bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical consequences following regulatory changes in respect to reimbursement of statins cost by the Icelandic Social Insurance Administration
Authors: Gizurarson Sveinbjörn , Björnsdóttir Linda Rós , Einarsdóttir Rannveig , Halldórsson Matthías , Andersen Karl
Published: October 2012

Introduction: On 1 March 2009, a new reimbursement system was introduced by the Ministry of Health of Iceland regarding drugs to treat hyperlipidaemia. The Social Insurance Administration was only authorised to reimburse 10 and 20 mg simvastatin unless patients were eligible to receive a medical card from the Social Insurance Administration. The purpose of this study was to evaluate the influence of this reimbursement regulation on the clinical outcome. Materials and methods: Patients that received hyperlipidaemia treatment and were admitted to the cardiac ward were enrolled. The criteria were that the patients had been admitted 1 year prior to the regulation change and were using other statins than simvastatin. Results: Out of 233 eligible patients 170 (73%) reached the treatment goal before the switch. After the switch, only 126 (54%) reached their goal ( p<0.05). Total cholesterol was found to be increased after the switch by a mean of 0.48 mmol/l (range 3.90−5.53 mmol/l, p<0.001). Low-density lipoprotein cholesterol increased by a mean of 0.48 mmol/l (range 1.62−3.11, p<0.001). The level of triglycerides did not change significantly. Before the introduction of the new regulations, 73% of subjects were well controlled, but after 1 March 2009, this figure dropped to 46% (37% decrease). Conclusions: In order to lower costs for subsidising drugs, a switch to simvastatin from other cholesterol-lowering drugs was implemented (by the Ministry of Health of Iceland). The result was a significant and unwanted increase in cholesterol levels among patients with heart disease. The reason seems to be inaccurate prescriptions due to lack of competence among physicians and pharmacists. The use of “one drug fits all” does not comply here.
From scrapbook to Facebook: A history of personal media assemblage and archives
Authors: Good Katie Day
Published: October 2012

This study surveys recent research on print-era scrapbooks and contemporary social media to highlight commonalities between the two formats, both in terms of the practices they have historically promoted for users, and the methodological challenges they produce for researchers. It argues that scrapbooks and social media can be conceptualized as sites of personal media assemblage and personal media archives, a designation that highlights the simultaneously social and archival dimensions of each form. After discussing these formal similarities, the author identifies three shared functions: (1) documenting friendship, (2) navigating new media abundance, and (3) communicating taste and building cultural capital. By drawing functional and formal parallels between the two media, the goal is to observe how these ‘old’ and ‘new’ technologies might mutually shed light on each other’s neglected social and archival dimensions, offering scholars a wider range of angles from which to approach them as cultural and biographical texts.
At the crossroads of participation and objectivity: Reinventing citizen engagement in the SBS newsroom
Authors: Hujanen Jaana
Published: October 2012

The article examines how the challenge of participation is becoming a part of professional journalism culture in a newsroom where news policy relies on articulating the plurality of its ethnically diverse audiences. This study moreover attempts to understand the dynamics of the organizational and professional discourses and practices determining how the culture of journalism evolves. The article relies on conceptualizations from critical discourse analysis and cultural historical activity theory. The data analyzed consists of in-depth interviews with journalists from the Australian Special Broadcasting Service. Two discourses are analyzed: those of participation and objectivity. The case study illustrates through the merging of the discourses and the emergence of hybrid news ideals how the process of change is inherently complex and contradictory and suggests how the notions of participation and objectivity need to be explored as historical and contextual constructions.
Participant characteristics and study features associated with high retention rates in a longitudinal investigation of type 1 diabetes mellitus
Authors: Kramer John R , Bayless Margaret L , Lorenzi Gayle M , Ziegler Georgia K , Larkin Mary E , Lackaye Mary E , Harth Judith , Diminick Lisa J , Anderson Karen L , Braffett Barbara H , Cleary Patricia A ,   The DCCT/EDIC Study Group
Published: October 2012

Background

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study has sustained an extraordinarily high level of participant involvement for over two decades.

Purpose

In order to identify specific characteristics of EDIC that contributed most strongly to retention, study-designed questionnaires were distributed to 1334 participants.

Methods

Confidential questionnaires were completed during EDIC Years 15–17. Participants were classified as Completely Adherent (completed all visits), Partly Adherent (missed >1 visit or major portion of a visit), or Inactive (did not participate for >5 years). Questionnaire items addressed specific aspects of clinic visits, evaluation procedures, staff–participant relationships, and medical/health-care support provided by EDIC.

Results

The most commonly cited reasons for continuing participation were Cutting Edge Tests to assess diabetes complications (79.3%), Annual Evaluations (67.7%), a desire to Help Others (65.2%), and Better Care for Diabetes (61.6%). Women chose Cutting Edge Tests as their first or second most important reason significantly more often than men, whereas men chose Better Care for Diabetes more frequently. Individuals with at least three diabetes-related complications were more likely than those with fewer complications to choose Annual Evaluations as their first or second reason for continued involvement.

