Prevalence and predictors of tuberculin skin positivity in Hellenic Army recruits

BACKGROUND: Tuberculosis (TB) remains one of the leading causes of death among infectious diseases worldwide. Despite its low incidence rates in countries of Western Europe and North America, the resurgence of TB in Eastern Europe and the increased immigration from high-incidence countries imply that extreme vigilance is required in order to detect early, treat, and isolate all new cases. In this study, we analyzed the prevalence and predictors of tuberculin skin testing positivity in Hellenic Army recruits. METHODS: The study population consisted of 953 Greek military recruits enlisted inthe Army during the period from November 2005 toFebruary 2006. Tuberculin skin testing was performed on all study subjects upon enrollment, according to the routine procedures. A tuberculin skin test reaction size >15 mm was considered positive for all study participants. Epidemiological data regarding age, repatriation status, geographic area of residence, smoking habits, and parental occupation were collected by means of personal interviews. In addition, body weight, height, and body mass index were measured. RESULTS: The mean age of the studied subjects (± SD) was 23.5 (± 6.4) years. The overall prevalence of tuberculin positivity was 3.9% (37/953), and bivariable analysis showed that it was associated with lower weight (p = 0.047) and repatriation status (p < 0.001). Tuberculin skin testing was positive in 2.6% of natives (24/900) and 24.5% of repatriates (13/53). A backward, stepwise multivariable logistic regression model showed that only repatriation status was independently associated with tuberculin positivity (p < 0.001; odds ratio [OR]: 14.1; 95% confidence interval [CI]: 6.5–30.3). CONCLUSION: While the incidence of tuberculosis in the native Greek population is low, and comparable to other Western European countries, the extremely high tuberculin positivity in repatriated persons underscores the importance of actively screening for TB in order to promptly identify, isolate, and treat cases of active and latent infection

Estimating the costs of school closure for mitigating an influenza pandemic

BACKGROUND: School closure is a key component of many countries' plans to mitigate the effect of an influenza pandemic. Although a number of studies have suggested that such a policy might reduce the incidence, there are no published studies of the cost of such policies. This study attempts to fill this knowledge gap METHODS: School closure is expected to lead to significant work absenteeism of working parents who are likely to be the main care givers to their dependent children at home. The cost of absenteeism due to school closure is calculated as the paid productivity loss of parental absenteeism during the period of school closure. The cost is estimated from societal perspective using a nationally representative survey. RESULTS: The results show that overall about 16% of the workforce is likely to be the main caregiver for dependent children and therefore likely to take absenteeism. This rises to 30% in the health and social care sector, as a large proportion of the workforce are women. The estimated costs of school closure are significant, at 0.2 pounds bn - 1.2 pounds bn per week. School closure is likely to significantly exacerbate the pressures on the health system through staff absenteeism. CONCLUSION: The estimates of school closure associated absenteeism and the projected cost would be useful for pandemic planning for business continuity, and for cost effectiveness evaluation of different pandemic influenza mitigation strategies

Genomic deletion and promoter methylation status of Hypermethylated in Cancer 1 (HIC1) in mantle cell lymphoma

Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity

Distinct glutaminyl cyclase expression in Edinger–Westphal nucleus, locus coeruleus and nucleus basalis Meynert contributes to pGlu-Aβ pathology in Alzheimer’s disease

Glutaminyl cyclase (QC) was discovered recently as the enzyme catalyzing the pyroglutamate (pGlu or pE) modification of N-terminally truncated Alzheimer’s disease (AD) Aβ peptides in vivo. This modification confers resistance to proteolysis, rapid aggregation and neurotoxicity and can be prevented by QC inhibitors in vitro and in vivo, as shown in transgenic animal models. However, in mouse brain QC is only expressed by a relatively low proportion of neurons in most neocortical and hippocampal subregions. Here, we demonstrate that QC is highly abundant in subcortical brain nuclei severely affected in AD. In particular, QC is expressed by virtually all urocortin-1-positive, but not by cholinergic neurons of the Edinger–Westphal nucleus, by noradrenergic locus coeruleus and by cholinergic nucleus basalis magnocellularis neurons in mouse brain. In human brain, QC is expressed by both, urocortin-1 and cholinergic Edinger–Westphal neurons and by locus coeruleus and nucleus basalis Meynert neurons. In brains from AD patients, these neuronal populations displayed intraneuronal pE-Aβ immunoreactivity and morphological signs of degeneration as well as extracellular pE-Aβ deposits. Adjacent AD brain structures lacking QC expression and brains from control subjects were devoid of such aggregates. This is the first demonstration of QC expression and pE-Aβ formation in subcortical brain regions affected in AD. Our results may explain the high vulnerability of defined subcortical neuronal populations and their central target areas in AD as a consequence of QC expression and pE-Aβ formation

An siRNA Screen in Pancreatic Beta Cells Reveals a Role for Gpr27 in Insulin Production

The prevalence of type 2 diabetes in the United States is projected to double or triple by 2050. We reasoned that the genes that modulate insulin production might be new targets for diabetes therapeutics. Therefore, we developed an siRNA screening system to identify genes important for the activity of the insulin promoter in beta cells. We created a subclone of the MIN6 mouse pancreatic beta cell line that expresses destabilized GFP under the control of a 362 base pair fragment of the human insulin promoter and the mCherry red fluorescent protein under the control of the constitutively active rous sarcoma virus promoter. The ratio of the GFP to mCherry fluorescence of a cell indicates its insulin promoter activity. As G protein coupled receptors (GPCRs) have emerged as novel targets for diabetes therapies, we used this cell line to screen an siRNA library targeting all known mouse GPCRs. We identified several known GPCR regulators of insulin secretion as regulators of the insulin promoter. One of the top positive regulators was Gpr27, an orphan GPCR with no known role in beta cell function. We show that knockdown of Gpr27 reduces endogenous mouse insulin promoter activity and glucose stimulated insulin secretion. Furthermore, we show that Pdx1 is important for Gpr27's effect on the insulin promoter and insulin secretion. Finally, the over-expression of Gpr27 in 293T cells increases inositol phosphate levels, while knockdown of Gpr27 in MIN6 cells reduces inositol phosphate levels, suggesting this orphan GPCR might couple to Gq/11. In summary, we demonstrate a MIN6-based siRNA screening system that allows rapid identification of novel positive and negative regulators of the insulin promoter. Using this system, we identify Gpr27 as a positive regulator of insulin production

Practicing stewardship: EU biofuels policy and certification in the UK and Guatemala

Biofuels have transitioned from a technology expected to deliver numerous benefits to a highly contested socio-technical solution. Initial hopes about their potential to mitigate climate change and to deliver energy security benefits and rural development, particularly in the Global South, have unravelled in the face of numerous controversies. In recognition of the negative externalities associated with biofuels, the European Union developed sustainability criteria which are enforced by certification schemes. This paper draws on the literature on stewardship to analyse the outcomes of these schemes in two countries: the UK and Guatemala. It explores two key issues: first, how has European Union biofuels policy shaped biofuel industries in the UK and Guatemala? And second, what are the implications for sustainable land stewardship? By drawing attention to the outcomes of European demand for biofuels, we raise questions about the ability of European policy to drive sustainable land practices in these two cases. The paper concludes that, rather than promoting stewardship, the current governance framework effectively rubberstamps existing agricultural systems and serves to further embed existing inequalities