bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5′-terminal regions of cap0-, cap1- and 5′ppp- mRNAs
Authors: Kumar Parimal , Sweeney Trevor R. , Skabkin Maxim A. , Skabkina Olga V. , Hellen Christopher U. T. , Pestova Tatyana V.
Published: December 2013

Ribosomal recruitment of cellular mRNAs depends on binding of eIF4F to the mRNA’s 5′-terminal ‘cap’. The minimal ‘cap0’ consists of N7-methylguanosine linked to the first nucleotide via a 5′-5′ triphosphate (ppp) bridge. Cap0 is further modified by 2′-O-methylation of the next two riboses, yielding ‘cap1’ (m7GpppNmN) and ‘cap2’ (m7GpppNmNm). However, some viral RNAs lack 2′-O-methylation, whereas others contain only ppp- at their 5′-end. Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed effectors of innate immunity that inhibit viral replication by incompletely understood mechanisms. Here, we investigated the ability of IFIT family members to interact with cap1-, cap0- and 5′ppp- mRNAs and inhibit their translation. IFIT1 and IFIT1B showed very high affinity to cap-proximal regions of cap0-mRNAs (K1/2,app ∼9 to 23 nM). The 2′-O-methylation abrogated IFIT1/mRNA interaction, whereas IFIT1B retained the ability to bind cap1-mRNA, albeit with reduced affinity (K1/2,app ∼450 nM). The 5′-terminal regions of 5′ppp-mRNAs were recognized by IFIT5 (K1/2,app ∼400 nM). The activity of individual IFITs in inhibiting initiation on a specific mRNA was determined by their ability to interact with its 5′-terminal region: IFIT1 and IFIT1B efficiently outcompeted eIF4F and abrogated initiation on cap0-mRNAs, whereas inhibition on cap1- and 5′ppp- mRNAs by IFIT1B and IFIT5 was weaker and required higher protein concentrations.
An H2A histone isotype regulates estrogen receptor target genes by mediating enhancer-promoter-3′-UTR interactions in breast cancer cells
Authors: Su Chia-Hsin , Tzeng Tsai-Yu , Cheng Ching , Hsu Ming-Ta
Published: December 2013

A replication-dependent histone H2A isotype, H2ac, is upregulated in MCF-7 cells and in estrogen receptor-positive clinical breast cancer tissues. Cellular depletion of this H2A isotype leads to defective estrogen signaling, loss of cell proliferation and cell cycle arrest at G0/G1 phase. H2ac mediates regulation of estrogen receptor target genes, particularly BCL2 and c-MYC, by recruiting estrogen receptor alpha through its HAR domain and facilitating the formation of a chromatin loop between the promoter, enhancer and 3′-untranslated region of the respective genes. These findings reveal a new role for histone isotypes in the regulation of gene expression in cancer cells, and suggest that these molecules may be targeted for anti-cancer drug discovery.
Using Mixed Methods to Examine the Role of Veterans’ Illness Perceptions on Depression Treatment Utilization and HEDIS Concordance
Authors: Elwy A. Rani , Glickman Mark E. , Bokhour Barbara G. , Dell Natalie S. , Mueller Nora M. , Zhao Shibei , Osei-Bonsu Princess E. , Rodrigues Stephanie , Coldwell Craig M. , Ngo Tu A. , Schlosser James , Vielhauer Melanie J. , Pirraglia Paul A. , Eisen Susan V.
Published: December 2013

Background:

Although depression screening occurs annually in the Department of Veterans Affairs (VA) primary care, many veterans may not be receiving guideline-concordant depression treatment.

Objectives:

To determine whether veterans’ illness perceptions of depression may be serving as barriers to guideline-concordant treatment.

Research Design:

We used a prospective, observational design involving a mailed questionnaire and chart review data collection to assess depression treatment utilization and concordance with Healthcare Effectiveness Data and Information Set guidelines adopted by the VA. The Self-Regulation Model of Illness Behavior guided the study.

Subjects:

Veterans who screened positive for a new episode of depression at 3 VA primary care clinics in the US northeast.

Measures:

The Illness Perceptions Questionnaire-Revised, measuring patients’ perceptions of their symptoms, cause, timeline, consequences, cure or controllability, and coherence of depression and its symptoms, was our primary measure to calculate veterans’ illness perceptions. Treatment utilization was assessed 3 months after the positive depression screen through chart review. Healthcare Effectiveness Data and Information Set (HEDIS) guideline-concordant treatment was determined according to a checklist created for the study.

Results:

A total of 839 veterans screened positive for a new episode of depression from May 2009–June 2011; 275 (32.8%) completed the survey. Ninety-two (33.9%) received HEDIS guideline-concordant depression treatment. Veterans’ illness perceptions of their symptoms, cause, timeline, and controllability of depression predicted receiving guideline-concordant treatment.

Conclusions:

Many veterans are not receiving guideline-concordant treatment for depression. HEDIS guideline measures may not be assessing all aspects of quality depression care. Conversations about veterans’ illness perceptions and their specific needs are encouraged to ensure that appropriate treatment is achieved.
Sensitivity of Medicare Claims to Identify Cancer Recurrence in Elderly Colorectal and Breast Cancer Patients
Authors: Warren Joan L. , Mariotto Angela , Melbert Danielle , Schrag Deborah , Doria-Rose Paul , Penson David , Yabroff K. Robin
Published: December 2013

Background:

Researchers are increasingly interested in using observational data to evaluate cancer outcomes following treatment, including cancer recurrence and disease-free survival. Because population-based cancer registries do not collect recurrence data, recurrence is often imputed from health claims, primarily by identifying later cancer treatments after initial treatment. The validity of this approach has not been established.

