bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of digestates from different biogas production systems on above and belowground grass growth and the nitrogen status of the plant‐soil‐system
Authors: Andruschkewitsch Meike , Wachendorf Christine , Wachendorf Michael
Published: October 2013

Biogas production from residual biomass (e.g. from extensively managed grassland) can help securing ecosystem services of such vegetation and may contribute to energy production from renewable resources. Proper management of fermentation residues is a major challenge within the technical concepts recently suggested for the conversion of this biomass. A 5‐month pot experiment was conducted to investigate the effects of digestates from separated grass silage (liquid fraction) (SGD), produced within the innovative integrated generation of solid fuel and biogas from biomass (IFBB) system and from conventional whole crop digestion (WCD) on grass growth, N uptake and N immobilization. Digestates and a mineral N fertilizer (MIN) as comparative variant were applied at N‐rates from 0 up to 20 g N m−2 based on fertilizer mineral N to three different grass species (Lolium perenne, Trisetum flavescens and Festuca rubra subsp. rubra). Digestate application increased harvestable biomass constantly with increasing N‐rate for L. perenne, but not for T. flavescens and F. rubra rubra. Type of digestate caused species‐specific differences in plant growth, as F. rubra rubra and L. perenne showed higher dry matter (DM) yields of harvestable and root biomass for WCD and T. flavescens for SGD application. However, for both digestates, reduced root biomasses were observed compared to the control. The mineral nitrogen use efficiency (NUEmin) was over all species 22% higher for harvestable and 33% for stubble biomass after application of SGD compared to WCD, due to greater N uptake related to lower gaseous N losses and favorable mineralization properties. N immobilization measured by soil microbial biomass N (MBN) was influenced by grass species but not by type of digestate or application rate. The lack of effect of digestate application on MBN was attributed to the compensation of the digestate carbon input by the reduced root biomass production.
DnaT is a single‐stranded DNA binding protein
Authors: Huang Yen‐Hua , Lin Min‐Jon , Huang Cheng‐Yang
Published: October 2013

DnaT is one of the replication restart primosomal proteins required for reinitiating chromosomal DNA replication in bacteria. In this study, we identified and characterized the single‐stranded DNA (ssDNA)‐binding properties of DnaT using electrophoretic mobility shift analysis (EMSA), bioinformatic tools and two deletion mutant proteins, namely, DnaT26‐179 and DnaT42‐179. ConSurf analysis indicated that the N‐terminal region of DnaT is highly variable. The analysis of purified DnaT and the deletion mutant protein DnaT42‐179 by gel filtration chromatography showed a stable trimer in solution, indicating that the N‐terminal region, amino acid 1–41, is not crucial for the oligomerization of DnaT. Contrary to PriB, which forms a single complex with a series of ssDNA homopolymers, DnaT, DnaT26‐179 and DnaT42‐179 form distinct complexes with ssDNA of different lengths and the size of binding site of 26 ± 2 nucleotides (nt). Using bioinformatic programs (ps)2 and the analysis of the positively charged/hydrophobic residue distribution, as well as the biophysical results in this study, we propose a binding model for the DnaT trimer–ssDNA complex, in which 25‐nt‐long ssDNA is tethered on the surface groove located in the highly conserved C‐terminal domain of DnaT. These results constitute the first study regarding ssDNA‐binding activity of DnaT. Consequently, a hand‐off mechanism for primosome assembly was modified.
Metabolomics reveals that carnitine palmitoyltransferase‐1 is a novel target for oxidative inactivation in human cells
Authors: Setoyama Daiki , Fujimura Yoshinori , Miura Daisuke
Published: October 2013

Oxidative dysfunction in the metabolism has long been implicated in diverse biological disorders. Although a substantial number of metabolic enzymes are targeted for inactivation by oxidative stress, identifying those targets remains difficult due to a lack of comprehensive observations of the metabolism acting through the stress response. We herein developed a metabolomics strategy using integrative liquid chromatography‐mass spectrometry (LC‐MS) and observing rapid metabolomic changes in response to hydrogen peroxide (H2O2)‐induced oxidative stress in HeLa cells. Among the many metabolite changes detected, the most characteristic metabolites uniquely indicated carnitine palmitoyltransferase‐1 (CPT1), the critical enzyme for mitochondrial β‐oxidation of long‐chain fatty acids, to be a target for oxidative inactivation. We showed that the enzymatic activity of CPT1 significantly declined by H2O2 in several human cells. Interestingly, the inactivation was shown to be a direct effect of H2O2 in vitro, but substantially occurred when cells were cultured with some reagents that generate reactive oxygen species (ROS). Thus, our results suggest the generality of CPT1 inhibition under various stress conditions associated with ROS generation, providing an insight into a mechanism for oxidative dysfunction in mitochondrial metabolism. Our metabolome data additionally suggest that certain methyltransferase(s) may be targets of oxidative stress as well.
Reducing Uncertainty in Calibrating Aquifer Flow Model with Multiple Scales of Heterogeneity
Authors: Zhang Ye
Published: October 2013

