Effects of short-term treatment with atorvastatin in smokers with asthma - a randomized controlled trial

<b>Background</b> The immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.<p></p> <b>Methods</b> Seventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 ug per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.<p></p> <b>Results</b> At 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p=0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p=0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.<p></p> <b>Conclusions</b> Short-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma. Clinicaltrials.gov identifier: NCT0046382

Saudi international students’ perceptions of their transition to the UK and the impact of social media

In their transition to a new country, international students often feel lost, anxious or stressed. Saudi students in the UK in particular may face further challenges due to the cultural, social and religious differences that they experience. There is a lot of evidence that social media play a crucial role in this experience. By interviewing 12 Saudi students from different cities in the UK, the aim of this study is to investigate how they perceive their transition to the UK and how social media is involved. The analysis indicates that Saudi students’ perceptions of transition tend to fall in to one of two markedly different camps. Some students see transition as an opportunity to detach themselves from their home country and to engage with the new society. Those students turn to social media as a tool allowing them to build bridges with the new society. Other students feel less enthusiastic to make a full engagement with the UK society. Those students find social media as a good tool to maintain connections and links with family and friends in their home country

Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity.

Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.This is the published version of the manuscript. It is available online from NPG in Cell Death and Differentiaiton here: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd2014151a.html

Analysis of Mycobacterium tuberculosis-Specific CD8 T-Cells in Patients with Active Tuberculosis and in Individuals with Latent Infection

CD8 T-cells contribute to control of Mycobacterium tuberculosis infection, but little is known about the quality of the CD8 T-cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopes from 6 different proteins of Mycobacterium tuberculosis were detected by tetramer staining. Intracellular cytokines staining for specific production of IFN-γ and IL-2 was performed, complemented by phenotyping of memory markers on antigen-specific CD8 T-cells. The ex-vivo frequencies of tetramer-specific CD8 T-cells in tuberculous patients before therapy were lower than in subjects with latent infection, but increased at four months after therapy to comparable percentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR7−). In contrast, tuberculous patients had only 35% of antigen-specific CD8 T-cells expressing this phenotype, while containing higher proportions of cells with an effector memory- and a central memory-like phenotype, and which did not change significantly after therapy. CD8 T-cells from subjects with latent infection showed a codominance of IL-2+/IFN-γ+ and IL-2−/IFN-γ+ T-cell populations; interestingly, only the IL-2+/IFN-γ+ population was reduced or absent in tuberculous patients, highly suggestive of a restricted functional profile of Mycobacterium tuberculosis-specific CD8 T-cells during active disease. These results suggest distinct Mycobacterium tuberculosis specific CD8 T-cell phenotypic and functional signatures between subjects which control infection (subjects with latent infection) and those who do not (patients with active disease)

Seeking legitimacy through CSR: Institutional Pressures and Corporate Responses of Multinationals in Sri Lanka

Arguably, the corporate social responsibility (CSR) practices of multinational enterprises (MNEs) are influenced by a wide range of both internal and external factors. Perhaps most critical among the exogenous forces operating on MNEs are those exerted by state and other key institutional actors in host countries. Crucially, academic research conducted to date offers little data about how MNEs use their CSR activities to strategically manage their relationship with those actors in order to gain legitimisation advantages in host countries. This paper addresses that gap by exploring interactions between external institutional pressures and firm-level CSR activities, which take the form of community initiatives, to examine how MNEs develop their legitimacy-seeking policies and practices. In focusing on a developing country, Sri Lanka, this paper provides valuable insights into how MNEs instrumentally utilise community initiatives in a country where relationship-building with governmental and other powerful non-governmental actors can be vitally important for the long-term viability of the business. Drawing on neo-institutional theory and CSR literature, this paper examines and contributes to the embryonic but emerging debate about the instrumental and political implications of CSR. The evidence presented and discussed here reveals the extent to which, and the reasons why, MNEs engage in complex legitimacy-seeking relationships with Sri Lankan institutions

Novel use of an exchange catheter to facilitate intubation with an Aintree catheter in a tall patient with a predicted difficult airway: a case report

