bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and self-assembly of amphiphilic poly(acrylicacid)–poly(ɛ-caprolactone)–poly(acrylicacid) block copolymer as novel carrier for 7-ethyl-10-hydroxy camptothecin
Authors: Djurdjic Beti , Dimchevska Simona , Geskovski Nikola , Petrusevska Marija , Gancheva Valerya , Georgiev Georgi , Petrov Petar , Goracinova Katerina
Published: September 2014

The process of molecular self-assembly plays a crucial role in formulation of polymeric nanoparticulated drug delivery carriers as it creates the possibility for enhanced drug encapsulation and carrier surface engineering. This study aimed to develop a novel self-assembled polymeric micelles for targeted delivery in tumor cells in order to overcome not only various drawbacks of 7-ethyl-10-hydroxy camptothecin (SN-38) but also various reported limitations of other drug delivery systems, especially low drug loading and premature release. Custom synthesized amphiphilic triblock copolymer poly(acrylic acid)–poly(ɛ-caprolactone)–poly(acrylic acid) (PAA13–PCL35–PAA13) was used to prepare kinetically stable micelles by nanoprecipitation and modified nanoprecipitation procedure. Core-shell micelles with diameter of 120–140 nm, negative zeta potential and satisfactory drug loading were produced. The prepared formulations were stable in pH range of 3–12 and in media with NaCl concentration <1 mol/l. Screening mixed level factorial 3 × 22 design identified that the process temperature as well as the type of organic solvent has influence upon the efficacy of encapsulation, particle size, dissolution rate and burst release. Fourier transform infrared and differential scanning calorimetry analyses confirmed the entrapment of the active substance into the micelles. The kinetic analysis of dissolution studies revealed that the main mechanism of drug release from the prepared formulations is Fickian diffusion. Growth inhibition studies as well as DNA fragmentation assay performed on SW-480 cell lines clearly demonstrated increased growth inhibition effect and presence of fragmented DNA in cells treated with loaded micelles compared to SN-38 solution. Altogether, these results point out to potential biomedical and clinical application of PAA–PCL–PAA systems in the future.
Structure and properties of irradiated HDPE high-density polyethylene/calcium carbonate composites
Authors: Jin Hui , Lu Yue , Ma Pei-Pei , Wu Shi-Shan , Shen Jian
Published: September 2014

First, some groups of C=O and C–O were introduced onto high-density polyethylene (HDPE) chains by ultraviolet irradiation for short time in ozone atmosphere. The content of the groups was increased with increasing the irradiation time. The irradiated HDPE was blended with calcium carbonate (CaCO3) to prepare the composites. The melting temperature and crystallinity of HDPE in irradiated HDPE/CaCO3 composites were lower than the HDPE in HDPE/CaCO3 composites. Compared with the HDPE/CaCO3 composites, the dispersion of CaCO3 and the interfacial interaction between CaCO3 and HDPE in the irradiated HDPE/CaCO3 composites increased respectively. With increasing the irradiation time, the mechanical properties (especially impact strength) of the irradiated HDPE/CaCO3 composites were markedly enhanced, while their thermal stability decreased slightly. For example, the tensile strength and impact strength of the irradiated (20 min) HDPE/CaCO3 composites increased from 25.7 MPa and 72 J m−1 to 30.3 MPa and 416 J m−1, respectively, compared with those of the HDPE/CaCO3 composites, and stiffened and toughened HDPE composites were obtained.
Interpreting the marketization of employment services in Great Britain and Denmark
Authors: Larsen Flemming , Wright Sharon
Published: September 2014

Marketization is an important component of international shifts in the governance of employment services. Despite contrasting underlying welfare systems and employment services of different scales and character, both Denmark and Great Britain were distinct from many other comparable countries in contracting out employment services in the late-1990s. By comparing the starting positions and divergent trajectories of marketization in these two very different welfare systems, we see some common traits in how it so far has been difficult to make marketization deliver on its promises. We find in both cases difficulties for the contracted-employment services to reduce bureaucracy, save money through innovation, realize user choice, prevent poor quality services or increase efficiency/effectiveness through better job outcomes. Instead we find, paradoxically, that the market could not operate without re-regulation. In the absence of the intended effects, we furthermore question why policymakers in such different socio-political contexts continued to support the marketization strategy. The explanation is found in combination with wider governance and policy shifts, which have contributed towards altering the governance mix to reposition key actors and interests in ways that would have otherwise been contested.
Dynamics of a piezoelectric beam subjected to water droplet impact with water layer formed on the surface
Authors: Wong Voon-Kean , Ho Jee-Hou , Yap Eng Hwa
Published: September 2014

Rain impact energy harvesting using piezoelectric energy harvester has gained much attention recently. However, previous works have only considered the effect of single water droplet. In the case of raindrop, water would accumulate on the surface of the energy harvester and form a shallow water layer. This article models the dynamics of a piezoelectric beam, served as a raindrop energy harvester, subjected to water droplet impact with water layer formed on the surface. The impact of water droplet on the tip of the energy harvester is modelled as an impulsive force, and the water layer on the surface of the energy harvester is modelled as an added mass to the energy harvester. An attempt to model the force generated by the water ripple as a distributed load on the piezoelectric beam is presented. Numerical studies have been conducted based upon the proposed mathematical model verified by experimental results. The results showed that the presence of the water layer affects the output voltage and the dominant frequency of the energy harvester. It reveals that the effect of water (or rain) accumulation on the piezoelectric surface should be considered in deriving an optimal operating condition of such energy harvester.
Prospective Randomized Study of Chevron Osteotomy Versus Mitchell’s Osteotomy in Hallux Valgus
Authors: Buciuto Robert
Published: September 2014

Background:

We conducted a prospective randomized trial to compare the most popular osteotomy types of operative treatment of hallux valgus (HV) used in Norway, Mitchell’s osteotomy (MO) and chevron osteotomy (CO).