Limitations

The small proportion of individuals who discontinued participation restricted our ability to identify factors associated with suspended involvement. In addition, our analysis is limited to a cohort with type 1 diabetes followed in an observational study after an average participation time of 6.5 years in a randomized trial.

Conclusions

The primary reasons identified by respondents for their long-term commitment are consistent with shorter-term studies and underscore the importance of expert medical care, supportive staff–participant relationships, and involvement with clinically and scientifically meaningful research.
Prolonged Profound Hypoxia and Cardiac Failure in a Young Woman Presenting to the Emergency Department
Authors: Breyer Kristine E. W. , Ou Joel , Durack Jeremy C. , Prakash Arun
Published: October 2012

Pulmonary emboli are rare occurrences in young patients, especially those who present precipitously to the emergency department. In a young unresponsive patient, recognition of thromboembolic etiology may be delayed due to atypical presenting physiology or competing diagnoses. In this report, the authors describe an initially confounding case of catastrophic bilateral pulmonary emboli in a young woman who presented to the emergency department having been found unconscious on the street. Despite severe and prolonged hypoxia as well as multi-organ failure, the patient achieved a near complete recovery.
Respiratory Complications and Management of Mechanical Ventilation in Cervical Spine Injury
Authors: Kearns Michel , Shimabukuro David
Published: October 2012

It is estimated that the annual incidence of spinal cord injury in the United States is 12 000 new cases per year. Victims of spinal cord injury are prone to developing respiratory complications such as atelectasis, pneumonia, and ventilatory failure secondary to physiologic derangements resulting from spinal shock and paralysis. Respiratory complications are the leading cause of death in those who survive the initial injury. The goal in ventilator management of spinal cord injury patients in the intensive care unit setting is to prevent these complications and optimize patients for early transfer to a spinal cord rehabilitation facility. To minimize atelectasis, current guidelines recommend the use of very high tidal volumes (15 mL/kg) or setting high tidal volumes (10 mL/kg) in addition to using positive end-expiratory pressure. In this article, the authors discuss the pulmonary complications that affect the mortality of these patients and review the evidence behind the current high tidal volume ventilation strategy.
Comprehensive review of JAK inhibitors in myeloproliferative neoplasms
Authors: Sonbol Mohamad Bassam , Firwana Belal , Zarzour Ahmad , Morad Mohammad , Rana Vishal , Tiu Ramon V.
Published: October 2012

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem-cell disorders, characterized phenotypically by the abnormal accumulation of mature-appearing myeloid cells. Polycythemia vera, essential thrombocythemia, primary myelofibrosis (also known as ‘ BCR-ABL1-negative’ MPNs), and chronic myeloid leukemia (CML) are the primary types of MPNs. After the discovery of the BCR-ABL1 fusion protein in CML, several oncogenic tyrosine kinases have been identified in ‘ BCR-ABL1-negative’ MPNs, most importantly, JAK2V617F mutation. The similarity in the clinical characteristics of the BCR-ABL1-negative MPN patients along with the prevalence of the Janus kinase mutation in this patient population provided a strong rationale for the development of a new class of pharmacologic inhibitors that target this pathway. The first of its class, ruxolitinib, has now been approved by the food and drug administration (FDA) for the management of patients with intermediate- to high-risk myelofibrosis. Ruxolitinib provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease. Although noncurative, ruxolitinib represents a milestone in the treatment of myelofibrosis patients. Other types of JAK2 inhibitors are being tested in various clinical trials at this point and may provide better efficacy data and safety profile than its predecessor. In this article, we comprehensively reviewed and summarized the available preclinical and clinical trials pertaining to JAK inhibitors.
SOCS3 promotes interleukin-17 expression of human T cells
Authors: Kleinsteuber Katja , Heesch Kerrin , Schattling Stefanie , Sander-Juelch Claudia , Mock Ulrike , Riecken Kristoffer , Fehse Boris , Fleischer Bernhard , Jacobsen Marc
Published: October 2012

SOCS3 is a feedback regulator of cytokine signaling that affects T-cell polarization. Human tuberculosis is accompanied by increased SOCS3 expression in T cells, and this may influence susceptibility against Mycobacterium tuberculosis. Because the role of SOCS3 in human T-cell function is not well defined, we characterized cytokine expression and proliferation of human T cells with differential SOCS3 expression in the present study. We established a flow cytometry–based method for SOCS3 protein quantification and detected higher SOCS3 levels induced by M tuberculosis specific T-cell activation and a transient decrease of SOCS3 expression in the presence of mycobacteria-infected macrophages. Notably increased SOCS3 expression was detected in IL-17–expressing T-cell clones and in CD161+ T helper type 17 cells ex vivo. Ectopic SOCS3 expression in primary CD4+ T cells by lentiviral transduction induced increased IL-17 production but diminished proliferation and viability. Recombinant IL-7 inhibited SOCS3 expression and reduced IL-17–expressing T-cell proportions. We concluded that higher SOCS3 expression in human T cells favors T helper type 17 cells. Therefore, increased SOCS3 expression in human tuberculosis may reflect polarization toward IL-17–expressing T cells as well as T-cell exhaustion marked by reduced proliferation.
A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma
Authors: Benson Don M. , Hofmeister Craig C. , Padmanabhan Swaminathan , Suvannasankha Attaya , Jagannath Sundar , Abonour Rafat , Bakan Courtney , Andre Pascale , Efebera Yvonne , Tiollier Jérôme , Caligiuri Michael A. , Farag Sherif S.
Published: October 2012

