bluuebunny/crossref_metadata_2025 huggingface dataset:
Long term benefit of multiple sclerosis treatment: an investigation using a novel data collection technique
Authors: Conway Devon S , Miller Deborah M , O’Brien Ralph G , Cohen Jeffrey A
Published: June 2012

Background:

The Knowledge Program (KP) is an initiative to collect self-reported patient data and objective clinician assessments electronically at each outpatient clinical encounter. Available outcomes include the EuroQoL-5D (EQ5D), Patient Health Questionnaire-9 (PHQ9), Multiple Sclerosis Performance Scales (MSPS), and the timed 25-foot walk (T25FW).

Objective:

This study was designed to use the KP to investigate the long-term benefits of early treatment (ET) in multiple sclerosis (MS).

Methods:

The KP was queried for patients with relapsing–remitting MS or secondary progressive MS who were ≥5 years from symptom onset. ET was defined as treatment with an approved agent for ≥3 of the first five years after symptom onset. Propensity scores for ET were calculated based on early clinical characteristics. Patients were divided into propensity score quintiles and linear regression models were constructed to determine the treatment effect sizes and confidence intervals.

Results:

From the 1082 patients that met entry criteria, 453 patients (41.9%) received ET. Those patients receiving ET showed significantly better scores on the EQ5D index, PHQ9, and MSPS, but only in the upper three propensity quintiles. For the T25FW, ET did not result in significantly better times in any quintile.

Conclusions:

These results suggest that ET of MS is beneficial but the effect appears modest.
Upper limb replantation
Authors: Lin Pao-Yuan , Jeng Seng-Feng , Lin Tsan-Shiun , Hsieh Ching-Hua
Published: June 2012

Since the first successful salvage of an amputated finger using microsurgical anastomoses in 1965, replantation has been widely used in these decades and is now firmly established as a viable treatment option in traumatic limb amputation. The current concepts of replantation surgery for upper limb amputation are discussed in this review article in terms of history of replantation, present indications for the procedure, pre-theater care, technical refinements, postoperative management and functional outcome. In this article, we demonstrated that the advent of microsurgery has led to replantation of almost every amputated part of the upper limb possible. Replantation of digits and the hand can restore not only circulation but also function and cosmetic appearance. However, major amputations remain a challenge and the functional outcome is often disappointing, albeit the success rate of replantation exceeds 80%. Proper patient selection, adequate pre-theater preservation, good operative skill and postoperative care, as well as tight cooperation among the patient, the surgeon, and the rehabilitation therapist will help to achieve a better final functional outcome.
Researching sensitive issues online: implications of a hybrid insider/outsider position in a retrospective ethnographic study
Authors: Paechter Carrie
Published: June 2012

This article is concerned with methodological issues arising from a retrospective partially insider study of a divorce support website. I argue that, while we need to conduct detailed retrospective studies into the development of online communities, such studies bring methodological challenges, due to their retrospective nature, the potential size of the data set, and the problems of dealing with past manifestations of sites that continue to function. After an introduction to online and offline ethnography and insider/outsider researcher positioning, I discuss my hybrid insider/outsider status with respect to the research site. I focus in particular on researcher positioning, field entry and delimitation, public/private boundaries, ethical issues, and questions of time with respect to carrying out retrospective online studies while maintaining an ongoing real-time engagement with a research site.
Touring TV Soap Operas: Genre in Film Tourism Research
Authors: Kim Sangkyun , Long Philip
Published: June 2012

There is a growing body of literature that addresses the relationships between film and television programmes and tourism. However, we argue in this paper that much of this research has not considered the critical issue of genre and how this may be a key factor in shaping tourist demand, expectation, experience and behaviour. In particular, we suggest that the distinctive characteristics of TV soap operas have been neglected, with much of the literature focused on English language, ‘blockbuster’ Hollywood produced film releases. In this paper, we address TV soap operas as genre in relation to audience consumption and their possible links with tourism. We discuss the defining features of soap operas including their serialisation, the level of audience exposure and emotional engagement along with their connections with personal and domestic everyday life. We note their being a platform for interpersonal, intercultural and inter-textual discourse. We argue in the context of film tourism, that viewing soap operas may promote identification, empathy, emotional connection and parasocial interactions, and that these may motivate some audience members to visit soap opera locations, and also contextualise their anticipation concerning what they might expect to experience.
Using vibration phase space topology changes for structural damage detection
Authors: Nie Zhenhua , Hao Hong , Ma Hongwei
Published: June 2012

Ideally, structural health monitoring of civil infrastructure consists of determining, by measured parameters, the location and severity of damage in the structure. Many structural vibration parameters have been used to identify and quantify damage. Using parameters based on structural vibration phase space features for damage detection is a new field in structural health monitoring. In this article, a new parameter based on topology changes of the phase space of vibration signals is proposed to identify structural damage, and an index named changes of phase space topology derived from vibration time history is used to locate the damage. A circular arch structure is used to demonstrate the method. Both numerical simulation and experimental tests of dynamic responses of a scaled arch structure to impact loads are carried out. The obtained structural response data are used to detect structural damage. Both the experimental and numerical results indicate that this method can successfully locate damage. It also demonstrated that this proposed method is more sensitive to damage but less sensitive to noise than modal-based parameters. The proposed damage index can be a good candidate in an online structural health monitoring system, as it depends on global vibration measurements but is more sensitive to structural damage than other global vibration-based parameters such as vibration frequencies and mode shapes.
Staying Put
Authors: Dawley David D. , Andrews Martha C.
Published: June 2012

