bluuebunny/crossref_metadata_2025 huggingface dataset:
Type of Renal Replacement Therapy (Hemodialysis versus Peritoneal Dialysis) Does Not Affect Cytokine Gene Expression or Clinical Parameters of Renal Transplant Candidates
Authors: Kamińska Dorota , Kościelska-Kasprzak Katarzyna , Chudoba Paweł , Mazanowska Oktawia , Banasik Mirosław , Żabinska Marcelina , Boratyńska Maria , Lepiesza Agnieszka , Korta Krzysztof , Gomółkiewicz Agnieszka , Dzięgiel Piotr , Klinger Marian
Published: July 2015

Patients with renal failure suffer from immune disturbances, caused by uremic toxins and influenced by dialysis treatment. The aim of the present study was to reveal whether type of dialysis modality (hemodialysis, HD, versus peritoneal dialysis, PD) differentially affects the immunocompetence, particularly the expression of genes involved in the immune response.Material. 87 renal transplant candidates (66 HD, 21 PD) were included in the study.Methods. The peripheral blood RNA samples were obtained with the PAXgene Blood system just before transplantation. The gene expression ofCASP3, FAS, TP53, FOXP3, IFNG, IL2, IL6, IL8, IL10, IL17, IL18, LCN2, TGFB1, andTNFwas assessed with real-time PCR on custom-designed low density arrays (TaqMan). Gene expression data were analyzed in relation to pretransplant clinical parameters.Results. The mean expression of examined genes showed no significant differences between PD and HD with the exception ofFAS, expression of which was 30% higher in PD patients compared to the HD group. There was nonsignificantly higher expression of proinflammatory cytokines in the PD group. The clinical inflammatory parameters (CRP, albumin, cholesterol, and hemoglobin levels) did not differ between the groups.Conclusion. Type of renal replacement therapy exerts no differential effect on cytokine gene expression or inflammatory clinical parameters.
Induction of Thioredoxin Reductase 1 by Korean Red Ginseng Water Extract Regulates Cytoprotective Effects on Human Endothelial Cells
Authors: Park Hye Rim , Lee Seung Eun , Yang Hana , Son Gun Woo , Jin Young-Ho , Park Yong Seek
Published: July 2015

Korean Red Ginseng is a popular herbal medicine and is widely used in many food products. KRG has biological benefits related to vascular diseases including diabetes, hypertension, atherosclerosis, and other cardiac diseases and KRG has antioxidant and anti-hyperlipidemic actions. KRG decreases the level of oxidative stress and suppresses proinflammatory cytokines and cell adhesion molecules, thus protecting endothelial dysfunction. Mammalian Thioredoxin reductase 1 is an NADPH-dependent selenoprotein, essential for antioxidant defense and DNA synthesis and repair, that regulates the redox system by modulating redox-sensitive transcription factors and thiol-containing proteins. Here, we show that KRG water extract increases the expression of TrxR1 in human umbilical vein endothelial cells via the p38 and PKC-δsignaling pathways. The induction of TrxR1 expression by KRG was confirmed by Western blot analysis and reverse transcription polymerase chain reaction. However, the increase in TrxR1 expression was abolished by specific silencing of the p38 and PKC-δgenes. In addition, we demonstrated that auranofin, a TrxR1 inhibitor, weakens the protective effect of KRG against H2O2-induced cell death as measured by the terminal transferase dUTP nick end labeling assay. These results suggest that KRG may have protective effects in vascular diseases by upregulating TrxR1 in endothelial cells, thereby inhibiting the generation of reactive oxygen species and cell death.
Late-Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337)
Authors: Dietsch Gregory N. , Randall Tressa D. , Gottardo Raphael , Northfelt Donald W. , Ramanathan Ramesh K. , Cohen Peter A. , Manjarrez Kristi L. , Newkirk Mona , Bryan James Kyle , Hershberg Robert M.
Published: July 2015

Purpose: Immunotherapy as a treatment for cancer holds the promise of complete and durable tumor remission, yet the immunosuppressive environment created by many tumors, advanced patient age, and previous treatments with cytotoxic agents may limit the approach. The activity of motolimod (VTX-2337), a potent and selective Toll-like receptor 8 (TLR8) agonist, was therefore assessed in the context of advanced, late-stage cancer patients.

Experimental Design: The repertoire of mediators induced from human peripheral blood mononuclear cells in response to motolimod was characterized. Translational studies in cynomolgus monkeys elucidated the activity of motolimod on an intact immune system, identified biomarkers of TLR8 activation, and defined the relationship between the pharmacokinetic and pharmacodynamic (PK/PD) response. The PK/PD relationship for motolimod in cancer patients was assessed, compared with preclinical findings, and contrasted with activity in healthy volunteers.

Results: In late-stage cancer patients, plasma levels of multiple biomarkers, including IL6, G-CSF, MCP-1, and MIP1-β, increased with increasing motolimod dose. The magnitude and breadth of the biomarker response closely aligned with the response seen in preclinical studies, demonstrating that advanced cancer patients remained responsive to TLR8 activation. In addition, the PK/PD response in cancer patients closely aligned with the activity of motolimod seen in healthy volunteers.

