bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review on the Effects of Botanicals on Skeletal Muscle Health in Order to Prevent Sarcopenia
Authors: Rondanelli M. , Miccono A. , Peroni G. , Guerriero F. , Morazzoni P. , Riva A. , Guido D. , Perna S.
Published: March 2016

We performed a systematic review to evaluate the evidence‐based medicine regarding the main botanical extracts and their nutraceutical compounds correlated to skeletal muscle health in order to identify novel strategies that effectively attenuate skeletal muscle loss and enhance muscle function and to improve the quality of life of older subjects. This review contains all eligible studies from 2010 to 2015 and included 57 publications. We focused our attention on effects of botanical extracts on growth and health of muscle and divided these effects into five categories: anti‐inflammation, muscle damage prevention, antifatigue, muscle atrophy prevention, and muscle regeneration and differentiation.
Anthropozoonotic Endoparasites in Free-Ranging “Urban” South American Sea Lions (Otaria flavescens)
Authors: Hermosilla Carlos , Silva Liliana M. R. , Navarro Mauricio , Taubert Anja
Published: March 2016

The present study represents the first report on the gastrointestinal endoparasite fauna of a free-ranging “urban” colony of South American sea lions (Otaria flavescens) living within the city of Valdivia, Chile. A total of 40 individual faecal samples of South American sea lions were collected during the year 2012 within their natural habitat along the river Calle-Calle and in the local fish market of Valdivia. Coprological analyses applying sodium acetate acetic formalin methanol (SAF) technique, carbol fuchsin-stained faecal smears and Giardia/Cryptosporidium coproantigen ELISAs, revealed infections with 8 different parasites belonging to protozoan and metazoan taxa with some of them bearing anthropozoonotic potential. Thus, five of these parasites were zoonotic (Diphyllobothriidae gen. sp., Anisakidae gen. sp., Giardia, Cryptosporidium, and Balantidium). Overall, these parasitological findings included four new parasite records for Otaria flavescens, that is, Giardia, Cryptosporidium, Balantidium, and Otostrongylus. The current data serve as a baseline for future monitoring studies on anthropozoonotic parasites circulating in these marine mammals and their potential impact on public health.
A High Rated Solar Water Distillation Unit for Solar Homes
Authors: Saxena Abhishek , Deval Navneet
Published: March 2016

India is presently focusing on complete utilization of solar energy and saving fossil fuels, which are limited. Various solar energy systems like solar cookers, solar water heaters, solar lanterns, solar PV lights, and solar lamps are continuously availing by the people of India at a low cost and on good subsidies. Apart from this, India is a solar energy promising country with a good number of solar homes (carrying solar energy systems) in its various locations. The present paper focuses on a unique combination of solar dish cooker (SDC) and solar water heater (SWH) to produce distilled water with a high distillate and a high daily productivity. The procedure has been discussed on the basis of experimental testing to produce distilled water by combining an evacuated type SWH and a SDC. Experimentation has been carried out in MIT, Moradabad (longitude, 28.83°N, and latitude, 78.78°E) by developing the same experimental setup on behalf of solar homes. The daily productivity of distilled water was found around 3.66 litres per day in full sunshine hours for an approximated pH value of 7.7 and a ppm value of 21. The payback period (PBP) has been estimated around 1.16 years of the present system.
The Three-Dimensional Velocity Distribution of Wide Gap Taylor-Couette Flow Modelled by CFD
Authors: Adebayo David Shina , Rona Aldo
Published: March 2016

A numerical investigation is conducted for the flow between two concentric cylinders with a wide gap, relevant to bearing chamber applications. This wide gap configuration has received comparatively less attention than narrow gap journal bearing type geometries. The flow in the gap between an inner rotating cylinder and an outer stationary cylinder has been modelled as an incompressible flow using an implicit finite volume RANS scheme with the realisablek-εmodel. The model flow is above the critical Taylor number at which axisymmetric counterrotating Taylor vortices are formed. The tangential velocity profiles at all axial locations are different from typical journal bearing applications, where the velocity profiles are quasilinear. The predicted results led to two significant findings of impact in rotating machinery operations. Firstly, the axial variation of the tangential velocity gradient induces an axially varying shear stress, resulting in local bands of enhanced work input to the working fluid. This is likely to cause unwanted heat transfer on the surface in high torque turbomachinery applications. Secondly, the radial inflow at the axial end-wall boundaries is likely to promote the transport of debris to the junction between the end-collar and the rotating cylinder, causing the build-up of fouling in the seal.
Possible Role of Interaction between PPARαand Cyclophilin D in Cardioprotection of AMPK againstIn VivoIschemia-Reperfusion in Rats
Authors: Barreto-Torres Giselle , Javadov Sabzali
Published: March 2016