This study examined the relationship between two forms of embeddedness and turnover intentions using a sample of 1,189 employees of a government agency and an additional sample of 346 nurses at a hospital. The authors propose that while both on-the-job and off-the-job embeddedness factors are negatively related to turnover intentions, on-the-job embeddedness is more strongly related to turnover intentions. More important, off-the-job factors moderate the relationship between on-the-job embeddedness and turnover intentions such that this relationship is weaker when off-the-job embeddedness is higher. These results highlight the mitigating role of off-the-job factors in helping to retain employees. Implications for researchers and practitioners are discussed.
Revisiting Decision Support Systems for Cognitive Readiness
Authors: Cegarra Julien , van Wezel Wout
Published: June 2012

In this article, the authors focus on scheduling situations. Because of their unstructured nature and hard combinatorial complexity, scheduling situations have always been a predominant application area for decision support systems (DSSes). After setting out the generic characteristics of a DSS, the authors summarize some of their known limitations in scheduling situations. They argue that scheduling situations focus excessively on performance and effectiveness and neglect the potential of human schedulers. The authors then review field studies to understand the way in which humans perform scheduling, demonstrating the importance of cognitive readiness if schedulers are to schedule efficiently. On the basis of design issues and field studies, the authors go on to refine three factors that influence cognitive readiness that therefore need to be taken into account when designing a DSS, namely, adaptability, flexibility, and acceptability. Finally, the authors show how these concepts can be used to assess DSS user interfaces and algorithms from a cognitive readiness perspective.
Sacral neuromodulation and refractory overactive bladder: an emerging tool for an old problem
Authors: Banakhar Mai Ahmed , Al-Shaiji Tariq , Hassouna Magdy
Published: June 2012

Overactive bladder (OAB) syndrome negatively affects the daily life of many people. Conservative treatments, such as antimuscarinics, do not always lead to sufficient improvement of the complaints and are often associated with considerable side effects resulting in treatment failure. In the case of failure or intolerable side effects, sacral neuromodulation (SNM) and botulinum toxin intravesical injections are minimally invasive and reversible alternatives. Currently, both SNM and botulinum toxin injection have FDA approval for use in OAB patients. This mini-review attempts to provide an update on SNM as a second-line management of adults with refractory OAB, based on the available clinical evidence concerning the efficacy and safety.
Communication Breakdowns in the Academic Intensive Care Unit
Authors: Lateef Omar , Chen Elaine , Darin Michael
Published: June 2012

The current work flow within a large urban intensive care unit is prone to communication errors that can result in less than optimal patient care. This article discusses several cases that highlight breakdowns in communication that potentially lead to adverse events. The article also discusses recommendations to minimize these potential errors by altering the current structure of care in the intensive care unit.
Inadvertent Hyperventilation During Intraoperative Anesthetic Care in the Pediatric Population
Authors: Rozmiarek Andrew , Taghon Thomas , Tobias Joseph D.
Published: June 2012

Background. Recent clinical data suggest that inadvertent intraoperative hyperventilation may have long-lasting deleterious effects during the postoperative period with the potential for exaggerating the respiratory depressant effect of opioids. The current study identified the incidence of inadvertent hyperventilation during intraoperative anesthetic care in a cohort of pediatric patients. Methods. A retrospective review of the electronic medical record system was performed on patients undergoing posterior spinal fusion. These patients were chosen as arterial blood gas (ABG) analysis is routinely performed for such cases. ABG data were analyzed for the occurrence of hyperventilation, defined as alkalosis (pH ≥ 7.45) concurrent with hypocarbia (PaCo2 ≤ 35 mm Hg). Results. The study cohort included 166 patients who ranged in age from 22 months to 21 years. There were a total of 452 ABG samples obtained. Hyperventilation with the combination of alkalosis and hypocarbia was noted in 40 of the 452 (9%) ABG samples. An episode of hyperventilation was noted at some point in 30 of 166 patients (18%). When comparing hyperventilated with nonhyperventilated patients, only the mode of ventilation showed a statistically significant relationship with hyperventilation being more common with pressure- versus volume-limited ventilation. Conclusion. Inadvertent intraoperative hyperventilation is common-place in the pediatric population. In the adult population, it is now being appreciated that such practices may have deleterious effects on physiologic function that last into the postoperative period.
An Algorithm for the Practical Management of the New Onset of Atrial Fibrillation in Patients Admitted to the ICU
Authors: Shapiro William A. , Schulze Katharine
Published: June 2012