Modeling and calibration of natural aquifers with multiple scales of heterogeneity is a challenging task due to limited subsurface access. While computer modeling plays an essential role in aquifer studies, large uncertainty exists in developing a conceptual model of an aquifer and in calibrating the model for decision making. Due to uncertainties such as a lack of understanding of subsurface processes and a lack of techniques to parameterize the subsurface environment (including hydraulic conductivity, source/sink rate, and aquifer boundary conditions), existing aquifer models often suffer nonuniqueness in calibration, leading to poor predictive capability. A robust calibration methodology is needed that can address the simultaneous estimations of aquifer parameters, source/sink, and boundary conditions. In this paper, we propose a multistage and multiscale approach that addresses subsurface heterogeneity at multiple scales, while reducing uncertainty in estimating the model parameters and model boundary conditions. The key to this approach lies in the appropriate development, verification, and synthesis of existing and new techniques of static and dynamic data integration. In particular, based on a given set of observation data, new inversion techniques can be first used to estimate aquifer large‐scale effective parameters and smoothed boundary conditions, based on which parameter and boundary condition estimation can be refined at increasing detail using standard or highly parameterized estimation techniques.
Hydraulic Tomography Offers Improved Imaging of Heterogeneity in Fractured Rocks
Authors: Illman Walter A.
Published: October 2013

Fractured rocks have presented formidable challenges for accurately predicting groundwater flow and contaminant transport. This is mainly due to our difficulty in mapping the fracture‐rock matrix system, their hydraulic properties and connectivity at resolutions that are meaningful for groundwater modeling. Over the last several decades, considerable effort has gone into creating maps of subsurface heterogeneity in hydraulic conductivity (K) and specific storage (Ss) of fractured rocks. Developed methods include kriging, stochastic simulation, stochastic inverse modeling, and hydraulic tomography. In this article, I review the evolution of various heterogeneity mapping approaches and contend that hydraulic tomography, a recently developed aquifer characterization technique for unconsolidated deposits, is also a promising approach in yielding robust maps (or tomograms) of K and Ss heterogeneity for fractured rocks. While hydraulic tomography has recently been shown to be a robust technique, the resolution of the K and Ss tomograms mainly depends on the density of pumping and monitoring locations and the quality of data. The resolution will be improved through the development of new devices for higher density monitoring of pressure responses at discrete intervals in boreholes and potentially through the integration of other data from single‐hole tests, borehole flowmeter profiling, and tracer tests. Other data from temperature and geophysical surveys as well as geological investigations may improve the accuracy of the maps, but more research is needed. Technological advances will undoubtedly lead to more accurate maps. However, more effort should go into evaluating these maps so that one can gain more confidence in their reliability.
Hydraulically Controlled Discrete Sampling from Open Boreholes
Authors: Harte Philip T.
Published: October 2013

Groundwater sampling from open boreholes in fractured‐rock aquifers is particularly challenging because of mixing and dilution of fluid within the borehole from multiple fractures. This note presents an alternative to traditional sampling in open boreholes with packer assemblies. The alternative system called ZONFLO (zonal flow) is based on hydraulic control of borehole flow conditions. Fluid from discrete fractures zones are hydraulically isolated allowing for the collection of representative samples. In rough‐faced open boreholes and formations with less competent rock, hydraulic containment may offer an attractive alternative to physical containment with packers. Preliminary test results indicate a discrete zone can be effectively hydraulically isolated from other zones within a borehole for the purpose of groundwater sampling using this new method.
Interpreting a Pumping Test Influenced by Another Well in an Anisotropic Aquifer
Authors: Weber Simon , Chapuis Robert P. , Duhaime François
Published: October 2013

In confined aquifers the influence of neighboring active wells is often neglected when interpreting a pumping test. This can, however, lead to an erroneous interpretation of the pumping test data. This article presents simple methods to evaluate the transmissivity tensor and storativity of an anisotropic confined aquifer when there is an interfering well in the neighborhood of the tested well. Two methods have been developed depending on whether the tested well or the interfering well is the first in operation. These new methods yield better estimates of the hydraulic parameters than when the influence of the interfering well is neglected. These methods have then been used on data obtained from numerical models with an interfering well and the results have been compared to an analytical method that neglects the influence of the interfering well. The methods require knowledge of the pumping rate of the interfering well and the time elapsed since the pumping started in each well. If the interfering well started pumping before the tested well, the method does not require knowledge of the aquifer piezometric level at the beginning of the test, which is often unknown in this case. As for the method without interference, at least three monitoring wells (MWs) are needed, the position of which influences the accuracy of the estimated parameters. Some recommendations concerning MWs position have been given to get more accurate results according to the sought parameter.
Influencing factors on the functional level of haemophilic patients assessed byFISH
Authors: Kachooei A. R. , Badiei Z. , Zandinezhad M. E. , Ebrahimzadeh M. H. , Mazloumi S. M. , Omidi‐Kashani F. , Moradi A. , Mahdavian‐Naghashzargar R. , Razi S.
Published: October 2013