Activated AMPK protects the heart from cardiac ischemia-reperfusion (IR) injury and is associated with inhibition of mitochondrial permeability transition pore (PTP) opening. On the other hand, pharmacological inhibition of the PTP reduces infarct size and improves cardiac function. However, it is unclear whether beneficial effects of AMPK are mediated through the PTP and, if they are not, whether simultaneous activation of AMPK and inhibition of the PTP exert synergistic protective effects against cardiac IR injury. Here, we examined the effects of the AMPK activator, A-769662 in combination with the PTP inhibitor, sanglifehrin A (SfA) onin vivocardiac IR. Cardiac dysfunction following IR injury was associated with decreased activity of the mitochondrial electron transport chain (ETC) and increased mitochondrial ROS and PTP opening. Administration of A-769662 or SfA individually upon reperfusion improved cardiac function, reduced infarction size, and inhibited ROS production and PTP opening. However, simultaneous administration of SfA and A-769662 did not provide synergistic improvement of postischemic recovery of cardiac and mitochondrial function, though both compounds disrupted IR-induced interaction between PPARαand CyP-D. In conclusion, A-769662 or SfA prevents PPARαinteraction with CyP-D, improving cardiac outcomes and increasing mitochondrial function, and simultaneous administration of the drugs does not provide synergistic effects.
The Effect of Oseltamivir on the Disease Progression of Lethal Influenza A Virus Infection: Plasma Cytokine and miRNA Responses in a Mouse Model
Authors: Chockalingam Ashok K. , Hamed Salaheldin , Goodwin David G. , Rosenzweig Barry A. , Pang Eric , Boyne II Michael T. , Patel Vikram
Published: March 2016

Lethal influenza A virus infection leads to acute lung injury and possibly lethal complications. There has been a continuous effort to identify the possible predictors of disease severity. Unlike earlier studies, where biomarkers were analyzed on certain time points or days after infection, in this study biomarkers were evaluated over the entire course of infection. Circulating proinflammatory cytokines and/or miRNAs that track with the onset and progression of lethal A/Puerto Rico/8/34 (PR8) influenza A virus infection and their response to oseltamivir treatment were investigated up to 10 days after infection. Changes in plasma cytokines (IL-1β, IL-10, IL-12p70, IL-6, KC, TNF-α, and IFN-γ) and several candidate miRNAs were profiled. Among the cytokines analyzed, IL-6 and KC/GRO cytokines appeared to correlate with peak viral titer. Over the selected 48 miRNAs profiled, certain miRNAs were up- or downregulated in a manner that was dependent on the oseltamivir treatment and disease severity. Our findings suggest that IL-6 and KC/GRO cytokines can be a potential disease severity biomarker and/or marker for the progression/remission of infection. Further studies to explore other cytokines, miRNAs, and lung injury proteins in serum with different subtypes of influenza A viruses with varying disease severity may provide new insight into other unique biomarkers.
Improved Delivery of Caffeic Acid through Liposomal Encapsulation
Authors: Katuwavila Nuwanthi P. , Perera A. D. L. Chandani , Karunaratne V. , Amaratunga Gehan A. J. , Karunaratne D. Nedra
Published: March 2016

Photoageing resulting from long term exposure of the skin to UV light can be minimized by scavenging the reactive photochemical intermediates with antioxidants. For effective photoprotection, the antioxidant must overcome the barrier properties of the skin and reach the target site in significant amounts. The present study aims to improve the skin penetration of caffeic acid, a very effective free radical scavenger, by encapsulating in liposomes. Caffeic acid loaded liposomes prepared using the reverse phase evaporation technique showed 70% encapsulation efficiency and size around 100 nm with zeta potential of −55 mV.In vitrodiffusion through a dialysis membrane enabled 70% release of encapsulated caffeic acid within 7 h, whereas 95% of free caffeic acid diffused within 4 h in PBS solution (pH 7.4). Liposomal caffeic acid permeation through pig skin epidermis in a Franz cell apparatus was 45 % during 7 h. In contrast, free caffeic acid was almost nonpermeable (<5%) to pig skin during this time. The DPPH assay indicated that skin penetration did not destroy the antioxidant activity of liposomal caffeic acid or free caffeic acid. In conclusion, we confirm that liposomal caffeic acid may be successfully employed as an effective photoprotective agent against UV mediated skin damage.
MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival
Authors: Mima Kosuke , Nishihara Reiko , Yang Juhong , Dou Ruoxu , Masugi Yohei , Shi Yan , da Silva Annacarolina , Cao Yin , Song Mingyang , Nowak Jonathan , Gu Mancang , Li Wanwan , Morikawa Teppei , Zhang Xuehong , Wu Kana , Baba Hideo , Giovannucci Edward L. , Meyerhardt Jeffrey A. , Chan Andrew T. , Fuchs Charles S. , Qian Zhi Rong , Ogino Shuji
Published: March 2016

Purpose: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2; a target of aspirin) produces inflammatory mediator prostaglandin E2 (PGE2), and contributes to colorectal neoplasia development. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE2 level by downregulating PGE2-metabolizing enzymes. We hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on inflammatory tumor microenvironment and be stronger in tumors expressing high-level PTGS2.

Experimental Design: Utilizing 765 rectal and colon cancer specimens in the Nurses' Health Study and the Health Professionals Follow-up Study, we measured MIR21 expression by quantitative reverse transcription PCR, and PTGS2 expression by immunohistochemistry. Cox proportional hazards regression model was used to assess statistical interaction between MIR21 and PTGS2 in colorectal cancer–specific survival analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations.

Results: Tumor MIR21 expression level was associated with higher colorectal cancer–specific mortality (Ptrend = 0.029), and there was a statistically significant interaction between MIR21 and PTGS2 (Pinteraction = 0.0004). The association between MIR21 expression and colorectal cancer–specific mortality was statistically significant in PTGS2-high cancers (multivariable hazard ratio of the highest vs. lowest quartile of MIR21, 2.28; 95% confidence interval, 1.42–3.67; Ptrend = 0.0004) but not in PTGS2-absent/low cancers (Ptrend = 0.22).