Currently, there are no ICU specific management guidelines for the new onset of atrial fibrillation (AF). This article provides a proposed treatment algorithm for paroxysmal AF that is based on recent separate consensus guidelines for the management of AF and for throbophrophylaxis. The AF treatment algorithm provides the intensivist with a decision tree approach based on the patients clinical findings at the time of ICU admission.
VEGFR1 stimulates a CXCR4-dependent translocation of megakaryocytes to the vascular niche, enhancing platelet production in mice
Authors: Pitchford Simon C. , Lodie Tracey , Rankin Sara M.
Published: June 2012

It has previously been reported that VEGF-A stimulates megakaryocyte (MK) maturation in vitro. Here we show that treatment of mice with the isoform VEGF-A165 resulted in a significant increase in circulating numbers of platelets. Using specific VEGFR1 and VEGFR2 blocking mAbs and selective VEGFR1 and 2 agonists, PlGF-2 and VEGF-E, respectively, we show directly that stimulation of VEGFR1, but not VEGFR2, increases circulating platelet numbers in vivo. Using flow cytometric analysis of harvested MKs, we show that while PlGF does not change the absolute numbers of MKs present in the bone marrow and the spleen, it increases both their maturation and cell-surface expression of CXCR4 in the bone marrow. Histology of the bone marrow revealed a redistribution of MKs from the endosteal to the vascular niche in response to both VEGF-A165 and PlGF-2 treatment in vivo. Antagonism of CXCR4 suppressed both the VEGFR1-stimulated redistribution of megakyocytes within the bone marrow compartment and the VEGF-A165–induced thrombocytosis. In conclusion, we define a novel proinflammatory VEGFR1-mediated pathway that stimulates the maturation and up-regulation of CXCR4 on megakaryocytes, leading to their redistribution within the bone marrow environment, thereby enhancing platelet production in vivo.
How I treat CML blast crisis
Authors: Hehlmann Rüdiger
Published: June 2012

Blast crisis (BC) remains the major challenge in the management of chronic myeloid leukemia (CML). It is now generally accepted that BC is the consequence of continued BCR-ABL activity leading to genetic instability, DNA damage, and impaired DNA repair. Most patients with BC carry multiple mutations, and up to 80% show additional chromosomal aberrations in a nonrandom pattern. Treatment with tyrosine kinase inhibitors has improved survival in BC modestly, but most long-term survivors are those who have been transplanted. Patients in BC should be treated with a tyrosine kinase inhibitor according to mutation profile, with or without chemotherapy, with the goal of achieving a second chronic phase and proceeding to allogeneic stem cell transplantation as quickly as possible. Although long-term remissions are rare, allogeneic stem cell transplantation provides the best chance of a cure in BC. Investigational agents are not likely to provide an alternative in the near future. In view of these limited options, prevention of BC by a rigorous and early elimination of BCR-ABL is recommended. Early response indicators should be used to select patients for alternative therapies and early transplantation. Every attempt should be made to reduce or eliminate BCR-ABL consistent with good patient care as far as possible.
Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates
Authors: Pandrea Ivona , Cornell Elaine , Wilson Cara , Ribeiro Ruy M. , Ma Dongzhu , Kristoff Jan , Xu Cuiling , Haret-Richter George S. , Trichel Anita , Apetrei Cristian , Landay Alan , Tracy Russell
Published: June 2012

HIV infection is associated with increased risk of cardiovascular complications, the underlying mechanism of which remains unclear. Plasma levels of the coagulation biomarker D-dimer (DD) correlate with increased mortality and cardiovascular events in HIV-infected patients. We compared the incidence of cardiovascular lesions and the levels of the coagulation markers DD and thrombin antithrombin in pathogenic SIV infections of rhesus and pigtailed macaques (PTMs) and in nonpathogenic SIV infection of African green monkeys (AGMs) and sooty mangabeys. Hypercoagulability and cardiovascular pathology were only observed in pathogenic SIV infections. In PTMs infected with SIV from AGMs (SIVagm), DD levels were highly indicative of AIDS progression and increased mortality and were associated with cardiovascular lesions, pointing to SIVagm-infected PTMs as an ideal animal model for the study of HIV-associated cardiovascular disease. In pathogenic SIV infection, DD increased early after infection, was strongly correlated with markers of immune activation/inflammation and microbial translocation (MT), and was only peripherally associated with viral loads. Endotoxin administration to SIVagm-infected AGMs (which lack chronic SIV-induced MT and immune activation) resulted in significant increases of DD. Our results demonstrate that hypercoagulation and cardiovascular pathology are at least in part a consequence of excessive immune activation and MT in SIV infection.
Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma
Authors: Groen Richard W. J. , Noort Willy A. , Raymakers Reinier A. , Prins Henk-Jan , Aalders Linda , Hofhuis Frans M. , Moerer Petra , van Velzen Jeroen F. , Bloem Andries C. , van Kessel Berris , Rozemuller Henk , van Binsbergen Ellen , Buijs Arjan , Yuan Huipin , de Bruijn Joost D. , de Weers Michel , Parren Paul W. H. I. , Schuringa Jan Jacob , Lokhorst Henk M. , Mutis Tuna , Martens Anton C. M.
Published: June 2012

