Malaria prophylaxis policy for travellers from Europe to the Indian Sub Continent

Analysis of malaria imported into eight European countries from the Indian sub-continent (ISC) (India, Pakistan, Bangladesh and Sri Lanka) led to a consensus statement on the use of chemoprophylaxis within TropNetEurop. The proportion of cases from the ISC in 2004 ranged from 1.4%–4.6% of total imported cases. Plasmodium falciparum cases reported from the eight countries was only 23 (13% of all cases from the region). Total malaria reports between 1999–2004 fell from 317 to 180. The risk of malaria in UK residents visiting the region was > 1 case per 1,000 years exposed. The group recommended non-selective prescribing of chemoprophylaxis for visitors to India, Pakistan, Bangladesh and Sri Lanka should be dropped

Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells

Chronic myeloid leukaemia (CML) is maintained by a rare population of tyrosine kinase inhibitor (TKI)-insensitive malignant stem cells. Our long-term aim is to find a BcrAbl-independent drug that can be combined with a TKI to improve overall disease response in chronic-phase CML. Omacetaxine mepesuccinate, a first in class cetaxine, has been evaluated by clinical trials in TKI-insensitive/resistant CML. Omacetaxine inhibits synthesis of anti-apoptotic proteins of the Bcl-2 family, including (myeloid cell leukaemia) Mcl-1, leading to cell death. Omacetaxine effectively induced apoptosis in primary CML stem cells (CD34<sup>+</sup>38<sup>lo</sup>) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells <i>in vitro</i>. Furthermore, the functionality of surviving stem cells following omacetaxine exposure was significantly reduced in a dose-dependant manner, as determined by colony forming cell and the more stringent long-term culture initiating cell colony assays. This stem cell-directed activity was not limited to CML stem cells as both normal and non-CML CD34<sup>+</sup> cells were sensitive to inhibition. Thus, although omacetaxine is not leukaemia stem cell specific, its ability to induce apoptosis of leukaemic stem cells distinguishes it from TKIs and creates the potential for a curative strategy for persistent disease

Aspirin and some other nonsteroidal anti-inflammatory drugs inhibit cystic fibrosis transmembrane conductance regulator protein gene expression in T-84 cells.

Cystic fibrosis (CF) is caused by mutations in the CF gene, which encodes CF transmembrane conductance regulator protein (CFTR), a transmembrane protein that acts as a cAMP-regulated chloride channel The disease is characterized by inflammation but the relationship between inflammation, abnormal transepithelial ion transport, and the clinical manifestations of CF are uncertain. The present study was undertaken to determine whether three nonsteroidal anti-inflammatory drugs (NSAIDs) (aspirin, ibuprofen, and indomethacin) modulate CFTR gene expression in T-84 cells. Treatment with NSAIDs reduced CFTR transcripts, and decreased cAMP-stimulated anion fluxes, an index of CFTR function. However, the two phenomena occurred at different concentrations of both drugs. The results indicate that NSAIDs can regulate both CFTR gene expression and the function of CFTR-related chloride transport, and suggest that NSAIDs act via multiple transduction pathways

Multimodal approach to predict neurological outcome after cardiac arrest: A single-center experience

Introduction: The aims of this study were to assess the concordance of different tools and to describe the accuracy of a multimodal approach to predict unfavorable neurological outcome (UO) in cardiac arrest patients. Methods: Retrospective study of adult (>18 years) cardiac arrest patients who underwent multimodal monitoring; UO was defined as cerebral performance category 3-5 at 3 months. Predictors of UO were neurological pupillary index (NPi) 64 2 at 24 h; highly malignant patterns on EEG (HMp) within 48 h; bilateral absence of N20 waves on somato-sensory evoked potentials; and neuron-specific enolase (NSE) > 75 \u3bcg/L. Time-dependent decisional tree (i.e., NPi on day 1; HMp on day 1-2; absent N20 on day 2-3; highest NSE) and classification and regression tree (CART) analysis were used to assess the prediction of UO. Results: Of 137 patients, 104 (73%) had UO. Abnormal NPi, HMp on day 1 or 2, the bilateral absence of N20 or NSE >75 mcg/L had a specificity of 100% to predict UO. The presence of abnormal NPi was highly concordant with HMp and high NSE, and absence of N20 or high NSE with HMp. However, HMp had weak to moderate concordance with other predictors. The time-dependent decisional tree approach identified 73/103 patients (70%) with UO, showing a sensitivity of 71% and a specificity of 100%. Using the CART approach, HMp on EEG was the only variable significantly associated with UO. Conclusions: This study suggests that patients with UO had often at least two predictors of UO, except for HMp. A multimodal time-dependent approach may be helpful in the prediction of UO after CA. EEG should be included in all multimodal prognostic models

Feasibility of a mass vaccination campaign using a two-dose oral cholera vaccine in an urban cholera-endemic setting in Mozambique.