Natural killer (NK) cells elicit cytotoxicity against multiple myeloma (MM); however, MM cells express HLA class I molecules as ligands to NK cell inhibitory killer immunoglobulin-like receptors (KIRs) as a means of immunoevasion. KIR-ligand mismatch may improve outcomes in allogeneic transplantation for MM. Extrapolating on this concept, we conducted a phase 1 trial of IPH2101, an anti-KIR antibody, in patients with relapsed/refractory MM. IPH2101 was administered intravenously every 28 days in 7 dose–escalated cohorts (0.0003-3 mg/kg) for up to 4 cycles. Pharmacokinetic, pharmacodynamic, and correlative immunologic studies were completed. A total of 32 patients were enrolled. The biologic endpoint of full KIR2D occupancy across the dosing cycle was achieved without dose-limiting toxicity or maximally tolerated dose. One severe adverse event was noted. Pharmacokinetic and pharmacodynamic findings approximated preclinical predictions, and IPH2101 enhanced ex vivo patient–derived NK cell cytotoxicity against MM. No objective responses were seen. No evidence of autoimmunity was observed. These findings suggest that IPH2101 is safe and tolerable at doses that achieve full inhibitory KIR saturation, and this approach warrants further development in MM. This trial was registered at www.clinicaltrials.gov as #NCT00552396.
Evolution of major histocompatibility complex class I and class II genes in the brown bear
Authors: Kuduk Katarzyna , Babik Wiesław , Bojarska Katarzyna , Śliwińska Ewa B , Kindberg Jonas , Taberlet Pierre , Swenson Jon E , Radwan Jacek
Published: October 2012

Background

Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bearUrsus arctosto characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism inUrsidae.

Results

We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant pandaAiluropoda melanoleuca.

Conclusions

Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South–north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.
Comparison of gait in progressive supranuclear palsy, Parkinson’s disease and healthy older adults
Authors: Egerton Thorlene , Williams David R , Iansek Robert
Published: October 2012

Background

Progressive supranuclear palsy and Parkinson’s disease have characteristic clinical and neuropathologic profiles, but also share overlapping clinical features. This study aimed to analyze the gait of people with progressive supranuclear palsy (n=19) and compare it with people with Parkinson’s disease (n=20) and healthy older adults (n=20).

Methods

Gait was recorded at self-selected preferred, fast, very fast, slow and very slow speeds. Stride length was normalized to leg length. Linear regression analyses were carried out between cadence and stride length. Other gait variables were compared for each participant’s ‘walk’ which had stride length closest to 1.4.

Results

All groups showed a strong linear relationship between stride length and cadence with no difference between groups (p>0.05). The intercept between cadence and stride length was lowest in the progressive supranuclear palsy group and highest for older adults (p<0.001). The progressive supranuclear palsy group had higher cadence than older adults (p>0.05), and greater step width and greater double support phase compared with the other two groups (p<0.05).

Conclusions

The temporal-spatial gait characteristics of progressive supranuclear palsy and Parkinson’s disease are largely similar, with similar disruption to scaling of stride length. The additional findings of increased step width and double support percentage suggest increased severity of gait abnormality compared to Parkinson’s disease, despite similar disease duration. The findings are consistent with the clinical features of greater instability and more rapid disease progression in progressive supranuclear palsy compared to Parkinson’s disease and implicates the early pathological involvement of brain regions involved in gait control.
Cost-effectiveness of a 21-gene recurrence score assay versus Canadian clinical practice in women with early-stage estrogen- or progesterone-receptor-positive, axillary lymph-node negative breast cancer
Authors: Hannouf Malek B , Xie Bin , Brackstone Muriel , Zaric Gregory S
Published: October 2012

Background

A 21-gene recurrence score (RS) assay may inform adjuvant systematic treatment decisions in women with early stage breast cancer. We sought to investigate the cost effectiveness of using the RS-assay versus current clinical practice (CCP) in women with early-stage estrogen- or progesterone-receptor-positive, axilliary lymph-node negative breast cancer (ER+/ PR + LN- ESBC) from the perspective of the Canadian public healthcare system.

Methods

We developed a Markov model to project the lifetime clinical and economic consequences of ESBC. We evaluated adjuvant therapy separately in post- and pre-menopausal women with ER+/ PR + LN- ESBC. We assumed that the RS-assay would reclassify pre- and post-menopausal women among risk levels (low, intermediate and high) and guide adjuvant systematic treatment decisions. The model was parameterized using 7 year follow up data from the Manitoba Cancer Registry, cost data from Manitoba administrative databases, and secondary sources. Costs are presented in 2010 CAD. Future costs and benefits were discounted at 5%.