Joint destruction in early adulthood brings the patients to the orthopaedic clinics. If a haemophilic patient becomes disabled, it shows a number of factors such as timely diagnosis, availability of appropriate treatment depending on the country, access and affordability to treatments and equally importantly the responsibility of the patient in managing self care by remaining compliant by prescribed treatment regimen. We assessed the functional level by functional independence score in haemophilia (FISH). Overall, 104 patients with haemophilia A and 29 with haemophilia B were evaluated. We assessed the function of the patients byFISH. We divided the sum scores into weak (FISHscore 8–16), moderate (17–24), and good (25–32). For evaluating the level of functional deficit in a 2 × 2 table, we categorized the weak and moderate levels into Disordered Group and the good level into Not‐Disordered Group. The average age was 26.9 ± 14.24. Each 1 year increase in age can increase 1.07 fold the possibility of being placed in Disordered Function Group. Severe haemophilia can increase 7.34 fold, presence of inhibitor can increase 9.75 fold and home self‐care increases 3.89 fold the possibility of being placed in Disordered Function Group. To decrease the burden of the cost on patient, family and the government, education plays the most important role. We suggest that we send a trained team of physician and nurses to the deprived villages and cities instead of waiting for the patient to refer to our Care Center.
A Critical Evaluation of Migraine Trigger Site Deactivation Surgery
Authors: Mathew Paul G.
Published: October 2013

Migraine headache trigger site deactivation surgery is a term that encompasses 4 different surgical procedures that are performed based on headache onset location for the preventative treatment of migraine headaches. Multiple studies have demonstrated some efficacy of these procedures, but closer evaluation of the methodology of these studies reveals major flaws in study design. In this article, the author provides an overview of the procedures and presurgical screening tools, as well as a critical evaluation of 2 of the major studies that have been published. In addition, the author provides his opinion on future study designs that may help to better determine the potential efficacy of these experimental procedures and potential headache subtypes (contact point headache, supraorbital neuralgia, and occipital neuralgia) that may respond to peripheral decompression surgery.
Clinical Aspects of Medication Overuse Headaches
Authors: Da Silva Arnaldo Neves , Lake Alvin E.
Published: October 2013

Medication overuse headache (MOH) is a subset of chronic daily headache, occurring from overuse of 1 or more classes of migraine abortive medication. Acetaminophen, combination analgesics (caffeine combinations), opioids, barbiturates (butalbital), non‐steroidal anti‐inflammatory drugs, and triptans are the main classes of drugs implicated in the genesis of MOH. Migraine seems to be the most common diagnosis leading to MOH. The development of MOH is associated with both frequency of use of medication and behavioral predispositions. MOH is not a unitary concept. The distinction between simple (type 1) vs complex (type 2) forms is based on both the class of overused medication and behavioral factors, including psychopathology and psychological drug dependence.

MOH is a challenging disorder causing decline in the quality of life and causing physical symptoms, such as daily and incapacitating headaches, insomnia, and non‐restorative sleep, as well as psychological distress and reduced functioning. MOH is associated with biochemical, structural, and functional brain changes. Relapse after detoxification is a challenge, but can be addressed if the patient is followed over a prolonged period of time with a combination of prophylactic pharmacotherapy, use of abortive medication with minimal risk of MOH, withholding previously overused medication, and providing psychological (cognitive‐behavioral) therapy.
Pathophysiology of Medication Overuse Headache—An Update
Authors: Srikiatkhachorn Anan , le Grand Supang Maneesri , Supornsilpchai Weera , Storer Robin James
Published: October 2013

The pathogenesis of medication overuse headache is unclear. Clinical and preclinical studies have consistently demonstrated increased excitability of neurons in the cerebral cortex and trigeminal system after medication overuse. Cortical hyperexcitability may facilitate the development of cortical spreading depression, while increased excitability of trigeminal neurons may facilitate the process of peripheral and central sensitization. These changes may be secondary to the derangement of central, probably serotonin (5‐HT)‐, and perhaps endocannabinoid‐dependent or other, modulating systems. Increased expression of excitatory cortical 5‐HT2A receptors may increase the susceptibility to developing cortical spreading depression, an analog of migraine aura. A reduction of diffuse noxious inhibitory controls may facilitate the process of central sensitization, activate the nociceptive facilitating system, or promote similar molecular mechanisms to those involved in kindling. Low 5‐HT levels also increase the expression and release of calcitonin gene‐related peptide from the trigeminal ganglion and sensitize trigeminal nociceptors. Thus, derangement of central modulation of the trigeminal system as a result of chronic medication use may increase sensitivity to pain perception and foster or reinforce medication overuse headache.
Sporadic Hemiplegic Migraine With Permanent Neurological Deficits
Authors: Schwedt Todd J. , Zhou Jiying , Dodick David W.
Published: October 2013

By definition, the neurologic impairments of hemiplegic migraine are reversible. However, a few cases of permanent neurologic deficits associated with hemiplegic migraine have been reported. Herein, we present the case of a patient with permanent impairments because of hemiplegic migraine despite normalization of associated brain magnetic resonance imaging abnormalities. Cases like these suggest the need to consider aggressive prophylactic therapy for patients with recurrent hemiplegic migraine attacks.
Mitochondrial reactive oxygen species as a mystery voice in hepatitis C
Authors: Hino Keisuke , Hara Yuichi , Nishina Sohji
Published: October 2013