Research Design:

We used the linked Surveillance, Epidemiology, and End Results-Medicare data to assess the sensitivity of Medicare claims for cancer recurrence in patients very likely to have had a recurrence. We selected newly diagnosed stage II/III colorectal (n=6910) and female breast cancer (n=3826) patients during 1994–2003 who received initial cancer surgery, had a treatment break, and then died from cancer in 1994–2008. We reviewed all claims from the treatment break until death for indicators of recurrence. We focused on additional cancer treatment (surgery, chemotherapy, radiation therapy) as the primary indicator, and used multivariate logistic regression analysis to evaluate patient factors associated with additional treatment. We also assessed metastasis diagnoses and end-of-life care as recurrence indicators.

Results:

Additional treatment was the first indicator of recurrence for 38.8% of colorectal patients and 35.2% of breast cancer patients. Patients aged 70 and older were less likely to have additional treatment (P < 0.05), in adjusted analyses. Over 20% of patients either had no recurrence indicator before death or had end-of-life care as their first indicator.

Conclusions:

Identifying recurrence through additional cancer treatment in Medicare claims will miss a large percentage of patients with recurrences; particularly those who are older.
Reconstitution of Purified VDAC1 into a Lipid Bilayer and Recording of Channel Conductance
Authors: Ben-Hail Danya , Shoshan-Barmatz Varda
Published: December 2013

The functional properties of purified voltage-dependent anion-selective channel protein 1 (VDAC1) have been examined in reconstituted systems based on artificially prepared phospholipid bilayers. The most widespread method for the characterization of the pore-forming activity of the mitochondrial VDAC1 protein requires reconstitution of the channel activity into a planar lipid bilayer (PLB) that separates two aqueous compartments. This system is able to produce a refined and large set of information on channel activity. The activity of the channel is reflected in the flow of ions (i.e., current) through a membrane that otherwise represents a barrier to ion flow. The setup thus requires the use of purified protein and a source of continuous current, as well as a sophisticated detector system able to amplify and record low, picoamper-level currents. This system is so efficient that the activity of even a single channel can be detected, allowing for study of VDAC1 at the molecular level.
Acquisition of Mouse Tumor Biopsies through Abdominal Laparotomy
Authors: Sastra Stephen A. , Olive Kenneth P.
Published: December 2013

The static analysis of tumor tissues at a single, terminal end point has been the mainstay of studies in mouse models of cancer. However, with the development of model systems that reproduce the intra- and intertumoral heterogeneity of human tumors, such studies are limited by the need for large numbers of animals to overcome increased intragroup variance. The shortcomings of a single-timepoint approach to molecular analysis are especially apparent in the context of therapeutic studies, in which the dynamic response to treatment is of particular consequence. To mitigate the effects of intertumoral heterogeneity, multiple tissue samples may be harvested from the same tumor at different time points through the use of surgical biopsies. For abdominal tumors, preprocedure imaging may be used to assess the suitability of tumors for biopsy. Sterile surgical techniques are used to access the abdominal cavity, and customized instruments facilitate the immobilization and retrieval of tissue samples from hard or fibrous tumors. Thermoregulation, hemostasis, and wound closure techniques are critical to successful surgical outcomes, whereas appropriate anesthetic, analgesic, and postoperative recovery regimens are important for maintenance of animal welfare. Using a mouse model of pancreatic ductal adenocarcinoma, we present a comprehensive protocol suitable for the routine acquisition of abdominal tumor biopsies.
Microarray Slide Hybridization Using Fluorescently Labeled cDNA
Authors: Ares Manuel
Published: December 2013

Microarray hybridization is used to determine the amount and genomic origins of RNA molecules in an experimental sample. Unlabeled probe sequences for each gene or gene region are printed in an array on the surface of a slide, and fluorescently labeled cDNA derived from the RNA target is hybridized to it. This protocol describes a blocking and hybridization protocol for microarray slides. The blocking step is particular to the chemistry of “CodeLink” slides, but it serves to remind us that almost every kind of microarray has a treatment step that occurs after printing but before hybridization. We recommend making sure of the precise treatment necessary for the particular chemistry used in the slides to be hybridized because the attachment chemistries differ significantly. Hybridization is similar to northern or Southern blots, but on a much smaller scale.
In Vivo Imaging of Axonal and Dendritic Structures in Neonatal Mouse Cortex
Authors: Cruz-Martin Alberto , Portera-Cailliau Carlos
Published: December 2013

