Cotrimoxazole for childhood febrile illness in Malaria-endemic regions

The efficacy of co-trimoxozole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P. falciparum parasitaemia, 37% of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection, were treated with 20 mglkg co-trimoxazole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and symptoms were rapidly abolished and improvement was maintained during follow-up for 14 days. Co-trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic, resources are few, and diagnosis must rely on clinical findings alone

The labor market regimes of Denmark and Norway – one Nordic model?

The literature on the Danish and Norwegian labor market systems emphasizes the commonalities of the two systems. We challenge this perception by investigating how employers in multinational companies in Denmark and Norway communicate with employees on staffing changes. We argue that the development of ‘flexicurity’ in Denmark grants Danish employers considerably greater latitude in engaging in staffing changes than its Nordic counterpart, Norway. Institutional theory leads us to suppose that large firms located in the Danish setting will be less likely to engage in employer–employee communication on staffing plans than their Norwegian counterparts. In addition, we argue that in the Danish context indigenous firms will have a better insight into the normative and cognitive aspects to flexicurity than foreign-owned firms, meaning that they are more likely to engage in institutional entrepreneurialism than their foreign owned counterparts. We supplement institutional theory with an actor perspective in order to take into account the role of labor unions. Our analysis is based on a survey of 203 firms in Norway and Denmark which are either indigenous multinational companies or the subsidiaries of foreign multinational companies. The differences we observe cause us to conclude that the notion of a common Nordic model is problematic

Multiple FadD Acyl-CoA Synthetases Contribute to Differential Fatty Acid Degradation and Virulence in Pseudomonas aeruginosa

A close interconnection between nutrient metabolism and virulence factor expression contributes to the pathophysiology of Pseudomonas aeruginosa as a successful pathogen. P. aeruginosa fatty acid (FA) degradation is complicated with multiple acyl-CoA synthetase homologs (FadDs) expressed in vivo in lung tissue during cystic fibrosis infections. The promoters of two genetically linked P. aeruginosa fadD genes (fadD1 and fadD2) were mapped and northern blot analysis indicated they could exist on two different transcripts. These FadDs contain ATP/AMP signature and FA-binding motifs highly homologous to those of the Escherichia coli FadD. Upon introduction into an E. coli fadD-/fadR- double mutant, both P. aeruginosa fadDs functionally complemented the E. coli fadD-/fadR- mutant, allowing degradation of different chain-length FAs. Chromosomal mutagenesis, growth analysis, induction studies, and determination of kinetic parameters suggested that FadD1 has a substrate preference for long-chain FAs while FadD2 prefers shorter-chain FAs. When compared to the wild type strain, the fadD2 mutant exhibited decreased production of lipase, protease, rhamnolipid and phospholipase, and retardation of both swimming and swarming motilities. Interestingly, fadD1 mutant showed only increased swarming motility. Growth analysis of the fadD mutants showed noticeable deficiencies in utilizing FAs and phosphatidylcholine (major components of lung surfactant) as the sole carbon source. This defect translated into decreased in vivo fitness of P. aeruginosa in a BALB/c mouse lung infection model, supporting the role of lipids as a significant nutrient source for this bacterium in vivo

Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig

Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus

The etiology of dental anomalies is multifactorial; and genetic and environmental factors that affect the dental lamina have been implicated. We investigated two families of European ancestry in which males were affected by taurodontism, microdontia and dens invaginatus. In both families, males were related to each other via unaffected females. A linkage analysis was conducted in a New Zealand family, followed by exome sequencing and focused analysis of the X-chromosome. In a US family, exome sequencing of the X-chromosome was followed by Sanger sequencing to conduct segregation analyses. We identified two independent missense variants in KIF4A that segregate in affected males and female carriers. The variant in a New Zealand family (p.Asp371His) predicts the substitution of a residue in the motor domain of the protein while the one in a US family (p.Arg771Lys) predicts the substitution of a residue in the domain that interacts with Protein Regulator of Cytokinesis 1 (PRC1). We demonstrated that the gene is expressed in the developing tooth bud during development, and that the p.Arg771Lys variant influences cell migration in an in vitro assay. These data implicate missense variations in KIF4A in a pathogenic mechanism that causes taurodontism, microdontia and dens invaginatus phenotypes

