published: October 2016

The Palawan Pangolin Manis culionensis is restricted to the Palawan faunal region in the Philippines.  The species’ distribution and natural history are poorly known due, in part, to it only recently being recognized as a distinct species.  Pangolin species around the world are threatened due to habitat loss and the illegal wildlife trade.  Understanding the conservation requirements of the Palawan Pangolin will inform efforts to avert its extinction.  Presently, information on the status, distribution, and natural history of pangolins is largely derived from interviews with local people, radio-telemetry, transect surveys for pangolin sign, and camera trapping.  Here we test the ability of fish oil- and pig blood-baited camera traps to document the presence of Palawan Pangolin.  We obtained three photos at two localities in Palawan in mangrove, lowland forest, and riverine forest.
A checklist of butterflies of Dakshina Kannada District, Karnataka, India
Authors: Naik Deepak , Mustak Mohammed S.
Published: October 2016

In a preliminary study on the butterflies of Dakshina Kannada District, located in the southwestern part of the Karnataka along the Western Ghats in Karnataka State in India, a total of 172 species of butterflies belonging to 117 genera, from six families was prepared by visiting various landscapes during the period September 2012 to December 2015.  Of the various species recorded, Papilio clytia (Linnaeus), Papilio lio medon (Moore), Pachlio ptahector (Linnaeus), Castalius rosimon (Fabricius), Acytolepis puspa (Horsefield), Lethe europa (Fabricius), Neptis jumbah (Moore), Dophlae velina (Stoll), Hypolimnas misippus (Linnaeus) and Doleschallia bisaltide (Cramer) comes under the Schedule I of the Indian Wildlife Protection Act 1972.  The present study provides the baseline data of butterfly species of Dakshina Kannada.
Readthrough-Promoting Drugs Gentamicin and PTC124 Fail to Rescue Na
v
1.5 Function of Human-Induced Pluripotent Stem Cell–Derived Cardiomyocytes Carrying Nonsense Mutations in the Sodium Channel Gene
SCN5A
Authors: Kosmidis Georgios , Veerman Christiaan C. , Casini Simona , Verkerk Arie O. , van de Pas Simone , Bellin Milena , Wilde Arthur A.M. , Mummery Christine L. , Bezzina Connie R.
Published: October 2016

Background—

Several compounds have been reported to induce translational readthrough of premature stop codons resulting in the production of full-length protein by interfering with ribosomal proofreading. Here we examined the effect of 2 of these compounds, gentamicin and PTC124, in human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes bearing nonsense mutations in the sodium channel gene
SCN5A
, which are associated with conduction disease and potential lethal arrhythmias.

Methods and Results—

We generated hiPSC from 2 patients carrying the mutations R1638X and W156X. hiPSC-derived cardiomyocytes from both patients recapitulated the expected electrophysiological phenotype, as evidenced by reduced Na
+
currents and action potential upstroke velocities compared with hiPSC-derived cardiomyocytes from 2 unrelated control individuals. While we were able to confirm the readthrough efficacy of the 2 drugs in Human Embryonic Kidney 293 cells, we did not observe rescue of the electrophysiological phenotype in hiPSC-derived cardiomyocytes from the patients.

Conclusions—

We conclude that these drugs are unlikely to present an effective treatment for patients carrying the loss-of-function
SCN5A
gene mutations examined in this study.
Clinical Utility of Multimarker Genetic Risk Scores for Prediction of Incident Coronary Heart Disease
Authors: Iribarren Carlos , Lu Meng , Jorgenson Eric , Martínez Manuel , Lluis-Ganella Carla , Subirana Isaac , Salas Eduardo , Elosua Roberto
Published: October 2016

Background—

We evaluated whether including multilocus genetic risk scores (GRSs) into the Framingham Risk Equation improves the predictive capacity, discrimination, and reclassification of asymptomatic individuals with respect to coronary heart disease (CHD) risk.

Methods and Results—

We performed a cohort study among 51 954 European-ancestry members of a Northern California integrated healthcare system (67% female; mean age 59) free of CHD at baseline (2007–2008). Four GRSs were constructed using between 8 and 51 previously identified genetic variants. After a mean (±SD) follow-up of 5.9 (±1.5) years, 1864 incident CHD events were documented. All GRSs were linearly associated with CHD in a model adjusted by individual risk factors: hazard ratio (95% confidence interval) per SD unit: 1.21 (1.15–1.26) for GRS_8, 1.20 (1.15–1.26) for GRS_12, 1.23 (1.17–1.28) for GRS_36, and 1.23 (1.17–1.28) for GRS_51. Inclusion of the GRSs improved the C statistic (ΔC statistic =0.008 for GRS_8 and GRS_36; 0.007 for GRS_12; and 0.009 for GRS_51; all
P
<0.001). The net reclassification improvement was 5% for GRS_8, GRS_12, and GRS_36 and 4% for GRS_51 in the entire cohort and was (after correcting for bias) 9% for GRS_8 and GRS_12 and 7% for GRS_36 and GRS_51 when analyzing those classified as intermediate Framingham risk (10%–20%). The number required to treat to prevent 1 CHD after selectively treating with statins up-reclassified subjects on the basis of genetic information was 36 for GRS_8 and GRS_12, 41 for GRS_36, and 43 for GRS_51.