Conclusions: MIR21 expression level in colorectal carcinoma is associated with worse clinical outcome, and this association is stronger in carcinomas expressing high-level PTGS2, suggesting complex roles of immunity and inflammation in tumor progression. Clin Cancer Res; 22(15); 3841–8. ©2016 AACR.
Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs)
Authors: Alfaro Carlos , Teijeira Alvaro , Oñate Carmen , Pérez Guiomar , Sanmamed Miguel F. , Andueza Maria Pilar , Alignani Diego , Labiano Sara , Azpilikueta Arantza , Rodriguez-Paulete Alfonso , Garasa Saray , Fusco Juan P. , Aznar Angela , Inogés Susana , De Pizzol Maria , Allegretti Marcello , Medina-Echeverz Jose , Berraondo Pedro , Perez-Gracia Jose L. , Melero Ignacio
Published: March 2016

Purpose: Myeloid-derived suppressor cells (MDSC) are considered an important T-cell immunosuppressive component in cancer-bearing hosts. The factors that attract these cells to the tumor microenvironment are poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes.

Experimental Design: MDSC were characterized and sorted by multicolor flow cytometry on ficoll-gradient isolated blood leucokytes from healthy volunteers (n = 10) and advanced cancer patients (n = 28). In chemotaxis assays, sorted granulocytic and monocytic MDSC were tested in response to recombinant IL8, IL8 derived from cancer cell lines, and patient sera. Neutrophil extracellular traps (NETs) formation was assessed by confocal microscopy, fluorimetry, and time-lapse fluorescence confocal microscopy on short-term MDSC cultures.

Results: IL8 chemoattracts both granulocytic (GrMDSC) and monocytic (MoMDSC) human MDSC. Monocytic but not granulocytic MDSC exerted a suppressor activity on the proliferation of autologous T cells isolated from the circulation of cancer patients. IL8 did not modify the T-cell suppressor activity of human MDSC. However, IL8 induced the formation of NETs in the GrMDSC subset.

Conclusions: IL8 derived from tumors contributes to the chemotactic recruitment of MDSC and to their functional control. Clin Cancer Res; 22(15); 3924–36. ©2016 AACR.
Transposon Mutagenesis Reveals Fludarabine Resistance Mechanisms in Chronic Lymphocytic Leukemia
Authors: Pandzic Tatjana , Larsson Jimmy , He Liqun , Kundu Snehangshu , Ban Kenneth , Akhtar-Ali Muhammad , Hellström Anders R. , Schuh Anna , Clifford Ruth , Blakemore Stuart J. , Strefford Jonathan C. , Baumann Tycho , Lopez-Guillermo Armando , Campo Elias , Ljungström Viktor , Mansouri Larry , Rosenquist Richard , Sjöblom Tobias , Hellström Mats
Published: March 2016

Purpose: To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control.

Experimental Design: We used piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line.

Results: In total, this screen identified 782 genes with transposon integrations in fludarabine-resistant pools of cells. One of the identified genes is a known resistance mediator DCK (deoxycytidine kinase), which encodes an enzyme that is essential for the phosphorylation of the prodrug to the active metabolite. BMP2K, a gene not previously linked to CLL, was also identified as a modulator of response to fludarabine. In addition, 10 of 782 transposon-targeted genes had previously been implicated in treatment resistance based on somatic mutations seen in patients refractory to fludarabine-based therapy. Functional characterization of these genes supported a significant role for ARID5B and BRAF in fludarabine sensitivity. Finally, pathway analysis of transposon-targeted genes and RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL.

Conclusions: To our knowledge, this is the first forward genetic screen for chemotherapy resistance in CLL. The screen pinpointed novel genes and pathways involved in fludarabine resistance along with previously known resistance mechanisms. Transposon screens can therefore aid interpretation of cancer genome sequencing data in the identification of genes modifying sensitivity to chemotherapy. Clin Cancer Res; 22(24); 6217–27. ©2016 AACR.
Pharmacology in the Era of Targeted Therapies: The Case of PI3K Inhibitors
Authors: Toska Eneda , Baselga José
Published: March 2016

The PI3K pathway is often aberrantly activated in estrogen receptor positive (ER+) breast cancer and therapies combining PI3K inhibitors and antiestrogens are under clinical development. Given that many PI3K inhibitors have substantial toxicities with continuous dosing and that alternate dosing schedules are equally active, further clinical exploration is warranted. Clin Cancer Res; 22(9); 2099–101. ©2016 AACR.

See related article by Yang et al., p. 2250
Predictive Biomarkers for PD-1 Axis Therapies: The Hidden Treasure or a Call for Research
Authors: Schalper Kurt A. , Kaftan Edward , Herbst Roy S.
Published: March 2016

Blockade of the PD-1 axis has emerged as an effective anticancer immunotherapy against various tumor types. Diverse studies have identified biomarkers associated with response to these therapies. However, the clinical use of such tests is limited by their variable performance and restricted understanding of their biologic significance. Clin Cancer Res; 22(9); 2102–4. ©2016 AACR.