There are several lines of evidence suggesting that oxidative stress is present in hepatitis C to a greater degree than in other inflammatory liver diseases and is closely related to disease progression. The main production site of reactive oxygen species (ROS) is assumed to be mitochondria, which concept is supported by evidence that hepatitis C virus (HCV) core protein is directly associated with them. The detoxification of ROS also is an important function of the cellular redox homeostasis system. These results draw our attention to how HCV‐induced mitochondrial ROS production is beyond redox regulation and affects the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis C. On the other hand, HCV‐related chronic liver diseases are characterized by metabolic alterations such as insulin resistance, hepatic steatosis and/or iron accumulation in the liver. These metabolic disorders also are relevant to the development of HCC in HCV‐related chronic liver diseases. Here, we review the mechanisms by which HCV increases mitochondrial ROS production and offer new insights as to how mitochondrial ROS are linked to metabolic disorders such as insulin resistance, hepatic steatosis and hepatic iron accumulation that are observed in HCV‐related chronic liver diseases.
Lamivudine resistance leading to de novo hepatitis B infection in recipients of hepatitis B core antibody positive liver allografts
Authors: Leong Jennifer , Coty Patrick , Fiel M. Isabel , Chang Charissa , Florman Sander , Schiano Thomas
Published: October 2013

Most studies have shown that lamivudine (LAM) prophylaxis is sufficient to prevent hepatitis B virus (HBV) transmission in recipients of hepatitis B core antibody positive (HBcAb+) allografts. However, de novo hepatitis B (DNHB) is known to occur in this patient population. Herein, we report a case series of four liver transplant recipients who developed DNHB after receiving HBcAb+ allografts due to acquisition of LAM resistance mutations, suggesting that LAM prophylaxis may be suboptimal. A retrospective chart review was performed of all adult liver transplants performed at Mount Sinai from 2001 to 2010. A total of 79 patients received HBcAb+ allografts for non‐hepatitis B‐related liver disease. Of these 79 recipients, four patients developed DNHB and were found to have documented LAM resistance. With the increasing use of HBcAb+ donor livers, we suspect that there will also be a growing number of cases of DNHB due to acquisition of LAM resistance. We suggest that other agents, such as entecavir or tenofovir, be considered for use as prophylaxis in this patient population to decrease this risk.
Elevation of serum cytokines preceding elevation of liver enzymes in a case of drug‐induced liver injury
Authors: Kakisaka Keisuke , Takikawa Yasuhiro
Published: October 2013

A 50‐year‐old man who was being treated for both pneumonia and type 2 diabetes mellitus complained of abdominal distention on the 16th hospital day. Liver enzyme elevation without symptoms was detected on the 17th hospital day. Based on a Roussel Uclaf Causality Assessment Method score of 10 and a Japan Digestive Disease Week score of 9, we diagnosed the patient as having drug‐induced liver injury (DILI). Simultaneous assays of the levels of cytokines revealed that the elevation of the levels of interleukin (IL)‐1β, IL‐10, IL‐12, IL‐13 and tumor necrosis factor‐α preceded the elevation of the serum liver enzymes. This case suggests that some cytokines or related molecules are potentially useful as early‐phase biomarkers for DILI.
Supporting public involvement in research design and grant development: a case study of a public involvement award scheme managed by a National Institute for Health Research (NIHR) Research Design Service (RDS)
Authors: Boote Jonathan D. , Twiddy Maureen , Baird Wendy , Birks Yvonne , Clarke Clare , Beever Daniel
Published: October 2013

Background

It is good practice for the public to be involved in developing health research. Resources should be available for researchers to fund the involvement of the public in the development of their grants.

Objective

To describe a funding award scheme to support public involvement in grant development, managed by an NIHR Research Design Service (RDS). Case examples of how the award contributed to successful grant applications and findings from a recent evaluation of the scheme are presented.

Design

A case study of resource provision to support public involvement activities in one region of England.

Participants

University and NHS‐based researchers, and members of the public.

Findings

Between 2009 and 2012, the RDS approved 45 public involvement funding awards (totalling nearly £19 000). These awards contributed to 27 submitted applications at the time of writing, of which 11 were successful (totalling over £7.5 million). The evaluation revealed difficulties encountered by some researchers when involving the public in grant development, which led to suggestions about how the scheme could be improved.

Conclusion

This award scheme represents an efficient method of providing researchers with resources to involve the public in grant development and would appear to represent good value for money.
Involving patients in clinical research: the Telescot Patient Panel
Authors: Fairbrother Peter , McCloughan Lucy , Adam Geraldine , Brand Richard , Brown Cecil , Watson Mary , Cotter Nicola , Mackellaig Juliet , McKinstry Brian
Published: October 2013

Background

To date, patient involvement in the development of clinical research work has been limited. In 2011, the Telescot research team commenced work on a feasibility trial to investigate home telemonitoring of blood pressure for people who have experienced stroke or transient ischaemic attack (TIA). The team decided to involve patients in the development of the research.

Objectives

To improve research design through patient involvement.

Method of patient involvement

A modified form of the ‘Scrutiny Panel’ approach was used to involve people who had stroke in the research project.

Results

The Patient Panel supported the research in three key ways: it informed patient communication; it presented patient perspectives on the applicability and usability of the intervention; and it guided the development of the qualitative study.

Discussion

The initiative was considered a positive experience for all. However, challenges were identified in terms of the time and cost implications of undertaking patient involvement.

Implication for research practice

Importance is attached to adequate project planning and development, partnership working with community‐based organizations and the necessity for clear role delineation between patients and professionals to enable effective collaborative working.