Results

The RS-assay compared to CCP generated cost-savings in pre-menopausal women and had an ICER of $60,000 per QALY gained in post-menopausal women. The cost effectiveness was most sensitive to the proportion of women classified as intermediate risk by the RS-assay who receive adjuvant chemotherapy and the risk of relapse in the RS-assay model.

Conclusions

The RS-assay is likely to be cost effective in the Canadian healthcare system and should be considered for adoption in women with ER+/ PR + LN- ESBC. However, ongoing assessment and validation of the assay in real-world clinical practice is warranted.
Physicians' Perceptions on the usefulness of contextual information for prioritizing and presenting alerts in computerized physician order entry systems
Authors: Jung Martin , Riedmann Daniel , Hackl Werner O , Hoerbst Alexander , Jaspers Monique W , Ferret Laurie , Lawton Kitta , Ammenwerth Elske
Published: October 2012

Background

One possible approach towards avoiding alert overload and alert fatigue in Computerized Physician Order Entry (CPOE) systems is to tailor their drug safety alerts to the context of the clinical situation. Our objective was to identify the perceptions of physicians on the usefulness of clinical context information for prioritizing and presenting drug safety alerts.

Methods

We performed a questionnaire survey, inquiring CPOE-using physicians from four hospitals in four European countries to estimate the usefulness of 20 possible context factors.

Results

The 223 participants identified the ‘ severity of the effect’ and the ‘clinical status of the patient’ as the most useful context factors. Further important factors are the ‘complexity of the case’ and the ‘risk factors of the patient’.

Conclusions

Our findings confirm the results of a prior, comparable survey inquiring CPOE researchers. Further research should focus on implementing these context factors in CPOE systems and on subsequently evaluating their impact.
Proteomic analysis reveals the diversity and complexity of membrane proteins in chickpea (Cicer arietinum L.)
Authors: Jaiswal Dinesh Kumar , Ray Doel , Subba Pratigya , Mishra Poonam , Gayali Saurabh , Datta Asis , Chakraborty Subhra , Chakraborty Niranjan
Published: October 2012

Background

Compartmentalization is a unique feature of eukaryotes that helps in maintaining cellular homeostasis not only in intra- and inter-organellar context, but also between the cells and the external environment. Plant cells are highly compartmentalized with a complex metabolic network governing various cellular events. The membranes are the most important constituents in such compartmentalization, and membrane-associated proteins play diverse roles in many cellular processes besides being part of integral component of many signaling cascades.

Results

To obtain valuable insight into the dynamic repertoire of membrane proteins, we have developed a proteome reference map of a grain legume, chickpea, using two-dimensional gel electrophoresis. MALDI-TOF/TOF and LC-ESI-MS/MS analysis led to the identification of 91 proteins involved in a variety of cellular functions viz., bioenergy, stress-responsive and signal transduction, metabolism, protein synthesis and degradation, among others. Significantly, 70% of the identified proteins are putative integral membrane proteins, possessing transmembrane domains.

Conclusions

The proteomic analysis revealed many resident integral membrane proteins as well as membrane-associated proteins including those not reported earlier. To our knowledge, this is the first report of membrane proteome from aerial tissues of a crop plant. The findings may provide a better understanding of the biochemical machinery of the plant membranes at the molecular level that might help in functional genomics studies of different developmental pathways and stress-responses.
Differences in lifestyle behaviors, dietary habits, and familial factors among normal-weight, overweight, and obese Chinese children and adolescents
Authors: Guo Xiaofan , Zheng Liqiang , Li Yang , Yu Shasha , Sun Guozhe , Yang Hongmei , Zhou Xinghu , Zhang Xingang , Sun Zhaoqing , Sun Yingxian
Published: October 2012

Background

Pediatric obesity has become a global public health problem. Data on the lifestyle behaviors, dietary habits, and familial factors of overweight and obese children and adolescents are limited. The present study aims to compare health-related factors among normal-weight, overweight, and obese Chinese children and adolescents.

Methods

We conducted a cross-sectional study consisted of 4262 children and adolescents aged 5–18 years old from rural areas of the northeast China. Anthropometric measurements and self-reported information on health-related variables, such as physical activities, sleep duration, dietary habits, family income, and recognition of weight status from the views of both children and parents, were collected by trained personnel.

Results

The prevalence rates of overweight and obesity were 15.3 and 6.4%, respectively. Compared to girls, boys were more commonly overweight (17.5% vs. 12.9%) and obese (9.5% vs. 3.1%). Approximately half of the parents with an overweight or obese child reported that they failed to recognize their child’s excess weight status, and 65% of patients with an overweight child reported that they would not take measures to decrease their child’s body weight. Obese children and adolescents were more likely to be nonsnackers [odds ratio (OR): 1.348; 95% confidence interval (CI): 1.039–1.748] and to have a family income of 2000 CNY or more per month (OR: 1.442; 95% CI: 1.045–1.99) and less likely to sleep longer (≥7.5 h) (OR: 0.475; 95% CI: 0.31–0.728) than the normal-weight participants.