Conclusions: Late-stage cancer patients are highly sensitive to TLR8 activation by motolimod. Tumor burden, advanced age, and prior treatment history with cytotoxic agents did not moderate or modify the response predicted by nonclinical studies and confirmed in healthy volunteers. Clin Cancer Res; 21(24); 5445–52. ©2015 AACR.
Physical Activity from Early Adulthood and Risk of Prostate Cancer: A 24-Year Follow-Up Study among Icelandic Men
Authors: Hrafnkelsdóttir Soffia M. , Torfadóttir Jóhanna E. , Aspelund Thor , Magnusson Kristjan T. , Tryggvadóttir Laufey , Gudnason Vilmundur , Mucci Lorelei A. , Stampfer Meir , Valdimarsdóttir Unnur A.
Published: July 2015

Physical activity in adult life may reduce prostate cancer risk. Data are scarce on the role of activity during early adulthood, as well as combined recreational and occupational physical activity on prostate cancer risk and mortality. We undertook a prospective study of 8,221 Icelandic men (born 1907 to 1935) in the population-based Reykjavik Study. At enrollment, between 1967 and 1987, the men provided information on regular recreational physical activity since the age of 20 years as well as current occupational activity. Through linkage to nationwide cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality through 2009. We used Cox models to calculate the relative risk of prostate cancer by level of physical activity. During a mean follow-up of 24.8 years, 1,052 men were diagnosed with prostate cancer, of whom 349 had advanced disease (stage 3+ or prostate cancer death). Neither recreational nor occupational physical activity was, independently or combined, associated with overall or localized prostate cancer. Compared with physically inactive men, we observed a nonsignificant lower risk of advanced prostate cancer [HR, 0.67; 95% confidence interval (CI), 0.42–1.07] among men reporting both recreational and occupational physical activities (P value for interaction = 0.03). Awaiting confirmation in larger studies with detailed assessment of physical activity, our data suggest that extensive physical activity beginning in early adulthood may reduce the risk of advanced prostate cancer. Cancer Prev Res; 8(10); 905–11. ©2015 AACR.
Inactivation of the PTS as a Strategy to Engineer the Production of Aromatic Metabolites in Escherichia coli
Authors: Carmona Susy Beatriz , Moreno Fabián , Bolívar Francisco , Gosset Guillermo , Escalante Adelfo
Published: July 2015

Laboratory and industrial cultures of Escherichia coli employ media containing glucose which is mainly transported and phosphorylated by the phosphotransferase system (PTS). In these strains, 50% of the phosphoenolpyruvate (PEP), which results from the catabolism of transported glucose, is used as a phosphate donor for its phosphorylation and translocation by the PTS. This characteristic of the PTS limits the production of industrial biocommodities that have PEP as a precursor. Furthermore, when E. coli is exposed to carbohydrate mixtures, the PTS prevents expression of catabolic and non-PTS transport genes by carbon catabolite repression and inducer exclusion. In this contribution, we discuss the main strategies developed to overcome these potentially limiting effects in production strains. These strategies include adaptive laboratory evolution selection of PTS- Glc+ mutants, followed by the generation of strains that recover their ability to grow with glucose as a carbon source while allowing the simultaneous consumption of more than one carbon source. We discuss the benefits of using alternative glucose transport systems and describe the application of these strategies to E. coli strains with specific genetic modifications in target pathways. These efforts have resulted in significant improvements in the production of diverse biocommodities, including aromatic metabolites, biofuels and organic acids.
Global Individual Ancestry Using Principal Components for Family Data
Authors: de Andrade Mariza , Ray Debashree , Pereira Alexandre C. , Soler Júlia P.
Published: July 2015

Studies of complex human diseases and traits associated with candidate genes are potentially vulnerable to bias (confounding) due to population stratification and inbreeding, especially in admixed population. In GWAS, the principal components (PCs) method provides a global ancestry value per subject, allowing corrections for population stratification. However, these coefficients are typically estimated assuming unrelated individuals, and if family structure is present and ignored, such substructures may induce artifactual PCs. Extensions of the PCs method have been proposed by Konishi and Rao [Biometrika 1992;79:631-641], taking into account only siblings' relatedness, and by Oualkacha et al. [Stat Appl Genet Mol Biol 2012, DOI: 10.2202/1544-6115.1711], taking into account large pedigrees and high-dimensional phenotype data. In this work, we extend these methods to estimate the global individual ancestry coefficients from PCs derived from different variance component matrix estimators using SNPs from two simulated data sets and two real data sets: the GENOA sibship data consisting of European and African-American subjects and the Baependi Heart Study consisting of 80 extended Brazilian families, both with genotyping data from the Affymetrix 6.0 chip. Our results show that the family structure plays an important role in the estimation of the global individual ancestry value for extended pedigrees but not for sibships.
Escin Increases the Survival Rate of LPS-Induced Septic Mice Through Inhibition of HMGB1 Release from Macrophages
Authors: Cheng Yajun , Wang Hongrui , Mao Min , Liang Chao , Zhang Yu , Yang Deijun , Wei Ziran , Gao Shunxiang , Hu Bo , Wang Lianghua , Cai Qingping
Published: July 2015

Background: Previous studies have described the effects of Escin on improving the survival rate of endotoxemic animals. The purpose of this study was to explore the molecular mechanisms of this potentially beneficial treatment. Methods: First, the survival rate of endotoxemic mice was monitored for up to 2 weeks after Escin pretreatment, Escin post-treatment, or Escin post-treatment + rHMGB1. The effects of Escin on the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 and HMGB1 in the serum of endotoxemic mice and LPS-induced macrophages were evaluated by ELISA. Furthermore, the mRNA and protein levels of HMGB1 in LPS-induced macrophages were measured by qRT-PCR and Western blot, respectively. Additionally, the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 was evaluated by ELISA in rHMGB1-induced macrophages. Finally, the protein levels and the activity of NF-κB in macrophages were checked by Western blot and ELISA, respectively. Results: Both pretreatment and post-treatment with Escin could improve the survival rate of endotoxemic mice, while exogenous rHMGB1 reversed this effect. In addition, Escin decreased the level of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 and HMGB1 in endotoxemic mice and in LPS-induced macrophages. Escin could also inhibit the mRNA levels and activity of HMGB1. The release of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 could be suppressed in rHMGB1-induced macrophages by Escin. Finally, Escin could suppress the activation of NF-κB in LPS-induced macrophages. Conclusion: Escin could improve the survival of mice with LPS-induced endotoxemia. This effect maybe meditated by reducing the release of HMGB1, resulting in the suppression of the release of pro-inflammatory cytokines.
Sex and Hemisphere - A Neglected, Nature-Determined Relationship in Acute Ischemic Stroke
Authors: Hametner Christian , Ringleb Peter , Kellert Lars
Published: July 2015