We conducted a study to assess the feasibility and the potential vaccine coverage of a mass vaccination campaign using a two-dose oral cholera vaccine in an urban endemic neighbourhood of Beira, Mozambique. The campaign was conducted from December 2003 to January 2004. Overall 98,152 doses were administered, and vaccine coverage of the target population was 58.6% and 53.6% for the first and second rounds, respectively. The direct cost of the campaign, which excludes the price of the vaccine, amounted to slightly over 90,000 dollars, resulting in the cost per fully vaccinated person of 2.09 dollars, which is relatively high. However, in endemic settings where outbreaks are likely to occur, integrating cholera vaccination into the routine activities of the public health system could reduce such costs

In vivo methylation of mtDNA reveals the dynamics of protein–mtDNA interactions

To characterize the organization of mtDNA–protein complexes (known as nucleoids) in vivo, we have probed the mtDNA surface exposure using site-specific DNA methyltransferases targeted to the mitochondria. We have observed that DNA methyltransferases have different accessibility to different sites on the mtDNA based on the levels of protein occupancy. We focused our studies on selected regions of mtDNA that are believed to be major regulatory regions involved in transcription and replication. The transcription termination region (TERM) within the tRNALeu(UUR) gene was consistently and strongly protected from methylation, suggesting frequent and high affinity binding of mitochondrial transcription termination factor 1 (mTERF1) to the site. Protection from methylation was also observed in other regions of the mtDNA, including the light and heavy strand promoters (LSP, HSP) and the origin of replication of the light strand (OL). Manipulations aiming at increasing or decreasing the levels of the mitochondrial transcription factor A (TFAM) led to decreased in vivo methylation, whereas manipulations that stimulated mtDNA replication led to increased methylation. We also analyzed the effect of ATAD3 and oxidative stress in mtDNA exposure. Our data provide a map of human mtDNA accessibility and demonstrate that nucleoids are dynamically associated with proteins

A comparison of the physical and chemical differences between cancellous and cortical bovine bone mineral at two ages

To assess possible differences between the mineral phases of cortical and cancellous bone, the structure and composition of isolated bovine mineral crystals from young (1–3 months) and old (4–5 years) postnatal bovine animals were analyzed by a variety of complementary techniques: chemical analyses, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and 31P solid-state magic angle spinning nuclear magnetic resonance spectroscopy (NMR). This combination of methods represents the most complete physicochemical characterization of cancellous and cortical bone mineral completed thus far. Spectra obtained from XRD, FTIR, and 31P NMR all confirmed that the mineral was calcium phosphate in the form of carbonated apatite; however, a crystal maturation process was evident between the young and old and between cancellous and cortical mineral crystals. Two-way analyses of variance showed larger increases of crystal size and Ca/P ratio for the cortical vs. cancellous bone of 1–3 month than the 4–5 year animals. The Ca/(P + CO3) remained nearly constant within a given bone type and in both bone types at 4–5 years. The carbonate and phosphate FTIR band ratios revealed a decrease of labile ions with age and in cortical, relative to cancellous, bone. Overall, the same aging or maturation trends were observed for young vs. old and cancellous vs. cortical. Based on the larger proportion of newly formed bone in cancellous bone relative to cortical bone, the major differences between the cancellous and cortical mineral crystals must be ascribed to differences in average age of the crystals

Urbanization and its implications for food and farming

This paper discusses the influences on food and farming of an increasingly urbanized world and a declining ratio of food producers to food consumers. Urbanization has been underpinned by the rapid growth in the world economy and in the proportion of gross world product and of workers in industrial and service enterprises. Globally, agriculture has met the demands from this rapidly growing urban population, including food that is more energy-, land-, water- and greenhouse gas emission-intensive. But hundreds of millions of urban dwellers suffer under-nutrition. So the key issues with regard to agriculture and urbanization are whether the growing and changing demands for agricultural products from growing urban populations can be sustained while at the same time underpinning agricultural prosperity and reducing rural and urban poverty. To this are added the need to reduce greenhouse gas emissions and to build resilience in agriculture and urban development to climate change impacts. The paper gives particular attention to low- and middle-income nations since these have more than three-quarters of the world's urban population and most of its largest cities and these include nations where issues of food security are most pressing