<p>Abstract</p> <p>Introduction</p> <p>The Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) has been shown to successfully facilitate difficult intubations when other methods have failed. The Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) has a fixed length of 56 cm, and it has been suggested in the literature that it may be too short for safe use in patients who are tall.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old, 180 cm tall Caucasian woman with a predicted difficult airway who presented to our facility for an emergency cesarean section. After several failed intubation attempts via direct laryngoscopy, an airway was established with a laryngeal mask airway. After delivery of a healthy baby, our patient's condition necessitated tracheal intubation. A fiber-optic bronchoscope loaded with an Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) was passed through the laryngeal mask airway into the trachea until just above the carina, but was too short to safely allow for the passage of an endotracheal tube.</p> <p>Conclusions</p> <p>We present a novel technique in which the Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) was replaced with a longer (100 cm) exchange catheter, over which an endotracheal tube was passed successfully into the trachea.</p

Quality assessment of an interferon-gamma release assay for tuberculosis infection in a resource-limited setting

<p>Abstract</p> <p>Background</p> <p>When a test for diagnosis of infectious diseases is introduced in a resource-limited setting, monitoring quality is a major concern. An optimized design of experiment and statistical models are required for this assessment.</p> <p>Methods</p> <p>Interferon-gamma release assay to detect tuberculosis (TB) infection from whole blood was tested in Hanoi, Viet Nam. Balanced incomplete block design (BIBD) was planned and fixed-effect models with heterogeneous error variance were used for analysis. In the first trial, the whole blood from 12 donors was incubated with nil, TB-specific antigens or mitogen. In 72 measurements, two laboratory members exchanged their roles in harvesting plasma and testing for interferon-gamma release using enzyme linked immunosorbent assay (ELISA) technique. After intervention including checkup of all steps and standard operation procedures, the second trial was implemented in a similar manner.</p> <p>Results</p> <p>The lack of precision in the first trial was clearly demonstrated. Large within-individual error was significantly affected by both harvester and ELISA operator, indicating that both of the steps had problems. After the intervention, overall within-individual error was significantly reduced (<it>P </it>< 0.0001) and error variance was no longer affected by laboratory personnel in charge, indicating that a marked improvement could be objectively observed.</p> <p>Conclusion</p> <p>BIBD and analysis of fixed-effect models with heterogeneous variance are suitable and useful for objective and individualized assessment of proficiency in a multistep diagnostic test for infectious diseases in a resource-constrained laboratory. The action plan based on our findings would be worth considering when monitoring for internal quality control is difficult on site.</p

Serial interferon-gamma release assays during treatment of active tuberculosis in young adults

<p>Abstract</p> <p>Background</p> <p>The role of interferon-γ release assay (IGRA) in monitoring responses to anti-tuberculosis (TB) treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT) assay over time during the anti-TB treatment of adults with no underlying disease.</p> <p>Methods</p> <p>We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline) and at 1, 3, and 6 months after initiating anti-TB medication.</p> <p>Results</p> <p>Of 67 eligible patients, 59 (88.1%) completed the study protocol. All participants were males who were human immunodeficiency virus (HIV)-negative and had no chronic diseases. Their median age was 21 years (range, 20-48). Initially, 57 (96.6%) patients had positive QFT-GIT results, and 53 (89.8%), 42 (71.2%), and 39 (66.1%) had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C) at diagnosis were associated with negative reversion of the QFT-GIT assay.</p> <p>Conclusion</p> <p>Although the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.</p

Protein kinase C inhibition attenuates vascular ET(B )receptor upregulation and decreases brain damage after cerebral ischemia in rat

BACKGROUND: Protein kinase C (PKC) is known to be involved in the pathophysiology of experimental cerebral ischemia. We have previously shown that after transient middle cerebral artery occlusion, there is an upregulation of endothelin receptors in the ipsilateral middle cerebral artery. The present study aimed to examine the effect of the PKC inhibitor Ro-32-0432 on endothelin receptor upregulation, infarct volume and neurology outcome after middle cerebral artery occlusion in rat. RESULTS: At 24 hours after transient middle cerebral artery occlusion (MCAO), the contractile endothelin B receptor mediated response and the endothelin B receptor protein expression were upregulated in the ipsilateral but not the contralateral middle cerebral artery. In Ro-32-0432 treated rats, the upregulated endothelin receptor response was attenuated. Furthermore, Ro-32-0432 treatment decreased the ischemic brain damage significantly and improved neurological scores. Immunohistochemistry showed fainter staining of endothelin B receptor protein in the smooth muscle cells of the ipsilateral middle cerebral artery of Ro-32-0432 treated rats compared to control. CONCLUSION: The results suggest that treatment with Ro-32-0432 in ischemic stroke decreases the ischemic infarction area, neurological symptoms and associated endothelin B receptor upregulation. This provides a new perspective on possible mechanisms of actions of PKC inhibition in cerebral ischemia