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Background: Adequate malaria diagnosis and treatment remain major difficulties in rural sub-Saharan Africa. These issues deserve renewed attention in the light of first-line treatment with expensive artemisinin-combination therapy (ACT) and changing patterns of transmission intensity. This study describes diagnostic and treatment practices in Mto wa Mbu, an area that used to be hyperendemic for malaria, but where no recent assessments of transmission intensity have been conducted. Methods: Retrospective and prospective data were collected from the two major village health clinics. The diagnosis in prospectively collected data was confirmed by microscopy. The level of transmission intensity was determined by entomological assessment and by estimating sero-conversion rates using anti-malarial antibody responses. Results: Malaria transmission intensity by serological assessment was equivalent to 40% of outpatients attending the clinics in 2006-2007 were diagnosed with malaria. Prospective

Background: Despite the widespread usage of DNA microarrays, questions remain about how best to interpret the wealth of gene-by-gene transcriptional levels that they measure. Recently, methods have been proposed which use biologically defined sets of genes in interpretation, instead of examining results gene-by-gene. Despite a serious limitation, a method based on Fisher's exact test remains one of the few plausible options for gene set analysis when an experiment has few replicates, as is typically the case for prokaryotes. Results: We extend five methods of gene set analysis from use on experiments with multiple replicates, for use on experiments with few replicates. We then use simulated and real data to compare these methods with each other and with the Fisher's exact test (FET) method. As a result of the simulation we find that a method named MAXMEAN-NR maintains the nominal rate of false positive findings (type I error rate) while offering good statistical power and robustn

Background: Image-guidance systems allow accurate interfractional repositioning of IMRT treatments, however, these may require up to 15 minutes. Therefore intrafraction motion might have an impact on treatment precision. 3D geometric data regarding intrafraction prostate motion are rare; we therefore assessed its magnitude with pre- and post-treatment fiducial-based imaging with cone-beam-CT (CBCT). Methods: 39 IMRT fractions in 5 prostate cancer patients after 125I-seed implantation were evaluated. Patient position was corrected based on the 125I-seeds after pre-treatment CBCT. Immediately after treatment delivery, a second CBCT was performed. Differences in bone- and fiducial position were measured by seed-based grey-value matching. Results: Fraction time was 13.6+/-1.6minutes. Median overall displacement vector length of 125I-seeds was 3mm (M=3mm, Sigma=0.9mm, sigma=1.7mm; M: group systematic error, Sigma: SD of systematic error, sigma: SD of random error). Median displacement vecto

Background: Thymidine phosphorylase (TP) is identical with platelet-derived endothelial cell growth factor (PD-ECGF) which promotes angiogenesis. The aim of this study was to evaluate the cytosol activity of TP in tumor samples from patients with endometrial cancer. Methods: The activity of TP was measured by the spectrophotometric method in the cytosol of endometrial tumor samples from 43 patients. Moreover, the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) protein and microvessel density (MD) were examined in the same endometrial tumor samples by immunohistochemical staining. Normal endometrium from 16 women, treated surgically due to nononcological reasons served as a control. A relationship between the cytosol TP activity, PD-ECGF/TP protein expression, MD and clinicopathologic features was investigated. Results: A significantly higher the cytosol TP activity, PD-ECGF/TP protein expression and MD was stated in malignant tumor sa

Background: Theory predicts that lower dispersal, and associated gene flow, leads to decreased genetic diversity in small isolated populations, which generates adverse consequences on fitness, and subsequently on demography. Here we report for the first time this effect in a well-connected natural butterfly metapopulation with high population densities at the edge of its distribution range. Results: We demonstrate that: (1) lower genetic diversity was coupled to a sharp decrease in adult lifetime expectancy, a key component of individual fitness; (2) genetic diversity was positively correlated to number of dispersing individuals (indicative of landscape functional connectivity) and adult population size; (3) parameters inferred from capture-recapture procedures (population size and dispersal events between patches) correlated much better with genetic diversity than estimates usually used as surrogates for population size (patch area and descriptors of habitat quality) and dispersal (st