Methods:

One hundred twenty adult female patients were prospectively randomized to treatment with either MO or CO. All operative procedures were performed with ankle block and with tourniquet applied. None of the patients received any antibiotic or antithrombotic prophylaxis. The follow-up period was 3 years. Clinical results were rated according to the American Orthopaedic Foot and Ankle Society (AOFAS) Clinical Rating System (CRS).

Results:

HV in the MO group was reduced from 30 (range, 20 to 44) to 15 (range, 8 to 24) degrees and IM angle from 11 (range, 6 to 14) to 7 (range, 4 to 11) degrees. HV in the CO group was reduced from 31 (range, 22 to 42) to 16 (range, 6 to 24) degrees and IM angle from 14 (range, 8 to 20) to 6 (range, 2 to 10) degrees. Transfer metatarsalgia occurred in 36 (60%) patients and hammertoe in 6 (10%) patients in the MO group. In the CO group, metatarsalgia occurred in 5 patients. The median loss of postoperative HV correction was 4 (range, 2 to 10) degrees in mild deformity and 6 (6 to 10) degrees in moderate deformity.

Conclusion:

Patients treated with CO had significantly better results for AOFAS CRS, number of postoperative complications, patient satisfaction, and length of sick leave for the employed patients. Based on our results, we consider that in female patients CO should be regarded as the first-line procedure for treatment of mild and moderate HV.

Level of Evidence:

Level I, prospective randomized study.
Pulmonary function in obese vs non-obese cats
Authors: García-Guasch Laín , Caro-Vadillo Alicia , Manubens-Grau Jordi , Carretón Elena , Camacho Aparecido A , Montoya-Alonso José Alberto
Published: September 2014

Obesity is a risk factor in the development of several respiratory diseases. Lung volumes tend to be decreased, especially expiratory reserve volume, increasing expiratory flow limitation during tidal breathing. Barometric whole-body plethysmography is a non-invasive pulmonary function test that allows a dynamic study of breathing patterns. The objective of this study was to compare pulmonary function variables between obese and non-obese cats through the use of barometric whole-body plethysmography. Nine normal-weight and six obese cats were placed in the plethysmograph chamber, and different respiratory variables were measured. There was a significant decrease in tidal volume per kilogram ( P = 0.003), minute volume per kilogram ( P = 0.001) and peak inspiratory and expiratory flows per kilogram ( P = 0.001) in obese cats compared with non-obese cats. Obesity failed to demonstrate a significant increase in bronchoconstriction index variable enhanced pause (Penh), as previously reported in humans and dogs. The results show that feline obesity impairs pulmonary function in cats, although a significant increase in bronchoconstriction indexes was not observed. Non-invasive barometric whole-body plethysmography can help characterise mechanical dysfunction of the airways in obese cats.
Promising ever more
Authors: Håkansson Nicklas , Naurin Elin
Published: September 2014

This study argues that three recent societal trends have increased parties’ incentives to give election promises in campaigns: the increasing volatility of voters, the professionalization and marketization of politics, and the mediatization of politics. Arguments are empirically tested on the case of Sweden between 1991 and 2010. All promises presented in election manifestos by Swedish parliamentary parties are analyzed, enabling analyses of six elections, nine parties, 44 manifestos and almost 4000 election promises. We find that Swedish parties increased their pledge making considerably during the period, from an average of 46 per manifesto to 149. Specific promises have increased, as have the pledges that are unrelated to other parties’ pledges. Altogether, the results point at an increasingly specific vote choice for voters.
Quality of care among patients undergoing lower extremity revascularization
Authors: Slovut David P , Kargoli Faraj , Fletcher Jason J , Etkin Yana , Lipsitz Evan C
Published: September 2014

Background:

Compliance with guidelines for treating patients with peripheral artery disease (PAD) lags compliance for treating patients with coronary artery disease. We assessed the gap between guidelines and practice for patients with PAD who underwent lower extremity revascularization (LER) at our institution from 2007 to 2010.

Methods:

Quality of care (QoC) was calculated by measuring provider performance on four indicators (antiplatelet therapy, dyslipidemia management, control of hypertension, and diabetes) derived from the ACCF/AHA PAD guidelines. The QoC score was calculated at the time of admission and at time of discharge for each patient, and reflects the proportion of indicated treatments received.

Results:

Patients ( n = 734, mean age 70±11, female 51%) were followed for a mean of 2.0±1.4 years (range 0–5.7) following LER. The indication for LER was claudication (24.8%), rest pain (16.7%), and tissue loss (58.4%). The percentage of patients with a perfect QoC score increased significantly during hospital admission (11% to 21%, p < 0.001). Significant multivariate predictors of perfect QoC score included race/ethnicity, Charlson score, severity of LE ischemia, and observation period (admission, discharge). Multivariate analysis demonstrated that age>75 years, heart failure, chronic kidney disease, rest pain, and tissue loss—but not compliance with four guideline-based therapies—were associated with decreased freedom from the composite endpoint of major amputation, repeat revascularization, and death.