Conclusions

The Telescot Patient Panel was beneficial in supporting the development of the feasibility trial. The Panel approach was considered transferable to other clinical research contexts.
‘Too much for one day’: a case study of disclosure in the paediatric HIV/AIDS clinic
Authors: Penn Claire
Published: October 2013

Background

Despite acknowledgement of the complexity and challenges of the process of disclosure of HIV status to adolescents, little work has been carried out on the communication features which facilitate or hinder the process. This qualitative case study reflects the interactional dynamics of an interaction between caregiver, physician and counsellor around the topic of disclosure in a South African clinic.

Methods

A 40‐minute encounter between a doctor, the grandmother of an adolescent with HIV/AIDS and a counsellor around the process of disclosure was transcribed and examined in detail in relation to its structure, topics, timing and sequence as well as its movement towards a collaborative ending. Analysis was based on elements of conversational and thematic analysis.

Results

The session was characterized by distinct stages and the emergence of multiple voices and perspectives from the participants. The negotiated management of the session sheds light on multiple barriers to care as well as the influence of contextual factors on the process. The important mediating role of the counsellor in the triad emerges. The analysis highlights both unique features of the consultation and common challenges to clinicians when disclosing.

Discussion and Conclusions

The task of disclosure is complex and intricate. Results suggest team processes are critical, as are temporal and contextual factors and the need for an understanding of communication. Implications for the clinic team are discussed and suggestions made for the development of collaborative partnership based on an understanding of roles and responsibilities, time factors and enhancement of features such as trust and communication.
‘Are we allowed to disclose?’: a healthcare team's experiences of talking with children and adolescents about their HIV status
Authors: Watermeyer Jennifer
Published: October 2013

Background

Talking with a child about their HIV status is a complex, emotionally laden and difficult task for caregivers and healthcare providers. Disclosure is an important process which may have psychosocial and health benefits. Despite existing guidelines and materials, disclosure does not always happen for various reasons.

Objective

This qualitative study explored a healthcare team's perspectives and experiences about disclosure practices.

Methods

Three focus groups were conducted with a total of 23 healthcare providers at a paediatric clinic in South Africa. The data were analysed using principles of thematic analysis.

Results

Results confirm the complexity of the disclosure process and highlight confusion, hesitancy and ethical dilemmas regarding disclosure practices. Tensions were noted within the team which seem linked to professional hierarchies. Counsellors and nurses preferred an indirect approach of encouraging caregivers to disclose to their children and providing psychosocial support, while doctors tended to become more directly involved in disclosing to children out of a sense of duty, legal responsibilities and knowledge of the child's rights.

Discussion and Conclusions

This study demonstrates how the complexities of disclosure with children and adolescents bring about additional challenges for healthcare teams. The legal and ethical implications as well as the roles and responsibilities of healthcare providers with disclosure remain unclear. Several recommendations for practice and policy emerge from this study, related particularly to the need for clarification of disclosure guidelines and legal implications. Implications for the healthcare team are also discussed.
TTF‐1 expression in breast carcinoma: an unusual but real phenomenon
Authors: Ni Yun‐Bi , Tsang Julia Y S , Shao Mu‐Min , Chan Siu‐Ki , Tong Joanna , To Ka‐Fai , Tse Gary M
Published: October 2013

Aims

To evaluate thyroid transcription factor‐1 (TTF‐1) expression in a large cohort of invasive breast carcinomas (IBCs) using two commercially available monoclonal antibody clones (8G7G3/1 and SPT24).

Methods and results

Nuclear and cytoplasmic TTF‐1 expression was evaluated in 1132 primary IBCs and 208 primary pulmonary carcinomas using tissue microarray (TMA) sections. TTF‐1 nuclear expression was detected in one of 1132 (0.09%) IBCs by 8G7G3/1. In pulmonary carcinoma, TTF‐1 expression was detected in 149 (71.6%) and 147 (70.6%) cases by 8G7G3/1 and SPT24, respectively, with no significant difference being seen between the two clones (P = 0.839), and there was good consistency between these two antibodies in differentiating breast and pulmonary carcinomas (kappa value 0.905; P < 0.001). Both clones showed high specificity but relatively low sensitivity. Cytoplasmic TTF‐1 expression was detected in 44 IBCs by 8G7G3/1, and this particular expression pattern was an independent adverse prognostic factor.

Conclusions

Both TTF‐1 antibodies (clones 8G7G3/1 and SPT24) were useful in differentiating breast from pulmonary carcinomas. Nuclear expression of TTF‐1 was detected in IBCs by 8G7G3/1, but not by SPT24. Cytoplasmic expression of 8G7G3/1 was seen in IBC for the first time, and was an independent unfavourable prognostic factor.
The apoptotic and proliferation rate of tumour budding cells in colorectal cancer outlines a heterogeneous population of cells with various impacts on clinical outcome
Authors: Dawson Heather , Koelzer Viktor H , Karamitopoulou Eva , Economou Mary , Hammer Caroline , Muller Dominique‐Elisabeth , Lugli Alessandro , Zlobec Inti
Published: October 2013

Aims

In colorectal cancer (CRC), tumour buds represent an aggressive cell type at the invasive front with apparently low proliferation. The aim of this study was to determine proliferation and apoptotic rates of buds in comparison to tumour centre, front and mucosa.