Background: Sex differences in the structural connectome of the brain are clinically highly relevant, but they have mostly been neglected in stroke trials. We investigated the impact of the interaction sex-by-hemisphere on outcome in stroke patients after intravenous thrombolysis (IVT). Methods: This is an observational study based on consecutively collected supratentorial stroke patients treated with IVT (n = 1,231). The 3-month modified Rankin scale (mRS) was estimated by adjusted binary (mRS 0-2 for good outcome) and ordinal regression analysis. As baseline characteristics differ substantially between the sexes, we aimed for better covariate balance by employing coarsened exact matching. Results: Sex-by-hemisphere predicted good outcome in the entire cohort (726 left, 505 right hemispheric strokes, p valueinteraction 0.032) and in the matched cohort (338 left, 273 right, p valueinteraction 0.003). Ordinal regression suggested a comparable estimate in the matched cohort (p valueinteraction 0.006). Further investigation revealed relevant between-sex and within-sex risk: right hemispheric strokes in men were 1.54 times (95% confidence intervals (CIs) 1.15-2.01) more likely than in women to achieve mRS 0-2. Women with right hemispheric strokes were 0.72 times (95% CI 0.54-0.92) less likely to reach mRS 0-2 than women with left hemispheric strokes. Conversely, men with right hemispheric strokes were 1.35 times (95% CI 1.06-1.70) more likely to achieve mRS 0-2 than men with left hemispheric strokes. Conclusion: This study suggests that outcomes are different in both sexes after IVT when different hemispheres are affected. Further consideration of this hypothesis in clinical trials might help in guiding individualized, injury-specific treatment approaches for acute ischemic stroke.
da Vinci and Open Radical Prostatectomy: Comparison of Clinical Outcomes and Analysis of Insurance Costs
Authors: Niklas Christina , Saar Matthias , Berg Britta , Steiner Katrin , Janssen Martin , Siemer Stefan , Stöckle Michael , Ohlmann Carsten-Henning
Published: July 2015

Purpose: To assess clinical outcomes and reimbursement costs of open and robotic-assisted radical prostatectomies in Germany. Methods: Perioperative data of 499 open (2003-2006) and 932 (2008-2010) robotic-assisted radical prostatectomies as well as longitudinal reimbursement costs of an anonymized health insurance research database from Germany containing data of patients who underwent robotic-assisted or open radical prostatectomy were retrospectively analysed in a single-centre study. Results: Significantly better outcomes after robotic-assisted vs. open prostatectomy were observed in regards to positive surgical margins (13.3 vs. 22.4%; p < 0.0001), intraoperative transfusions (0.1 vs. 2.6%; p < 0.0001), hospitalization (8.7 vs. 15.2 days; p < 0.0001) and duration of catheter (6.6 vs. 12.8 days; p < 0.0001). Operating time was significantly longer with robotic-assisted radical prostatectomy when compared to open surgery (184.4 vs. 128.0 min; p < 0.0001), while intraoperative complications showed a similar occurrence between both groups. Significant fewer postoperative complications were observed after robotic-assisted radical prostatectomy (26.5 vs. 42.5%; p < 0.0001) and rate of re-admission was lower for the robotic patients (13.6 vs. 19.4%; p = 0.0050). While insurance costs were higher in the 2 years before radical prostatectomy for the patients who underwent a robotic procedure (4,241.60 vs. 3,410.23 €; p = 0.202), additive costs of care of the year of surgery plus the 2 following years were less for the robotic cohort when compared to the costs incurred by the open group (21,673.71 vs. 24,512.37 €; p = 0.1676). Conclusions: The observed clinical advantages of robotic-assisted radical prostatectomy seem to result in reduced health insurance cost postoperatively when compared to open surgery. This should be taken into consideration regarding reimbursement and implementation of a clinically superior method.
Biochemical, Histopathological and Immunohistochemical Evaluation of the Protective and Therapeutic Effects of Thymoquinone against Ischemia and Ischemia/Reperfusion Injury in the Rat Ovary
Authors: Mete Ural Ülkü , Bayoğlu Tekin Yeşim , Şehitoğlu İbrahim , Kalkan Yıldıray , Cumhur Cüre Medine
Published: July 2015

Aim: To evaluate the antioxidant effects of thymoquinone (TQ) and to investigate the biochemical, histopathological and immunohistochemical changes in experimental rat ovarian torsion. Methods: A total of 48 female adult rats were used in this study and randomly divided into 7 groups: (1) sham operation; (2) bilateral 3-hour ovarian ischemia; (3) 3-hour ischemia and 3-hour reperfusion; (4) and (5) rats were administered 20 and 40 mg/kg of TQ, respectively, before 0.5 h of ischemia, and then 3 h of ovarian ischemia was applied; (6) and (7) 3-hour ovarian ischemia was applied; 2.5 h after the induction of ischemia, rats were administered the same doses of TQ; at the end of 3 h of ischemia, a 3-hour reperfusion was applied. Histologic changes under light microscopy, immunoreactivity for anticaspase-3 and serum levels of malondialdehyde, interleukin-6, catalase and glutathione peroxidase were noted and compared between the 7 groups. Results: Ischemia and ischemia/reperfusion cause a deterioration of biochemical and histopathological parameters. Administration of TQ seems to reverse these alterations and alleviate the injury. Antioxidant defense mechanisms appear to be enhanced by the administration of TQ. Conclusion: TQ at different doses attenuates ovarian ischemia and ischemia/reperfusion injury in rats.
Clinical Expression of Multiple Sclerosis in Hispanic Whites of Primarily Caribbean Ancestry
Authors: Hadjixenofontos Athena , Beecham Ashley H. , Manrique Clara P. , Pericak-Vance Margaret A. , Tornes Leticia , Ortega Melissa , Rammohan Kottil W. , McCauley Jacob L. , Delgado Sylvia R.
Published: July 2015