Time-lapse in vivo imaging of neuronal structures is critical for understanding the assembly of neural circuits during development. Imaging developing neurons in vivo can be performed with relative ease in lower vertebrates, but ideally, one would also like to image the developing mammalian brain. In vivo chronic imaging of mice is particularly desirable because of the availability of transgenic lines that model human neuropsychiatric disease or those that allow cell- or region-specific expression of fluorescent proteins (e.g., green fluorescent protein [GFP], channelrhodopsins, and genetically encoded calcium indicators). Unfortunately, although chronic imaging of neural structures in adult mice that express GFP is now commonplace, similar approaches in neonatal mice face several additional challenges. First, the small size of the animal complicates the cranial window surgery. Second, there is a tendency for dams to cannibalize pups with head caps. Third, the head cap can impede the normal growth of the skull in neonates, which can limit the duration of imaging. Here, we describe a method for implanting chronic glass-covered cranial windows in the skulls of early postnatal mice through which axonal and dendritic structures can be imaged in vivo over a period of hours or even days.
Imaging MDCK Cysts with a Single (Selective) Plane Illumination Microscope
Authors: Swoger Jim , Pampaloni Francesco , Stelzer Ernst H.K.
Published: December 2013

In modern biology, most optical imaging technologies are applied to two-dimensional cell culture systems. However, investigation of physiological context requires specimens that display the complex three-dimensional (3D) relationship of cells that occurs in tissue sections and in naturally developing organisms. The imaging of highly scattering multicellular specimens presents a number of challenges, including limited optical penetration depth, phototoxicity, and fluorophore bleaching. Light-sheet-based fluorescence microscopy (LSFM) overcomes many drawbacks of conventional fluorescence microscopy by using an orthogonal/azimuthal fluorescence arrangement with independent sets of lenses for illumination and detection. The specimen is illuminated from the side with a thin light sheet that overlaps with the focal plane of a wide-field fluorescence microscope. Optical sectioning and minimal phototoxic damage or photobleaching outside a small volume close to the focal plane are intrinsic properties of LSFM. The principles of LSFM are implemented in the single (or selective) plane illumination microscope (SPIM). Madin–Darby canine kidney (MDCK) cysts grown in extracellular matrix (ECM) hydrogels provide a useful model system for studies of 3D cell biology. Here, we describe protocols for growing MDCK cysts within 3D type I collagen or reconstituted basement membrane (Matrigel) and for imaging these cysts by SPIM.
Light-Sheet-Based Fluorescence Microscopy for Three-Dimensional Imaging of Biological Samples
Authors: Swoger Jim , Pampaloni Francesco , Stelzer Ernst H.K.
Published: December 2013

In modern biology, most optical imaging technologies are applied to two-dimensional cell culture systems; that is, they are used in a cellular context that is defined by hard and flat surfaces. However, a physiological context is not found in single cells cultivated on coverslips. It requires the complex three-dimensional (3D) relationship of cells cultivated in extracellular matrix (ECM) gels, tissue sections, or in naturally developing organisms. In fact, the number of applications of 3D cell cultures in basic research as well as in drug discovery and toxicity testing has been increasing over the past few years. Unfortunately, the imaging of highly scattering multicellular specimens is still challenging. The main issues are the limited optical penetration depth, the phototoxicity, and the fluorophore bleaching. Light-sheet-based fluorescence microscopy (LSFM) overcomes many drawbacks of conventional fluorescence microscopy by using an orthogonal/azimuthal fluorescence arrangement with independent sets of lenses for illumination and detection. The basic idea is to illuminate the specimen from the side with a thin light sheet that overlaps with the focal plane of a wide-field fluorescence microscope. Optical sectioning and minimal phototoxic damage or photobleaching outside a small volume close to the focal plane are intrinsic properties of LSFM. We discuss the basic principles of LSFM and methods for the preparation, embedding, and imaging of 3D specimens used in the life sciences in an implementation of LSFM known as the single (or selective) plane illumination microscope (SPIM).
Application of diffracted wave analysis to time‐lapse seismic data for CO2 leakage detection
Authors: Alonaizi Faisal , Pevzner Roman , Bóna Andrej , Alshamry Mohammad , Caspari Eva , Gurevich Boris
Published: December 2013

Time‐lapse seismic analysis is utilized in CO2 geosequestration to verify the CO2 containment within a reservoir. A major risk associated with geosequestration is a possible leakage of CO2 from the storage formation into overlaying formations. To mitigate this risk, the deployment of carbon capture and storage projects requires fast and reliable detection of relatively small volumes of CO2 outside the storage formation. To do this, it is necessary to predict typical seepage scenarios and improve subsurface seepage detection methods. In this work we present a technique for CO2 monitoring based on the detection of diffracted waves in time‐lapse seismic data. In the case of CO2 seepage, the migrating plume might form small secondary accumulations that would produce diffracted, rather than reflected waves. From time‐lapse data analysis, we are able to separate the diffracted waves from the predominant reflections in order to image the small CO2 plumes. To explore possibilities to detect relatively small amounts of CO2, we performed synthetic time‐lapse seismic modelling based on the Cooperative Research Centre for Greenhouse Gas Technologies (CO2CRC) Otway project data. The detection method is based on defining the CO2 location by measuring the coherency of the signal along diffraction offset‐traveltime curves. The technique is applied to a time‐lapse stacked section using a stacking velocity to construct offset‐traveltime curves. Given the amount of noise found in the surface seismic data, the predicted minimum detectable amount of CO2 is 1000–2000 tonnes. This method was also applied to real data obtained from a time‐lapse seismic physical model. The use of diffractions rather than reflections for monitoring small amounts of CO2 can enhance the capability of subsurface monitoring in CO2 geosequestration projects.
A 27‐point scheme for a 3D frequency‐domain scalar wave equation based on an average‐derivative method
Authors: Chen Jing‐Bo
Published: December 2013