Conclusions

Our study revealed a high prevalence of overweight and obesity in a large Chinese pediatric population. Differences in sleep duration, snacking, family income, and parental recognition of children’s weight status among participants in different weight categories were observed, which should be considered when planning prevention and treatment programs for pediatric obesity.
On radiation effects on hydromagnetic Newtonian liquid flow due to an exponential stretching sheet
Authors: Kameswaran PK , Narayana M , Sibanda P , Makanda G
Published: October 2012

The paper investigates the radiation effect on the magnetohydrodynamic Newtonian fluid flow over an exponentially stretching sheet. The effects of frictional heating and viscous dissipation on the heat transport are taken into account. The governing partial differential equations are transformed into ordinary differential equations using a suitable similarity transformation. Zero-order analytical solutions of the momentum equation and confluent hypergeometric solutions of heat and mass transport equations are obtained. The accuracy of analytical solutions is verified by numerical solutions obtained using a shooting technique that uses a Runge-Kutta-Felhberg integration scheme and a Newton-Raphson correction scheme. The effects of the radiation parameter, the magnetic parameter, Gebhart and Schmidt numbers on the momentum, heat and mass transports are discussed. The skin friction and heat and mass transfer coefficients for various physical parameters are discussed.
Lipopolysaccharide-induced neuroinflammation leads to the accumulation of ubiquitinated proteins and increases susceptibility to neurodegeneration induced by proteasome inhibition in rat hippocampus
Authors: Pintado Cristina , Gavilán María P , Gavilán Elena , García-Cuervo Luisa , Gutiérrez Antonia , Vitorica Javier , Castaño Angélica , Ríos Rosa M , Ruano Diego
Published: October 2012

Background

Neuroinflammation and protein accumulation are characteristic hallmarks of both normal aging and age-related neurodegenerative diseases. However, the relationship between these factors in neurodegenerative processes is poorly understood. We have previously shown that proteasome inhibition produced higher neurodegeneration in aged than in young rats, suggesting that other additional age-related events could be involved in neurodegeneration. We evaluated the role of lipopolysaccharide (LPS)-induced neuroinflammation as a potential synergic risk factor for hippocampal neurodegeneration induced by proteasome inhibition.

Methods

Young male Wistar rats were injected with 1 μL of saline or LPS (5 mg/mL) into the hippocampus to evaluate the effect of LPS-induced neuroinflammation on protein homeostasis. The synergic effect of LPS and proteasome inhibition was analyzed in young rats that first received 1 μL of LPS and 24 h later 1 μL (5 mg/mL) of the proteasome inhibitor lactacystin. Animals were sacrificed at different times post-injection and hippocampi isolated and processed for gene expression analysis by real-time polymerase chain reaction; protein expression analysis by western blots; proteasome activity by fluorescence spectroscopy; immunofluorescence analysis by confocal microscopy; and degeneration assay by Fluoro-Jade B staining.

Results

LPS injection produced the accumulation of ubiquitinated proteins in hippocampal neurons, increased expression of the E2 ubiquitin-conjugating enzyme UB2L6, decreased proteasome activity and increased immunoproteasome content. However, LPS injection was not sufficient to produce neurodegeneration. The combination of neuroinflammation and proteasome inhibition leads to higher neuronal accumulation of ubiquitinated proteins, predominant expression of pro-apoptotic markers and increased neurodegeneration, when compared with LPS or lactacystin (LT) injection alone.

Conclusions

Our results identify neuroinflammation as a risk factor that increases susceptibility to neurodegeneration induced by proteasome inhibition. These results highlight the modulation of neuroinflammation as a mechanism for neuronal protection that could be relevant in situations where both factors are present, such as aging and neurodegenerative diseases.
CD20-positive NK/T-cell lymphoma with indolent clinical course: report of case and review of literature
Authors: Jiang Qing-ping , Liu Shao-yan , Yang Yue-xin , Tan Xue-xian , Peng Juan , Xiong Zhong-tang , Li Zhi
Published: October 2012

CD20-positive T-cell lymphoma is extremely rare and only two cases of CD20-positive NK/T-cell lymphoma with aggressive clinical courses have been described in the literature. We present a case of unusual NK/T-cell lymphoma with CD20 expression in nasal cavity occurring in an elder female patient. The patient had presented with left nasal cavity nodule for 10 years. CT scan revealed a mass was located at the left anterior nasal cavity and was observed to extend into the ethmoid sinus. There was no regional lymph node involvement. Biopsy was performed and microscopical inspection revealed the lesion was composed of small- to middle-size atypical lymphoid cell, histiocytes, eosinophils, and neutrophils. The lymphoid cells were strongly immunoreactive to CD3, CD20, CD56, TIA-1 and granzyme-B. The Epstein-Barr virus genomes were also found in tumor cells by in situ hybridization. By genetic analysis, however, no clonal rearrangement of the T cell receptor-γ genes (TCRG), or the immunoglobulin heavy chain (IgH) gene was found. A diagnosis of CD20-positive extranodal NK/T-cell lymphoma, nasal type was made. The patient refused chemotherapy, and had been only on regular follow-up for 6 months. There was no sign of enlargement of tumor and extra-nasal dissemination by whole body positron emission tomography/computed tomography (PET/CT) study. The accurate diagnosis of NK/T-cell lymphoma with CD20 expression is important, but the indolent behavior of the present case is more unusual. A long-term follow-up is suggested to be performed to inspect the progression for this tumor.