Molecular Pathogenesis and Therapy of Polycythemia Induced in Mice by JAK2 V617F

BACKGROUND: A somatic activating mutation (V617F) in the JAK2 tyrosine kinase was recently discovered in the majority of patients with polycythemia vera (PV), and some with essential thrombocythemia (ET) and chronic idiopathic myelofibrosis. However, the role of mutant JAK2 in disease pathogenesis is unclear. METHODS AND FINDINGS: We expressed murine JAK2 WT or V617F via retroviral bone marrow transduction/transplantation in the hematopoietic system of two different inbred mouse strains, Balb/c and C57Bl/6 (B6). In both strains, JAK2 V617F, but not JAK2 WT, induced non-fatal polycythemia characterized by increased hematocrit and hemoglobin, reticulocytosis, splenomegaly, low plasma erythropoietin (Epo), and Epo-independent erythroid colonies. JAK2 V617F also induced leukocytosis and neutrophilia that was much more prominent in Balb/c mice than in B6. Platelet counts were not affected in either strain despite expression of JAK2 V617F in megakaryocytes and markedly prolonged tail bleeding times. The polycythemia tended to resolve after several months, coincident with increased spleen and marrow fibrosis, but was resurrected by transplantation to secondary recipients. Using donor mice with mutations in Lyn, Hck, and Fgr, we demonstrated that the polycythemia was independent of Src kinases. Polycythemia and reticulocytosis responded to treatment with imatinib or a JAK2 inhibitor, but were unresponsive to the Src inhibitor dasatinib. CONCLUSIONS: These findings demonstrate that JAK2 V617F induces Epo-independent expansion of the erythroid lineage in vivo. The fact that the central erythroid features of PV are recapitulated by expression of JAK2 V617F argues that it is the primary and direct cause of human PV. The lack of thrombocytosis suggests that additional events may be required for JAK2 V617F to cause ET, but qualitative platelet abnormalities induced by JAK2 V617F may contribute to the hemostatic complications of PV. Despite the role of Src kinases in Epo signaling, our studies predict that Src inhibitors will be ineffective for therapy of PV. However, we provide proof-of-principle that a JAK2 inhibitor should have therapeutic effects on the polycythemia, and perhaps myelofibrosis and hemostatic abnormalities, suffered by MPD patients carrying the JAK2 V617F mutation

Reversal of the ΔdegP Phenotypes by a Novel rpoE Allele of Escherichia coli

RseA sequesters RpoE (σE) to the inner membrane of Escherichia coli when envelope stress is low. Elevated envelope stress triggers RseA cleavage by the sequential action of two membrane proteases, DegS and RseP, releasing σE to activate an envelope stress reducing pathway. Revertants of a ΔdegP ΔbamB strain, which fails to grow at 37°C due to high envelope stress, harbored mutations in the rseA and rpoE genes. Null and missense rseA mutations constitutively hyper-activated the σE regulon and significantly reduced the major outer membrane protein (OMP) levels. In contrast, a novel rpoE allele, rpoE3, resulting from the partial duplication of the rpoE gene, increased σE levels greater than that seen in the rseA mutant background but did not reduce OMP levels. A σE-dependent RybB::LacZ construct showed only a weak activation of the σE pathway by rpoE3. Despite this, rpoE3 fully reversed the growth and envelope vesiculation phenotypes of ΔdegP. Interestingly, rpoE3 also brought down the modestly activated Cpx envelope stress pathway in the ΔdegP strain to the wild type level, showing the complementary nature of the σE and Cpx pathways. Through employing a labile mutant periplasmic protein, AcrAL222Q, it was determined that the rpoE3 mutation overcomes the ΔdegP phenotypes, in part, by activating a σE-dependent proteolytic pathway. Our data suggest that a reduction in the OMP levels is not intrinsic to the σE-mediated mechanism of lowering envelope stress. They also suggest that under extreme envelope stress, a tight homeostasis loop between RseA and σE may partly be responsible for cell death, and this loop can be broken by mutations that either lower RseA activity or increase σE levels

Postnatal depression in Southern Brazil: prevalence and its demographic and socioeconomic determinants

<p>Abstract</p> <p>Background</p> <p>Studies investigating the prevalence of postnatal depression (PND) show rates ranging from 5% to 36.7%. The investigation of age, race, educational levels, religion and income as risk factors for PND has yielded conflicting results. The aim of this study is to investigate the prevalence of PND in women residing in Southern Brazil and the associated risk factors.</p> <p>Methods</p> <p>This is population-based cross-sectional study of women residing in Porto Alegre who delivered in June 2001. A sample of 271 participants were selected from the Record of Living Newborn Infants of the State Health Department (the official Brazilian database and stores the name and address of all women who give birth to living newborn infants) using a process based on pseudo-random numbers which choose a random sample from 2.000 records. Once the addresses were identified, the women were visited at their place of residence (home, hotel, boarding house and prison), with the interviews taking place between the 6^thand the 8^thweek after delivery.</p> <p>The association between the risk factors and PND was investigated through bivariate analysis using Pearson's chi-square test. Student's t-test was used to analyze the continuous variables. To identify independent risk factors, multivariate analysis was performed using hierarchical levels with a predefined model that took into account the time relationship between PND and the risk factors. Cox's regression was used to calculate the prevalence ratios.</p> <p>Results</p> <p>The PND prevalence rate found was 20.7% (CI 95% 15.7 – 25.7). After adjusting for confounding variables, per capita income was found to have a significant association with PND.</p> <p>Conclusion</p> <p>The prevalence of PND is higher than the figures found in most developed countries and similar to the figures found in developing countries. Differences in PND by regions or countries can be partially explained by the effect of income on the mediation of risk factors. In low income populations, women should be routinely evaluated for postnatal depression, and those with no partner or spouse are likely to require further care from health services and should be given the benefit of mental health prevention programs.</p