Objective: The clinical characteristics of multiple sclerosis (MS) are not well defined in Hispanic populations. We hypothesized that disease presentation in Hispanic white (HW) patients will be different from non-Hispanic white (NHW) patients given their ancestral background and reported lower disease prevalence. This study was undertaken to compare HW of primarily Caribbean ancestry to NHW on clinical characteristics of MS. Methods: We assessed 312 HW and 312 NHW patients with definite MS for clinical disease characteristics obtained through consented review of medical records. In order to assess the relationship between age-related phenotypes and ethnicity, linear regression was used. Logistic regression was used to assess the relationship between ethnicity and descriptors of disease presentation and severity as well as presence of neurological symptoms. Results: We observed a significantly younger age at diagnosis (p = 1.38E-02) and age at exam (p = 2.36E-05) in HW. However, age at first symptom did not differ significantly between the two groups. Furthermore, within HW, the mean age at first symptom and age at diagnosis was significantly younger in those born in the United States (p < 1.00E-03 for both). Interestingly, we noted an increase in ambulatory disability in HW patients, primarily among those with relapsing disease (p = 4.18E-03). Conclusions: We found several differences in age-related phenotypes and disease severity between HW of primarily Caribbean origin and NHW patients. To our knowledge, this is the largest study to date that examined the clinical characteristics of MS in Hispanic patients of largely Caribbean origin.
Outcomes of Proton Beam Radiotherapy for Large Non-Peripapillary Choroidal and Ciliary Body Melanoma at TRIUMF and the BC Cancer Agency
Authors: Weber Britta , Paton Katherine , Ma Roy , Pickles Tom
Published: July 2015

Background and Purpose: To report outcomes and toxicity after proton beam radiotherapy for non-peripapillary choroidal and ciliary body melanoma considered unsuitable for other eye-sparing therapies. Materials and Methods: An existing database of 77 patients with non-peripapillary tumors treated at TRIUMF, Canada, including patient, tumor, and treatment characteristics, was updated with ocular complications and follow-up status from chart reviews. Results: Most of the patients had large tumors: 61% were T3/T4 tumors (AJCC classification), while 48% were large by the Collaborative Ocular Melanoma Study classification. The median thickness was 7.1 mm, and the ciliary body was involved in 35%. After 5 and 10 years, the actuarial ocular tumor control rate was 85 and 85%, metastasis-free survival was 72 and 57%, overall survival was 77 and 63%, the enucleation rate was 22 and 22%, and complete blindness was found in 38 and 38%, respectively. On univariate analysis, patients with ciliary body involvement had significantly worse metastasis-free survival and overall survival rates compared to patients without ciliary body involvement (p < 0.001). Conclusions: Proton therapy for large anteriorly located tumors resulted in acceptable ocular tumor control and survival rates. The risk of blindness and severe toxicity requiring enucleation was low, and a substantial proportion of patients maintained useful vision.
Postsurgical Cystoid Macular Edema following Posterior Chamber Toric Phakic Intraocular Lens Implantation Surgery: A Case Report
Authors: Umurhan Akkan Julide Canan , Tuncer Kemal , Elbay Ahmet
Published: July 2015

Purpose: To describe a case of cystoid macular edema (CME) developing after posterior chamber toric phakic intraocular lens (PIOL) implantation. Methods: Case report. Results: A 33-year-old male underwent implantation of toric implantable collamer lenses (ICL), a new generation of PIOLs, for both eyes. Preoperative best spectacle-corrected distance visual acuity (BCVA) was 20/25 in the right eye and 20/32 in the left eye, with a manifest refraction of -9.25 -4.0 × 4° and -9.75 -4.25 × 171°, respectively. On day 1 postoperatively, the left eye had an uncorrected distance visual acuity (UDVA) of 20/60 with a refraction of +2.0 -3.5 × 11°. Despite the rotation of the PIOL, the cylindrical refractive component persisted in the left eye with a refraction of +2.0 -3.5 × 11°. Two weeks after the initial surgery, he presented with a decrease in his visual acuity in the left eye. The UDVA and BCVA were both 20/100 in the left eye with a refraction of +2.0 -4.25 × 3°. Dilated fundus examination and macular optical coherence tomography revealed a CME in the left eye. Following topical nepafenac therapy and explantation of the ICL, we observed a complete resolution of the CME at 3 months with an improvement in BCVA to 20/32 in the left eye. Conclusions: To our knowledge, this is the first reported case of postsurgical CME following toric ICL implantation. In cases of phakic eyes with an intact posterior capsule, postsurgical CME can develop, thus highlighting the purpose of this report.
Infarct Topography and Detection of Atrial Fibrillation in Cryptogenic Stroke: Results from CRYSTAL AF
Authors: Bernstein Richard A. , Di Lazzaro Vincenzo , Rymer Marilyn M. , Passman Rod S. , Brachmann Johannes , Morillo Carlos A. , Sanna Tommaso , Thijs Vincent , Rogers Tyson , Liu Shufeng , Ziegler Paul D. , Diener Hans-Christoph
Published: July 2015