Virtual slides

The virtual slides for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1320848277788495
Ethanol and anaerobic conditions reversibly inhibit commercial cellulase activity in thermophilic simultaneous saccharification and fermentation (tSSF)
Authors: Podkaminer Kara K , Kenealy William R , Herring Christopher D , Hogsett David A , Lynd Lee R
Published: October 2012

Background

A previously developed mathematical model of low solids thermophilic simultaneous saccharification and fermentation (tSSF) with Avicel was unable to predict performance at high solids using a commercial cellulase preparation (Spezyme CP) and the high ethanol yield Thermoanaerobacterium saccharolyticum strain ALK2. The observed hydrolysis proceeded more slowly than predicted at solids concentrations greater than 50 g/L Avicel. Factors responsible for this inaccuracy were investigated in this study.

Results

Ethanol dramatically reduced cellulase activity in tSSF. At an Avicel concentration of 20 g/L, the addition of ethanol decreased conversion at 96 hours, from 75% in the absence of added ethanol down to 32% with the addition of 34 g/L initial ethanol. This decrease is much greater than expected based on hydrolysis inhibition results in the absence of a fermenting organism. The enhanced effects of ethanol were attributed to the reduced, anaerobic conditions of tSSF, which were shown to inhibit cellulase activity relative to hydrolysis under aerobic conditions. Cellulose hydrolysis in anaerobic conditions was roughly 30% slower than in the presence of air. However, this anaerobic inhibition was reversed by exposing the cellulase enzymes to air.

Conclusion

This work demonstrates a previously unrecognized incompatibility of enzymes secreted by an aerobic fungus with the fermentation conditions of an anaerobic bacterium and suggests that enzymes better suited to industrially relevant fermentation conditions would be valuable. The effects observed may be due to inactivation or starvation of oxygen dependent GH61 activity, and manipulation or replacement of this activity may provide an opportunity to improve biomass to fuel process efficiency.
Molecular Gene Expression Profiling to Predict the Tissue of Origin and Direct Site-Specific Therapy in Patients With Carcinoma of Unknown Primary Site: A Prospective Trial of the Sarah Cannon Research Institute
Authors: Hainsworth John D. , Rubin Mark S. , Spigel David R. , Boccia Ralph V. , Raby Samuel , Quinn Raven , Greco F. Anthony
Published: October 2012

Purpose

Molecular tumor profiling is a promising diagnostic technique to determine the tissue of origin in patients with carcinoma of unknown primary site (CUP). However, the clinical value of these molecular predictions is unknown. We used tumor profiling results to direct site-specific therapy for patients with CUP.

Patients and Methods

Tumor biopsy specimens from previously untreated patients with CUP were tested with a 92-gene reverse transcriptase polymerase chain reaction cancer classification assay. When a tissue of origin was predicted, patients who were treatment candidates received standard site-specific first-line therapy.

Results

Of 289 patients enrolled, 252 had successful assays performed, and 247 (98%) had a tissue of origin predicted. Sites most commonly predicted were biliary tract (18%), urothelium (11%), colorectal (10%), and non–small-cell lung (7%). Two hundred twenty-three patients were treatment candidates, and 194 patients received assay-directed site-specific treatment. In these 194 patients, the median survival time was 12.5 months (95% CI, 9.1 to 15.4 months). When the assay predicted tumor types that were clinically more responsive, the median survival was significantly improved when compared with predictions of more resistant tumors (13.4 v 7.6 months, respectively; P = .04).

Conclusion

In this large prospective trial, molecular tumor profiling predicted a tissue of origin in most patients with CUP. The median survival time of 12.5 months for patients who received assay-directed site-specific therapy compares favorably with previous results using empiric CUP regimens. Patients with CUP predicted to have more responsive tumor types had longer survival compared with patients with less responsive tumor types. Molecular tumor profiling contributes to the management of patients with CUP and should be a part of their standard evaluation.
Radio-opacity and incidental identified mechanical complications of totally implantable venous access devices placed in the chest
Authors: Surov Alexey , Rusner Carsten , Weigand Karl , John Endres , Spielmann Rolf Peter , Behrmann C
Published: October 2012

Background

Totally implantable venous access devices (TIVAD) may be associated with different complications. Certain mechanical port disorders can easily be diagnosed on chest radiographs if the implanted systems are radiopaque and well visible. There are no reports regarding the visibility of TIVAD on chest X-rays.

Purpose

To assess the radio opacity of TIVAD implanted in the chest as well as type and frequency of mechanical complications of ports on chest X-ray images.

Material and Methods

Chest X-rays of 985 patients from the time period 2007-2009 were analyzed retrospectively. In these patients 1190 TIVAD were inserted. All parts of the TIVAD, i.e. port chamber, connection, and port catheter, were checked for their visibility on chest radiographs. An opacity score was used here as follows: ++ well visible; + visible; - partly or completely invisible. Mechanical complications of TIVAD incidentally detected on chest X-ray were also analyzed retrospectively.