Based on an average‐derivative method and optimization techniques, a 27‐point scheme for a 3D frequency‐domain scalar wave equation is developed. Compared to the rotated‐coordinate approach, the average‐derivative optimal method is not only concise but also applies to equal and unequal directional sampling intervals. The resulting 27‐point scheme uses a 27‐point operator to approximate spatial derivatives and the mass acceleration term. The coefficients are determined by minimizing phase velocity dispersion errors and the resultant optimal coefficients depend on ratios of directional sampling intervals. Compared to the classical 7‐point scheme, the number of grid points per shortest wavelength is reduced from approximately 13 to approximately 4 by this 27‐point optimal scheme for equal directional sampling intervals and unequal directional sampling intervals as well. Two numerical examples are presented to demonstrate the theoretical analysis. The average‐derivative algorithm is also extended to a 3D frequency‐domain viscous scalar wave equation.
Surgical management of placenta accreta: to leave or remove the placenta?
Authors: Perez‐Delboy A , Wright JD
Published: December 2013

Abnromalities of placentation, including placenta accreta, represent a major source of morbidity and mortality among women. Traditional management consists of peripartum hysterectomy at the time of delivery, although more conservative treatments have also been developed recently. In this review we describe the available literature describing the operative approach and considerations for management of women with placenta accreta.
Minimally invasive therapy for gynaecological symptoms related to a niche in the caesarean scar: a systematic review
Authors: van der Voet LF , Vervoort AJ , Veersema S , BijdeVaate AJ , Brölmann HAM , Huirne JAF
Published: December 2013

Background

Various therapies are currently used to treat symptoms related to the niche (an anechoic area) in the caesarean scar, in particular to treat abnormal uterine bleeding (AUB).

Objective

To systematically review the available literature reporting on the effect of various therapies on niche‐related symptoms.

Search strategy

A systematic search of MEDLINE, Embase, Cochrane, trial registers and congress abstracts from AAGL and ESGE was performed.

Selection criteria

Articles reporting on the effectiveness of therapies other than hysterectomy in women with niche‐related symptoms were included. Studies were included if they reported one of the following outcomes: effect on AUB, pain relief, sexual function, quality of life (QOL), and surgical, anatomic, fertility, or pregnancy outcome.

Data collection and analysis

Two authors independently selected the articles to be included. The Meta‐analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. A standardised checklist was used to score the methodological quality of the included studies.

Main results

Twelve studies were included, reporting on hysteroscopic niche resection (eight studies, 384 patients), laparoscopic repair (one study, 13 patients), (laparoscopic assisted) vaginal repair (two studies, 47 patients), and oral contraceptives (OCs) (one study, 11 patients). Reported AUB improved in the vast majority of the patients after these interventions, ranging from 87 to 100%. The rate of complications was low. Pregnancies were reported after therapy; however, sample sizes and follow‐up were insufficient to study fertility or pregnancy outcome. The methodological quality of the selected papers was considered to be moderate to poor, and was therefore insufficient to make solid conclusions.

Author's conclusions

More evidence is needed before (surgical) niche interventions are implemented in daily practice.
Vaginal birth after a caesarean section: the development of a Western European population‐based prediction model for deliveries at term
Authors: Schoorel ENC , van Kuijk SMJ , Melman S , Nijhuis JG , Smits LJM , Aardenburg R , de Boer K , Delemarre FMC , van Dooren IM , Franssen MTM , Kaplan M , Kleiverda G , Kuppens SMI , Kwee A , Lim FTH , Mol BWJ , Roumen FJME , Sikkema JM , Smid‐Koopman E , Visser H , Woiski M , Hermens RPMG , Scheepers HCJ
Published: December 2013

Objective

To develop and internally validate a model that predicts the outcome of an intended vaginal birth after caesarean (VBAC) for a Western European population that can be used to personalise counselling for deliveries at term.

Design

Registration‐based retrospective cohort study.

Setting

Five university teaching hospitals, seven non‐university teaching hospitals, and five non‐university non‐teaching hospitals in the Netherlands.

Population

A cohort of 515 women with a history of one caesarean section and a viable singleton pregnancy, without a contraindication for intended VBAC, who delivered at term.

Methods

Potential predictors for a vaginal delivery after caesarean section were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques.

Main outcome measures

Predictors for VBAC. For model validation, the area under the receiver operating characteristic curve (AUC) for discriminative capacity and calibration‐per‐risk‐quantile for accuracy were calculated.

Results

A total of 371 out of 515 women had a VBAC (72%). Variables included in the model were: estimated fetal weight greater than the 90th percentile in the third trimester; previous non‐progressive labour; previous vaginal delivery; induction of labour; pre‐pregnancy body mass index; and ethnicity. The AUC was 71% (95% confidence interval, 95% CI = 69–73%), indicating a good discriminative ability. The calibration plot shows that the predicted probabilities are well calibrated, especially from 65% up, which accounts for 77% of the total study population.

