bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex Posttraumatic Stress Disorder
Authors: Spermon Deborah , Darlington Yvonne , Gibney Paul
Published: October 2012

In this article, we report on a phenomenological study of experiences of recovery of 7 women with histories of childhood maltreatment. We propose a model that recalls the Anglo-Franc etymological origins of rekeverer: to regain consciousness, health, or strength. Dimensions include development of a selfhood; tasks of connection and separation; regulation of overwhelming emotions; management of choices; and internalization of therapeutic relational dynamics. Based on the findings, we suggest that theory and research need to extend concepts of healing, add methodologies privileging victim/survivor voices, and revisit concepts such as neutrality and resistance as they apply to dissociative disorders. Practitioners should have specific training in trauma models, although they need to hold these theories lightly because therapeutic goals and pathways of change might well differ for each client. Integrated whole-of-government initiatives need to identify those at risk of abuse as early as possible, and provide response funding beyond assessment services.
Modifying the Diary Interview Method to Research the Lives of People With Dementia
Authors: Bartlett Ruth
Published: October 2012

Debates about involving people with dementia in qualitative research are extensive, yet the range of methods used is limited. Researchers tend to rely on interview and/or observation methods to collect data, even though these tools might preclude participation. I modified the conventional diary interview method to include photo and audio diaries in an effort to investigate the lives of people with dementia in a participatory way. Sixteen people with dementia kept a diary—written, photo, or audio, whichever suited them best—for 1 month. The purposes of this article are to share the methodological insights gained from this process in the context of emerging literature on sensory ethnography, and to argue for the broader application of the diary interview method in dementia-related research, on the grounds that it mediates an equal relationship and makes visible the “whole person,” including the environment in which that person lives.
Organizational Approaches to Integrated Health Care Delivery: A Taxonomic Analysis of Physician-Organization Arrangements
Authors: Alexander Jeffrey A. , Vaughn Thomas , Burns Lawton R. , Zuckerman Howard S. , Andersen Ronald M. , Torrens Paul , Hilberman Diana W.
Published: October 2012

Integrated health care organizations depend fundamentally on bringing organizations and physicians into closer alignment. Little empirical research has been conducted on the organizational mechanisms by which such alignment is attempted. This study employed primary data from 79 hospitals and health care systems to identify current approaches to aligning the strategic and economic interests of organizations and physicians. An empirical classification of both unbundled and structured physician-organization arrangements (POAs) resulted in 5 distinct strategic configurations. These configurations were differentiated by key contextual factors that shape patterns of development and operation of POAs. Particularly salient among these were managed care penetration, organization size, locus of control, and organization strategy. Results of the taxonomic analysis underscore the facts that most delivery organizations employ multifaceted rather than single approaches to physician integration and that these approaches are endemic to particular environmental and organizations conditions.
Tyrosine kinase inhibitor induced pancreatitis
Authors: Sevin Adrienne , Chen Adrienne , Atkinson Brad
Published: October 2012

Sorafenib and sunitinib are oral tyrosine kinase inhibitors, commonly used in the treatment of metastatic renal cell carcinoma. Known adverse events associated with tyrosine kinase inhibitors include hypertension and palmarplantar erythrodysesthesia. We report two cases of acute pancreatitis associated with tyrosine kinase inhibitors.
Proposing paradigm peace: Mixed methods in feminist tourism research
Authors: Heimtun Bente , Morgan Nigel
Published: October 2012

This article attempts to engage and advance tourism’s epistemological and methodological discussions. It explores how the transformative paradigm offers an opportunity to feminist tourism researchers to broaden their methods base and obtain nuanced understandings of systematic and localised oppression without compromising research principles, such as positionality and reflexivity. To illustrate the value of this approach, we combine a qualitative study of midlife (35–55 years) single women’s holiday experiences with a follow-up quantitative study of young (18–30 years) single women’s experiences. We argue that merging these studies creates new understandings of intersecting power relations related to gender, age and singlehood and that in a broader sense working within the transformative paradigm has the potential to promote paradigm peace in feminist tourism research.
Learning outcomes assessment and History: TEQSA, the After Standards Project and the QA/QI challenge in Australia
Authors: Brawley Sean , Clark Jennifer , Dixon Chris , Ford Lisa , Ross Shawn , Upton Stuart , Nielsen Erik
Published: October 2012

Higher education in Australia is currently in a state of flux, with the Federal Government’s Tertiary Education Quality and Standards Agency commencing operations in January 2012. The ‘After Standards Project’ has been working with Australian university history departments and the Australian Historical Association, educating and empowering the discipline to act as a united community and assert ownership of a standards process. This article provides a stocktake of the achievements and challenges the After Standards Project has faced in coming to terms with the new environment and resultant new demands around compliance and accountability. It discusses the After Standards Project’s work in terms of both quality assurance and quality improvement, with reference to the establishment of a set of discipline standards and the trial of an accreditation scheme.
A Preliminary Examination of a General Social Outcome Measure
Authors: Stichter Janine Peck , Herzog Melissa J. , O’Connor Karen V. , Schmidt Carla
Published: October 2012