Conclusions:

Although adherence to guidelines improved over time, we found a significant gap between guidelines and practice for this cohort of patients at increased risk for adverse cardiovascular events.
Defining personal reflexivity
Authors: Caetano Ana
Published: September 2014

Margaret Archer plays a leading role in the sociological analysis of the relation between structure and agency, and particularly in the study of reflexivity. The main aim of this article is to discuss her approach, focusing on the main contributions and limitations of Archer’s theory of reflexivity. It is argued that even though her research is a pioneering one, proposing an operationalization of the concept of reflexivity in view of its empirical implementation, it also minimizes crucial social factors and the dimensions necessary for a more complex and multi-dimensional study of the concept, such as social origins, family socialization, processes of internalization of exteriority, the role of other structure–agency mediation mechanisms and the persistence of social reproduction.
Association of echocardiographic left ventricular structure and −344C/T aldosterone synthase gene variant: A meta-analysis
Authors: Wang Lijuan , Zhou Jiapeng , Zhang Bei , Wang Hao , Li Mei , Niu Qiuli , Chen Yubao , Chen Runsheng , Wen Shaojun
Published: September 2014

Background:

Aldosterone synthase (CYP11B2) is one of the most studied candidate genes related to essential hypertension (EH) and left ventricular hypertrophy (LVH). Some studies have focused on the relationship between −344C/T polymorphism (rs1799998) in the CYP11B2 gene and LVH, but the results are controversial. This meta-analysis is purposed to reveal the relationship between the −344C/T and the left ventricular structure and function, including left ventricular end diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular mass/left ventricular mass index (LVM/LVMI), left ventricular posterior wall thickness (LVPWT), and interventricular septal wall thickness (IVS).

Methods:

A literature search of PubMed and Embase databases was conducted on articles published before January 27, 2014. The odds ratios with 95% confidence intervals were calculated. Heterogeneity analyses were performed using meta-regression. Tests for publication bias were also performed and biased studies should be removed from subsequent analyses.

Results:

There were 20 studies with a total of 6780 subjects meeting the inclusion criteria. The main finding was that concentration levels of LVEDD and LVESD were higher in CC homozygous individuals than in TT homozygous individuals in the whole group. In the Asian subgroup, TT homozygous individuals had larger IVS than CC homozygous individuals. In the Caucasian normotension subgroup, CC homozygous individuals had larger LVM/LVMI than TT homozygous individuals. In the Asian essential hypertension subgroup, TT homozygous individuals had larger LVPWT values than CC homozygous individuals.

Conclusions:

The present findings support the hypothesis that CC homozygous individuals may have greater left ventricular diameters (LVEDD and LVESD) regardless of their ethnicities or physical conditions.
The Conceptual Act Theory: A Précis
Authors: Barrett Lisa Feldman
Published: September 2014

According to the conceptual act theory, emotions emerge when physical sensations in the self and physical actions in others are meaningfully linked to situations during a process that can be called both cognitive and perceptual (creating emotional experiences, and emotion perceptions, respectively). There are key four hypotheses: (a) an emotion (like anger) is a conceptual category, populated with instances that are tailored to the environment; (b) each instance of emotion is constructed within the brain’s functional architecture of domain-general core systems; (c) the workings of each system must be holistically understood within the momentary state of the brain, the body, and the surrounding context; (d) being emergent states, emotional episodes have functional features that physical states, alone, do not have. Similarities and differences to other theoretical approaches to emotion are discussed.
Author Reply: Toward a Multilevel Mechanistic Explanation of Complex Regularities Between Environment and Emotional Components
Authors: Moors Agnes
Published: September 2014

In reply to the commentaries of Clay-Warner (2014), Gendolla (2014), Nesse (2014), Shweder (2014), and Zachar (2014), I repeat the essential features of appraisal theories of the second flavor: They take emotional components (and not specific emotions) as the phenomenon to be explained, and they strive for a multilevel mechanistic explanation that leaves room for complex and dynamical processes or mechanisms. Every mechanistic explanation starts with an accurate description of regularities between inputs and outputs. Regularities do not preclude context-dependent variety, because there is no limit to the number of input factors that can influence the output, and back.
The Attributional Approach to Emotion and Motivation: Introduction to a Special Section of Emotion Review
Authors: Reisenzein Rainer
Published: September 2014

In this introduction to the special section on the attributional approach to emotion and motivation, the character of Weiner’s attributional theory as an appraisal theory is discussed. I argue that the theory, although focusing on appraisal dimensions related to causal attribution, is actually a fairly general appraisal theory of emotion. Distinctive features of the attributional approach are its pioneering role in emotion research, its emphasis on the functional role of emotions, particularly for the motivation of action, and the existence of a large supportive data base. Given the solid evidence compiled by attributional researchers for emotion-specific effects of emotion on motivation, I propose that future research should focus on the details of the mental mechanisms through which emotions affect motivation, and formulate five questions that could guide this inquiry.
Electrocardiogram-based scoring system for predicting secondary pulmonary hypertension: A cross-sectional study
Authors: Pancholy Samir Bipin , Palamaner Subash Shantha Ghanshyam , Patel Nimesh Kirit , Boruah Pranjal , Nanavaty Sukrut , Chandran Sindu , Sethi Arjinder , Sheth Jignesh
Published: September 2014

Objectives

In this study, we have developed an electrocardiogram-based scoring system to predict secondary pulmonary hypertension.