Conclusion

We developed an appropriate Western European population‐based prediction model that is aimed to personalise counselling for term deliveries.
First‐Price Sealed‐Bid Tender versus English Open Auction: Evidence from Land Auctions
Authors: Chow Yuen Leng , Ooi Joseph T.L.
Published: December 2013

This article compares whether the first‐price sealed‐bid tender or the ascending English open auction generates higher revenue for the seller. Using a unique set of data for land sales and accounting for the presence of an endogenous discrete mechanism choice variable, our results show that the first‐price sealed‐bid tender generates a lower land price, in the range of 1.2–9.6%, than the English open auction. Our results validate the theoretical prediction that open auctions result in higher prices because bidders can infer other bidders’ information by observing their bids in the common value auction paradigm.
HR outsourcing: the impact on HR role, competency development and relationships
Authors: Glaister Alison J.
Published: December 2013

The business benefits of an outsourcing strategy are well documented, and HR is encouraged to outsource in order to add value. Yet little is known about how HR outsourcing affects the HR role, competencies and relationships with senior management. These issues are examined through 27 semi‐structured interviews with senior HR professionals, comparing HR departments engaged in HR outsourcing with those maintaining full in‐house HR provision. The findings indicate that HR outsourcing stymies HR role transformation. HR outsourcers experienced limited skill development and an increased focus on cost reduction at the expense of their strategic position. In contrast, non‐HR outsourcers actively engaged in other parts of the business, developing competencies that garnered trust and support of senior managers. The benefits of an external HR community appear limited. The study suggests that an ‘internal’ HR community is better placed to enhance HR departmental roles.
Differentiation therapy for solid tumors
Authors: Xu Wen Ping , Zhang Xin , Xie Wei Fen
Published: December 2013

Differentiation therapy for tumors refers to treating malignant tumors via the induction of cell differentiation. The best characterized clinical application of differentiation therapy is the use of all‐trans retinoic acid in the treatment of acute promyelocytic leukemia (APL), which markedly improved the outcome of this disease. Unlike the situation with APL, the development of differentiation therapy for solid tumors is far from satisfactory. To date, no differentiation‐inducing agents have been demonstrated to exert a curative effect on solid tumors. However, over the past decade progress in understanding the differentiation pathways and the development of differentiation‐inducing agents might shed new light on the differentiation therapy for solid tumors.
Risk factors for acute gastrointestinal bleeding following myocardial infarction in veteran patients who are prescribed clopidogrel
Authors: Cuschieri Justin R , Drawz Paul , Falck‐Ytter Yngve , Wong Richard C K
Published: December 2013

Objective

Our aim was to identify risk factors for acute gastrointestinal (GI) bleeding in patients with myocardial infarction (MI) who were prescribed clopidogrel following hospital discharge.

Methods

Data were collected retrospectively from patients treated in Veteran Affairs hospitals in Ohio, USA, from 2001 to 2008 with a primary diagnosis of MI (International Classification of Diseases, 9th Revision) and a prescription for clopidogrel filled within 48 h of discharge. Primary outcome was acute GI bleeding after discharge.

Results

Acute GI bleeding occurred in 107 of 3218 patients. Bleeding occurred in those who were elder (66.2 vs 62.4 years, P = 0.0002), had lower glomerular filtration rate (74 vs 81 mL/min, P = 0.024), had filled prescription for warfarin (15.9% vs 6.9%, P = 0.0004), diagnosed as atrial fibrillation (20.6% vs 11.1%, P = 0.003), chronic liver (5.6% vs 2.2%, P = 0.018) or kidney disease (29.0% vs 19.4%, P = 0.016). A risk model and GI bleed risk score were developed and showed that patients with age >65 years, use of warfarin, the presence of chronic liver or kidney disease were at increased risk for GI bleeding.

Conclusions

Veterans patients of advanced age, using warfarin and with chronic liver and kidney disease may be at increased risk of GI bleeding when prescribed clopidogrel following MI. A scoring system may help to identify patients at high risk for GI bleeding.
Entomopathogenic fungi of the oil palm pest, Zophiuma butawengi (Fulgoromorpha: Lophopidae), and potential for use as biological control agents
Authors: Woruba Deane N , Priest Michael J , Dewhurst Charles F , Gitau Catherine W , Fletcher Murray J , Nicol Helen I , Gurr Geoff M
Published: December 2013

Oil palm, Elaeis guineensis Jacq., is an important cash crop in Papua New Guinea. Production is currently under threat from Finschhafen disorder caused by the planthopper Zophiuma butawengi (Heller), a native pest of coconut. The need for a non‐chemical strategy to manage Z. butawengi is high because the industry is committed to sustainable production. One possible option is the development of biological control using entomopathogenic fungi, and this study aimed to assess the scope for such a technology. Field collections extending over three regions of West New Britain in the 2010 monsoon season yielded 38 mycosed cadavers. Only three yielded entomopathogenic fungi: two of Hirsutella citriformis Speare and one each of Metarhizium flavoviride var. minus Rombach, Humber and D.W. Roberts, and Purpureocillium lilacinum (Thom) Luangsa‐ard, Houbraken, Hywel‐Jones and Samson. The pathogenicity of each isolate to Z. butawengi was confirmed in a laboratory study. M. flavoviride var. minus killed Z. butawengi significantly more rapidly over the course of a 15‐day period, and day 7 mortality was significantly greater than in water or nil control treatments. Given this pathogenic fungus was readily culturable and congenerics are used in other biological control treatments, it merits further investigation as a potential inundative entomopathogenic agent against Z. butawengi.
Acoustic Analysis of a Mechanical Circulatory Support
Authors: Hubbert Laila , Sundbom Per , Loebe Matthias , Peterzén Bengt , Granfeldt Hans , Ahn Henrik
Published: December 2013