Individuals with Pervasive Developmental Disorders (PDD) have social competence impairments that can result in negative adult outcomes. Despite considerable research on social skills training, little is available to evaluate these programs. This study describes the development, administration, and utility of a progress-monitoring tool for assessing social skill constructs. The General Social Outcome Measure (GSOM) was developed to capture change in social competence abilities. The GSOM assessed students before, during, and after a scaffolded five-unit social competence intervention (SCI) for youth (ages 10–15 years) with PDD. Repeated measures ANOVAs on GSOM scores ( N = 42) revealed significant changes. This study provides initial direction for the design and use of performance-based assessments, such as the GSOM, for effective decision making in the evaluation of SCIs.
TLR3 activation efficiency by high or low molecular mass poly I:C
Authors: Zhou Yu , Guo Ming , Wang Xu , Li Jielang , Wang Yizhong , Ye Li , Dai Ming , Zhou Li , Persidsky Yuri , Ho Wenzhe
Published: October 2012

Toll-like receptor 3 (TLR3) plays a critical role in initiating type I IFN-mediated innate immunity against viral infections. TLR3 recognizes various forms of double stranded (ds) RNA, including viral dsRNA and a synthetic mimic of dsRNA, poly I:C, which has been used extensively as a TLR3 ligand to induce antiviral immunity. The activation efficiency of TLR3 by poly I:C is influenced by various factors, including size of the ligands, delivery methods and cell types. In this study, we examined the stimulatory effect of two commercially-available poly I:Cs [high molecular mass (HMM) and low molecular mass (LMM)] on TLR3 activation in various human cell types by determining the induction of type I and type III IFNs, as well as the antiviral effect. We demonstrated that the direct addition of both HMM- and LMM-poly I:C to the cultures of primary macrophages or a neuroplastoma cell line could activate TLR3. However, the transfection of poly I:C was necessary to induce TLR3 activation in other cell types studied. In all the cell lines tested, the efficiency of TLR3 activation by HMM-poly I:C was significantly higher than that by LMM-poly I:C. These observations indicate the importance and necessity of developing effective TLR3 ligands for antiviral therapy.
A lifespan perspective on job design: Fitting the job and the worker to promote job satisfaction, engagement, and performance
Authors: Truxillo Donald M. , Cadiz David M. , Rineer Jennifer R. , Zaniboni Sara , Fraccaroli Franco
Published: October 2012

The workforce in most industrialized countries is aging. However, the role of age in job design has largely been ignored. In the present paper, we apply lifespan development perspectives to the interaction between job characteristics and age. Specifically, we examine the possible joint effects of age and job characteristics on job satisfaction, engagement, and performance, developing a series of propositions to guide future research. We also discuss possible boundary conditions, mediating mechanisms, and future research challenges.
Role of Dietary Advanced Glycation End Products in Diabetes Mellitus
Authors: Luevano-Contreras Claudia , Garay-Sevilla Ma. Eugenia , Chapman-Novakofski Karen
Published: October 2012

Dietary advanced glycation end products (AGEs) can be formed via the Maillard reaction and several alternative pathways. AGEs exert their deleterious effects by damaging protein structure and function, as well as through activation of cellular mechanisms. At the cellular level, the damaging effects of AGEs have been attributed to several AGE-binding proteins. Increased levels of AGEs have been implicated in several chronic diseases, including diabetes-related complications such as renal diseases, retinopathy, neuropathy, and cardiovascular diseases, as well as delayed wound healing. To investigate the role of AGEs thoroughly, a reliable assessment of dietary AGEs is needed. Varying methodology, diverse food preparation, and quantification of a variety of dietary AGEs makes this a complex goal. In addition, some antiglycation food products may balance or offset the negative impact of dietary AGEs.
Microstructural studies of electrospark deposited aluminide coatings on 9Cr steels
Authors: Jamnapara N I , Frangini S , Avtani D U , Nayak V S , Chauhan N L , Jhala G , Mukherjee S , Khanna A S
Published: October 2012

Electrospark deposition (ESD) technique has been used to apply an iron aluminide coating on 9Cr reduced activation steel, which is a structural material for test blanket modules of fusion reactors. Phase identification and microstructural analysis of the aluminide coating along with the interface region were performed with the support of X-ray diffraction technique, optical microscopy, scanning electron microscopy and nanoindentation hardness measurements. Microstructural examination indicated prominent changes in the near interface microstructure of the steels processed by the ESD process. The substrate side of the coating/substrate interface consisted of a soft zone that is possibly of quasi-amorphous nature and of an M23C6 type carbide segregation rich area below this interface. The coating, however, showed extensive crack defects that need to be removed for reliably assessing its suitability as a barrier layer for blanket applications.
Hyperfunctional coagulation factor IX improves the efficacy of gene therapy in hemophilic mice
Authors: Cantore Alessio , Nair Nisha , Della Valle Patrizia , Di Matteo Mario , Màtrai Janka , Sanvito Francesca , Brombin Chiara , Di Serio Clelia , D'Angelo Armando , Chuah Marinee , Naldini Luigi , VandenDriessche Thierry
Published: October 2012