Results

Nineteen TIVAD models with diverse configuration and visibility of port chambers, connections, and catheters were identified in our study. Eighty-eight percent of the analyzed port systems were well visible or visible on chest radiographs. Twelve percent of the port chambers and catheters were partly visible or completely invisible. In 9% of the TIVAD, different mechanical complications were diagnosed on chest X-ray images.

Conclusion

TIVADs should be evaluated carefully on every chest X-ray. Ideally, they should be radio-opaque and well visible on thoracic X-ray images. Unfortunately, this is not always the case. Therefore, manufacturers of TIVAD should take into consideration to use exclusively radio-opaque materials that allow sufficient visibility of each port component on chest radiographs.
Treatment outcome, mortality and their predictors among HIV-associated tuberculosis patients
Authors: Tabarsi P , Chitsaz E , Moradi A , Baghaei P , Farnia P , Marjani M , Shamai M , Amiri M , Nikaein S , Mansouri D , Masjedi M , Altice F
Published: October 2012

The risk of death is significantly higher in HIV-infected patients with tuberculosis (TB). This study aims to evaluate the impact of demographic, clinical and laboratory characteristics on the treatment outcome and mortality of TB/HIV co-infected patients in a tertiary TB centre in Iran. In total, 111 patients were recruited from 2004 to 2007. Mycobacteriological studies and demographic, clinical, and laboratory data from all patients were analysed and predictors of unsuccessful outcomes as well as mortality were determined. The mean age for all 111 TB-HIV patients was 38 ± 9 years (range 22–70) and 107 (96.3%) were men; 104 (93.7%) had a history of drug abuse and 96 (86.4%) had a history of imprisonment. The method of HIV transmission was intravenous drug use in 88 (79.3%). Twenty-three (20.7%) had a history of Category 1 (CAT I) TB treatment and six (5.4%) Category 2 (CAT II) treatment. Combination antiretroviral therapy (cART) was given to 48 (43.2%). No significant associations were found between treatment outcomes or mortality and gender, smoking, drug and alcohol abuse, imprisonment, method of transmission, history of CAT I and CAT II treatments, CD4 counts or adverse effects ( P > 0.05). Administration of cART led to significantly better outcomes ( P < 0.001). Lower serum albumin levels and low body weight were significantly associated with mortality.
Dynamics of the HIV epidemic in southern China: sexual and drug-using behaviours among female sex workers and male clients in Yunnan
Authors: Xu J J , Smith M K , Chu J , Ding G W , Chang D F , Sharp G B , Qian H Z , Lu L , Bi A M , Wang N
Published: October 2012

To examine the HIV/sexually transmitted infection (STI)-related risk behaviours among community-based female sex workers (FSWs) and their clients in Yunnan Province, China, we performed a cross-sectional study of 705 FSWs and 100 male clients. We found that HIV seroprevalence among FSWs was 13.0% and the most prevalent STI was herpes simplex virus type 2 (HSV-2) (71.1%), followed by Chlamydia trachomatis (18.1%) and syphilis (8.8%). The 20% of FSWs who reported injection drug use also reported needle-sharing behaviours in the last three months. Drug-using FSWs had substantially higher HIV and HSV-2 prevalence, serviced more clients and had a longer history of sex work than non-using FSWs. In total, 57.0% of male clients did not consistently use condoms with FSWs, 2.0% reported illicit drug use and 17.0% had STI symptoms in the last year. The dual risk behaviours of drug-using FSWs and clients place them at greater risk of HIV infection. Intervention programmes must adopt comprehensive methods.
What do we need to learn for policy decision-making on sexually transmitted infections prevention and treatment in Israel?
Authors: Chemtob D , Zenilman JM , Gandacu D
Published: October 2012

The rising trend of sexually transmitted infections (STIs) reported in several western countries has also affected Israel. To review epidemiological trends and to address additional issues needed for a wider overview on STIs in Israel, we analysed notified data on infectious syphilis, gonorrhoea, Chlamydia trachomatis and HIV/AIDS during 1998–2007, by age groups, and each available publication on STIs in Israel. The trend of each disease had a unique pattern, probably influenced by different screening procedures, case definition, mix of populations and better access to care for high-risk populations. Higher rates were found among patients aged 25–34 years. Rates found in different peak years for gonorrhoea, HIV, chlamydia and infectious syphilis reached 43.6, 18.9, 10.8 and 8.1 cases per 100,000 population, respectively. We compare trends to those of countries from World Health Organization (WHO) European Region and discuss interventions for subpopulations on which additional data are needed for evidence-based policy-making. Incidence rates of syphilis, gonorrhoea, chlamydia and HIV/AIDS are still low in Israel. We propose additional components needed for a more comprehensive evidence-based policy on STIs.
Barriers to contraception among HIV-positive women in a periurban district of Uganda
Authors: Mbonye A K , Hansen K S , Wamono F , Magnussen P
Published: October 2012