Mechanical circulatory support technology is continually improving. However, adverse complications do occur with devastating consequences, for example, pump thrombosis that may develop in several parts of the pump system. The aim of this study was to design an experimental clot/thrombosis model to register and analyze acoustic signals from the left ventricular assist device (LVAD) HeartMate II (HMII) (Thoratec Corporation, Inc., Pleasanton, CA, USA) and detect changes in sound signals correlating to clots in the inflow, outflow, and pump housing. Using modern telecom techniques, it was possible to register and analyze the HMII pump‐specific acoustic fingerprint in an experimental model of LVAD support using a mock loop. Increase in pump speed significantly (P < 0.005) changed the acoustic fingerprint at certain frequency (0–23 000 Hz) intervals (regions: R1–3 and peaks: P1,3–4). When the ball valves connected to the tubing were narrowed sequentially by ∼50% of the inner diameter (to mimic clot in the out‐ and inflow tubing), the frequency spectrum changed significantly (P < 0.005) in P1 and P2 and R1 when the outflow tubing was narrowed. This change was not seen to the same extent when the lumen of the ball valve connected to the inflow tube was narrowed by ∼50%. More significant (P < 0.005) acoustic changes were detected in P1 and P2 and R1 and R3, with the largest dB figs. in the lower frequency ranges in R1 and P2, when artificial clots and blood clots passed through the pump system. At higher frequencies, a significant change in dB figs. in R3 and P4 was detected when clots passed through the pump system. Acoustic monitoring of pump sounds may become a valuable tool in LVAD surveillance.
Three intravitreal bevacizumab versus two intravitreal triamcinolone injections in recent onset central retinal vein occlusion
Authors: Ramezani Alireza , Esfandiari Hamed , Entezari Morteza , Moradian Siamak , Soheilian Masoud , Dehsarvi Babak , Yaseri Mehdi
Published: December 2013

Purpose

To evaluate the effects of repeated intravitreal injections of bevacizumab (IVB) versus triamcinolone acetonide (IVT) in the treatment of acute central retinal vein occlusion (CRVO).

Methods

In this randomized clinical trial, 86 eyes with recent onset (<12 weeks) CRVO were assigned to two groups: IVB group (43 eyes) that received three monthly injections of 1.25 mg of IVB, and IVT group (43 eyes) that received two injections of 2 mg IVT 2 months apart. Outcomes were best‐corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) changes.

Results

Mean BCVA improved significantly at 6 months in both groups; from 0.87 ± 0.49 to 0.41 ± 0.35 logMAR in IVB group, and from 0.81 ± 0.45 to 0.62 ± 0.48 logMAR in IVT group (p < 0.001). However, between‐group differences reach a significant level at months 4 (p = 0.003) and 6 (p < 0.001) in favour of the IVB group. In terms of CMT reduction, the difference between the groups was statistically significant (p = 0.002) at month 6. Significant differences were noted more in the ischaemic cases in favour of the IVB group. Mean IOP rise was significantly higher in the IVT group at all visits.

Conclusions

Both 3‐times monthly IVB injections and 2‐times IVT injections could be effective in cases with recent onset CRVO up to 6 months. However, considering the better outcomes after IVB injections and the potential complications of IVT injections, we would recommend prescheduled repeated IVB injections for such cases. The observed favourable responses were more pronounced in the ischaemic types; nevertheless, this should be confirmed in larger studies.
Lack of association between TPH2 gene polymorphisms with major depressive disorder in multiethnic Malaysian population
Authors: Nazree Nur Elia , Loke Ai Chin , Zainal Nor Zuraida , Mohamed Zahurin
Published: December 2013

Introduction

Numerous association studies of candidate genes studies with major depressive disorder (MDD) have been conducted for many years; however, the evidence of association between genes and the risk of developing MDD still remains inconclusive. In this study, we aimed to investigate the association between the tryptophan hydroxylase 2 (TPH2) gene and MDD in three ethnic groups (Malay, Chinese and Indian) within the Malaysian population.

Methods

Two hundred and sixty five MDD patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders‐IV criteria for MDD and 332 healthy controls were recruited for the study. All cases and controls were then genotyped for TPH2 polymorphisms rs1386494, rs1386495 and rs7305115.

Results

Single locus analysis in pooled and ethnically stratified subjects revealed no association between each of the three variants of the TPH2 gene with susceptibility to MDD. Strong linkage disequilibrium was detected between rs1386495 and rs1386494 in pooled subjects; however, no significant association was found in the haplotype analysis.