Gene therapy may provide a cure for hemophilia and overcome the limitations of protein replacement therapy. Increasing the potency of gene transfer vectors may allow improvement of their therapeutic index, as lower doses can be administered to achieve therapeutic benefit, reducing toxicity of in vivo administration. Here we generated codon-usage optimized and hyperfunctional factor IX (FIX) transgenes carrying an R338L amino acid substitution (FIX Padua), previously associated with clotting hyperactivity and thrombophilia. We delivered these transgenes to hemophilia B mice by hepatocyte-targeted integration-competent and -defective lentiviral vectors. The hyperfunctional FIX transgenes increased FIX activity reconstituted in the plasma without detectable adverse effects, allowing correction of the disease phenotype at lower vector doses and resulting in improved hemostasis in vivo. The combined effect of codon optimization with the hyperactivating FIX-R338L mutation resulted in a robust 15-fold gain in potency and therefore provides a promising strategy to improve the efficacy, feasibility, and safety of hemophilia gene therapy.
Systematic and searchable classification of cytochrome P450 proteins encoded by fungal and oomycete genomes
Authors: Moktali Venkatesh , Park Jongsun , Fedorova-Abrams Natalie D , Park Bongsoo , Choi Jaeyoung , Lee Yong-Hwan , Kang Seogchan
Published: October 2012

Background

Cytochrome P450 proteins (CYPs) play diverse and pivotal roles in fungal metabolism and adaptation to specific ecological niches. Fungal genomes encode extremely variable “CYPomes” ranging from one to more than 300 CYPs. Despite the rapid growth of sequenced fungal and oomycete genomes and the resulting influx of predicted CYPs, the vast majority of CYPs remain functionally uncharacterized. To facilitate the curation and functional and evolutionary studies of CYPs, we previously developed Fungal Cytochrome P450 Database (FCPD), which included CYPs from 70 fungal and oomycete species. Here we present a new version of FCPD (1.2) with more data and an improved classification scheme.

Results

The new database contains 22,940 CYPs from 213 species divided into 2,579 clusters and 115 clans. By optimizing the clustering pipeline, we were able to uncover 36 novel clans and to assign 153 orphan CYP families to specific clans. To augment their functional annotation, CYP clusters were mapped to David Nelson’s P450 databases, which archive a total of 12,500 manually curated CYPs. Additionally, over 150 clusters were functionally classified based on sequence similarity to experimentally characterized CYPs. Comparative analysis of fungal and oomycete CYPomes revealed cases of both extreme expansion and contraction. The most dramatic expansions in fungi were observed in clans CYP58 and CYP68 (Pezizomycotina), clans CYP5150 and CYP63 (Agaricomycotina), and family CYP509 (Mucoromycotina). Although much of the extraordinary diversity of the pan-fungal CYPome can be attributed to gene duplication and adaptive divergence, our analysis also suggests a few potential horizontal gene transfer events. Updated families and clans can be accessed through the new version of the FCPD database.

Conclusions

FCPD version 1.2 provides a systematic and searchable catalogue of 9,550 fungal CYP sequences (292 families) encoded by 108 fungal species and 147 CYP sequences (9 families) encoded by five oomycete species. In comparison to the first version, it offers a more comprehensive clan classification, is fully compatible with Nelson’s P450 databases, and has expanded functional categorization. These features will facilitate functional annotation and classification of CYPs encoded by newly sequenced fungal and oomycete genomes. Additionally, the classification system will aid in studying the roles of CYPs in the evolution of fungal adaptation to specific ecological niches.
Annotated genetic linkage maps of Pinus pinaster Ait. from a Central Spain population using microsatellite and gene based markers
Authors: de Miguel Marina , de Maria Nuria , Guevara M Ángeles , Diaz Luis , Sáez-Laguna Enrique , Sánchez-Gómez David , Chancerel Emilie , Aranda Ismael , Collada Carmen , Plomion Christophe , Cabezas José-Antonio , Cervera María-Teresa
Published: October 2012

Background

Pinus pinaster Ait. is a major resin producing species in Spain. Genetic linkage mapping can facilitate marker-assisted selection (MAS) through the identification of Quantitative Trait Loci and selection of allelic variants of interest in breeding populations. In this study, we report annotated genetic linkage maps for two individuals (C14 and C15) belonging to a breeding program aiming to increase resin production. We use different types of DNA markers, including last-generation molecular markers.

Results

We obtained 13 and 14 linkage groups for C14 and C15 maps, respectively. A total of 211 and 215 markers were positioned on each map and estimated genome length was between 1,870 and 2,166 cM respectively, which represents near 65% of genome coverage. Comparative mapping with previously developed genetic linkage maps for P. pinaster based on about 60 common markers enabled aligning linkage groups to this reference map. The comparison of our annotated linkage maps and linkage maps reporting QTL information revealed 11 annotated SNPs in candidate genes that co-localized with previously reported QTLs for wood properties and water use efficiency.

Conclusions

This study provides genetic linkage maps from a Spanish population that shows high levels of genetic divergence with French populations from which segregating progenies have been previously mapped. These genetic maps will be of interest to construct a reliable consensus linkage map for the species. The importance of developing functional genetic linkage maps is highlighted, especially when working with breeding populations for its future application in MAS for traits of interest.
Inhibition of phenylpropanoid biosynthesis increases cell wall digestibility, protoplast isolation, and facilitates sustained cell division in American elm (Ulmus americana)
Authors: Jones A Maxwell P , Chattopadhyay Abhishek , Shukla Mukund , Zoń Jerzy , Saxena Praveen K
Published: October 2012

Background

Protoplast technologies offer unique opportunities for fundamental research and to develop novel germplasm through somatic hybridization, organelle transfer, protoclonal variation, and direct insertion of DNA. Applying protoplast technologies to develop Dutch elm disease resistant American elms (Ulmus americana L.) was proposed over 30 years ago, but has not been achieved. A primary factor restricting protoplast technology to American elm is the resistance of the cell walls to enzymatic degradation and a long lag phase prior to cell wall re-synthesis and cell division.