See related article by Ock et al., p. 2261
Functional Gene Markers for Fumarate-Adding and Dearomatizing Key Enzymes in Anaerobic Aromatic Hydrocarbon Degradation in Terrestrial Environments
Authors: von Netzer Frederick , Kuntze Kevin , Vogt Carsten , Richnow Hans H. , Boll Matthias , Lueders Tillmann
Published: March 2016

Anaerobic degradation is a key process in many environments either naturally or anthropogenically exposed to petroleum hydrocarbons. Considerable advances into the biochemistry and physiology of selected anaerobic degraders have been achieved over the last decades, especially for the degradation of aromatic hydrocarbons. However, researchers have only recently begun to explore the ecology of complex anaerobic hydrocarbon degrader communities directly in their natural habitats, as well as in complex laboratory systems using tools of molecular biology. These approaches have mainly been facilitated by the establishment of a suite of targeted marker gene assays, allowing for rapid and directed insights into the diversity as well as the identity of intrinsic degrader populations and degradation potentials established at hydrocarbon-impacted sites. These are based on genes encoding either peripheral or central key enzymes in aromatic compound breakdown, such as fumarate-adding benzylsuccinate synthases or dearomatizing aryl-coenzyme A reductases, or on aromatic ring-cleaving hydrolases. Here, we review recent advances in this field, explain the different detection methodologies applied, and discuss how the detection of site-specific catabolic gene markers has improved the understanding of processes at contaminated sites. Functional marker gene-based strategies may be vital for the development of a more elaborate population-based assessment and prediction of aromatic degradation potentials in hydrocarbon-impacted environments.
Metabolism of Hydrocarbons in n-Alkane-Utilizing Anaerobic Bacteria
Authors: Wilkes Heinz , Buckel Wolfgang , Golding Bernard T. , Rabus Ralf
Published: March 2016

The glycyl radical enzyme-catalyzed addition of n-alkanes to fumarate creates a C-C-bond between two concomitantly formed stereogenic carbon centers. The configurations of the two diastereoisomers of the product resulting from n-hexane activation by the n-alkane-utilizing denitrifying bacterium strain HxN1, i.e. (1-methylpentyl)succinate, were assigned as (2S,1′R) and (2R,1′R). Experiments with stereospecifically deuterated n-(2,5-2H2)hexanes revealed that exclusively the pro-S hydrogen atom is abstracted from C2 of the n-alkane by the enzyme and later transferred back to C3 of the alkylsuccinate formed. These results indicate that the alkylsuccinate-forming reaction proceeds with an inversion of configuration at the carbon atom (C2) of the n-alkane forming the new C-C-bond, and thus stereochemically resembles a SN2-type reaction. Therefore, the reaction may occur in a concerted manner, which may avoid the highly energetic hex-2-yl radical as an intermediate. The reaction is associated with a significant primary kinetic isotope effect (kH/kD ≥3) for hydrogen, indicating that the homolytic C-H-bond cleavage is involved in the first irreversible step of the reaction mechanism. The (1-methylalkyl)succinate synthases of n-alkane-utilizing anaerobic bacteria apparently have very broad substrate ranges enabling them to activate not only aliphatic but also alkyl-aromatic hydrocarbons. Thus, two denitrifiers and one sulfate reducer were shown to convert the nongrowth substrate toluene to benzylsuccinate and further to the dead-end product benzoyl-CoA. For this purpose, however, the modified β-oxidation pathway known from alkylbenzene-utilizing bacteria was not employed, but rather the pathway used for n-alkane degradation involving CoA ligation, carbon skeleton rearrangement and decarboxylation. Furthermore, various n-alkane- and alkylbenzene-utilizing denitrifiers and sulfate reducers were found to be capable of forming benzyl alcohols from diverse alkylbenzenes, putatively via dehydrogenases. The thermophilic sulfate reducer strain TD3 forms n-alkylsuccinates during growth with n-alkanes or crude oil, which, based on the observed patterns of homologs, do not derive from a terminal activation of n-alkanes.
Clinical and Echocardiographic Factors Associated with Right Ventricular Systolic Dysfunction in Hemodialysis Patients
Authors: López-Quijano Juan Manuel , Gordillo-Moscoso Antonio , Viana-Rojas Jesús Antonio , Carrillo-Calvillo Jorge , Mandeville Peter B. , Chevaile-Ramos Alejandro
Published: March 2016

Background: Chronic kidney disease is a disorder of epidemic proportions that impairs cardiac function. Cardiovascular diseases are the leading cause of death in hemodialysis patients, and the understanding of new nontraditional predictors of mortality could improve their outcomes. Right ventricular systolic dysfunction (RVSD) has recently been recognized as a predictor of cardiovascular death in heart failure and hemodialysis patients. However, the factors contributing to RVSD in hemodialysis patients remain unknown. The aim of this study was to evaluate the clinical and echocardiographic factors associated with RVSD in hemodialysis patients. Methods: A cross-sectional study was conducted in which 100 outpatients with end-stage renal disease on chronic hemodialysis were evaluated. A transthoracic echocardiographic examination was performed at optimal dry weight. Right ventricular systolic function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Clinical and echocardiographic data were recorded for each patient. A multivariate linear logistic regression was created using RVSD (TAPSE <14 mm) as the dependent variable. Results: Fifteen patients with RVSD and 85 patients without RVSD were analyzed. TAPSE had a positive correlation with left ventricular ejection fraction (LVEF) and myocardial relaxation velocity. Independent contributors to RVSD were LVEF (OR 1.14, 95% CI 1.05-1.26), left ventricular mass index (OR 1.02, 95% CI 1.00-1.04), and myocardial relaxation velocity (OR 1.81, 95% CI 1.18-3.19). Conclusions: Echocardiographic factors were significant contributors to RVSD. These measurements could be included as part of the routine workup in all end-stage renal disease patients on hemodialysis.
Growth Hormone Deficiency in Prepubertal Children: Predictive Markers of Cardiovascular Disease
Authors: De Leonibus Chiara , De Marco Stefania , Stevens Adam , Clayton Peter , Chiarelli Francesco , Mohn Angelika
Published: March 2016