Methods and results

Whole tissue sections from 188 CRC patients underwent immunohistochemistry for Ki67. Ten high‐power fields (HPFs) were evaluated in mucosa, tumour centre, tumour front and tumour buds (total = 40 HPFs/case). Caspase‐3 and M30 immunohistochemistry were performed on a multipunch tissue microarray from the same cohort. Ki67, caspase‐3 and M30 immunoreactivity were correlated with outcome. The average percentage of cells showing Ki67 positivity was 5.2% in mucosa, and was not significantly different between the centre and front of the tumour (38.2% and 34.9%; P < 0.0001); 0.3% of buds showed Ki67 positivity (P < 0.0001). Caspase‐3 expression was similar in mucosa, tumour centre and tumour front, but lower in tumour buds (<0.1%; P < 0.0001). M30 staining in buds was decreased (0.01%; P < 0.0001) in comparison to other areas. Ki67 positivity in buds was detrimental to survival in univariate (P = 0.0352) and multivariate (P = 0.0355) analysis. Caspase‐3‐positive tumours showed better outcome than negative tumours (P = 0.0262); but tumours with caspase‐3‐positive buds showed a worse outcome than those with caspase‐3‐negative buds (P = 0.0235).

Conclusions

Ki67, caspase‐3 and M30 staining is absent in most tumour buds, suggesting decreased proliferation and apoptosis. However, the fact that Ki67 and caspase‐3 immunoreactivity was associated with unfavourable prognosis points to a heterogeneous population of tumour buds.
Loss of special AT‐rich sequence‐binding protein 1 (SATB1) predicts poor survival in patients with colorectal cancer
Authors: Al‐Sohaily Sam , Henderson Christopher , Selinger Christina , Pangon Laurent , Segelov Eva , Kohonen‐Corish Maija R. J. , Warusavitarne Janindra
Published: October 2013

Aim

Special AT‐rich sequence‐binding protein 1 (SATB1) is a cell type‐specific matrix attachment region binding protein, functioning as a global genome organizer. This study aims to investigate the expression pattern and the prognostic value of SATB1 in colorectal cancer.

Methods and results

Prospectively collected data were obtained and tissue microarrays were constructed from a cohort of 352 patients. SATB1 protein expression was evaluated by immunohistochemistry and scored by two independent investigators. SATB1 expression was predominantly nuclear in both normal and cancer tissues. Loss of SATB1 nuclear expression was seen in 22% of colorectal cancers compared to 1.5% of adjacent normal colorectal tissue, and was associated with worse overall survival (P = 0.02) independent of age and stage of disease (HR 2.48 with 95% CI 1.31–4.70). Loss of SATB1 expression was more evident in younger patients (P = 0.03), tumours with mucinous or signet ring histology (P = 0.0001) and poor differentiation (P = 0.005). SATB1 expression was associated with a survival advantage in patients with Dukes C tumours who received adjuvant chemotherapy.

Conclusion

Loss of SATB1 nuclear expression correlates with poor survival and a less favourable response to adjuvant chemotherapy in colorectal cancer. The value of SATB1 in individualized colorectal cancer therapy warrants further evaluation.
Reduced expression of αGlcNAc in Barrett's oesophagus adjacent to Barrett's adenocarcinoma – a possible biomarker to predict the malignant potential of Barrett's oesophagus
Authors: Iwaya Yugo , Hasebe Osamu , Koide Naohiko , Kitahara Kei , Suga Tomoaki , Shinji Akihiro , Muraki Takashi , Yokosawa Shuichi , Yamada Shigenori , Arakura Norikazu , Tanaka Eiji , Nakayama Jun
Published: October 2013

Aims

Gastric gland mucin contains O‐glycans exhibiting terminal α1,4‐linked N‐acetylglucosamine residues (αGlcNAc). Recently we demonstrated that mice deficient in αGlcNAc in gastric gland mucin develop gastric adenocarcinoma spontaneously, indicating that αGlcNAc is a tumour suppressor for gastric cancer. However, the role of αGlcNAc in Barrett's oesophagus (BO) remains unknown. In this study, we investigated whether reduced αGlcNAc expression in BO is associated with development of Barrett's adenocarcinoma (BAC).

Methods and results

Thirty‐five BO lesions adjacent to BAC were examined by immunohistochemistry for αGlcNAc, MUC6 and CDX2. As controls, 35 BO lesions without BAC obtained from patients with oesophageal squamous cell carcinoma were also analysed. Expression of αGlcNAc relative to its scaffold MUC6 in BO adjacent to BAC was reduced significantly compared to control BO. Decreased αGlcNAc expression in BO adjacent to BAC was particularly significant in patients with smaller tumour size (<20 mm) and minimal invasion of tumour cells to the superficial muscularis mucosae. There was also a significant inverse correlation between αGlcNAc and CDX2 expression in BO adjacent to BAC.