Discussions

In this study, we suggest that in both the Chinese and Indian populations, gender distribution differ significantly between cases and controls, showing that women are more at risk of developing MDD compared with men. Therefore, we suggest that the occurrence of MDD in both Chinese and Indians in the Malaysian population may be influenced by gender.
Insight into the Structural Features of Pyrazolopyrimidine‐ and Pyrazolopyridine‐based B‐RafV600E Kinase Inhibitors by Computational Explorations
Authors: Li Yan , Han Chunxiao , Wang Jinghui , Yang Yinfeng , Zhang Jingxiao , Zhang Shuwei , Yang Ling
Published: December 2013

Presently, both ligand‐based and receptor‐based 3D‐QSAR modelings were performed on 107 pyrazolopyrimidine‐ and pyrazolopyridine‐based inhibitors of B‐RafV600E kinase. The optimal model is successful to predict the inhibitors' activity with Q2 of 0.504, R2ncv of 0.960, and R2pred of 0.872. Besides, the 3D contour maps explain well the structural requirements of the interaction between the ligand and the receptor. Furthermore, molecular docking and MD were also carried out to study the binding mode. Our findings are the following: (i) Bulky substituents at position 3, 10 and ring D improve the inhibitory activity, but impair the activity at position 5, 11, and 19. (ii) Electropositive groups at position 10, 13 and 20 and electronegative groups at position 2 increase the biological activity. (iii) Hydrophobic substituents at ring C are beneficial to improve the biological activity, while hydrophilic substituents at position 11 and ring D are good for the activity. (4) This scaffold of inhibitors may bind to the B‐Raf kinase with an ‘L’ conformation and belong to type III binding mode, which is fixed by hydrophobic interaction and hydrogen bonds with residues from hinge region and DFG motif. These results may be a guidance to develop new B‐RafV600E kinase inhibitors.
In vitro adhesion of fibroblastic cells to titanium alloy discs treated with sodium hydroxide
Authors: Al Mustafa Maisa , Agis Hermann , Müller Heinz‐Dieter , Watzek Georg , Gruber Reinhard
Published: December 2013

Objective

Adhesion of osteogenic cells on titanium surfaces is a prerequisite for osseointegration. Alkali treatment can increase the hydrophilicity of titanium implant surfaces, thereby supporting the adhesion of blood components. However, it is unclear if alkali treatment also supports the adhesion of cells with a fibroblastic morphology to titanium.

Materials and methods

Here, we have used a titanium alloy (Ti‐6AL‐4V) processed by alkali treatment to demonstrate the impact of hydrophilicity on the adhesion of primary human gingival fibroblast and bone cells. Also included were the osteosarcoma and fibroblastoma cell lines, MG63 and L929, respectively. Cell adhesion was determined by scanning electron microscopy. We also measured viability, proliferation, and protein synthesis of the adherent cells.

Results

Alkali treatment increased the adhesion of gingival fibroblasts, bone cells, and the two cell lines when seeded onto the titanium alloy surface for 1 h. At 3 h, no significant changes in cell adhesion were observed. Cells grown for 1 day on the titanium alloy surfaces processed by alkali treatment behave similarly to untreated controls with regard to viability, proliferation, and protein synthesis.

Conclusion

Based on these preliminary In vitro findings, we conclude that alkali treatment can support the early adhesion of cells with fibroblastic characteristics to a titanium alloy surface.
Multidimensional evaluation of vocal quality in children with cochlear implants: a cross‐sectional, case‐controlled study
Authors: Hsu H.‐W. , Fang T.‐J. , Lee L.‐A. , Tsou Y.‐T. , Chen S.H. , Wu C.‐M.
Published: December 2013

Objectives

This study aimed to compare the differences in vocal quality between Mandarin‐speaking children with cochlear implants and normal‐hearing peers and to understand which cochlear implant usage parameters may predict unfavourable voice outcomes.

Design

A cross‐sectional, case‐controlled study.

Setting

A tertiary medical centre.

Participants

Thirty‐five pre‐lingually deaf children (age = 10.3 ± 1.6 years; 17 boys and 18 girls) who had used cochlear implants for >2 years and 35 age‐ and gender‐matched controls with normal hearing.

Main outcome measures

Through sustained phonation of /a/ and reading of the Hare and Tortoise passage, the subjects' voice quality was analysed with aerodynamics and acoustics. A six‐point scale was used for auditory‐perceptual evaluation. A Pediatric Voice‐Related Quality of Life Survey was filled out by the caregivers.

Results

The implanted subjects had significantly lower mean airflow rate (P = 0.006), higher phonation threshold pressure (P < 0.001), higher fundamental frequency variations (P < 0.001) and peak‐amplitude variations (P < 0.001), wider fundamental frequency range (P = 0.043), wider speaking intensity range (P = 0.015) and greater perceptual severity level of monotone (P < 0.001), resonance (P < 0.001), loudness (P < 0.001) and strain (P = 0.006) than their normal‐hearing peers. Duration of postoperative rehabilitation was an independent predictor of unfavourable mean speaking fundamental frequency (odds ratio = 8.56, P = 0.008).