Background: Insertable cardiac monitors (ICM) have been shown to detect atrial fibrillation (AF) at a higher rate than routine monitoring methods in patients with cryptogenic stroke (CS). However, it is unknown whether there are topographic patterns of brain infarction in patients with CS that are particularly associated with underlying AF. If such patterns exist, these could be used to help decide whether or not CS patients would benefit from long-term monitoring with an ICM. Methods: In this retrospective analysis, a neuro-radiologist blinded to clinical details reviewed brain images from 212 patients with CS who were enrolled in the ICM arm of the CRYptogenic STroke And underLying AF (CRYSTAL AF) trial. Kaplan-Meier estimates were used to describe rates of AF detection at 12 months in patients with and without pre-specified imaging characteristics. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were calculated using Cox regression. Results: We did not find any pattern of acute brain infarction that was significantly associated with AF detection after CS. However, the presence of chronic brain infarctions (15.8 vs. 7.0%, HR 2.84, 95% CI 1.13-7.15, p = 0.02) or leukoaraiosis (18.2 vs. 7.9%, HR 2.94, 95% CI 1.28-6.71, p < 0.01) was associated with AF detection. There was a borderline significant association of AF detection with the presence of chronic territorial (defined as within the territory of a first or second degree branch of the circle of Willis) infarcts (20.9 vs. 10.0%, HR 2.37, 95% CI 0.98-5.72, p = 0.05). Conclusions: We found no evidence for an association between brain infarction pattern and AF detection using an ICM in patients with CS, although patients with coexisting chronic, as well as acute, brain infarcts had a higher rate of AF detection. Acute brain infarction topography does not reliably predict or exclude detection of underlying AF in patients with CS and should not be used to select patients for ICM after cryptogenic stroke.
Ticagrelor Versus Clopidogrel in Black Patients With Stable Coronary Artery Disease
Authors: Waksman Ron , Maya Juan , Angiolillo Dominick J. , Carlson Glenn F. , Teng Renli , Caplan Richard J. , Ferdinand, Keith C.
Published: July 2015

Background—

The burden of coronary artery disease (CAD) is high in blacks, highlighting the need for clinical research of antiplatelet agents in this population. We sought to evaluate platelet reactivity during loading and maintenance dosing of ticagrelor versus clopidogrel, and the pharmacokinetic profile of ticagrelor and its metabolite AR-C124910XX, in black patients with stable CAD taking low-dose aspirin (acetylsalicylic acid).

Methods and Results—

In a multicenter, randomized, open-label, crossover study, 34 blacks with stable CAD receiving acetylsalicylic acid 75 to 100 mg/d were randomized to clopidogrel (600 mg, then 75 mg QD for 7–9 days) or ticagrelor (180 mg, then 90 mg BID for 7–9 days). After washout 10 to 14 days, patients switched regimens. The primary end point was platelet reactivity 2 hours post loading dose (P2Y
12
reactivity units [PRU] measured by the VerifyNow assay). Least-squares mean PRU at 2 hours post loading dose was lower with ticagrelor (27.6) versus clopidogrel (211.2); least-squares mean difference was –183.6 (95% confidence interval, –213.9 to –153.3;
P
<0.001). At all time points, the least-squares mean PRU was significantly lower, and the percent reduction in PRU from baseline was statistically greater, with ticagrelor versus clopidogrel. At 2 hours post dose, the prevalence of high on-treatment platelet reactivity (≥208 PRU) was lower with ticagrelor (0%) than with clopidogrel (57.1%). Pharmacokinetic profiles of ticagrelor and AR-C124910XX were consistent with previous reports in stable CAD populations.

Conclusions—

In black patients with stable CAD receiving low-dose acetylsalicylic acid, ticagrelor provided a faster onset and greater degree of platelet inhibition than clopidogrel.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01523392.
Percutaneous Coronary Intervention at Centers With and Without On-Site Surgical Backup
Authors: Lee Joo Myung , Hwang Doyeon , Park Jonghanne , Kim Kyung-Jin , Ahn Chul , Koo Bon-Kwon
Published: July 2015

Background—

Emergency coronary artery bypass grafting for unsuccessful percutaneous coronary intervention (PCI) is now rare. We aimed to evaluate the current safety and outcomes of primary PCI and nonprimary PCI at centers with and without on-site surgical backup.

Methods and Results—

We performed an updated systematic review and meta-analysis by using mixed-effects models. We included 23 high-quality studies that compared clinical outcomes and complication rates of 1 101 123 patients after PCI at centers with or without on-site surgery. For primary PCI for ST-segment–elevation myocardial infarction (133 574 patients), all-cause mortality (without on-site surgery versus with on-site surgery: observed rates, 4.8% versus 7.2%; pooled odds ratio [OR], 0.99; 95% confidence interval, 0.91–1.07;
P
=0.729;
I
2
=3.4%) or emergency coronary artery bypass grafting rates (observed rates, 1.5% versus 2.4%; pooled OR, 0.76; 95% confidence interval, 0.56–1.01;
P
=0.062;
I
2
=42.5%) did not differ by presence of on-site surgery. For nonprimary PCI (967 549 patients), all-cause mortality (observed rates, 1.6% versus 2.1%; pooled OR, 1.15; 95% confidence interval, 0.94–1.41;
P
=0.172;
I
2
=67.5%) and emergency coronary artery bypass grafting rates (observed rates, 0.5% versus 0.8%; pooled OR, 1.14; 95% confidence interval, 0.62–2.13;
P
=0.669;
I
2
=81.7%) were not significantly different. PCI complication rates (cardiogenic shock, stroke, aortic dissection, tamponade, recurrent infarction) also did not differ by on-site surgical capability. Cumulative meta-analysis of nonprimary PCI showed a temporal decrease of the effect size (OR) for all-cause mortality after 2007.