Results

This study suggests that resistance to enzymatic degradation in American elm was due to water soluble phenylpropanoids. Incubating tobacco (Nicotiana tabacum L.) leaf tissue, an easily digestible species, in aqueous elm extract inhibits cell wall digestion in a dose dependent manner. This can be mimicked by p-coumaric or ferulic acid, phenylpropanoids known to re-enforce cell walls. Culturing American elm tissue in the presence of 2-aminoindane-2-phosphonic acid (AIP; 10-150 μM), an inhibitor of phenylalanine ammonia lyase (PAL), reduced flavonoid content, decreased tissue browning, and increased isolation rates significantly from 11.8% (±3.27) in controls to 65.3% (±4.60). Protoplasts isolated from callus grown in 100 μM AIP developed cell walls by day 2, had a division rate of 28.5% (±3.59) by day 6, and proliferated into callus by day 14. Heterokaryons were successfully produced using electrofusion and fused protoplasts remained viable when embedded in agarose.

Conclusions

This study describes a novel approach of modifying phenylpropanoid biosynthesis to facilitate efficient protoplast isolation which has historically been problematic for American elm. This isolation system has facilitated recovery of viable protoplasts capable of rapid cell wall re-synthesis and sustained cell division to form callus. Further, isolated protoplasts survived electrofusion and viable heterokaryons were produced. Together, these results provide the first evidence of sustained cell division, callus regeneration, and potential application of somatic cell fusion in American elm, suggesting that this source of protoplasts may be ideal for genetic manipulation of this species. The technological advance made with American elm in this study has potential implications in other woody species for fundamental and applied research which require availability of viable protoplasts.
Identification of a rare 17p13.3 duplication including the BHLHA9 and YWHAEgenes in a family with developmental delay and behavioural problems
Authors: Capra Valeria , Mirabelli-Badenier Marisol , Stagnaro Michela , Rossi Andrea , Tassano Elisa , Gimelli Stefania , Gimelli Giorgio
Published: October 2012

Background

Deletions and duplications of the PAFAH1B1 and YWHAE genes in 17p13.3 are associated with different clinical phenotypes. In particular, deletion of PAFAH1B1 causes isolated lissencephaly while deletions involving both PAFAH1B1 and YWHAE cause Miller-Dieker syndrome. Isolated duplications of PAFAH1B1 have been associated with mild developmental delay and hypotonia, while isolated duplications of YWHAE have been associated with autism. In particular, different dysmorphic features associated with PAFAH1B1 or YWHAE duplication have suggested the need to classify the patient clinical features in two groups according to which gene is involved in the chromosomal duplication.

Methods

We analyze the proband and his family by classical cytogenetic and array-CGH analyses. The putative rearrangement was confirmed by fluorescence in situ hybridization.

Results

We have identified a family segregating a 17p13.3 duplication extending 329.5 kilobases by FISH and array-CGH involving the YWHAE gene, but not PAFAH1B1, affected by a mild dysmorphic phenotype with associated autism and mental retardation. We propose that BHLHA9, YWHAE, and CRK genes contribute to the phenotype of our patient. The small chromosomal duplication was inherited from his mother who was affected by a bipolar and borderline disorder and was alcohol addicted.

Conclusions

We report an additional familial case of small 17p13.3 chromosomal duplication including only BHLHA9, YWHAE, and CRK genes. Our observation and further cases with similar microduplications are expected to be diagnosed, and will help better characterise the clinical spectrum of phenotypes associated with 17p13.3 microduplications.
Monocytes and the 38kDa-antigen of mycobacterium tuberculosis modulate natural killer cell activity and their cytolysis directed against ovarian cancer cell lines
Authors: Gottschalk Nina , Lang Stephan , Kimmig Rainer , Singh Mahavir , Brandau Sven
Published: October 2012

Background

Despite strong efforts to improve clinical outcome of ovarian cancer patients by conventional and targeted immuno-based therapies, the prognosis of advanced ovarian cancer is still poor. Natural killer (NK) cells mediate antibody-dependent cellular cytotoxicity (ADCC), release immunostimulatory cytokines and thus function as potent anti-tumour effector cells. However, tumour cells developed mechanisms to escape from an effective immune response. So highly immunogenic substances, like the 38 kDa-preparation of M. tuberculosis, PstS-1, are explored for their potential to enhance cancer-targeted immune responses. In this study we examined the modulation of different NK cell functions by accessory monocytes and PstS-1. We focussed on NK cell activation as well as natural and antibody-dependent cellular cytotoxicity directed against epidermal-growth-factor-receptor (EGFR)-positive ovarian cancer cell lines.

