107 research outputs found
Argemone mexicana decoction for the treatment of uncomplicated falciparum malaria
A prospective, dose-escalating, quasi-experimental clinical trial was conducted with a traditional healer using a decoction of Argemone mexicana for the treatment of malaria in Mali. The remedy was prescribed in three regimens: once daily for 3 days (Group A; n = 23); twice daily for 7 days (Group B; n = 40); and four times daily for the first 4 days followed by twice daily for 3 days (Group C; n = 17). Thus, 80 patients were included, of whom 80% were aged 2000/μl but no signs of severe malaria. The proportions of adequate clinical response (ACR) at Day 14 were 35%, 73% and 65% in Groups A, B and C, respectively (P = 0.011). At Day 14, overall proportions of ACR were lower in children aged 5 years (81%) (P = 0.027). Very few patients had complete parasite clearance, but at Day 14, 67% of patients with ACR had a parasitaemia <2000/μl. No patient needed referral for severe disease. Only minor side effects were observed. Further research should determine whether this local resource could represent a first-aid home treatment in remote area
Large-Eddy Simulations of Fluid and Magnetohydrodynamic Turbulence Using Renormalized Parameters
In this paper a procedure for large-eddy simulation (LES) has been devised
for fluid and magnetohydrodynamic turbulence in Fourier space using the
renormalized parameters. The parameters calculated using field theory have been
taken from recent papers by Verma [Phys. Rev. E, 2001; Phys. Plasmas, 2001]. We
have carried out LES on grid. These results match quite well with direct
numerical simulations of . We show that proper choice of parameter is
necessary in LES.Comment: 12 pages, 4 figures: Proper figures inserte
Host Defense against Viral Infection Involves Interferon Mediated Down-Regulation of Sterol Biosynthesis
Upon infection, our immune cells produce a small protein called interferon, which in turn signals a protective response through a series of biochemical reactions that involves lowering the cells' ability to make cholesterol by targeting a gene essential for controlling the pathway for cholesterol metabolism
Pre-hospital risk factors for inpatient death from severe febrile illness in Malian children.
BACKGROUND: Inpatient case fatality from severe malaria remains high in much of sub-Saharan Africa. The majority of these deaths occur within 24 hours of admission, suggesting that pre-hospital management may have an impact on the risk of case fatality. METHODS: Prospective cohort study, including questionnaire about pre-hospital treatment, of all 437 patients admitted with severe febrile illness (presumed to be severe malaria) to the paediatric ward in Sikasso Regional Hospital, Mali, in a two-month period. FINDINGS: The case fatality rate was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were associated with significantly higher mortality. In multiple logistic regression models and in a survival analysis to examine pre-admission risk factors for case fatality, the only consistent and significant risk factor was sex. Girls were twice as likely to die as boys (AOR 2.00, 95% CI 1.08-3.70). There was a wide variety of pre-hospital treatments used, both modern and traditional. None had a consistent impact on the risk of death across different analyses. Reported use of traditional treatments was not associated with post-admission outcome. INTERPRETATION: Aside from well-recognised markers of severity, the main risk factor for death in this study was female sex, but this study cannot determine the reason why. Differences in pre-hospital treatments were not associated with case fatality
An Interferon Regulated MicroRNA Provides Broad Cell-Intrinsic Antiviral Immunity through Multihit Host-Directed Targeting of the Sterol Pathway.
In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. In contrast, antiviral mechanisms initiated by interferon (IFN) signaling predominate in mammals. Whilst mammalian IFN-induced miRNA are known to inhibit specific viruses, it is not known whether host-directed microRNAs, downstream of IFN-signaling, have a role in mediating broad antiviral resistance. By performing an integrative, systematic, global analysis of RNA turnover utilizing 4-thiouridine labeling of newly transcribed RNA and pri/pre-miRNA in IFN-activated macrophages, we identify a new post-transcriptional viral defense mechanism mediated by miR-342-5p. On the basis of ChIP and site-directed promoter mutagenesis experiments, we find the synthesis of miR-342-5p is coupled to the antiviral IFN response via the IFN-induced transcription factor, IRF1. Strikingly, we find miR-342-5p targets mevalonate-sterol biosynthesis using a multihit mechanism suppressing the pathway at different functional levels: transcriptionally via SREBF2, post-transcriptionally via miR-33, and enzymatically via IDI1 and SC4MOL. Mass spectrometry-based lipidomics and enzymatic assays demonstrate the targeting mechanisms reduce intermediate sterol pathway metabolites and total cholesterol in macrophages. These results reveal a previously unrecognized mechanism by which IFN regulates the sterol pathway. The sterol pathway is known to be an integral part of the macrophage IFN antiviral response, and we show that miR-342-5p exerts broad antiviral effects against multiple, unrelated pathogenic viruses such Cytomegalovirus and Influenza A (H1N1). Metabolic rescue experiments confirm the specificity of these effects and demonstrate that unrelated viruses have differential mevalonate and sterol pathway requirements for their replication. This study, therefore, advances the general concept of broad antiviral defense through multihit targeting of a single host pathway
Scientific Periodicals : The Philosophical Transactions and the Edinburgh Medical Journal
Peer reviewe
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