Background: Cardiovascular (CV) risk factors have been identified in adults with untreated growth hormone deficiency (GHD). Existing evidence suggests that the development of the atheromatous plaque begins early in childhood. Previous reports have shown that GHD children are prone to increased CV risks including impaired cardiac function, dyslipidemia and abnormalities in body composition. Recent studies in epigenetics and metabolomics have defined specific fingerprints that might be associated with an increased risk of CV disease. Aim: The aim of this review is to point out the most significant biochemical and clinical predictive markers of CV disease in prepubertal children and to evaluate the effect of recombinant human growth hormone therapy on most of these alterations. The novel findings in epigenetics and metabolomics are also reviewed, with a particular focus on translating them into clinical practice.
Plagiocephaly due to Frontosphenoidal Suture Synostosis: Report of 2 Cases and Literature Review
Authors: Ben Nsir Atef , Darmoul Mehdi , Zemmali Maroua , Slimane Abdelhafidh , Hattab Nejib
Published: March 2016

Background/Aims: The most common cause of anterior plagiocephaly is the fusion of the unilateral coronal suture. In some rare cases, however, the fusion of the frontosphenoidal suture may lead to a resembling pattern with specific clinical and radiological features. The aim of the present study is to further enlighten this entity as it is misdiagnosed most of the time. Methods: A report of 2 cases of plagiocephaly due to frontosphenoidal synostosis with a review of the literature. Results: One female and one male baby were identified. The mean age at presentation was 11.5 months (range: 1-22). Head circumference was normal in each patient. The two fusions were on the left side. Unilateral frontal flattening and recession of the supraorbital rim were the most important physical findings. Computed tomography confirmed the patency of the frontoparietal suture and the closure of the frontosphenoidal suture. Fronto-orbital advancement was performed in both cases with good cosmetic outcome. Conclusion: Frontosphenoidal synostosis should be suspected and carefully searched when dealing with plagiocephaly with patent coronal suture. Good outcome requires a prompt diagnosis and early correction.
Impact of Pre-Dialysis Care on Clinical Outcomes in Peritoneal Dialysis Patients
Authors: Spigolon Dandara N. , de Moraes Thyago P. , Figueiredo Ana E. , Modesto Ana Paula , Barretti Pasqual , Bastos Marcus Gomes , Barreto Daniela V. , Pecoits-Filho Roberto ,   on behalf of BRAZPD Investigators
Published: March 2016

Background: Structured pre-dialysis care is associated with an increase in peritoneal dialysis (PD) utilization, but not with peritonitis risk, technical and patient survival. This study aimed at analyzing the impact of pre-dialysis care on these outcomes. Methods: All incident patients starting PD between 2004 and 2011 in a Brazilian prospective cohort were included in this analysis. Patients were divided into 2 groups: early pre-dialysis care (90 days of follow-up by a nephrology team); and late pre-dialysis care (absent or less than 90 days follow-up). The socio-demographic, clinical and biochemical characteristics between the 2 groups were compared. Risk factors for the time to the first peritonitis episode, technique failure and mortality based on Cox proportional hazards models. Results: Four thousand one hundred seven patients were included. Patients with early pre-dialysis care presented differences in gender (female - 47.0 vs. 51.1%, p = 0.01); race (white - 63.8 vs. 71.7%, p < 0.01); education (<4 years - 61.9 vs. 71.0%, p < 0.01), respectively, compared to late care. Patients with early pre-dialysis care presented a higher prevalence of comorbidities, lower levels of creatinine, phosphorus, and glucose with a significantly better control of hemoglobin and potassium serum levels. There was no impact of pre-dialysis care on peritonitis rates (hazard ratio (HR) 0.88; 95% CI 0.77-1.01) and technique survival (HR 1.12; 95% CI 0.92-1.36). Patient survival (HR 1.20; 95% CI 1.03-1.41) was better in the early pre-dialysis care group. Conclusion: Earlier pre-dialysis care was associated with improved patient survival, but did not influence time to the first peritonitis nor technique survival in this national PD cohort.
5-Methylcytosine-Rich Heterochromatin in the Indian Muntjac
Authors: Schmid Michael , Steinlein Claus , Lomb Christian , Sperling Karl , Neitzel Heidemarie
Published: March 2016

Two 5-methylcytosine (5-MeC)-rich heterochromatic regions were demonstrated in metaphase chromosomes of the Indian muntjac by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. The metaphases were obtained from diploid and triploid cell lines. A major region is located in the ‘neck' of the 3;X fusion chromosome and can be detected after denaturation of the chromosomal DNA with UV-light irradiation for 1 h. It is located exactly at the border of the X chromosome and the translocated autosome 3. A minor region is found in the centromeric region of the free autosome 3 after denaturing the chromosomal DNA for 3 h or longer. The structure and possible function of the major hypermethylated region as barrier against spreading of the X-inactivation process into the autosome 3 is discussed.
Neoadjuvant Dose-Dense and Dose-Intensified Chemotherapy in Breast Cancer - Review of the Literature
Authors: Reinisch Mattea , Ataseven Beyhan , Kümmel Sherko
Published: March 2016