Conclusion

Inadequate postoperative rehabilitation may hinder the normalisation of Mandarin‐speaking implantees' voice quality. A multidimensional analysis may precisely evaluate the voice of paediatric implantees; however, the generalisability of these findings requires different forms of validation, including data from other languages and other institutions.
Use of Ancient Sedimentary DNA as a Novel Conservation Tool for High‐Altitude Tropical Biodiversity
Authors: BOESSENKOOL SANNE , MCGLYNN GAYLE , EPP LAURA S. , TAYLOR DAVID , PIMENTEL MANUEL , GIZAW ABEL , NEMOMISSA SILESHI , BROCHMANN CHRISTIAN , POPP MAGNUS
Published: December 2013

Conservation of biodiversity may in the future increasingly depend upon the availability of scientific information to set suitable restoration targets. In traditional paleoecology, sediment‐based pollen provides a means to define preanthropogenic impact conditions, but problems in establishing the exact provenance and ecologically meaningful levels of taxonomic resolution of the evidence are limiting. We explored the extent to which the use of sedimentary ancient DNA (sedaDNA) may complement pollen data in reconstructing past alpine environments in the tropics. We constructed a record of afro‐alpine plants retrieved from DNA preserved in sediment cores from 2 volcanic crater sites in the Albertine Rift, eastern Africa. The record extended well beyond the onset of substantial anthropogenic effects on tropical mountains. To ensure high‐quality taxonomic inference from the sedaDNA sequences, we built an extensive DNA reference library covering the majority of the afro‐alpine flora, by sequencing DNA from taxonomically verified specimens. Comparisons with pollen records from the same sediment cores showed that plant diversity recovered with sedaDNA improved vegetation reconstructions based on pollen records by revealing both additional taxa and providing increased taxonomic resolution. Furthermore, combining the 2 measures assisted in distinguishing vegetation change at different geographic scales; sedaDNA almost exclusively reflects local vegetation, whereas pollen can potentially originate from a wide area that in highlands in particular can span several ecozones. Our results suggest that sedaDNA may provide information on restoration targets and the nature and magnitude of human‐induced environmental changes, including in high conservation priority, biodiversity hotspots, where understanding of preanthropogenic impact (or reference) conditions is highly limited.

Uso de ADN Sedimentario Antiguo como una Herramienta Novedosa de Conservación para la Biodiversidad Tropical de Grandes Altitudes
Occupational contact dermatitis in hairdressers: an analysis of patch test data from the Danish Contact Dermatitis Group, 2002–2011
Authors: Schwensen Jakob F. , Johansen Jeanne D. , Veien Niels K. , Funding Anne T. , Avnstorp Christian , Østerballe Morten , Andersen Klaus E. , Paulsen Evy , Mortz Charlotte G. , Sommerlund Mette , Danielsen Anne , Andersen Bo L. , Thormann Jens , Kristensen Ove , Kristensen Berit , Vissing Susanne , Nielsen Niels H. , Thyssen Jacob P. , Søsted Heidi
Published: December 2013

Background

Occupational contact dermatitis among hairdressers is frequent, owing to daily exposure to irritants and allergens.

Objectives

To identify sensitization to the most common allergens associated with the occupation of hairdressing.

Methods

Patch test results of 399 hairdressers and 1995 matched controls with contact dermatitis, registered by the Danish Contact Dermatitis Group between January 2002 and December 2011, were analysed. All patients were patch tested with the European baseline series, and hairdressers were additionally tested with the hairdressing series.

Results

Occupational contact dermatitis (p < 0.001) and hand eczema (p < 0.001) were observed significantly more often among hairdressers than among controls. Atopic dermatitis was less commonly observed among hairdressers (21.3%) than among controls (29.4%) (p < 0.01). Allergens from the European baseline series with a statistically significant association with the occupation of hairdressing were p‐phenylenediamine, thiuram mix, and benzocaine. Frequent sensitizers from the hairdressing series were ammonium persulfate, toluene‐2,5‐diamine, 3‐aminophenol, and 4‐aminophenol. Cysteamine hydrochloride and chloroacetamide emerged as new sensitizers.

Conclusions

These results indicate a healthy worker effect among hairdressers diagnosed with eczema. Ammonium persulfate and p‐phenylenediamine remain frequent sensitizers in hairdressers with contact dermatitis. Cysteamine hydrochloride and chloroacetamide should be included in future surveillance studies.
Proteinuria and sirolimus after renal transplantation: a retrospective analysis from a large German multicenter database
Authors: Naik Marcel G. , Heller Katharina M. , Arns Wolfgang , Budde Klemens , Diekmann Fritz , Eitner Frank , Fischereder Michael , Goßmann Jan , Heyne Nils , Morath Christian , Riester Udo , Gwinner Wilfried , Jürgensen Jan Steffen
Published: December 2013

The German Sirolimus Study Group has established a database among 10 transplant centers throughout Germany to study the outcomes in 726 renal transplant patients being converted to a sirolimus‐containing therapy between 2000 and 2008 with a total of more than 1500 recorded patient years on therapy. In this study, we present a detailed description of the cohort, of characteristic changes over the observation period, proteinuria and graft survival, and new‐onset proteinuria after conversion. Over the study period, age, graft function at the time of conversion, and the proportion of patients switched to sirolimus because of malignancy increased, whereas the proportion of patients with significant proteinuria at conversion decreased. Already modest proteinuria (151–268 mg/L) at conversion and new‐onset proteinuria (>500 mg/L) after conversion were associated with inferior graft survival. Even mild proteinuria (>71 mg/L) at conversion was associated with new‐onset proteinuria (>500 mg/L) post‐conversion. Serum creatinine and urinary protein excretion at conversion together with age at transplantation had a significant impact on patient and graft survival. This large data set confirms and extends previous observations that proteinuria is an important indicator for graft outcome after conversion to sirolimus. We conclude that patients without any proteinuria have the greatest benefit from conversion to sirolimus.