Conclusions—

Clinical outcomes and complication rates of PCI at centers without on-site surgery did not differ from those with on-site surgery, for both primary and nonprimary PCI. Temporal trends indicated improving clinical outcomes in nonprimary PCI at centers without on-site surgery.
Body Mass Index, Outcomes, and Mortality Following Cardiac Surgery in Ontario, Canada
Authors: Johnson Ana P. , Parlow Joel L. , Whitehead Marlo , Xu Jianfeng , Rohland Susan , Milne Brian
Published: July 2015

Background

The “obesity paradox” reflects an observed relationship between obesity and decreased morbidity and mortality, suggesting improved health outcomes for obese individuals. Studies examining the relationship between high body mass index (
BMI
) and adverse outcomes after cardiac surgery have reported conflicting results.

Methods and Results

The study population (N=78 762) was comprised of adult patients who had undergone first‐time coronary artery bypass (
CABG
) or combined
CABG
/aortic valve replacement (
AVR
) surgery from April 1, 1998 to October 31, 2011 in Ontario (data from the Institute for Clinical Evaluative Sciences). Perioperative outcomes and 5‐year mortality among pre‐defined
BMI
(kg/m
2
) categories (underweight <20, normal weight 20 to 24.9, overweight 25 to 29.9, obese 30 to 34.9, morbidly obese >34.9) were compared using Bivariate analyses and Cox multivariate regression analysis to investigate multiple confounders on the relationship between
BMI
and adverse outcomes. A reverse J‐shaped curve was found between
BMI
and mortality with their respective hazard ratios. Independent of confounding variables, 30‐day, 1‐year, and 5‐year survival rates were highest for the obese group of patients (99.1% [95% Confidence Interval {
CI
}, 98.9 to 99.2], 97.6% [95%
CI
, 97.3 to 97.8], and 90.0% [95%
CI
, 89.5 to 90.5], respectively), and perioperative complications lowest. Underweight and morbidly obese patients had higher mortality and incidence of adverse outcomes.

Conclusions

Overweight and obese patients had lower mortality and adverse perioperative outcomes after cardiac surgery compared with normal weight, underweight, and morbidly obese patients. The “obesity paradox” was confirmed for overweight and moderately obese patients. This may impact health resource planning, shifting the focus to morbidly obese and underweight patients prior to, during, and after cardiac surgery.
Estimating Total Cerebral Microinfarct Burden From Diffusion-Weighted Imaging
Authors: Auriel Eitan , Westover M. Brandon , Bianchi Matt T. , Reijmer Yael , Martinez-Ramirez Sergi , Ni Jun , Van Etten Ellis , Frosch Matthew P. , Fotiadis Panagiotis , Schwab Kris , Vashkevich Anastasia , Boulouis Grégoire , Younger Alayna P. , Johnson Keith A. , Sperling Reisa A. , Hedden Trey , Gurol M. Edip , Viswanathan Anand , Greenberg Steven M.
Published: July 2015

Background and Purpose—

Cerebral microinfarcts (CMI) are important contributors to vascular cognitive impairment. Magnetic resonance imaging diffusion-weighted imaging (DWI) hyperintensities have been suggested to represent acute CMI. We aim to describe a mathematical method for estimating total number of CMI based on the presence of incidental DWI lesions.

Methods—

We reviewed magnetic resonance imaging scans of subjects with cognitive decline, cognitively normal subjects and previously reported subjects with past intracerebral hemorrhage (ICH). Based on temporal and spatial characteristics of DWI lesions, we estimated the annual rate of CMI needed to explain the observed rate of DWI lesion detection in each group. To confirm our estimates, we performed extensive sampling for CMI in the brain of a deceased subject with past lobar ICH who found to have a DWI lesion during life.

Results—

Clinically silent DWI lesions were present in 13 of 343 (3.8%) cognitively impaired and 10 of 199 (5%) cognitively intact normal non-ICH patients, both lower than the incidence in the past ICH patients (23 of 178; 12.9%;
P
<0.0006). The predicted annual incidence of CMI ranges from 16 to 1566 for non-ICH and 50 to 5041 for ICH individuals. Histological sampling revealed a total of 60 lesions in 32 sections. Based on previously reported methods, this density of CMI yields an estimated total brain burden maximum likelihood estimate of 9321 CMIs (95% confidence interval, 7255–11 990).

Conclusions—

Detecting even a single DWI lesion suggests an annual incidence of hundreds of new CMI. The cumulative effects of these lesions may directly contribute to small-vessel–related vascular cognitive impairment.
Duration of Diabetes Mellitus and Risk of Thromboembolism and Bleeding in Atrial Fibrillation
Authors: Overvad Thure Filskov , Skjøth Flemming , Lip Gregory Y.H. , Lane Deirdre A. , Albertsen Ida Ehlers , Rasmussen Lars Hvilsted , Larsen Torben Bjerregaard
Published: July 2015

Background and Purpose—

Guidelines advocate anticoagulant treatment to all patients with atrial fibrillation and concomitant diabetes mellitus. The potential refinement to thromboembolic risk stratification that may spring from subdividing diabetes mellitus is unexplored. The purpose was to investigate duration of diabetes mellitus as a predictor of thromboembolism and anticoagulant-related bleeding in patients with atrial fibrillation.

Methods—

Using nationwide Danish registries, we identified all patients discharged from hospital with an incident diagnosis of atrial fibrillation from 2000 to 2011. Hazard ratios with 95% confidence intervals for thromboembolism and bleeding according to years of diabetes mellitus duration in categories (0–4, 5–9, 10–14, and ≥15) and as a continuous variable using cubic splines were calculated by Cox regression.