Dose-dense chemotherapy in the adjuvant and neoadjuvant setting has been intensively examined over the past few decades, and even seems to have become a standard regimen in certain subgroups of patients with increased risk of relapse. Nevertheless, there are conflicting data regarding the absolute benefit of this regimen, especially in the neoadjuvant setting. Pathological complete response (pCR) is used as a surrogate marker for disease-free and overall survival. Meta-analyses have recently questioned the use of pCR as a generalized prognostic tool for all subgroups, but also determined a correlation between treatment effects on the surrogate outcome and the treatment effect on the clinical outcome in the cohort of patients receiving dose-dense chemotherapy. The present paper gives an overview of the definitions of dose-dense and dose-intensified chemotherapy regimens and of the literature for neoadjuvant dose-dense, dose-intensified studies, and summarizes the outcome of these studies.
The Use of a Novel Optical Algorithm in the Diagnosis of Cervical Pre-Invasive Pathology - A Preliminary Proof of Principal Study
Authors: Eitan Ram , Krissi Haim , Peled Yoav , Braslavsky Diana , Binyamin Liat , Peretz-Davidi Yael , Seadia Oz , Landesman Ilan
Published: March 2016

Objective: To develop a novel optical probe monitoring cervical tissues in real-time and to compare the new imaging technique to actual cervical pathologic findings on resected cone biopsy specimens. Methods: A loop electro-excisional procedure was performed on 15 women with a biopsy diagnosis of dysplasia. The conization specimen was then assessed with the novel optical system and results recorded. The ‘normal' and ‘abnormal' areas were tested by the optical setup at several points. Extracted parameters were used as the input of the classifier function of a logistic regression algorithm model to assess for system accuracy vs. clinical examination. Results: Ninety-seven samples were taken - forty-five samples from ‘abnormal zones' and 42 samples from ‘normal zones', as defined by the surgeon. The pathologist diagnosed 58 samples as dysplastic and 39 samples as normal. The novel optical method predicted 58 sample points as abnormal and 39 points as normal. The sensitivity of the system was 90% with a specificity of 77%. The probability of correct differentiation of dysplastic cervical tissue from normal cervical tissue was 85%. Conclusions: The optical probe and the algorithms of image processing in combination with the logistic regression algorithm correlated well with pathology results for cervical dysplasia ex-vivo.
Elevated Triglyceride Level Is Independently Associated With Increased All-Cause Mortality in Patients With Established Coronary Heart Disease
Authors: Klempfner Robert , Erez Aharon , Sagit Ben-Zekry , Goldenberg Ilan , Fisman Enrique , Kopel Eran , Shlomo Nir , Israel Ariel , Tenenbaum Alexander
Published: March 2016

Background—

The independent association between elevated triglycerides and all-cause mortality among patients with established coronary heart disease is controversial. The aim of this study was to investigate this association in a large cohort of patients with proven coronary heart disease.

Methods and Results—

The study cohort comprised 15 355 patients who were screened for the Bezafibrate Infarction Prevention (BIP) trial. Twenty-two–year mortality data were obtained from the national registry. Patients were divided into 5 groups according to strata of fasting serum triglycerides: (1) low-normal triglycerides (<100 mg/dL); (2) high-normal triglycerides (100–149 mg/dL); (3) borderline hypertriglyceridemia triglycerides (150–199 mg/dL); (4) moderate hypertriglyceridemia triglycerides (200–499 mg/dL); (5) severe hypertriglyceridemia triglycerides (≥500 mg/dL). Age- and sex-adjusted survival was 41% in the low-normal triglycerides group than 37%, 36%, 35%, and 25% in groups with progressively higher triglycerides (
P
<0.001). In an adjusted Cox-regression for various covariates including high-density lipoprotein cholesterol, each 1 unit of natural logarithm (Ln) triglycerides elevation was associated with a corresponding 6% (
P
=0.016) increased risk of 22-year all-cause mortality. The 22-year mortality risk for patients with severe hypertriglyceridemia was increased by 68% when compared with patients with low-normal triglycerides (
P
<0.001).

Conclusions—

In patients with established coronary heart disease, higher triglycerides levels are independently associated with increased 22-year mortality. Even in patients with triglycerides of 100 to 149 mg/dL, the elevated risk for death could be detected than in patients with lower triglycerides levels, whereas severe hypertriglyceridemia denotes a population with particularly increased mortality risk.
Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo
Authors: Shen Yujun , Zuo Shengkai , Wang Yuanyang , Shi Hongfei , Yan Shuai , Chen Di , Xiao Bing , Zhang Jian , Gong Yanjun , Shi Maohua , Tang Juan , Kong Deping , Lu Luheng , Yu Yu , Zhou Bin , Duan Sheng-Zhong , Schneider Claudio , Funk Colin D. , Yu Ying
Published: March 2016

Rationale:

Autologous adipose-derived stromal cells (ASCs) offer great promise as angiogenic cell therapy for ischemic diseases. Because of their limited self-renewal capacity and pluripotentiality, the therapeutic efficacy of ASCs is still relatively low. Thromboxane has been shown to play an important role in the maintenance of vascular homeostasis. However, little is known about the effects of thromboxane on ASC-mediated angiogenesis.

Objective:

To explore the role of the thromboxane-prostanoid receptor (TP) in mediating the angiogenic capacity of ASCs in vivo.