Design

A cross-sectional study.

Setting

Single tertiary-care hospital in Scranton, Pennsylvania, USA.

Participants

Five hundred and fifty-two consecutive patients undergoing right heart catheterization between 2006 and 2009.

Main outcome measures

Surface electrocardiogram was assessed for R-wave in lead V1 ≥ 6mm, R-wave in V6 ≤ 3mm, S-wave in V6 ≥ 3mm, right atrial enlargement, right axis deviation and left atrial enlargement. Pulmonary hypertension was defined as mean pulmonary artery pressure ≥25 mmHg, determined by right heart catheterization.

Results

A total of 297 (54%) patients in the study cohort had pulmonary hypertension. In total, 332 patients from the study cohort formed the development cohort and the remaining 220 patients formed the validation cohort. In the development cohort, based on log odds ratios of association, RAE, LAE, RAD, R-wave in V1 ≥ 6 mm were assigned scores of 5, 2, 2 and 1, respectively, to form a 10-point scoring system “Scranton PHT (SP) score”. SP scores of 5 points and 7 points in DC showed C-statistic of 0.83 and 0.89, respectively, for discriminating pulmonary hypertension. C-statistic for RAE alone was significantly lower compared to an SP score of 7 (0.83 vs. 0.89, P = 0.021). The reliability of SP score in the validation cohort was acceptable.

Conclusion

SP score provides a good point-of-care tool to predict pulmonary hypertension in patients with clinical suspicion of it.
Surgical repair of anomalous connection of the left coronary artery
Authors: Tsutsumi Koji
Published: September 2014

An asymptomatic 10-year-old girl with anomalous connection of the left coronary artery to the pulmonary artery underwent successful surgical repair to create a two-artery coronary system with a coronary elongation technique using an autologous pulmonary arterial wall flap. This technique facilitates direct and tension-free coronary artery re-implantation.
Commodities and Stock Investment
Authors: Shahzad Syed Jawad Hussain , Raza Naveed , Awan Aneese Hayat
Published: September 2014

This study is a multivariate analysis of commodities and stock investment in a newly established market scenario. Return distribution asymmetry is examined with higher order movements. Skewness in commodity future’s return is largely insignificant, whereas kurtosis is highly significant for both stock and commodity future contracts. Correlation analysis is done with Pearson’s and Kendall’s tau measures. Commodities provide significant diversification benefits when added in a portfolio of stocks. Compared with stocks, commodity future’s returns show stronger correlation with unexpected inflation. The volatility is measured through Glosten-Jagannathan-Runkle - Generalized Autoregressive Conditional Heteroskedasticity (GJR-GARCH) model and reflects that commodities have inverted asymmetric behavior, that is, more impact from the upward shocks compared with downward. Stocks have asymmetric volatility, that is, more impact from negative shocks compared with positive. Gold has highest inverted asymmetric volatility. Tail dependence, measured through Student’s t copula, shows no combined downside movement. In conclusion, commodity investments provide diversification and inflation protection.
Correlates of Peer Violence Among 13- to 15-Year-Olds in Gampaha District Schools in Sri Lanka
Authors: Wijeratne Monika Priyadarshani , Seneviratne Rohini , Gunawardena Nalika , Lynch Catherine , Sandøy Ingvild Fossgard , Ostbye Truls
Published: September 2014

Violence among adolescents in schools is a relatively new research area in South Asian countries. Limited knowledge about factors associated with peer violence hinders the design of prevention programs. This study was carried out to assess correlates of peer violence among 13- to 15-year-old adolescents in Gampaha district schools in Sri Lanka. A cross-sectional study was carried out to identify “violent” and “non-violent” adolescents. Study and control populations were identified based on their participatory roles in violence, and an unmatched case–control (1 case: 1 control) analysis was carried out to assess correlates of peer violence. Bronfenbrenner’s ecological model was used, and correlates were determined for both physical and relational (verbal and non-verbal) violence. Correlates of both physical and relational peer violence were male sex, being 13 years of age, mental health difficulties, dating relationships, school absenteeism, witnessing physical fights among neighbors, and crime-dense residence. Factors associated with peer violence operate at several levels: individual, family/peer relationships, community, and societal. Most of these factors are modifiable and can be targeted by prevention programs.
Vocal Sight-Reading Assessment
Authors: Henry Michele
Published: September 2014

This study investigated choral singers’ comfort level using computer technology for vocal sight-reading assessment. High school choral singers ( N = 138) attending a summer music camp completed a computer-based sight-reading assessment and accompanying pre- and posttest surveys on their musical backgrounds and perceptions about technology. A large majority reported both frequent sight-reading instruction (74%) and individual assessment (70%) in their prior instruction. Whereas 94% of these students previously had been assessed live, only five students had been assessed through recording and one by computer. Preassessment opinions (69% favorable/neutral) shifted substantially (69% negative) after experiencing computer-based assessment. Inability to set the tempo was cited as the predominant reason for disliking the technology. Results indicate great potential for using technology in vocal sight-reading instruction and assessment. However, it is important that students’ introduction to it be intentional and thorough. Adequate practice and comfort must be established for students to trust and appreciate this new instructional tool.
Female community health volunteers service utilization for childhood illness- improving quality of health services only is not enough: a cross-sectional study in mid-western region, Nepal
Authors: Miyaguchi Moe , Yasuoka Junko , Poudyal Amod Kumar , Silwal Ram Chandra , Jimba Masamine
Published: September 2014