Results—

The study population comprised 137 222 patients with atrial fibrillation, of which 12.4% had diabetes mellitus. Compared with patients without diabetes mellitus and after adjustment for anticoagulant treatment and CHA
2
DS
2
-VASc components (congestive heart failure, hypertension, age, previous stroke, vascular disease, and sex), the risk of thromboembolism was lowest in the 0 to 4 years duration category (hazard ratio, 1.11; 95% confidence interval, 1.03–1.20), and highest in the longest duration category of ≥15 years (hazard ratio, 1.48; 95% confidence interval, 1.29–1.70). When analyzed as a continuous variable, duration of diabetes mellitus was associated with risk of thromboembolism in a dose-response-dependent manner, but not with a higher risk of bleeding during anticoagulant treatment.

Conclusions—

In patients with atrial fibrillation, longer duration of diabetes mellitus was associated with a higher risk of thromboembolism, but not with a higher risk of anticoagulant-related bleeding. Considering the critical balance between preventing thromboembolism and avoiding bleeding, longer duration of diabetes mellitus may favor initiation of anticoagulant therapy.
The presence of Alpheus lobidens De Haan, 1849 (Decapoda, Alpheidae) on the Turkish Aegean Sea coast
Authors: Bakir Kerem , İlkyaz Akin T. , Aydin Celalettin , Türkmen Gürel
Published: July 2015

A male specimen of Alpheus lobidens De Haan, 1849 was collected on the Aegean coast of Turkey. It is the second Lessepsian species belonging to the genus Alpheus from the Turkish coast of the Aegean Sea.
A new species of the genus Austinogebia Ngoc-Ho, 2001 (Decapoda, Gebiidea, Upogebiidae) from the Bohai Sea, China
Authors: Liu Wenliang , Sha Zhongli
Published: July 2015

A new species of the upogebiid mud shrimp genusAustinogebiaNgoc-Ho, 2001,A. liuin. sp., collected from the Bohai Sea, is described and illustrated. It is closely similar toA. takaoensis(Sakai & Türkay, 1995) andA. spinifrons(Haswell, 1881) in the fixed finger of the male pereopod 1 bearing a large blunt tooth on the outer (or lateral) surface, but differs markedly from the latter two in the rostrum being 1.7 times as long as its basal width, and the lower margin of the antennal peduncle being unarmed, respectively.
Lectotypification of the name Cistus stipulatus, basyonim of Helianthemum stipulatum (Cistaceae)
Authors: FERRER-GALLEGO PEDRO PABLO , BOISSET FERNANDO
Published: July 2015

The typification of the name Cistus stipulatus Forsskål (≡ Helianthemum stipulatum (Forsskål) Christensen) is discussed. The designation of the nomenclatural type is based on an assessment of Forsskål’s original material. The name is lectotypified selecting a specimen from the Herbarium Forsskålii in the National Herbarium Copenhagen at C.
Miconia solearis, a new combination to replace the illegitimate Miconia magnifolia (Melastomataceae: Miconieae) in Tropical America
Authors: Gamba Diana , Almeda Frank
Published: July 2015

In our recently published monograph of the Octopleura clade of Miconia Ruiz & Pavón (1794: 60, Gamba & Almeda 2014) we proposed a number of new combinations and new names to reflect the nested position of this assemblage of 33 species within the large and diverse Neotropical genus Miconia based on morphological and molecular data sets. In proposing the new name, Miconia magnifolia Gamba & Almeda (2014: 91), we overlooked the epithet of a heterotypic synonym that should have been adopted. Miconia magnifolia is therefore illegitimate and nomenclaturally superfluous according to Article 52.1 of the International Code of Nomenclature (McNeill et al. 2012) and is to be rejected because it included the type of a heterotypic synonym whose epithet was available and not already pre-empted in Miconia.
Vulcanochloris (Trebouxiales, Trebouxiophyceae), a new genus of lichen photobiont from La Palma, Canary Islands, Spain
Authors: Vančurová Lucie , Peksa Ondřej , Němcová Yvonne , Škaloud Pavel
Published: July 2015

This paper describes a new genus of lichen photobionts, Vulcanochloris, with three newly proposed species, V. canariensis, V. guanchorum and V. symbiotica. These algae have been discovered as photobionts of lichen Stereocaulon vesuvianum growing on slopes of volcanos and lava fields on La Palma, Canary Islands, Spain. Particular species, as well as the newly proposed genus, are delimited based on ITS rDNA, 18S rDNA and rbcL sequences, chloroplast morphology, and ultrastructural features. Phylogenetic analyses infer the genus Vulcanochloris as a member of Trebouxiophycean order Trebouxiales, in a sister relationship with the genus Asterochloris. Our data point to the similar lifestyle and morphology of these two genera; however, Vulcanochloris can be well distinguished by a unique formation of spherical incisions within the pyrenoid. Mycobiont specificity and geographical distribution of the newly proposed genus is further discussed.
Taxonomic notes on some problematic Carex (Cyperaceae) names from SW Asia
Authors: Jimenez-Mejias Pedro , Rodríguez-Palacios Giovanni Edenilson , Amini-Rad Mohammad , Martín-Bravo Santiago
Published: July 2015