Conclusions

Decreased expression of αGlcNAc compared with MUC6 in BO is a possible hallmark in predicting BAC development.
Targeted therapies for sarcomas: new roles for the pathologist
Authors: Al‐Zaid Tariq , Somaiah Neeta , Lazar Alexander J
Published: October 2013

Sarcomas are a heterogeneous family of mesenchymal malignancies that employ an impressive variety of pathogenetic mechanisms. The traditional role of the pathologist in this field has been to ensure accurate diagnosis and histological grading to direct therapy. More recently, with the advent of targeted therapies directed at particular molecular alterations, the role of the pathologist has expanded and increased awareness of the genetic features of sarcomas is needed to deliver optimal multidisciplinary care. This review discusses these trends and briefly enumerates many of the molecular derangements and targeted agents currently used or under investigation in soft tissue sarcoma. A few sarcomas are highlighted in more detail to illustrate how pathologists can exert positive influence on patient care – not just through diagnosis and grading, but also with molecular characterizations. Featured sarcomas include alveolar soft part sarcoma, dermatofibrosarcoma protuberans, gastrointestinal stromal tumour, inflammatory myofibroblastic tumour and PEComas.
Loss of membranous expression of the intracellular domain of EpCAM is a frequent event and predicts poor survival in patients with pancreatic cancer
Authors: Fong Dominic , Moser Patrizia , Kasal Armin , Seeber Andreas , Gastl Guenther , Martowicz Agnieszka , Wurm Martin , Mian Christine , Obrist Peter , Mazzoleni Guido , Spizzo Gilbert
Published: October 2013

Aims

Epithelial cell adhesion molecule (EpCAM) is a widely used immunohistochemical marker for epithelial human malignancies. Antibodies to target EpCAM are usually directed against its ectodomain (EpEX), but do not detect the intracellular domain (EpICD). The aim of this study was to compare membranous EpEX versus EpICD expression by immunohistochemistry.

Methods and results

Concurrent EpEX and EpICD expression was investigated retrospectively in cancerous and matched non‐neoplastic tissue samples from patients with pancreatic adenocarcinoma. In total, 317 paired samples of pancreatic tissue from 88 patients were analysed and correlated with clinicopathological parameters. In non‐cancerous tissue, a high concordance of membranous EpEX and EpICD expression was observed and defined as the expression of the full‐length EpCAM (EpEX+/EpICD+ phenotype, EpCAMMF), which was highly predominant. In contrast, while most tumour samples were EpEX positive, loss of membranous EpICD expression (EpEX+/EpICD− phenotype, EpCAMMT) was observed in one‐third of cases, and these patients had a significantly shortened disease‐free and overall survival.

Conclusions

This study demonstrates for the first time that loss of membranous EpICD expression is a frequent event and predicts poor prognosis in patients with pancreatic cancer. Additional studies evaluating the predictive and prognostic value of the expression of different membranous EpCAM variants are warranted in epithelial cancers.
Care, Oppression, and Marriage
Authors: Marin Mara
Published: October 2013

This article draws attention to a form of injustice in intimate relationships of care that is largely ignored in discussions about the legal rights and obligations of intimate partners. This form of injustice is connected to a feature of caregiving I call “flexibility,” in virtue of which caregiving requires “skills of flexibility.” I argue that the demands placed by these skills on caregivers create constraints that amount to “vulnerability to oppression.” To lift these constraints, caregivers are entitled to open‐ended responses to their work, responses that would enable them to pursue their own projects while providing care. Instead of protecting individual choice of intimate relationships, marriage law should protect these entitlements.
Determination of the influence of factors (ethanol, pH and aw) on the preservation of cosmetics using experimental design
Authors: Berthele H. , Sella O. , Lavarde M. , Mielcarek C. , Pense‐Lheritier A.‐M. , Pirnay S.
Published: October 2013

Synopsis

Objective

Ethanol, pH and water activity are three well‐known parameters that can influence the preservation of cosmetic products. With the new constraints regarding the antimicrobial effectiveness and the restrictive use of preservatives, a D‐optimal design was set up to evaluate the influence of these three parameters on the microbiological conservation.

Methods

To monitor the effectiveness of the different combination of these set parameters, a challenge test in compliance with the International standard ISO 11930: 2012 was implemented. The formulations established in our study could support wide variations of ethanol concentration, pH values and glycerin concentration without noticeable effects on the stability of the products.

Results

In the conditions of the study, determining the value of a single parameter, with the tested concentration, could not guarantee microbiological conservation. However, a high concentration of ethanol associated with an extreme pH could inhibit bacteria growth from the first day (D0). Besides, it appears that despite an aw above 0.6 (even 0.8) and without any preservatives incorporated in formulas, it was possible to guarantee the microbiological stability of the cosmetic product when maintaining the right combination of the selected parameters.

Conclusion

Following the analysis of the different values obtained during the experimentation, there seems to be a correlation between the aw and the selected parameters aforementioned. An application of this relationship could be to define the aw of cosmetic products by using the formula, thus avoiding the evaluation of this parameter with a measuring device.
In vitro anti‐Malassezia activity and potential use in anti‐dandruff formulation of Asparagus racemosus
Authors: Onlom C. , Khanthawong S. , Waranuch N. , Ingkaninan K.
Published: October 2013

Synopsis

Objective

Malassezia species are frequently associated with dandruff and seborrhoeic dermatitis. The study was conducted to evaluate anti‐fungal activities of the extracts obtained from the roots of Asparagus racemosus Willd against Malassezia furfur and M. globosa.