Interactions within the hematopoietic niche in the BM microenvironment are essential for maintenance of the stem cell pool. In addition, this niche is thought to serve as a sanctuary site for malignant progenitors during chemotherapy. Therapy resistance induced by interactions with the BM microenvironment is a major drawback in the treatment of hematologic malignancies and bone-metastasizing solid tumors. To date, studying these interactions was hampered by the lack of adequate in vivo models that simulate the human situation. In the present study, we describe a unique human-mouse hybrid model that allows engraftment and outgrowth of normal and malignant hematopoietic progenitors by implementing a technology for generating a human bone environment. Using luciferase gene marking of patient-derived multiple myeloma cells and bioluminescent imaging, we were able to follow pMM cells outgrowth and to visualize the effect of treatment. Therapeutic interventions in this model resulted in equivalent drug responses as observed in the corresponding patients. This novel human-mouse hybrid model creates unprecedented opportunities to investigate species-specific microenvironmental influences on normal and malignant hematopoietic development, and to develop and personalize cancer treatment strategies.
Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study
Authors: Messinger Yoav H. , Gaynon Paul S. , Sposto Richard , van der Giessen Jeannette , Eckroth Elena , Malvar Jemily , Bostrom Bruce C.
Published: June 2012

Therapy of relapsed pediatric acute lymphoblastic leukemia (ALL) is hampered by low remission rates and high toxicity, especially in second and subsequent relapses. Our phase 1 study, T2005-003, showed that the combination of bortezomib with vincristine, dexamethasone, pegylated asparaginase, and doxorubicin had acceptable toxicity. We report the phase 2 expansion of this combination in patients with relapsed ALL who failed 2-3 previous regimens. Twenty-two patients with relapsed ALL were treated with bortezomib combined with this regimen; their ages ranged from 1 to 22 years, and they had either B-precursor ALL (n = 20) or T-cell ALL (n = 2). Grade 3 peripheral neuropathy developed in 2 (9%) patients. After 3 patients died from bacterial infections, treatment with vancomycin, levofloxacin, and voriconazole prophylaxis resulted in no further infectious mortality in the last 6 patients. Fourteen patients achieved complete remission (CR), and 2 achieved CR without platelet recovery, for an overall 73% response rate, meeting predefined criteria allowing for early closure. B-precursor patients faired best, with 16 of 20 (80%) CR + CR without platelet recovery, whereas the 2 patients with T-cell ALL did not respond. Thus, this combination of bortezomib with chemotherapy is active in B-precursor ALL, and prophylactic antibiotics may be useful in reducing mortality. Bortezomib merits further evaluation in combination therapy in pediatric B-precursor ALL. This study is registered at http://www.clinicaltrials.gov as NCT00440726.
Multicentre European study for the treatment of advanced emphysema with bronchial valves
Authors: Ninane Vincent , Geltner Christian , Bezzi Michela , Foccoli Pierfranco , Gottlieb Jens , Welte Tobias , Seijo Luis , Zulueta Javier J. , Munavvar Mohammed , Rosell Antoni , Lopez Marta , Jones Paul W. , Coxson Harvey O. , Springmeyer Steven C. , Gonzalez Xavier
Published: June 2012

This multicentre, blinded, sham-controlled study was performed to assess the safety and effectiveness of bronchial valve therapy using a bilateral upper lobe treatment approach without the goal of lobar atelectasis.

Patients with upper lobe predominant severe emphysema were randomised to bronchoscopy with (n=37) or without (n=36) IBV Valves for a 3-month blinded phase. A positive responder was defined as having both a ≥4-point improvement in St George’s Respiratory Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative computed tomography.

At 3 months, there were eight (24%) positive responders in the treated groupversusnone (0%) in the control group (p=0.002). Also, there was a significant shift in volume in the treated group from the upper lobes (mean±sd-7.3±9.0%) to the non-treated lobes (6.7±14.5%), with minimal change in the control group (p<0.05). Mean SGRQ total score improved in both groups (treatment: -4.3±16.2; control: -3.6±10.7). The procedure and devices were well tolerated and there were no differences in adverse events reported in the treatment and control groups.

Treatment with bronchial valves without complete lobar occlusion in both upper lobes was safe, but not effective in the majority of patients.
Barriers to an early switch from intravenous to oral antibiotic therapy in hospitalised patients with CAP
Authors: Engel Madelon F. , Postma Douwe F. , Hulscher Marlies E.J.L. , Teding van Berkhout Ferdinand , Emmelot-Vonk Marielle H. , Sankatsing Sanjay , Gaillard Carlo A.J.M. , Bruns Anke H.W. , Hoepelman Andy I.M. , Oosterheert Jan Jelrik
Published: June 2012

Do physicians apply an early-switch strategy (from intravenous to oral antibiotics) in clinically stable patients hospitalised with community-acquired pneumonia (CAP)? If not, why not?