A taxonomic survey based on revision of herbarium material and critical study of bibliography is conducted to elucidate the taxonomic and nomenclatural status of four problematic Carex names: C. eremitica, C. mediterranea, C. orbicularis subsp. kotschyana var. caucasica, and C. transcaucasica, all described from SW Asia. We find that C. eremitica should be considered a synonym of C. stenophylla (section Boernerae). We perform the lectotypification of C. mediterranea, a synonym of C. hispida (section Thuringiacae). We discuss the taxonomic affinities of C. transcaucasica (section Phacocystis) and combine this name under C. nigra (C. nigra subsp. transcaucasica). We synonymize C. orbicularis subsp. kotschyana var. caucasica to C. nigra subsp. transcaucasica. Eventually, we indicate that populations previously believed to be C. orbicularis actually belong to C. nigra subsp. transcaucasica, confirming its presence in Iran, and expanding its range to Iraq.
An annotated catalogue of the Buprestidae of Iran (Coleoptera: Buprestoidea)
Authors: GHAHARI HASSAN , VOLKOVITSH MARK G. , BELLAMY CHARLES L.
Published: July 2015

An annotated taxonomic catalogue of the jewel beetles (Coleoptera: Buprestidae) of Iran is given. Original descriptions and recent revisionary or catalogue data are included along with the distribution, both within and outside of Iran, ecological data and host plant associations, junior synonyms, and comments. A complete bibliography completes the catalogue. In total 428 species and 52 subspecies of jewel beetles belonging to 6 subfamilies (Julodinae, Polycestinae, Galbellinae, Chrysochroinae, Buprestinae, and Agrilinae), 20 tribes, and 38 genera are known from Iran including doubtful records and 4 nomina nuda. It is likely that the number of jewel beetle species from Iran will be between 460–480 and possibly even more species.
A new insular species of Rock Gecko (Cnemaspis Boulenger) from Pulau Langkawi, Kedah, Peninsular Malaysia
Authors: GRISMER L. LEE , WOOD P. L. JR. , QUAH EVAN S. H. , ANUAR SHAHRUL , NGADI EHWAN , AHMAD NORHAYATI
Published: July 2015

A new, diminutive species of Rock Gecko Cnemaspis mahsuriae sp. nov. of the affinis group, is described from Gunung Raya on Pulau Langkawi, Kedah, Peninsular Malaysia and is differentiated from all other species in the affinis group by having a unique combination of characters including a maximum SVL of 36.6 mm; keeled subtibials and ventrals; 21–24 paravertebral tubercles; no tubercles in the lateral caudal furrows; caudal tubercles not encircling tail; no precloacal pores; 23–26 subdigital lamellae on the fourth toe; no white ocelli in the shoulder region; no yellow postscapular band; and faint yellow bars on the flanks. Cnemaspis mahsuriae sp. nov. is a forest-dwelling species living in close sympatry or paraptry with the insular endemic C. roticanai Grismer & Chan. The Langkawi Archipelago harbors a unique mix of Malaysian and Indochinese taxa and the frequency of new discoveries from this group of islands is increasing.
Molecular phylogenetics, diversification, and systematics of Tibicen Latreille 1825 and allied cicadas of the tribe Cryptotympanini, with three new genera and emphasis on species from the USA and Canada
(Hemiptera: Auchenorrhyncha: Cicadidae)
Authors: HILL KATHY B. R. , MARSHALL DAVID C. , MOULDS MAXWELL S. , SIMON CHRIS
Published: July 2015

North America has a diverse cicada fauna with multiple genera from all three Cicadidae subfamilies, yet molecular phylogenetic analyses have been completed only for the well-studied periodical cicadas (Magicicada Davis). The genus Tibicen Latreille, a large group of charismatic species, is in need of such work because morphological patterns suggest multiple groups with complicated relationships to other genera in the tribe Cryptotympanini. In this paper we present a molecular phylogenetic analysis, based on mitochondrial and nuclear DNA, of 35 of the 38 extant USA species and subspecies of the genus Tibicen together with their North American tribal allies (Cornuplura Davis, Cacama Davis), selected Tibicen species from Eurasia, and representatives of other Eurasian and Pacific cryptotympanine genera. This tree shows that Tibicen contains several well-supported clades, one predominating in eastern and central North America and related to Cryptotympana Stål and Raiateana Boulard, another in western North America related to Cacama and Cornuplura, and at least two clades in Eurasia. We also present a morphological cladistic analysis of Tibicen and its close allies based on 27 characters. Character states identified in the cladistic analysis define three new genera, two for North American taxa (Hadoa gen. n. and Neotibicen gen. n.) including several Mexican species, and one for Asian species (Subsolanus gen. n.). Using relaxed molecular clocks and literature-derived mtDNA rate estimates, we estimate the timeframe of diversification of Tibicen clades and find that intergeneric divergence has occurred since the late Eocene, with most extant species within the former Tibicen originating after the mid-Miocene. We review patterns of ecology, behavior, and geography among Tibicen clades in light of the phylogenetic results and note that the study of these insects is still in its early stages. Some Mexican species formerly placed in Tibicen are here transferred to Diceroprocta, following refinement of the definition of that genus.
Garra robertsi, a new cyprinid (Cypriniformes: Cyprinidae) fish species from Borneo
Authors: THONI RYAN J. , MAYDEN RICHARD L.
Published: July 2015

Garra robertsi is described from specimens collected from the Sungai Bongan and Tempassuk rivers in Sabah, Borneo. The species is differentiated from G. borneensis, its only congener on the island of Borneo, in having five (versus four) transverse scale rows above lateral line, the first branched dorsal-fin ray extending beyond the posterior-most extent of any other part of the dorsal fin when depressed (versus not extending posteriorly beyond last ray when depressed), breast with deeply embedded scales (versus exposed scales), fewer tubercles on snout, thin (versus thick) anteromedial fold on the lower lip, absence (versus presence) of a lateral stripe, absence (versus presence) of a stark, contrasting black stripe on lower caudal-fin rays, and other pigmentation characteristics.