Background

Female Community Health Volunteers (FCHVs) are considered service providers for major health problems at the community level in Nepal. However, few studies have been conducted about the roles of FCHVs from the users’ perspective. This study sought to examine the current status of FCHV service utilization and identify the determinants of caregivers’ utilization of FCHVs’ health services in the mid-western region of Nepal.

Methods

This cross-sectional study targeted 446 caregivers of children under five years of age and whose children had ever fallen ill in the study village development committees (VDCs) of three districts of Nepal. Caregivers were asked about their usual health practices for childhood illness, health service utilization for childhood illness, children’s health condition, satisfaction with health services, and socio-demographic status. Descriptive statistics and multiple logistic regression were used for analysis.

Results

Among 446 caregivers, 66.8% had never sought care from FCHVs for their children’s illnesses in their lifetime, and more than 50% of them were unaware of FCHVs’ services for acute respiratory infection and diarrhea. Among 316 caregivers whose child had an illness during the last seven months, 92.3% of them (n = 293) did not take their child to FCHVs. The main reasons were the lack of medicine available from them and their incompetency in providing care. Among the 446 caregivers, those who participated in a mothers’ group (n = 82) were more likely to use FCHVs’ services in their lifetime (AOR = 3.23, 95% CI =1.81-5.76).

Conclusions

Caregivers can gain benefit by using FCHV’s health services, but a majority of the caregivers did not seek care from FCHVs due to its limited quality. Raising caregivers’ awareness on FCHV is equally important at community level.
HCOR: a high-throughput coding-aware opportunistic routing for inter-flow network coding in wireless mesh networks
Authors: Hai Long , Wang Hongyu , Wang Jie , Tang Zhenzhou
Published: September 2014

Coding-aware routing is an effective approach to create more coding opportunities in inter-flow network coding. To the best of our knowledge, most of the coding-aware routing schemes focus on maximizing the coding opportunities. However, for opportunistic transmission, the throughput is not always increased with the increase of coding opportunities. In this paper, we explore why this case will happen and how to measure the benefits of network coding in the opportunistic routing. According to the above conclusions, we propose a novel high-throughput coding-aware opportunistic routing (HCOR) to achieve the maximal throughput gain in wireless mesh networks. HCOR is based on anypath routing and takes advantage of the network coding gain to find out the route with minimal anypath cost reasonably. Meanwhile, it is also a ‘multihop’ network coding and changes the route with dynamical data loads adaptively. Simulation results demonstrate that HCOR has better performance than coding opportunity-aware routing and also obtains a significant throughput gain in wireless mesh networks.
Penicillium sp. as an organism that degrades endosulfan and reduces its genotoxic effects
Authors: Romero-Aguilar Mariana , Tovar-Sánchez Efrain , Sánchez-Salinas Enrique , Mussali-Galante Patricia , Sánchez-Meza Juan Carlos , Castrejón-Godínez María Luisa , Dantán-González Edgar , Trujillo-Vera Miguel Ángel , Ortiz-Hernández Ma Laura
Published: September 2014

Endosulfan is an organochloride and persistent pesticide that has caused concern because of its impact in the environment and its toxicity to and bioaccumulation in living organisms. In this study, we isolated an endosulfan-degrading fungus from the activated sludge from an industrial wastewater treatment plant. Through repetitive enrichment and successive subculture in media containing endosulfan as the sole carbon source, a fungus designated CHE 23 was isolated. Based on a phylogenetic analysis, strain CHE 23 was assigned to the genus Penicillium sp. In a mineral salt medium with 50 mg/l endosulfan as the sole source carbon, CHE 23 removed the added endosulfan in a period of six days. To verify the decrease in endosulfan toxicity due to the activity of the fungus, we performed genotoxicity tests trough the single cell gel electrophoresis assay or comet assay, with Eisenia fetida as the bioindicator species. This organism was exposed to the supernatants of the culture of the fungus and endosulfan. Our results indicated that the genotoxicity of endosulfan was completely reduced due the activity of this fungus. These results suggest that the Penicillium sp. CHE 23 strain can be used to degrade endosulfan residues and/or for water and soil bioremediation processes without causing toxicity problems, which are probably due to the generation of no-toxic metabolites during biodegradation.
Positive end-expiratory airway pressure does not aggravate ventilator-induced diaphragmatic dysfunction in rabbits
Authors: Sassoon Catherine SH , Zhu Ercheng , Fang Liwei , Sieck Gary C , Powers Scott K
Published: September 2014

Introduction

Immobilization of hindlimb muscles in a shortened position results in an accelerated rate of inactivity-induced muscle atrophy and contractile dysfunction. Similarly, prolonged controlled mechanical ventilation (CMV) results in diaphragm inactivity and induces diaphragm muscle atrophy and contractile dysfunction. Further, the application of positive end-expiratory airway pressure (PEEP) during mechanical ventilation would result in shortened diaphragm muscle fibers throughout the respiratory cycle. Therefore, we tested the hypothesis that, compared to CMV without PEEP, the combination of PEEP and CMV would accelerate CMV-induced diaphragm muscle atrophy and contractile dysfunction. To test this hypothesis, we combined PEEP with CMV or with assist-control mechanical ventilation (AMV) and determined the effects on diaphragm muscle atrophy and contractile properties.