In a multicentre prospective cohort study, adult patients admitted fori.v.CAP treatment were included. On day 3 of antibiotic treatment, clinical stability was assessed and treating resident physicians were interviewed on their switch strategies. Additionally, treating physicians were interviewed to evaluate their knowledge of and adherence to guideline advice.

149 (92%) out of 162 patients were included and 97 (91%) out of 107 physicians were interviewed. A switch to oral antibiotics was possible in 68 (46%) out of 149 patients on day 3 of treatment but not performed in 27 (40%) out of 68. Patient factors delaying the switch were high CURB-65 (confusion of new onset, urea >7 mmol·L−1, respiratory rate of ≥30 breaths·min−1, blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg, and age ≥65 yrs) score (on admission) (p=0.04) and oxygen treatment (p=0.04), high temperature (p=0.00) and high respiration rate (p=0.04) (day 3). Physicians' barriers to an early switch in clinically stable patients included misconceptions (26 (55%) out of 47), practical considerations (13 (28%) out of 47) and organisational factors (eight (17%) out of 47). Strikingly, 91 (94%) out of 97 interviewed physicians were not aware of guideline advice.

The switch fromi.v.to oral antibiotics is often unnecessarily delayed in patients hospitalised with CAP due to different types of barriers.
Minimum package for cross-border TB control and care in the WHO European region: a Wolfheze consensus statement
Authors: Dara Masoud , de Colombani Pierpaolo , Petrova-Benedict Roumyana , Centis Rosella , Zellweger Jean-Pierre , Sandgren Andreas , Heldal Einar , Sotgiu Giovanni , Jansen Niesje , Bahtijarevic Rankica , Migliori Giovanni Battista
Published: June 2012

The World Health Organization (WHO) European region estimates that more than 400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among migrants.

A coordinated public health mechanism to guarantee TB prevention, diagnosis, treatment and care across borders is not in place. A consensus paper describing the minimum package of cross-border TB control and care was prepared by a task force following a literature review, and with input from the national TB control programme managers of the WHO European region and the Wolfheze 2011 conference. A literature review focused on the subject of TB in migrants was carried out, selecting documents published during the 11-yr period 2001–2011.

Several issues were identified in cross-border TB control and care, varying from the limited access to early TB diagnosis, to the lack of continuity of care and information during migration, and the availability of, and access to, health services in the new country.

The recommended minimum package addresses the current shortcomings and intends to improve the situation by covering several areas: political commitment (including the implementation of a legal framework for TB cross-border collaboration), financial mechanisms and adequate health service delivery (prevention, infection control, contact management, diagnosis and treatment, and psychosocial support).
Lung cancer risk and solid fuel smoke exposure: a systematic review and meta-analysis
Authors: Kurmi Om Prakash , Arya Pallavi Huma , Lam Kin-Bong Hubert , Sorahan Tom , Ayres Jon G.
Published: June 2012

The aim of this systematic review was to quantify the impact of biomass fuel and coal use on lung cancer and to explore reasons for heterogeneity in the reported effect sizes.

A systematic review of primary studies reporting the relationship between solid fuel use and lung cancer was carried out, based on pre-defined criteria. Studies that dealt with confounding factors were used in the meta-analysis. Fuel types, smoking, country, cancer cell type and sex were considered in sub-group analyses. Publication bias and heterogeneity were estimated.

The pooled effect estimate for coal smoke as a lung carcinogen (OR 1.82, 95% CI 1.60–2.06) was greater than that from biomass smoke (OR 1.50, 95% CI 1.17–1.94). The risk of lung cancer from solid fuel use was greater in females (OR 1.81, 95% CI 1.54–2.12) compared to males (OR 1.16, 95% CI 0.79–1.69). The pooled effect estimates were 2.33 (95% CI 1.72–3.17) for adenocarcinoma, 3.58 (1.58–8.12) for squamous cell carcinoma and 1.57 (1.38–1.80) for tumours of unspecified cell type.

These findings suggest that in-home burning of both coal and biomass is consistently associated with an increased risk of lung cancer.
Early detection of asthma exacerbations by using action points in self-management plans
Authors: Honkoop Persijn J. , Taylor D. Robin , Smith Andrew D. , Snoeck-Stroband Jiska B. , Sont Jacob K.
Published: June 2012

Our aim was to validate optimal action points in written action plans for early detection of asthma exacerbations.

We analysed daily symptoms and morning peak expiratory flows (PEFs) from two previous studies. Potential action points were based on analysis of symptom scores (standard deviations) percentage of personal best PEF, PEF variability in relation to a run-in period or combinations of these measures. Sensitivity and specificity for predicting exacerbations were obtained for each action point. The numbers needed to treat to prevent one exacerbation and the time interval between reaching action point criteria and the start of the exacerbation were calculated. Based on these parameters, the optimal action points for symptoms, PEF and PEF plus symptoms were determined, and their performance compared with published guidelines’ action points.

The optimal action points were, for symptoms, statistical variability (standard deviations) and, for PEF, <70% of personal best. The combination of PEF plus symptoms performed best, with improved specificity and earlier detection. The main benefits associated with using these action points was to reduce false positive rates for detecting exacerbations.