Methods

Activation, cytokine release and cytotoxicity of NK cells stimulated by monocytes and PstS-1 were determined by FACS-analysis, ELISA, Bioplex assay and quantitative polymerase-chain reaction (qPCR). Transwell assays were used to discriminate cell-cell contact-dependent from contact-independent mechanisms. Five ovarian cancer cell lines (A2780, IGROV-1, OVCAR-3, OVCAR-4 and SKOV-3) with different EGFR-expression were used as target cells for natural and antibody-dependent cellular cytotoxicity assays. Cetuximab (anti-EGFR-antibody) was used for ADCC studies.

Results

Our data show that monocytes effectively enhance activation as well natural and antibody-dependent cytolytic activity of NK cells. PstS-1 directly stimulated monocytes and further activated monocyte-NK-co-cultures. However, PstS-1 did not directly influence purified NK cells and did also not affect natural and antibody-dependent cellular cytotoxicity directed against EGFR-positive ovarian cancer cells, even in presence of monocytes. Direct cell-cell contact between NK cells and monocytes was required for NK activation, while released cytokines seemed to play a minor role.

Conclusions

Our data suggest that monocytes enhance natural and antibody-dependent cytotoxic activity of NK cells in a cell-cell contact dependent manner. The TLR-agonist PstS-1 provides additional monocyte activation and induces NK activation markers, while NK cytotoxicity remains unaffected. We conclude that monocytes provide accessory function for ADCC exerted by NK during antibody-based cancer immunotherapy directed against EGFR-positive ovarian cancer cells.
What determines patient preferences for treating low risk basal cell carcinoma when comparing surgery vs imiquimod? A discrete choice experiment survey from the SINS trial
Authors: Tinelli Michela , Ozolins Mara , Bath-Hextall Fiona , Williams Hywel C
Published: October 2012

Background

The SINS trial (Controlled Clinical Trials ISRCTN48755084; Eudract No. 2004-004506-24) is a randomised controlled trial evaluating long term success of excisional surgery vs. imiquimod 5% cream for low risk nodular and superficial basal cell carcinoma (BCC). The trial included a discrete choice experiment questionnaire to explore patient preferences of a cream versus surgery for the treatment of their skin cancer.

Methods

The self-completed questionnaire was administered at baseline to 183 participants, measuring patients’ strength of preferences when choosing either alternative ‘surgery’ or ‘imiquimod cream’ instead of a fixed ‘current situation’ option (of surgical excision as standard practice in UK). The treatments were described according to: cost, chance of complete clearance, side effects and appearance. Participants had to choose between various scenarios. Analysis was performed using a mixed logit model, which took into account the impact of previous BCC treatment and sample preference variability.

Results

The analysis showed that respondents preferred ‘imiquimod cream’ to their ‘current situation’ or ‘surgery’, regardless of previous experience of BCC symptoms and treatment. Respondents were more likely to be worried about their cosmetic outcomes and side effects they might experience over and above their chance of clearance and cost. Those with no experience of surgery (compared with experience) valued more the choice of ‘imiquimod cream’ (£1013 vs £781). All treatment characteristics were significant determinants of treatment choice, and there was significant variability in the population preferences for all of them.

Conclusions

Patients with BCC valued more ‘imiquimod cream’ than alternative ‘surgery’ options, and all treatment characteristics were important for their choice of care. Understanding how people with a BCC value alternative interventions may better inform the development of health care interventions.
Simultaneous detection of Plasmodium vivax and Plasmodium falciparum gametocytes in clinical isolates by multiplex-nested RT-PCR
Authors: Kuamsab Napaporn , Putaporntip Chaturong , Pattanawong Urassaya , Jongwutiwes Somchai
Published: October 2012

Background

Gametocyte carriage is essential for malaria transmission and endemicity of disease; thereby it is a target for malaria control strategies. Malaria-infected individuals may harbour gametocytes below the microscopic detection threshold that can be detected by reverse transcription polymerase chain reaction (RT-PCR) targeting gametocyte-specific mRNA. To date, RT-PCR has mainly been applied to the diagnosis of Plasmodium falciparum gametocytes but very limited for that of Plasmodium vivax.

Methods

A multiplex-nested RT-PCR targeting Pfs25 and Pvs25 mRNA specific to mature gametocytes of P. falciparum and P. vivax, respectively, was developed. The assay was evaluated using blood samples collected in rainy and dry seasons from febrile patients,in a malaria-endemic area in Thailand. Malaria diagnosis was performed by Giemsa-stained blood smears and 18S rRNA PCR.

Results

The multiplex-nested RT-PCR detected Pfs25 mRNA in 75 of 86 (87.2%) P. falciparum-infected individuals and Pvs25 mRNA in 82 of 90 (91.1%) P. vivax malaria patients diagnosed by 18S rRNA PCR. Gametocytes were detected in 38 (eight P. falciparum and 30 P. vivax) of 157 microscopy positive samples, implying that a large number of patients harbour sub-microscopic gametocytaemia. No seasonal differences in gametocyte carriage were observed for both malaria species diagnosed by multiplex-nested RT-PCR. With single-nested RT-PCR targeting Pfs25 or Pvs25 mRNA as standard, the multiplex-nested RT-PCR offered sensitivities of 97.4% and 98.9% and specificities of 100% and 98.8% for diagnosing mature gametocytes of P. falciparum and P. vivax, respectively. The minimum detection limit of the multiplex-nested PCR was 10 copies of templates.