This study explored perceptions and care-seeking practices for HIV testing and contraception in order to obtain data for designing effective interventions to increase contraception among HIV-positive women. A triangulation of methods (household survey, focus group discussions and key informant interviews) were conducted in Wakiso district, central Uganda from January to April 2009. Results show that a majority of women, 2062/2896 (71.2%) would like to have an HIV test, while access to antiretroviral therapy (ART) was low at 237/879 (27%). Of the women who were on ART, 133/266 (50.0%) could not use contraception due to negative perceptions that a combination of ART and contraceptives would weaken them, as these drugs were perceived to be ‘strong’. Fear of side-effects for contraceptives and resistance from spouses were other main reasons. Constraints to HIV testing included fear of clients knowing their own HIV status and fear of their spouses’ reactions to the test results. Private midwives were identified as a potential outlet for delivering contraception to HIV-positive women.
Anal cytology screening in HIV-positive men who have sex with men: experience in a city centre HIV clinic
Authors: Goodall L , Clutterbuck D
Published: October 2012

The objectives of this study were to describe the findings of anal cytology screening during the first year of a unit protocol offering yearly screening to all HIV-positive men who have sex with men (MSM). Of 285 patients seen, 75% were offered anal cytology screening. Sixty-two percent of patients offered screening accepted and 21% of anal smears performed were reported as abnormal. Anal cytology screening may lead to earlier detection of anal intraepithelial neoplasia allowing for treatment before progression to cancer. This study revealed potential difficulties in follow-up of patients with high-grade precancerous disease and highlighted potential resource implications of implementing a routine screening programme.
Pre-elective HIV postexposure prophylaxis clinic for medical students: design, protocol, uptake and effectiveness
Authors: Stacey K , Sellers L , Barrett S
Published: October 2012

We sought to evaluate medical student need for HIV postexposure prophylaxis (PEP) prior to their elective and introduce a ‘Pilot PEP Clinic’. We undertook a survey of 388 medical students to assess their elective plans. All were offered an appointment in a clinic, assessed via a protocol and provided a PEP ‘starter-pack’ prescription if criteria were met. A follow-up questionnaire was sent to assess the acceptability of the clinic. The pre-elective questionnaire response rate was 232/388 (60%); 72/232 (31%) of respondents planned their elective in areas of high HIV prevalence and, of these, 32/72 (45%) attended the clinic. Of 32, 31 (97%) met the clinic protocol criteria and received a prescription for PEP. Of 32, 29 (90%) completed the follow-up questionnaire and every respondent rated the clinic as acceptable. The main concern was the cost of antiretroviral medications. We conclude that a ‘Pre-elective HIV PEP Clinic’ is an acceptable way to provide students with safe access to PEP prior to their elective.
Herpes simplex virus and HIV: genital infection synergy and novel approaches to dual prevention
Authors: Thurman A R , Doncel G F
Published: October 2012

Sexual transmission of HIV-1, in the absence of co-factors, is poorly efficient. Data support that herpes simplex virus type-2 (HSV-2) may increase a woman's susceptibility to HIV-1. Potential mechanisms by which HSV-2 serves as an HIV-1 enhancing co-factor include (1) initiation of a clinical or subclinical mucosal inflammatory response, (2) alteration of innate mucosal immunity and (3) weakening or breaching the protective genital epithelia. No clinical trial has examined prevention of primary HSV-2 infection to eliminate the major morbidities of this recurrent disease and as a strategy to reduce HIV-1 transmission. Topical administration of potent antivirals can achieve local concentrations that are orders of magnitude higher than those obtained with oral administration. This paper reviews major advances in oral and topical pre-exposure prophylaxis of HIV-1 and HSV-2 and, based on these data, hypothesizes that simultaneous prevention of sexual acquisition of HSV-2 and HIV-1 via topical antiretroviral agents will have a synergistic impact on both epidemics.
The value of testing multiple anatomic sites for gonorrhoea and chlamydia in sexually transmitted infection centres in the Netherlands, 2006–2010
Authors: Koedijk F D H , van Bergen J E A M , Dukers-Muijrers N H T M , van Leeuwen A P , Hoebe C J P A , van der Sande M A B
Published: October 2012

National surveillance data from 2006 to 2010 of the Dutch sexually transmitted infection (STI) centres were used to analyse current practices on testing extragenital sites for chlamydia and gonorrhoea in men who have sex with men (MSM) and women. In MSM, 76.0% and 88.9% were tested at least at one extragenital site (pharyngeal and/or anorectal) for chlamydia and gonorrhoea, respectively; for women this was 20.5% and 30.2%. Testing more than one anatomic site differed by STI centre, ranging from 2% to 100%. In MSM tested at multiple sites, 63.0% and 66.5% of chlamydia and gonorrhoea diagnoses, respectively, would have been missed if screened at the urogenital site only, mainly anorectal infections. For women tested at multiple sites, the proportions of missed chlamydia and gonorrhoea diagnoses would have been 12.9% and 30.0%, respectively. Testing extragenital sites appears warranted, due to the numerous infections that would have been missed. Adding anorectal screening to urogenital screening for all MSM visiting an STI centre should be recommended. Since actual testing practices differ by centre, there is a need for clearer guidelines. Routine gonorrhoea and chlamydia screening at multiple sites in STI centres should be investigated further as this might be a more effective approach to reduce transmission than current practice.