Early detection of asthma exacerbations can be improved using a composite action point comprising symptoms and PEF measurements over 1 week.
Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis
Authors: Günther Andreas , Korfei Martina , Mahavadi Poornima , von der Beck Daniel , Ruppert Clemens , Markart Philipp
Published: June 2012

Idiopathic pulmonary fibrosis (IPF) is a life-threatening condition, with a median survival of <3 yrs. The pathophysiology is not fully understood, but chronic injury of alveolar epithelial type II cells (AECII) is considered key.

In IPF, disturbed folding and processing of surfactant proteins and impaired DNA repair may represent underlying reasons for maladaptive endoplasmic reticulum stress responses, increased reactive oxygen species production and/or DNA damage. Excessive AECII apoptosis occurs, leading to permanently perturbed epithelial homeostasis. The role of secondary hits also becomes evident. These may aggravate the disease and result in increased epithelial turnover, exhausting the regenerative capacity of progenitors and disturbing epithelial–mesenchymal interactions. Fibroblast proliferation, transdifferentiation and matrix deposition may be mediated through various mechanisms including epithelial–mesenchymal transition, fibrocyte invasion or expansion of a local fibroblast population.

Treatment modalities aiming to attenuate epithelial injury are currently in early pre-clinical development and may reach the clinical arena in only a few years. Meanwhile, novel drugs acting on highly activated fibroblasts such as pirfenidone, an anti-fibrotic drug authorised for IPF in the European Union, or BIBF 1120, a novel triple-kinase inhibitor (blocking vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor) currently under clinical investigation, seem to attenuate the progression of IPF.
Changing the idiopathic pulmonary fibrosis treatment approach and improving patient outcomes
Authors: Cottin Vincent
Published: June 2012

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic disease, with no effective treatment and a median survival time of 2–5 yrs. The search for effective treatment has involved numerous clinical trials of investigational agents without significant success until 2011, when European approval was given for the first treatment for IPF, pirfenidone. Four key clinical trials supported the efficacy and tolerability of pirfenidone.

In recently published results from two phase III randomised, double-blind, placebo-controlled, multinational trials evaluating pirfenidone (studies 004 and 006), patients with mild-to-moderate IPF were screened for eligibility using the following functional criteria: forced vital capacity (FVC) ≥50% predicted; diffusing capacity of the lung for carbon monoxide ≥35%; and 6-min walk test (6MWT) distance ≥150 m.

Only study 004 met the primary end-point of change in per cent predicted FVC at week 72 (p<0.001). Pooled analysis of primary end-point data from both studies also showed that pirfenidone significantly reduced the decline in per cent predicted FVC compared to placebo (p<0.005). Evidence of beneficial effects of pirfenidone treatment was also observed with regard to several secondary end-points, including progression-free survival time, categorical FVC change, and mean change from baseline to week 72 in 6MWT distance.

Pirfenidone was generally well tolerated, with the most common side-effects being gastrointestinal discomfort and photosensitivity. The pooled study results, coupled with recent data regarding the prognostic significance of changes in FVC and 6MWT, provide further evidence of a clinically meaningful treatment benefit with pirfenidone in patients with IPF.
Primary prevention: exposure reduction, skin exposure and respiratory protection
Authors: Heederik Dick , Henneberger Paul K. , Redlich Carrie A.
Published: June 2012

Interventions for the primary prevention of occupational asthma have been reported in the medical literature, understanding the effectiveness of these efforts could help future interventions.

The aim of our study was to evaluate the existing knowledge regarding the impact of controlling work exposure on the prevention of occupational asthma. We conducted systematic literature searches through April 2010 to examine if control of workplace exposures is effective for primary prevention of sensitisation and occupational asthma.

The literature search for primary prevention of occupational asthma yielded 29 studies. Assessment of the available information led to the following conclusions and recommendations concerning primary prevention of occupational asthma. Exposure elimination is the strongest and preferred primary preventive approach to reduce the burden of occupational asthma. If elimination is not possible, exposure reduction is the second best option for primary prevention of occupational asthma.

The evidence for the effectiveness of respirators in preventing occupational asthma is limited, and other options higher in the list of controls for occupational exposures, notably eliminating or minimising exposures at the source or in the environment, should be used preferentially. There is strong evidence to recommend not using powdered allergen-rich natural rubber latex gloves. There is weak evidence that suggests workers should minimise skin exposure to asthma-inducing agents.
Construction of a Salmonella Gallinarum ghost as a novel inactivated vaccine candidate and its protective efficacy against fowl typhoid in chickens
Authors: Chaudhari Atul A , Jawale Chetan V , Kim Sam Woong , Lee John Hwa
Published: June 2012