Conclusions

The multiplex-nested RT-PCR developed herein is useful for simultaneous assessment of both P. falciparum and P. vivax gametocyte carriage that is prevalent and generally sympatric in several malaria-endemic areas outside Africa.
Is a multispecies probiotic mixture effective in constipation during pregnancy? 'A pilot study'
Authors: de Milliano Inge , Tabbers Merit M , van der Post Joris A , Benninga Marc A
Published: October 2012

Background

Constipation during pregnancy is a common problem. Nowadays only few effective interventions are published preventing or treating constipation during pregnancy. However, their use is limited due to side-effects. This uncontrolled intervention study was performed to determine if a mixture of probiotics in the treatment of constipation during pregnancy is effective.

Methods

Women aged ≥ 18 years with functional constipation were included at the Obstetrical outpatient clinic and midwife practices. Patients received during four weeks a daily dose of Ecologic®Relief (Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Bifidobacterium longum W108, Lactobacillus casei W79, Lactobacillus plantarum W62 and Lactobacillus rhamnosus W71 (total 4*109 CFU)). For all analyses, the non-parametric paired Wilcoxon test was used. Primary outcome measure was change in defecation frequency. Secondary outcome measures were stool consistency, sensation of incomplete evacuation, sensation of anorectal obstruction, manual manoeuvres to facilitate defecation, abdominal pain, adverse effects, presence of reflux episodes and intake of Bisacodyl.

Results

20 women were included. Defecation frequency significantly increased from 3.1 at baseline to 6.7 in week four (p < 0.01). Compared to baseline, a significant decrease in 1) sensation of anorectal obstruction from 90.0% to 45.0% (p < 0.01), 2) sensation of incomplete evacuation from 90.0% to 40.0% (p < 0.01), 3) straining during defecation from 100% to 65% (p = 0.01), 4) episodes of abdominal pain from 60% to 20% (p = 0.01) and 5) the presence of reflux episodes from 60% to 20% in week four (p = 0.01) was found. Other secondary outcomes did not decrease significantly. No side effects were reported.

Conclusions

Ecologic®Relief is effective in the treatment of constipation during pregnancy. A randomised placebo controlled trial is required to confirm these data.
Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A
Authors: Shinde Ravikumar B , Chauhan Nitin M , Raut Jayant S , Karuppayil Sankunny M
Published: October 2012

Background

Biofilms formed by Candida albicans are resistant towards most of the available antifungal drugs. Therefore, infections associated with Candida biofilms are considered as a threat to immunocompromised patients. Combinatorial drug therapy may be a good strategy to combat C. albicans biofilms.

Methods

Combinations of five antifungal drugs- fluconazole (FLC), voriconazole (VOR), caspofungin (CSP), amphotericin B (AmB) and nystatin (NYT) with cyclosporine A (CSA) were tested in vitro against planktonic and biofilm growth of C. albicans. Standard broth micro dilution method was used to study planktonic growth, while biofilms were studied in an in vitro biofilm model. A chequerboard format was used to determine fractional inhibitory concentration indices (FICI) of combination effects. Biofilm growth was analyzed using XTT-metabolic assay.

Results

MICs of various antifungal drugs for planktonic growth of C. albicans were lowered in combination with CSA by 2 to 16 fold. Activity against biofilm development with FIC indices of 0.26, 0.28, 0.31 and 0.25 indicated synergistic interactions between FLC-CSA, VOR-CSA, CSP-CSA and AmB-CSA, respectively. Increase in efficacy of the drugs FLC, VOR and CSP against mature biofilms after addition of 62.5 μg/ml of CSA was evident with FIC indices 0.06, 0.14 and 0.37, respectively.

Conclusions

The combinations with CSA res ulted in increased susceptibility of biofilms to antifungal drugs. Combination of antifungal drugs with CSA would be an effective prophylactic and therapeutic strategy against biofilm associated C. albicans infections.
Metabolic syndrome and population attributable risk among HIV/AIDS patients: comparison between NCEP-ATPIII, IDF and AHA/NHLBI definitions
Authors: Alencastro Paulo R , Wolff Fernando H , Oliveira Renato R , Ikeda Maria Letícia R , Barcellos Nêmora T , Brandão Ajácio B M , Fuchs Sandra C
Published: October 2012

Background

Metabolic Syndrome (MetS) is based on the same individual components, but has received several amendments to the original definition. In this study, we verified the prevalence of metabolic syndrome according to different criteria, and the impact of each component on the diagnostic.

Methods

This cross-sectional study enrolled HIV infected patients from a HIV/AIDS reference Center in southern Brazil. Metabolic syndrome was identified according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII), the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) criteria, and using a standardized questionnaire and blood testing.

Results

A sample of 1240, out of 1295, HIV-infected patients was enrolled. Males were on average older, more educated, and had shorter time since the HIV diagnosis. The population attributable risk (PAR) for waist circumference explained 80% of the prevalence among men and women (AHA/NHLBI criteria). Triglycerides had the highest impact on prevalence of metabolic syndrome according to all criteria, independently of age, skin color and HAART use, among men.