Methods

The PEEP level (8 cmH2O) that did not induce lung overdistension or compromise circulation was determined. In vivo segmental length changes of diaphragm muscle fiber were then measured using sonomicrometry. Sedated rabbits were randomized into seven groups: surgical controls and those receiving CMV, AMV or continuous positive airway pressure (CPAP) with or without PEEP for 2 days. We measured in vitro diaphragmatic force, diaphragm muscle morphometry, myosin heavy-chain (MyHC) protein isoforms, caspase 3, insulin-like growth factor 1 (IGF-1), muscle atrophy F-box (MAFbx) and muscle ring finger protein 1 (MuRF1) mRNA.

Results

PEEP shortened end-expiratory diaphragm muscle length by 15%, 14% and 12% with CMV, AMV and CPAP, respectively. Combined PEEP and CMV reduced tidal excursion of segmental diaphragm muscle length; consequently, tidal volume (VT) decreased. VT was maintained with combined PEEP and AMV. CMV alone decreased maximum tetanic force (Po) production by 35% versus control (P < 0.01). Combined PEEP and CMV did not decrease Po further. Po was preserved with AMV, with or without PEEP. Diaphragm muscle atrophy did not occur in any fiber types. Diaphragm MyHC shifted to the fast isoform in the combined PEEP and CMV group. In both the CMV and combined PEEP and CMV groups compared to controls, IGF-1 mRNAs were suppressed, whereas Caspase-3, MAFbx and MuRF1 mRNA expression were elevated.

Conclusions

Two days of diaphragm muscle fiber shortening with PEEP did not exacerbate CMV-induced diaphragm muscle dysfunction.
In-hospital mortality following treatment with red blood cell transfusion or inotropic therapy during early goal-directed therapy for septic shock: a retrospective propensity-adjusted analysis
Authors: Mark Dustin G , Morehouse John W , Hung Yun-Yi , Kene Mamata V , Elms Andrew R , Liu Vincent , Ballard Dustin W , Vinson David R
Published: September 2014

Introduction

We sought to investigate whether treatment of subnormal (<70%) central venous oxygen saturation (ScvO2) with inotropes or red blood cell (RBC) transfusion during early goal-directed therapy (EGDT) for septic shock is independently associated with in-hospital mortality.

Methods

Retrospective analysis of a prospective EGDT patient database drawn from 21 emergency departments with a single standardized EGDT protocol. Patients were included if, during EGDT, they concomitantly achieved a central venous pressure (CVP) of ≥8 mm Hg and a mean arterial pressure (MAP) of ≥65 mm Hg while registering a ScvO2 < 70%. Treatment propensity scores for either RBC transfusion or inotrope administration were separately determined from independent patient sub-cohorts. Propensity-adjusted logistic regression analyses were conducted to test for associations between treatments and in-hospital mortality.

Results

Of 2,595 EGDT patients, 572 (22.0%) met study inclusion criteria. The overall in-hospital mortality rate was 20.5%. Inotropes or RBC transfusions were administered for an ScvO2 < 70% to 51.9% of patients. Patients were not statistically more likely to achieve an ScvO2 of ≥70% if they were treated with RBC transfusion alone (29/59, 49.2%, P = 0.19), inotropic therapy alone (104/226, 46.0%, P = 0.15) or both RBC and inotropic therapy (7/12, 58.3%, P = 0.23) as compared to no therapy (108/275, 39.3%). Following adjustment for treatment propensity score, RBC transfusion was associated with a decreased adjusted odds ratio (aOR) of in-hospital mortality among patients with hemoglobin values less than 10 g/dL (aOR 0.42, 95% CI 0.18 to 0.97, P = 0.04) while inotropic therapy was not associated with in-hospital mortality among patients with hemoglobin values of 10 g/dL or greater (aOR 1.16, 95% CI 0.69 to 1.96, P = 0.57).

Conclusions

Among patients with septic shock treated with EGDT in the setting of subnormal ScvO2 values despite meeting CVP and MAP target goals, treatment with RBC transfusion may be independently associated with decreased in-hospital mortality.
Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase
Authors: Fu Xiaoyong , Creighton Chad J , Biswal Nrusingh C , Kumar Vijetha , Shea Martin , Herrera Sabrina , Contreras Alejandro , Gutierrez Carolina , Wang Tao , Nanda Sarmistha , Giuliano Mario , Morrison Gladys , Nardone Agostina , Karlin Kristen L , Westbrook Thomas F , Heiser Laura M , Anur Pavana , Spellman Paul , Guichard Sylvie M , Smith Paul D , Davies Barry R , Klinowska Teresa , Lee Adrian V , Mills Gordon B , Rimawi Mothaffar F , Hilsenbeck Susan G , Gray Joe W , Joshi Amit , Osborne C Kent , Schiff Rachel
Published: September 2014

Introduction

Activation of the phosphatidylinositol 3-kinase (PI3K) pathway in estrogen receptor α (ER)-positive breast cancer is associated with reduced ER expression and activity, luminal B subtype, and poor outcome. Phosphatase and tensin homolog (PTEN), a negative regulator of this pathway, is typically lost in ER-negative breast cancer. We set out to clarify the role of reduced PTEN levels in endocrine resistance, and to explore the combination of newly developed PI3K downstream kinase inhibitors to overcome this resistance.