Methods and Results:

ASCs were prepared from mouse epididymal fat pads and induced to differentiate into endothelial cells (ECs) by vascular endothelial growth factor. Cyclooxygenase-2 expression, thromboxane production, and
TP
expression were upregulated in ASCs on vascular endothelial growth factor treatment. Genetic deletion or pharmacological inhibition of TP in mouse or human ASCs accelerated EC differentiation and increased tube formation in vitro, enhanced angiogenesis in in vivo Matrigel plugs and ischemic mouse hindlimbs. TP deficiency resulted in a significant cellular accumulation of β-catenin by suppression of calpain-mediated degradation in ASCs. Knockdown of β-catenin completely abrogated the enhanced EC differentiation of TP-deficient ASCs, whereas inhibition of calpain reversed the suppressed angiogenic capacity of TP re-expressed ASCs. Moreover, TP was coupled with Gαq to induce calpain-mediated suppression of β-catenin signaling through calcium influx in ASCs.

Conclusion:

Thromboxane restrained EC differentiation of ASCs through TP-mediated repression of the calpain-dependent β-catenin signaling pathway. These results indicate that TP inhibition could be a promising strategy for therapy utilizing ASCs in the treatment of ischemic diseases.
Impaired Arm Function and Finger Dexterity in a Nonhuman Primate Model of Stroke
Authors: McEntire Caleb R.S. , Choudhury Gourav R. , Torres April , Steinberg Gary K. , Redmond D. Eugene , Daadi Marcel M.
Published: March 2016

Background and Purpose—

Ischemic stroke is the leading cause of upper extremity motor impairments. Although several well-characterized experimental stroke models exist, modeling of upper extremity motor impairments, which are unique to primates, is not well established. Cortical representation of dexterous movements in nonhuman primates is functionally and topographically similar to that in humans. In this study, we characterize the African green monkey model of focal ischemia reperfusion with a defined syndrome, impaired dexterous movements.

Methods—

Cerebral ischemia was induced by transient occlusion of the M3 segment of the left middle cerebral artery. Motor and cognitive functions after stroke were evaluated using the object retrieval task with barrier-detour. Postmortem magnetic resonance imaging and histopathology were performed to map and characterize the infarct.

Results—

The middle cerebral artery occlusion consistently produced a necrotic infarct localized in the sensorimotor cortex in the middle cerebral artery territory. The infarction was reproducible and resulted in significant loss of fine motor function characterized by impaired dexterity. No significant cognitive impairment was detected. Magnetic resonance imaging and histopathology demonstrated consistent and significant loss of tissue on the left parietal cortex by the central sulcus covering the sensorimotor area. The results suggest that this species has less collateralization, which closely resembles humans.

Conclusions—

The reported nonhuman primate model produces a defined and reproducible syndrome relevant to our understanding of ischemic stroke, cortical representation, and sensorimotor integration controlling dexterous movements. This model will be useful in basic and translational research addressing loss of arm function and dexterity.
Ein Text aus Palästina? Gedanken zur einleitungswissenschaftlichen Verortung der Apokalypse des Abraham
Authors: Sommer Michael
Published: March 2016

Nearly all scholars focusing on the Apocalypse of Abraham agree that the text originated in Palestine. The reason for this is generally quite simple: on the one hand, the text refers directly to the destruction of the Second Temple, and on the other hand, its storyline has a very strong “Jewish” character. I question the plausibility of this argument. The literary treatment of Jerusalem, the use of Exodus motifs, as well as the role of the cult in the Apocalypse of Abraham differ substantially from other works that were written more likely in the region around Jerusalem. Instead, it is more reasonable to regard the text as a response to the invasion of foreign cults into synagogal structures in a diaspora context. Although it is not possible to locate the text with any certainty, I tentatively propose the area around Alexandria as its place of origin.
Protests against Oil Exploration at Sea: Lessons from the Arctic Sunrise Arbitration
Authors: Mossop Joanna
Published: March 2016

The decision of the Arbitral Tribunal in the Arctic Sunrise case between the Netherlands and Russia offers considerable guidance to coastal States on how to deal with protesters who violate the safety zone of installations under the Law of the Sea Convention. This article considers these lessons and applies them to another recent type of protest: against vessels conducting seismic surveys above the continental shelf. Some countries provide for a non-interference zone around these vessels to prevent protesters from getting close to the survey vessels. Although this was not directly at issue in the Arctic Sunrise case, the Tribunal’s jurisprudence gives guidance as to whether these measures by coastal states to prevent interference are consistent with the Law of the Sea Convention.
The Chagos Marine Protected Area Arbitration: Has the Scope of losc Compulsory Jurisdiction Been Clarified?
Authors: Nguyen Lan Ngoc
Published: March 2016

This article focuses on the jurisdictional issues that arose from the losc Annex vii Arbitral Award of the Chagos Marine Protected Area Arbitration (Mauritius v. United Kingdom). In this case, the arbitral tribunal for the first time answered the long-debated question of whether it has jurisdiction to hear a dispute concerning territorial sovereignty issues. This article argues that in the process of answering this question, the arbitral tribunal managed to identify the steps in order to determine the extent to which its jurisdiction extends to sovereignty disputes. However, the manner in which the tribunal, and the dissenting arbitrators, proceeded with each of these steps left much to be desired in terms of clarity and coherence. The Arbitral Award nonetheless managed to clarify the scope of Article 297 regarding the limitations to compulsory jurisdiction and in determining the threshold for the fulfilment of Article 283 on the obligation to exchange views.
Bonding during the Night of the Churches Converging and Differing Experiences of Churchgoers and Non-Churchgoers
Authors: de Boer Elpine M. , de Roest Henk
Published: March 2016