Conclusions

In this large sample of HIV infected patients, the overall prevalence of metabolic syndrome, under either classification, was noticeable and the AHA/NHLBI definition accounted for the highest prevalence.
What are the key conditions associated with lower limb amputations in a major Australian teaching hospital?
Authors: Lazzarini Peter A , O'Rourke Sharon R , Russell Anthony W , Clark Damien , Kuys Suzanne S
Published: October 2012

Background

Lower extremity amputation results in significant global morbidity and mortality. Australia appears to have a paucity of studies investigating lower extremity amputation. The primary aim of this retrospective study was to investigate key conditions associated with lower extremity amputations in an Australian population. Secondary objectives were to determine the influence of age and sex on lower extremity amputations, and the reliability of hospital coded amputations.

Methods

Lower extremity amputation cases performed at the Princess Alexandra Hospital (Brisbane, Australia) between July 2006 and June 2007 were identified through the relevant hospital discharge dataset (n = 197). All eligible clinical records were interrogated for age, sex, key condition associated with amputation, amputation site, first ever amputation status and the accuracy of the original hospital coding. Exclusion criteria included records unavailable for audit and cases where the key condition was unable to be determined. Chi‐squared, t‐tests, ANOVA and post hoc tests were used to determine differences between groups. Kappa statistics were used to measure reliability between coded and audited amputations. A minimum significance level of p < 0.05 was used throughout.

Results

One hundred and eighty‐six cases were eligible and audited. Overall 69% were male, 56% were first amputations, 54% were major amputations, and mean age was 62 ± 16 years. Key conditions associated included type 2 diabetes (53%), peripheral arterial disease (non‐diabetes) (18%), trauma (8%), type 1 diabetes (7%) and malignant tumours (5%). Differences in ages at amputation were associated with trauma 36 ± 10 years, type 1 diabetes 52 ± 12 years and type 2 diabetes 67 ± 10 years (p < 0.01). Reliability of original hospital coding was high with Kappa values over 0.8 for all variables.

Conclusions

This study, the first in over 20 years to report on all levels of lower extremity amputations in Australia, found that people undergoing amputation are more likely to be older, male and have diabetes. It is recommended that large prospective studies are implemented and national lower extremity amputation rates are established to address the large preventable burden of lower extremity amputation in Australia.
Role of Omega-3 fatty acids in preventing metabolic disturbances in patients on olanzapine plus either sodium valproate or lithium: a randomized double-blind placebo-controlled trial
Authors: Faghihi Toktam , Jahed Adel , Mahmoudi-Gharaei Javad , Sharifi Vandad , Akhondzadeh Shahin , Ghaeli Padideh
Published: October 2012

Background

Metabolic and cardiovascular side effects have been noted with the use of second generation antipsychotics (SGAs) and mood stabilizers. Since Omega-3 fatty acids have been known to prevent some cardiovascular risks, this preliminary study was designed to evaluate the cardiovascular benefits of omega-3 when added to the combinations of olanzapine with mood stabilizers.

Methods

This study was a randomized, double-blind, placebo-controlled, within-subject trial in adult psychiatric patients who were receiving olanzapine combined with lithium (Li) or valproate sodium (VPA). Omega-3 as fish oil with less than 1 g/day of EPA/DHA or its placebo was added to patients’ olanzapine and mood stabilizer regimens for 6 weeks. Metabolic parameters including anthropometric variables, lipid profile, metabolic syndrome indices, C-reactive protein, fibrinogen and lipoprotein (a) [(Lp) (a)] were assessed for participants.

Results

Forty one participants completed this study; 20 patients received omega-3 and 21 patients received placebo, added to their regimen of SGA and mood stabilizer. Omega-3 addition did not modulate anthropometric, metabolic syndrome and lipid parameter changes in 6 weeks. However, fibrinogen levels significantly decreased, Lp (a) did not increase and non-high-density lipoprotein cholesterol (non-HDL-C) did not go beyond its target level after omega-3 supplementation. Additionally, a significant inter-group effect was noted for Lp(a).

Conclusions

This study suggests that use of short-term omega-3 supplementation added to a combined regimen of olanzapine and mood stabilizer may have a small modulating effect on some cardiovascular risk factors. Trials in longer periods of time and with larger number of patients are needed to further evaluate the effects of omega-3 supplements on preventing cardiovascular risk factors.

This trial is registered at irct.ir and its Identifier is as following: IRCT138712231764N1
n-3 fatty acid-enriched parenteral nutrition regimens in elective surgical and ICU patients: a meta-analysis
Authors: Pradelli Lorenzo , Mayer Konstantin , Muscaritoli Maurizio , Heller Axel R
Published: October 2012

Introduction

Previous studies and a meta-analysis in surgical patients indicate that supplementing parenteral nutrition regimens with n-3 polyunsaturated fatty acids (PUFAs), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with improved laboratory and clinical outcomes in the setting of hyper-inflammatory conditions. Refined or synthetic fish oils are commonly used as a source of EPA and DHA. The objective of the present meta-analysis was to evaluate n-3 PUFA-enriched parenteral nutrition regimens in elective surgical and intensive care unit (ICU) patients.

Methods

Medline was searched for randomized controlled trials comparing n-3 PUFA-enriched lipid emulsions with standard non-enriched lipid emulsions (i.e. soybean oil, MCT/LCT or olive/soybean oil emulsions) in surgical and ICU patients receiving parenteral nutrition. Extracted data were pooled by means of both random and fixed effects models, and subgroup analyses were carried forward to compare findings in ICU versus non-ICU patients.