Methods

Altered cellular signaling, gene expression, and endocrine sensitivity were determined in inducible PTEN-knockdown ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer cell and/or xenograft models. Single or two-agent combinations of kinase inhibitors were examined to improve endocrine therapy.

Results

Moderate PTEN reduction was sufficient to enhance PI3K signaling, generate a gene signature associated with the luminal B subtype of breast cancer, and cause endocrine resistance in vitro and in vivo. The mammalian target of rapamycin (mTOR), protein kinase B (AKT), or mitogen-activated protein kinase kinase (MEK) inhibitors, alone or in combination, improved endocrine therapy, but the efficacy varied by PTEN levels, type of endocrine therapy, and the specific inhibitor(s). A single-agent AKT inhibitor combined with fulvestrant conferred superior efficacy in overcoming resistance, inducing apoptosis and tumor regression.

Conclusions

Moderate reduction in PTEN, without complete loss, can activate the PI3K pathway to cause endocrine resistance in ER-positive breast cancer, which can be overcome by combining endocrine therapy with inhibitors of the PI3K pathway. Our data suggests that the ER degrader fulvestrant, to block both ligand-dependent and -independent ER signaling, combined with an AKT inhibitor is an effective strategy to test in patients.
The forkhead transcription factor FOXM1 promotes endocrine resistance and invasiveness in estrogen receptor-positive breast cancer by expansion of stem-like cancer cells
Authors: Bergamaschi Anna , Madak-Erdogan Zeynep , Kim Yu Jin , Choi Yoon-La , Lu Hailing , Katzenellenbogen Benita S
Published: September 2014

Introduction

The forkhead transcription factor FOXM1 coordinates expression of cell cycle-related genes and plays a pivotal role in tumorigenesis and cancer progression. We previously showed that FOXM1 acts downstream of 14-3-3ζ signaling, the elevation of which correlates with a more aggressive tumor phenotype. However, the role that FOXM1 might play in engendering resistance to endocrine treatments in estrogen receptor-positive (ER+) patients when tumor FOXM1 is high has not been clearly defined yet.

Methods

We analyzed FOXM1 protein expression by immunohistochemistry in 501 ER-positive breast cancers. We also mapped genome-wide FOXM1, extracellular signal-regulated kinase 2 and ERα binding events by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in hormone-sensitive and resistant breast cancer cells after tamoxifen treatment. These binding profiles were integrated with gene expression data derived from cells before and after FOXM1 knockdown to highlight specific FOXM1 transcriptional networks. We also modulated the levels of FOXM1 and newly discovered FOXM1-regulated genes and examined their impact on the cancer stem-like cell population and on cell invasiveness and resistance to endocrine treatments.

Results

FOXM1 protein expression was high in 20% of the tumors, which correlated with significantly reduced survival in these patients (P = 0.003 by logrank Mantel-Cox test). ChIP-seq analyses revealed that FOXM1 binding sites were enriched at the transcription start site of genes involved in cell-cycle progression, maintenance of stem cell properties, and invasion and metastasis, all of which are associated with a poor prognosis in ERα-positive patients treated with tamoxifen. Integration of binding profiles with gene expression highlighted FOXM1 transcriptional networks controlling cell proliferation, stem cell properties, invasion and metastasis. Increased expression of FOXM1 was associated with an expansion of the cancer stem-like cell population and with increased cell invasiveness and resistance to endocrine treatments. Use of a selective FOXM1 inhibitor proved very effective in restoring endocrine therapy sensitivity and decreasing breast cancer aggressiveness.

Conclusions

Collectively, our findings uncover novel roles for FOXM1 and FOXM1-regulated genes in promoting cancer stem-like cell properties and therapy resistance. They highlight the relevance of FOXM1 as a therapeutic target to be considered for reducing invasiveness and enhancing breast cancer response to endocrine treatments.
Pro: Are we ready to translate Alzheimer's disease modifying therapies to people with Down syndrome?
Authors: Rafii Michael S
Published: September 2014

Background

Down Syndrome (DS) is caused by trisomy of chromosome 21, which includes the gene for the amyloid precursor protein (APP) and leads to overproduction of beta-amyloid. Clinical-pathological studies indicate that individuals with DS begin demonstrating Alzheimer’s disease (AD) pathology during adolescence and that 100% exhibit such changes by age 40. Individuals with DS therefore represent a highly enriched population for AD. Additionally, owing to their baseline intellectual disability, people with DS represent a more vulnerable group of individuals as compared with other populations. Given the recent developments in AD biomarkers, combined with the prospect of achieving greater efficacy with earlier therapeutic intervention, it is logical to include adults with DS in prevention trials for AD.

