Barriers to the use of a diagnostic oral microbiology laboratory by general dental practitioners

OBJECTIVE: To identify barriers on the use of diagnostic microbiology facilities in general dental practice. DESIGN: A cross-sectional survey using a postal questionnaire. SETTING: Primary/secondary care interface between the diagnostic oral microbiology laboratory, University of Glasgow Dental Hospital and School, Glasgow and dental practitioners within the surrounding health boards, 1998. SUBJECTS: All GDPs (797) within Argyll and Clyde, Ayrshire and Arran, Lanarkshire and Greater Glasgow Health Boards. MAIN OUTCOME MEASURES: The responses were expressed as both absolute and relative frequencies. RESULTS: Responses were received from 430 (55%). The most frequent reason for failure to use the service was lack of information, with more than half of the respondents claiming to be unaware of the facility. Lack of request forms and sampling equipment were also viewed as barriers to using the service. CONCLUSIONS: The laboratory is failing to successfully communicate its role in addressing the growing burden of antibiotic resistance in the community and must be more proactive in encouraging appropriate use and increasing accessibility of the service to GDPs

GPR35 as a Novel Therapeutic Target

G protein-coupled receptors (GPCRs) remain the best studied class of cell surface receptors and the most tractable family of proteins for novel small molecule drug discovery. Despite this, a considerable number of GPCRs remain poorly characterized and in a significant number of cases, endogenous ligand(s) that activate them remain undefined or are of questionable physiological relevance. GPR35 was initially discovered over a decade ago but has remained an “orphan” receptor. Recent publications have highlighted novel ligands, both endogenously produced and synthetic, which demonstrate significant potency at this receptor. Furthermore, evidence is accumulating which highlights potential roles for GPR35 in disease and therefore, efforts to characterize GPR35 more fully and develop it as a novel therapeutic target in conditions that range from diabetes and hypertension to asthma are increasing. Recently identified ligands have shown marked species selective properties, indicating major challenges for future drug development. As we begin to understand these issues, the continuing efforts to identify novel agonist and antagonist ligands for GPR35 will help to decipher its true physiological relevance; translating multiple assay systems in vitro, to animal disease systems in vivo and finally to man

Operation Moshtarak and the manufacture of credible, “heroic” warfare

Richard Lance Keeble argues that Fleet Street’s coverage of the Afghan conflict has served largely to promote the interests of the military/industrial/media complex – and marginalise the views of the public who have consistently appealed in polls for the troops to be brought back hom

Constituting monetary conservatives via the 'savings habit': New Labour and the British housing market bubble

The ongoing world credit crunch might well kill off the most recent bubble dynamics in the British housing market by driving prices systematically downwards from their 2007 peak. Nonetheless, the experience of that bubble still warrants analytical attention. The Labour Government might not have been responsible for consciously creating it, but it has certainly grasped the opportunities the bubble has provided in an attempt to enforce a process of agential change at the heart of the British economy. The key issue in this respect is the way in which the Government has challenged the legitimacy of passive welfare receipts in favour of establishing a welfare system based on incorporating the individual into an active asset-holding society. The housing market has taken on new political significance as a means for individuals first to acquire assets and then to accumulate wealth on the back of asset ownership. The ensuing integration of the housing market into an increasingly reconfigured welfare system has permeated into the politics of everyday life. It has been consistent with individuals remaking their political subjectivities in line with preferences for the type of conservative monetary policies that typically keep house price bubbles inflated

Platelet Accumulation in Brain Microvessels in Fatal Pediatric Cerebral Malaria

The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the diseas

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

Japan Tobacco International: : To ‘be the most successful and respected tobacco company in the world’

Japan Tobacco International (JTI) is the international division of Japan Tobacco Incorporated, and the world's third largest transnational tobacco company. Founded in 1999, JTI's rapid growth has been the result of a global business strategy that potentially serves as a model for other Asian tobacco companies. This paper analyses Japan Tobacco Incorporated's global expansion since the 1980s in response to market opening, foreign competition, and declining share of a contracting domestic market. Key features of its global strategy include the on-going central role and investment by the Japanese government, and an expansion agenda based on mergers and acquisitions. The paper also discusses the challenges this global business strategy poses for global tobacco control and public health. This paper is part of the special issue 'The Emergence of Asian Tobacco Companies: Implications for Global Health Governance'.19 page(s

Impact of socio-economic deprivation on death rates after surgery for upper gastrointestinal tract cancer

We hypothesised that socio-economic deprivation in England may be a prognostic factor for death after oesophagectomy or gastrectomy for cancer of the upper gastrointestinal tract. We analysed statistical data from hospital records linked to death records for patients who underwent operations for oesophageal and gastric cancer in England from April 1998 to March 2002. The patients were stratified into quintiles according to the index of multiple deprivation (IMD) (2000) for their place (ward) of residence. Age and sex standardised death rates at 30 and 90 days for each deprivation quintile were calculated. Following oesophagectomy, death rates showed a significant association with IMD. They increased with increasing levels of deprivation: the odds ratio for death, comparing highest with lowest quintile for deprivation, was 1.37 (95% confidence interval 1.03–1.85) at 30 days and 1.30 (1.04–1.64) at 90 days. Following gastrectomy, the death rates showed smaller and nonsignificant associations with IMD with odds ratios of 1.16 (0.84–1.62) and 1.10 (0.86–1.41), respectively. There is a significant association between social deprivation and death after oesophagectomy, but less of an association, if any, after gastrectomy in current UK practice

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1