Conclusions—

Our results demonstrate significant and clinically relevant incremental discriminative/predictive capability of 4 multilocus GRSs for incident CHD among subjects of European ancestry.
Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data
Authors: Mosley Jonathan D. , van Driest Sara L. , Wells Quinn S. , Shaffer Christian M. , Edwards Todd L. , Bastarache Lisa , McCarty Catherine A. , Thompson Will , Chute Christopher G. , Jarvik Gail P. , Crosslin David R. , Larson Eric B. , Kullo Iftikhar J. , Pacheco Jennifer A. , Peissig Peggy L. , Brilliant Murray H. , Linneman James G. , Denny Josh C. , Roden Dan M.
Published: October 2016

Background—

Continued reductions in morbidity and mortality attributable to ischemic heart disease (IHD) require an understanding of the changing epidemiology of this disease. We hypothesized that we could use genetic correlations, which quantify the shared genetic architectures of phenotype pairs and extant risk factors from a historical prospective study to define the risk profile of a contemporary IHD phenotype.

Methods and Results—

We used 37 phenotypes measured in the ARIC study (Atherosclerosis Risk in Communities; n=7716, European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19 093). All subjects had genome-wide single-nucleotide polymorphism genotyping. We measured pairwise genetic correlations (rG) between the ARIC and EHR phenotypes using linear mixed models. The genetic correlation estimates between the ARIC risk factors and the EHR IHD were modestly linearly correlated with hazards ratio estimates for incident IHD in ARIC (Pearson correlation [
r
]=0.62), indicating that the 2 IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes mellitus phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes, including total:high-density lipoprotein cholesterol ratio (rG=−0.44,
P
=0.005), high-density lipoprotein (rG=−0.48,
P
=0.005), systolic blood pressure (rG=0.44,
P
=0.02), and triglycerides (rG=0.38,
P
=0.02). EHR phenotypes related to type 2 diabetes mellitus, atherosclerotic, and hypertensive diseases were also genetically correlated with these ARIC risk factors.

Conclusions—

The EHR IHD risk profile differed from ARIC and indicates that treatment and prevention efforts in this population should target hypertensive and metabolic disease.
Variation in Hospital Use and Outcomes Associated With Pulmonary Artery Catheterization in Heart Failure in the United States
Authors: Khera Rohan , Pandey Ambarish , Kumar Nilay , Singh Rajeev , Bano Shah , Golwala Harsh , Kumbhani Dharam J. , Girotra Saket , Fonarow Gregg C.
Published: October 2016

Background—

There has been an increase in the use of pulmonary artery (PA) catheters in heart failure (HF) in the United States in recent years. However, patterns of hospital use and trends in patient outcomes are not known.

Methods and Results—

In the National Inpatient Sample 2001 to 2012, using
International Classification of Diseases
-Ninth Revision codes, we identified 11 888 525 adult (≥18 years) HF hospitalizations nationally, of which an estimated 75 209 (SE 0.6%) received a PA catheter. In 2001, the number of hospitals with ≥1 PA catheterization was 1753, decreasing to 1183 in 2011. The mean PA catheter use per hospital trended from 4.9 per year in 2001 (limits 1–133) to 3.8 per year in 2007 (limits 1–46), but increased to 5.5 per year in 2011 (limits 1–70). During 2001 to 2006, PA catheterization declined across hospitals; however, in 2007 to 2012, there was a disproportionate increase at hospitals with large bedsize, teaching programs, and advanced HF capabilities. The overall in-hospital mortality with PA catheter use was higher than without PA catheter use (13.1% versus 3.4%;
P
<0.0001); however, in propensity-matched analysis, differences in mortality between these groups have attenuated over time—risk-adjusted odds ratio for mortality for PA catheterization, 1.66 (95% confidence interval, 1.60–1.74) in 2001 to 2003 down to 1.04 (95% confidence interval, 0.97–1.12) in 2010 to 2012.

Conclusions—

There is substantial hospital-level variability in PA catheterization in HF along with increasing volume at fewer hospitals over-represented by large, academic hospitals with advanced HF capabilities. This is accompanied by a decline in excess mortality associated with PA catheterization.