Discussion

The US Food and Drug Administration has released draft guidance on drug development for early-stage AD, based on the understanding that AD is a progressive disease with symptoms developing decades after the disease process has begun. New biomarkers now permit detection of AD pathology in asymptomatic individuals such that there now exists an opportunity to conduct clinical trials of potentially disease-modifying drugs in the earliest stages of the disease and perhaps have the greatest chance of demonstrating efficacy. As such, clinical trials are being actively planned or conducted in individuals with causative mutations in the APP, presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes.

Individuals with DS comprise perhaps the largest group of people with genetically determined AD, with a worldwide population of about 6 million people. Only by inclusion can we provide access to rational therapies that offer the greatest chance of benefiting this highly at-risk population.
Con: are we ready to translate Alzheimer’s disease-modifying therapies to people with down syndrome?
Authors: Head Elizabeth , Schmitt Frederick A
Published: September 2014

Background

Adults with Down syndrome develop Alzheimer’s disease neuropathology in an age-dependent manner. This unique feature provides an opportunity to test interventions targeted for prevention of Alzheimer’s disease neuropathology and dementia in Down syndrome.

Discussion

In considering clinical trial designs, however, there are several challenges that we believe will be critical to examine further. These include: accuracy in dementia, mild cognitive impairment and preclinical Alzheimer’s disease diagnoses in Down syndrome; clinical trial outcome measures appropriate for individuals with Down syndrome; in vivo imaging outcome measures (and practical considerations); and contributions of medical co-morbidities to disease progression. Also, when studies are designed, the molecular target may appear to be obvious (for example, targeting beta-amyloid pathology), but chromosome 21 has over 200 additional genes that could influence both positive and negative clinical trial outcomes.

Observational longitudinal studies of aging in Down syndrome will be critically important as there is a need to establish sensitive clinical outcome measures and understand the consequences of gene overexpression in relation to specific interventions.
Excellent enhancement in the device performance of nitrogen plasma treated ZnO nanorods based diodes
Authors: Reddy Nandanapalli Koteeswara , Devika Mudusu , Hahn Yoon-Bong
Published: September 2014

Impact of the plasma exposure time on the physical properties of homo-epitaxial ZnO nanorods (NRs) and their devices was investigated. Here, ZnO NRs were synthesized by chemical solution method on glass substrates and treated under high intensity nitrogen plasma at different exposure timings. The as-grown as well as treated ZnO NRs exhibited hexagonal crystal structure and (001) as a preferential orientation. While increasing the plasma exposure time from 1 to 15 min, the structural and optical quality of ZnO NRs gradually improved and above this exposure time, both the properties degraded. The devices fabricated with 15 min plasma treated ZnO NRs showed excellent diode performance than the untreated nanostructures based devices. The diodes developed with treated ZnO NRs showed a low turn-on voltage (3.3 V) than the devices developed with untreated NRs.
The dynamic regulation of nitrogen and phosphorus in the early phase of fermentation improves the erythromycin production by recombinant Saccharopolyspora erythraea strain
Authors: Zhang Qiang , Chen Yong , Hong Ming , Gao Yang , Chu Ju , Zhuang Ying-ping , Zhang Si-liang
Published: September 2014

Background

Erythromycin production often has concern with the consumption rate of amino nitrogen and phosphate, especially in the early fermentation phase. The dynamic regulation of nitrogen and phosphorus was put forward based on the comprehensive analysis of the contents of phosphorus and nitrogen in different nitrogen sources as well as the relations between nitrogen consumption and phosphorus consumption.

Results

Firstly, the unstable nitrogen source, corn steep liquor, was substituted with the stable nitrogen source, yeast powder, with little effects on erythromycin production. Secondly, feeding phosphate in the early fermentation stage accelerated the consumption of amino nitrogen and ultimately increased erythromycin production by approximately 24% as compared with the control (without feeding potassium dihydrogen phosphate). Thirdly, feeding phosphate strategy successfully applied to 500 L fermenter with the final erythromycin concentration of 11839 U/mL, which was 17.3% higher than that of the control. Finally, the application of condensed soy protein (a cheap nitrogen source with low phosphorus content) combined with phosphate feed strategy led to a 13.0% increase of the erythromycin production as compared with the control (condensed soy protein, without feeding potassium dihydrogen phosphate).

Conclusions

Appropriately feeding phosphate combined with rational nitrogen regulation in the early fermentation phase was an effective way to improve erythromycin production.
Impact of Financial Burden of Cancer on Survivors' Quality of Life
Authors: Fenn Kathleen M. , Evans Suzanne B. , McCorkle Ruth , DiGiovanna Michael P. , Pusztai Lajos , Sanft Tara , Hofstatter Erin W. , Killelea Brigid K. , Knobf M. Tish , Lannin Donald R. , Abu-Khalaf Maysa , Horowitz Nina R. , Chagpar Anees B.
Published: September 2014

Increased financial burden as a result of cancer care costs is the strongest independent predictor of poor quality of life among cancer survivors.
Simple Prognostic Model for Patients With Advanced Cancer Based on Performance Status
Authors: Jang Raymond W. , Caraiscos Valerie B. , Swami Nadia , Banerjee Subrata , Mak Ernie , Kaya Ebru , Rodin Gary , Bryson John , Ridley Julia Z. , Le Lisa W. , Zimmermann Camilla
Published: September 2014

The authors present a simple tool that uses performance status alone to prognosticate in advanced cancer, and has discriminatory ability similar to that of more complex models.