Results

A total of 23 studies (n = 1502 patients: n = 762 admitted to the ICU) were included. No statistically significant difference in mortality rate was found between patients receiving n-3 PUFA-enriched lipid emulsions and those receiving standard lipid emulsions (RR= 0.89; 0.59, 1.33), possibly reflecting a relatively low underlying mortality risk. However, n-3 PUFA-enriched emulsions are associated with a statistically and clinically significant reduction in the infection rate (RR =0.61; 0.45, 0.84) and the lengths of stay, both in the ICU (-1.92; -3.27, -0.58) and in hospital overall (-3.29; -5.13, -1.45). Other beneficial effects included reduced markers of inflammation, improved lung gas exchange, liver function, antioxidant status and fatty acid composition of plasma phospholipids, and a trend towards less impairment of kidney function.

Conclusions

These results confirm and extend previous findings, indicating that n-3 PUFAs-enriched parenteral nutrition regimens are safe and effective in reducing the infection rate and hospital/ICU stay in surgical and ICU patients.
Reversal of Vitamin K Antagonist (VKA) effect in patients with severe bleeding: a French multicenter observational study (Optiplex) assessing the use of Prothrombin Complex Concentrate (PCC) in current clinical practice
Authors: Desmettre Thibaut , Dehours Emilie , Samama Charles-Marc , Jhundoo Suchin , Pujeau Frédéric , Guillaudin Christian , Hecquart Claudine , Clerson Pierre , Crave Jean Charles , Jaussaud Roland
Published: October 2012

Introduction

Prothrombin Complex Concentrate (PCC) is a key treatment in the management of bleeding related to Vitamin K antagonists (VKA). This study aimed to evaluate prospectively PCC use in patients with VKA-related bleeding in view of the French guidelines published in 2008.

Methods

All consecutive patients with VKA-related bleeding treated with a 4-factor PCC (Octaplex®) were selected in 33 French hospitals. Collected data included demographics, site and severity of bleeding, modalities of PCC administration, International Normalized Ratio (INR) values before and after PCC administration, outcomes and survival rate 15 days after infusion.

Results

Of 825 patients who received PCC between August 2008 and December 2010, 646 had severe bleeding. The main haemorrhage sites were intracranial (43.7%) and abdominal (24.3%). Mean INR before PCC was 4.4 ± 1.9; INR was unavailable in 12.5% of patients. The proportions of patients who received a PCC dose according to guidelines were 15.8% in patients with initial INR 2-2.5, 41.5% in patients with INR 2.5-3, 40.8% in patients with INR 3-3.5, 26.9% in patients with INR > 3.5, and 63.5% of patients with unknown INR. Vitamin K was administered in 84.7% of patients. The infused dose of PCC did not vary with initial INR; the mean dose was 25.3 ± 9.8 IU/Kg. Rates of controlled bleeding and target INR achievement were similar, regardless of whether or not patients were receiving PCC doses as per the guidelines. No differences in INR after PCC treatment were observed, regardless of whether or not vitamin K was administered. INR was first monitored after a mean time frame of 4.5 ± 5.6 hours post PCC. The overall survival rate at 15 days after PCC infusion was 75.4% (65.1% in patients with intracranial haemorrhage). A better prognosis was observed in patients reaching the target INR.

Conclusions

Severe bleeding related to VKA needs to be better managed, particularly regarding the PCC infused dose, INR monitoring and administration of vitamin K. A dose of 25 IU/kg PCC appears to be efficacious in achieving a target INR of 1.5. Further studies are required to assess whether adjusting PCC dose and/or better management of INR would improve outcomes.
Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme
Authors: Hiremath Minoti , Dann Pamela , Fischer Jennifer , Butterworth Daniela , Boras-Granic Kata , Hens Julie , Van Houten Joshua , Shi Wei , Wysolmerski John
Published: October 2012

Parathyroid hormone-related protein (PTHrP) regulates cell fate and specifies the mammary mesenchyme during embryonic development. Loss of PTHrP or its receptor (Pthr1) abolishes the expression of mammary mesenchyme markers and allows mammary bud cells to revert to an epidermal fate. By contrast, overexpression of PTHrP in basal keratinocytes induces inappropriate differentiation of the ventral epidermis into nipple-like skin and is accompanied by ectopic expression of Lef1, β-catenin and other markers of the mammary mesenchyme. In this study, we document that PTHrP modulates Wnt/β-catenin signaling in the mammary mesenchyme using a Wnt signaling reporter, TOPGAL-C. Reporter expression is completely abolished by loss of PTHrP signaling and ectopic reporter activity is induced by overexpression of PTHrP. We also demonstrate that loss of Lef1, a key component of the Wnt pathway, attenuates the PTHrP-induced abnormal differentiation of the ventral skin. To characterize further the contribution of canonical Wnt signaling to embryonic mammary development, we deleted β-catenin specifically in the mammary mesenchyme. Loss of mesenchymal β-catenin abolished expression of the TOPGAL-C reporter and resulted in mammary buds with reduced expression of mammary mesenchyme markers and impaired sexual dimorphism. It also prevented the ectopic, ventral expression of mammary mesenchyme markers caused by overexpression of PTHrP in basal keratinocytes. Therefore, we conclude that a mesenchymal, canonical Wnt pathway mediates the PTHrP-dependent specification of the mammary mesenchyme.