Background: Leucine-rich repeats (LRRs) are present in more than 6000 proteins. They are found in organisms ranging from viruses to eukaryotes and play an important role in protein-ligand interactions. To date, more than one hundred crystal structures of LRR containing proteins have been determined. This knowledge has increased our ability to use the crystal structures as templates to model LRR proteins with unknown structures. Since the individual three-dimensional LRR structures are not directly available from the established databases and since there are only a few detailed annotations for them, a conformational LRR database useful for homology modeling of LRR proteins is desirable. Description: We developed LRRML, a conformational database and an extensible markup language (XML) description of LRRs. The release 0.2 contains 1261 individual LRR structures, which were identified from 112 PDB structures and annotated manually. An XML structure was defined to exchange and store the LRR

: Recent progress in neuroscience revealed diverse regions of the CNS which moderate autonomic and affective responses. The ventro-medial prefrontal cortex (vmPFC) plays a key role in these regulations. There is evidence that vmPFC activity is associated with cardiovascular changes during a motor task that are mediated by parasympathetic activity. Moreover, vmPFC activity makes important contributions to regulations of affective and stressful situations. This review selectively summarizes literature in which vmPFC activation was studied in healthy subjects as well as in patients with affective disorders. The reviewed literature suggests that vmPFC activity plays a pivotal role in biopsychosocial processes of disease. Activity in vmPFC might link affective disorders, stressful environmental conditions, and immune function.

Background: The Anopheles gambiae heat shock cognate gene (hsc70B) encodes a constitutively expressed protein in the hsp70 family and it functions as a molecular chaperone for protein folding. However, the expression of hsc70B can be further induced by certain stimuli such as heat shock and infection. We previously demonstrated that the An. gambiae hsc70B is induced during o'nyong-nyong virus (ONNV) infection and subsequently suppresses ONNV replication in the mosquito. To further characterize the inducibility of hsc70B by ONNV infection in An. gambiae, we cloned a 2.6-kb region immediately 5' upstream of the starting codon of hsc70B into a luciferase reporter vector (pGL3-Basic), and studied its promoter activity in transfected Vero cells during infection with O'nyong-nyong, West Nile and La Crosse viruses. Results: Serial deletion analysis of the hsc70B upstream sequence revealed that the putative promoter is likely located in a region 1615-2150 bp upstream of the hsc70B starting c

Background: MRI is an emerging modality in the diagnosis and follow-up of patients with Pulmonary Arterial Hypertension (PAH). Derivation of stroke volume (SV) from the pulmonary flow curves is considered as a standard in this respect. Our aim was to investigate the accuracy of pulmonary artery (PA) flow for measuring SV. Methods: Thirty-four PAH patients underwent both cardiac MRI and right-sided heart catheterisation. MRI-derived SV was measured by PA flow, left (LV) and right ventricular (RV) volumes, and, in a subset of nine patients also by aortic flow. These SV values were compared to the SV obtained by invasive Fick method. Results: For SV by PA flow versus Fick, r=0.71, mean difference was -4.2 ml with limits of agreement 26.8 and -18.3 ml. For SV by LV volumes versus Fick, r=0.95, mean difference was -0.8 ml with limits of agreement of 8.7 and -10.4 ml. For SV by RV volumes versus Fick, r=0.73, mean difference -0.75 ml with limits of agreement 21.8 and -23.3 ml. In the subset

Background: Participation restriction is defined as "problems an individual may experience in involvement in life situations" and refers to the personal and societal consequences of health conditions. There is a growing interest in participation restriction because (i) problems with work or looking after others may be more concerning to individuals than the signs and symptoms of health conditions and (ii) even when poor health persists, participation may still be maintained. The natural history of participation restriction in the general population is unknown and the aim of this report is to describe change in status of person-perceived participation restriction over three years in community-dwelling adults aged 50 years and over. MethodProspective cohort study (baseline and 3-year follow-up) using postal questionnaires mailed to a population-based sample of older adults. Responders were included in this study if they completed all items of the Keele Assessment of Participation, at bot