In order to develop a novel, safe and immunogenic fowl typhoid (FT) vaccine candidate, a Salmonella Gallinarum ghost with controlled expression of the bacteriophage PhiX174 lysis gene E was constructed using pMMP99 plasmid in this study. The formation of the Salmonella Gallinarum ghost with tunnel formation and loss of cytoplasmic contents was observed by scanning electron microscopy and transmission electron microscopy. No viable cells were detectable 24 h after the induction of gene E expression by an increase in temperature from 37 °C to 42 °C. The safety and protective efficacy of the Salmonella Gallinarum ghost vaccine was tested in chickens that were divided into four groups: group A (non-immunized control), group B (orally immunized), group C (subcutaneously immunized) and group D (intramuscularly immunized). The birds were immunized at day 7 of age. None of the immunized animals showed any adverse reactions such as abnormal behavior, mortality, or signs of FT such as anorexia, depression, or diarrhea. These birds were subsequently challenged with a virulent Salmonella Gallinarum strain at 3 weeks post-immunization (wpi). Significant protection against the virulent challenge was observed in all immunized groups based on mortality and post-mortem lesions compared to the non-immunized control group. In addition, immunization with the Salmonella Gallinarum ghosts induced significantly high systemic IgG response in all immunized groups. Among the groups, orally-vaccinated group B showed significantly higher levels of secreted IgA. A potent antigen-specific lymphocyte activation response along with significantly increased percentages of CD4+ and CD8+ T lymphocytes found in all immunized groups clearly indicate the induction of cellular immune responses. Overall, these findings suggest that the newly constructed Salmonella Gallinarum ghost appears to be a safe, highly immunogenic, and efficient non-living bacterial vaccine candidate that protects against FT.
Interaction of the European genotype porcine reproductive and respiratory syndrome virus (PRRSV) with sialoadhesin (CD169/Siglec-1) inhibits alveolar macrophage phagocytosis
Authors: De Baere Miet I , Van Gorp Hanne , Delputte Peter L , Nauwynck Hans J
Published: June 2012

Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus that shows a restricted in vivo tropism for subsets of porcine macrophages, with alveolar macrophages being major target cells. The virus is associated with respiratory problems in pigs of all ages and is commonly isolated on farms with porcine respiratory disease complex (PRDC). Due to virus-induced macrophage death early in infection, PRRSV hampers the innate defence against pathogens in the lungs. In addition, the virus might also directly affect the antimicrobial functions of macrophages. This study examined whether interaction of European genotype PRRSV with primary alveolar macrophages (PAM) affects their phagocytic capacity. Inoculation of macrophages with both subtype I PRRSV (LV) and subtype III PRRSV (Lena) showed that the virus inhibits PAM phagocytosis. Similar results were obtained using inactivated PRRSV (LV), showing that initial interaction of the virion with the cell is sufficient to reduce phagocytosis, and that no productive infection is required. When macrophages were incubated with sialoadhesin- (Sn) or CD163-specific antibodies, two entry mediators of the virus, only Sn-specific antibodies downregulated the phagocytic capacity of PAM, indicating that interaction with Sn, but not CD163, mediates the inhibitory effect of PRRSV on phagocytosis. In conclusion, this study shows that European genotype PRRSV inhibits PAM phagocytosis in vitro, through the interaction with its internalization receptor Sn. If similar events occur in vivo, this interaction may be important in the development of PRDC, as often seen in the field.
Expression of Nucleophosmin/NPM1 correlates with migration and invasiveness of colon cancer cells
Authors: Liu Yan , Zhang Fei , Zhang Xiao-fang , Qi Li-sha , Yang Lei , Guo Hua , Zhang Ning
Published: June 2012

Background

We aimed to examine the expression level of Nucleophosmin (NPM1) protein in colon cancer tissues and to investigate the potential role of NPM1 in the regulation of cell migration and invasiveness.

Methods

Immunohistochemical assay was performed to examine the expression pattern of NPM1 in 31 groups of colonic carcinoma samples, including colon tumors, adjacent normal tissues, and matched metastatic lymph nodes from the same patients. Small interfering RNA technique and exogenous expression of wild type NPM1 methods were used to further verify the function of NPM1.

Results

High-expression of NPM1 correlates with lymph node metastasis (P = 0.0003) and poor survival rate of human colon cancer patients (P = 0.017). SiRNA-mediated reduction of NPM1 was also shown to inhibit the migration and invasiveness of metastatic colon cancer HCT116 cell line. In addition, the exogenous expression of NPM1 in HT29 cells, a NPM1 low expression and low invasive colon cancer cell line, enhanced cell migration and invasiveness along with increased cell proliferation.

Conclusions

The current study uncovered the critical role of NPM1 in the regulation of colon cancer cells migration and invasion, and NPM1 may serve as a potential marker for the prognosis of colon cancer patients.
Immunocytochemical analysis of P2X2 in rat circumvallate taste buds
Authors: Yang Ruibiao , Montoya Alana , Bond Amanda , Walton Jenna , Kinnamon John C
Published: June 2012

Background

Our laboratory has shown that classical synapses and synaptic proteins are associated with Type III cells. Yet it is generally accepted that Type II cells transduce bitter, sweet and umami stimuli. No classical synapses, however, have been found associated with Type II cells. Recent studies indicate that the ionotropic purinergic receptors P2X2/P2X3 are present in rodent taste buds. Taste nerve processes express the ionotropic purinergic receptors (P2X2/P2X3). P2X2/P2X3Dbl−/− mice are not responsive to sweet, umami and bitter stimuli, and it has been proposed that ATP acts as a neurotransmitter in taste buds. The goal of the present study is to learn more about the nature of purinergic contacts in rat circumvallate taste buds by examining immunoreactivity to antisera directed against the purinergic receptor P2X2.