Methods

Asparagus racemosus roots were successively extracted with the series of solvents, that is, hexane, ethanol and water, and also a saponin‐enriched fraction was prepared. The amounts of saponin (equivalent to shatavarin IV) in the extracts were determined using ELISA. The extracts were tested for anti‐fungal activity by disc diffusion and broth microdilution methods.

Results

By disc diffusion, only the ethanolic and saponin‐enriched extracts demonstrated anti‐fungal activity against M. furfur and M. globosa at the concentration of 1 mg per disc whereas the extracts with other solvents were ineffective. Multiple concentrations using the broth microdilution method against M. furfur and M. globosa yielded minimum inhibitory concentrations (MICs) of 25 mg mL−1 for the ethanolic extract but much higher potency for the saponin‐enriched extract: MICs to 0.20 and 0.40 mg mL−1 for M. furfur and M. globosa, respectively. These extracts showed no antagonist effect with the anti‐fungal agents, ketoconazole and zinc pyrithione.

Conclusion

These studies revealed the antifungal activity of A. racemosus roots extracts. Because A. racemosus is also anti‐inflammatory agent, it has the potential use as an active ingredient in an anti‐dandruff formulation.
The effects of two 10% carbamide peroxide nightguard bleaching agents, with and without desensitizer, on enamel and sensitivity: an in vivo study
Authors: Navarra CO , Reda B , Diolosà M , Casula I , Di Lenarda R , Breschi L , Cadenaro M
Published: October 2013

Objectives

This study aimed to compare the effects of two 10% carbamide peroxide (CP) agents with or without desensitizers on tooth sensitivity, colour and enamel morphological changes.

Methods

Twenty subjects used a 10% carbamide peroxide gel with or without fluoride and potassium nitrate for 2 weeks. Sensitivity, spectrophotometric evaluation of colour and morphological analyses of replicas with scanning electron microscope (SEM) were performed before and after treatment. All data were analysed statistically.

Results

Both bleaching agents induced sensitivity; however, the 10% CP bleaching agent with fluoride and potassium nitrate produced significantly lower sensitivity (P < 0.05) than the bleaching product without desensitizing agents. In spectrophotometric evaluation, no difference in bleaching effectiveness was found between the tested bleaching gels, and the SEM analysis confirmed the absence of relevant alterations of the enamel surface in both groups.

Conclusion

The use of 10% carbamide peroxide gel with fluoride and potassium nitrate reduced the incidence of sensitivity during the bleaching treatment compared to a bleaching agent that did not contain desensitizing agents. The bleaching effectiveness of the tested products was comparable.
Synthesis of High‐Purity Ti3SiC2by Microwave Sintering
Authors: Wang Qian , Hu Chunfeng , Cai Shu , Sakka Yoshio , Grasso Salvatore , Huang Qing
Published: October 2013

High‐purity ternary laminated compound Ti3SiC2was successfully synthesized by a microwave heating method in the flowing argon for the first time. The mixtures of titanium, silicon, and graphitic carbon (Cgc) or activated carbon (Cac) with different molar ratios were used to investigate the reaction mechanisms. It was confirmed that Ti3SiC2with high purity of 98 vol.% was achieved without the aids of Al. The optimum experimental parameters were determined as Ti/Si/Cgchaving the molar ratio of 3/2.2/2, first holding at 1480°C for 30 min, and subsequent dwelling at 1300°C for 60 min.
Structural and Magnetic Property of Co1‐xNixFe2O4Nanoparticles Synthesized by Hydrothermal Method
Authors: He Hai‐Yan
Published: October 2013

The cobalt nickel ferrite (Co1‐xNixFe2O4 x = 0–1.0) nanoparticles were synthesized by a hydrothermal method. Effects of nickel content and organic template on the microstructure and magnetic property of the nanoparticles were studied. The experimental results indicate that Ni2+ substitution for Co2+ and special synthesis technique leads to obvious change in microstructure and magnetic property of the ferrites. The ferrites show nonlinear variations in the saturation magnetization and the coercivity with nickel substitution, which are explained by shape anisotropy and supernormal cation distribution. The organic template also leads to variation in the microstructure and properties of the nanoparticles.
Effects of Mg‐Doping and of Reinforcing Multiwalled Carbon Nanotubes Content on the Structure and Properties of Hydroxyapatite Nanocomposite Ceramics
Authors: Bricha Meriame , Belmamouni Younes , El Mabrouk Khalil , Ferreira José M. F.
Published: October 2013

Surfactant‐assisted hydrothermal synthesis of magnesium‐doped hydroxyapatite (Ca10−xMgx(PO4)6(OH)2) with 0 ≤ x ≤ 1) was realized in aqueous solution at 90°C. β‐TCP phase was formed in the Mg0.6‐HA sample after heat treatment at 1000°C. Magnesium was found to degrade the sintering ability of Mgx‐HA ceramics. Flexural strength (σf) was found to decrease as a function of Mg‐doped HA. The using of carbon nanotubes as reinforcing agents mitigated the strength loss of Mg‐HA ceramics. The flexural strength of Mg0.6‐HA was then increased by nearly 20% from approximately 33 to 39 MPa with an optimum addition of 3 wt% of multi‐walled nanotubes.