How should we understand the paradoxical phenomenon that people are showing substantial interest in new events organized by the church in a western-European society that is characterized by dwindling church attendance? An explorative questionnaire study among churchgoers ( n = 1016) and non-churchgoers ( n = 317) was conducted who chose to attend the so-called Night of the Churches in the Netherlands. The majority of the respondents indicated that they experience the Night of the Churches to be a qualitatively different phenomenon from other festivals (e.g., museum night or music festival). Our data suggest that for both churchgoers and non-churchgoers shared bonding experiences (e.g., a special feeling of connectedness, contact with a higher spirit, together with unknown people) are what makes a Night of the Churches unique. Additionally, the results reveal that this event hardly changed respondents’ image of the church and that more churchgoers (22%) than non-churchgoers (13%) were interested in new forms of being church. Again, shared bonding experiences make the difference when it comes to being open to new ways of being church.
A review of the genus Atrovirensis Kononenko, 2001 with description of four new species from China (Lepidoptera, Noctuidae: Xyleninae, Apameini)
Authors: HAN H.L. , PAN Z.H. , Kononenko V.S.
Published: March 2016

The genus Atrovirensis Kononenko, 2001 is reviewed. Four new species (Atrovirensis parannamita sp. n., Atrovirensis furcatus sp. n., Atrovirensis sacculatus sp. n. and Atrovirensis miraculosus sp. n.) are described from China. A new combination Atrovirensis euplexina (Draudt, 1950), comb. n. [Valeria] is proposed. Two taxa of uncertain status (Atrovirensis sp. cf. parannamita and Atrovirensis sp. cf. furcatus) are included to the review. The updated checklist of the genus is presented. All taxa of the genus Atrovirensis are illustrated in colour with black and white photographs of their genitalia in 48 figures.
“The Stippling Shows Statistically Significant Grid Points”: How Research Results are Routinely Overstated and Overinterpreted, and What to Do about It
Authors: Wilks D. S.
Published: March 2016

Special care must be exercised in the interpretation of multiple statistical hypothesis tests—for example, when each of many tests corresponds to a different location. Correctly interpreting results of multiple simultaneous tests requires a higher standard of evidence than is the case when evaluating results of a single test, and this has been known in the atmospheric sciences literature for more than a century. Even so, the issue continues to be widely ignored, leading routinely to overstatement and overinterpretation of scientific results, to the detriment of the discipline. This paper reviews the history of the multiple-testing issue within the atmospheric sciences literature and illustrates a statistically principled and computationally easy approach to dealing with it—namely, control of the false discovery rate.
Prevalence, characterization, and antibiotic susceptibility of Vibrio parahaemolyticus isolated from retail aquatic products in North China
Authors: Xu Xiaoke , Cheng Jianheng , Wu Qingping , Zhang Jumei , Xie Tengfei
Published: March 2016

Background

Vibrio parahaemolyticus is a major foodborne pathogen, particularly in Asian countries. Increased occurrence of outbreaks of V. parahaemolyticus gastroenteritis in China indicates the need to evaluation of the prevalence of this pathogenic species. V. parahaemolyticus distribution in shellfish from the eastern coast of China has been reported previously. However, to date, the prevalence of V. parahaemolyticus in retail aquatic products in North China has not been determined. To investigate the prevalence of V. parahaemolyticus in aquatic products in North China, 260 aquatic product samples were obtained from retail markets in 6 provinces of North China from November to December in 2012 and July to August in 2013.

Results

V. parahaemolyticus was detected in 94 (36.2 %) of the samples by the most probable number method. The density of V. parahaemolyticus ranged from 1.50 to 1100 MPN/g. V. parahaemolyticus was detected at a rate of 50.0 % and 22.7 % in summer and in winter, respectively. The density of V. parahaemolyticus was significantly higher in summer than in winter, with mean levels of 16.5 MPN/g and 5.0 MPN/g, respectively. Among 145 V. parahaemolyticus isolates examined, none of the isolates possessed tdh and trh. In multiplex PCR-based O-antigen serotyping of these 145 isolates, all serotypes, other than O6, O7, and O9, were detected, and serotype O2 was found to be the most prevalent (detected in 54 isolates). The 145 isolates were grouped into 7 clusters by enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) at a similarity coefficient of 0.66. The antimicrobial resistance patterns of these 145 isolates to 12 antimicrobial agents revealed that most of the isolates were resistant to streptomycin (86.2 %), while fewer were resistant to ampicillin (49.6 %), cefazolin (43.5 %), cephalothin (35.9 %), and kanamycin (22.1 %). All of the examined isolates were susceptible to azithromycin and chloramphenicol.

Conclusions

The findings of this study will help in defining appropriate monitoring programs, understanding of the dissemination of antibiotic resistant strains, and providing information for the assessment of exposure to this microorganism at the consumption level.
Draft genome sequence and overview of the purple non sulfur bacterium Rhodopseudomonas palustris 42OL
Authors: Adessi Alessandra , Spini Giulia , Presta Luana , Mengoni Alessio , Viti Carlo , Giovannetti Luciana , Fani Renato , De Philippis Roberto
Published: March 2016

Rhodopseudomonas palustris strain 42OL was isolated in 1973 from a sugar refinery waste treatment pond. The strain has been prevalently used for hydrogen production processes using a wide variety of waste-derived substrates, and cultured both indoors and outdoors, either freely suspended or immobilized. R. palustris 42OL was suitable for many other applications and capable of growing in very different culturing conditions, revealing a wide metabolic versatility. The analysis of the genome sequence allowed to identify the metabolic pathways for hydrogen and poly-β-hydroxy-butyrate production, and confirmed the ability of using a wide range of organic acids as substrates.