Results

P2X2-like immunoreactivity is present in intragemmal nerve processes in rat circumvallate taste buds. Intense immunoreactivity can also be seen in the subgemmal nerve plexuses located below the basal lamina. The P2X2 immunoreactive nerve processes also display syntaxin-1-LIR. The immunoreactive nerves are in close contact with the IP3R3-LIR Type II cells and syntaxin-1-LIR and/or 5-HT-LIR Type III cells. Taste cell synapses are observed only from Type III taste cells onto P2X2-LIR nerve processes. Unusually large, “atypical” mitochondria in the Type II taste cells are found only at close appositions with P2X2-LIR nerve processes. P2X2 immunogold particles are concentrated at the membranes of nerve processes at close appositions with taste cells.

Conclusions

Based on our immunofluorescence and immunoelectron microscopical studies we believe that both perigemmal and most all intragemmal nerve processes display P2X2-LIR. Moreover, colloidal gold immunoelectron microscopy indicates that P2X2-LIR in nerve processes is concentrated at sites of close apposition with Type II cells. This supports the hypothesis that ATP may be a key neurotransmitter in taste transduction and that Type II cells release ATP, activating P2X2 receptors in nerve processes.
Service suspension for mental disorders in armed forces draftees in the Penghu area
Authors: Chuang Wei-Chen , Kao Chin-Han , Chen Chih-Kang , Peng Chia-He , Wang Wu-Hsi
Published: June 2012

Background

It is important to monitor draftees for mental disorders before or at an early stage of military service. The aim of this study was to characterize the draftees who were suspended from service for mental disorders among draftees in a high readiness military zone in the Taiwan Strait.

Method

A total of 152 draftees consulted the outpatient service of the Department of Psychiatry at Penghu branch, Tri-Service General Hospital in Taiwan during the period between August 2004 and July 2008, and whose severity of mental disorder fit the criteria for service suspension were recruited as the study group (SG). Draftees who had adjusted normally were the control group (CG).

Results

The major causes for suspension were major depressive disorders and personality disorders. In the study group, the number of draftees seeking psychiatric outpatient treatment increased from 49.3% before service to 100% during service. In addition, higher rates of suicidal ideation, suicide plans, attempted suicide, and homicidal ideation were found in the study group than in the control group. The percentages of draftees who were unwilling to serve and absent without official leave (AWOL) during military service in Penghu were also significantly higher in the study group than in the control group.

Conclusions

Based on the characteristics of the draftees who were suspended from service for mental disorders, psychological factors such as suicidal ideation, suicide attempts and adjustment disorders should be surveyed and monitored before the draft and at an early stage of military service.
Predictors of condom use and refusal among the population of Free State province in South Africa
Authors: Chandran Thoovakkunon Moorkoth , Berkvens Dirk , Chikobvu Perpetual , Nöstlinger Christiana , Colebunders Robert , Williams Brian Gerard , Speybroeck Niko
Published: June 2012

Background

This study investigated the extent and predictors of condom use and condom refusal in the Free State province in South Africa.

Methods

Through a household survey conducted in the Free Sate province of South Africa, 5,837 adults were interviewed. Univariate and multivariate survey logistic regressions and classification trees (CT) were used for analysing two response variables ‘ever used condom’ and ‘ever refused condom’.

Results

Eighty-three per cent of the respondents had ever used condoms, of which 38% always used them; 61% used them during the last sexual intercourse and 9% had ever refused to use them. The univariate logistic regression models and CT analysis indicated that a strong predictor of condom use was its perceived need. In the CT analysis, this variable was followed in importance by ‘knowledge of correct use of condom’, condom availability, young age, being single and higher education. ‘Perceived need’ for condoms did not remain significant in the multivariate analysis after controlling for other variables. The strongest predictor of condom refusal, as shown by the CT, was shame associated with condoms followed by the presence of sexual risk behaviour, knowing one’s HIV status, older age and lacking knowledge of condoms (i.e., ability to prevent sexually transmitted diseases and pregnancy, availability, correct and consistent use and existence of female condoms). In the multivariate logistic regression, age was not significant for condom refusal while affordability and perceived need were additional significant variables.

Conclusions

The use of complementary modelling techniques such as CT in addition to logistic regressions adds to a better understanding of condom use and refusal. Further improvement in correct and consistent use of condoms will require targeted interventions. In addition to existing social marketing campaigns, tailored approaches should focus on establishing the perceived need for condom-use and improving skills for correct use. They should also incorporate interventions to reduce the shame associated with condoms and individual counselling of those likely to refuse condoms.