Mahidol University

About: Mahidol University is a education organization based out in Bangkok, Nakhon Pathom, Thailand. It is known for research contribution in the topics: Population & Malaria. The organization has 23758 authors who have published 39761 publications receiving 878781 citations.

3FHL: The Third Catalog of Hard Fermi-LAT Sources

Abstract: We present a catalog of sources detected above 10 GeV by the Fermi Large Area Telescope (LAT) in the first 7 years of data using the Pass 8 event-level analysis. This is the Third Catalog of Hard Fermi-LAT Sources (3FHL), containing 1556 objects characterized in the 10 GeV–2 TeV energy range. The sensitivity and angular resolution are improved by factors of 3 and 2 relative to the previous LAT catalog at the same energies (1FHL). The vast majority of detected sources (79%) are associated with extragalactic counterparts at other wavelengths, including 16 sources located at very high redshift (z > 2). Eight percent of the sources have Galactic counterparts and 13% are unassociated (or associated with a source of unknown nature). The high-latitude sky and the Galactic plane are observed with a flux sensitivity of 4.4 to 9.5 ×10 −11 ph cm −2 s −1 , respectively (this is approximately 0.5 % and 1 % of the Crab Nebula flux above 10 GeV). The catalog includes 214 new γ-ray sources. The substantial increase in the number of photons (more than 4 times relative to 1FHL and 10 times to 2FHL) also allows us to measure significant spectral curvature for 32 sources and find flux variability for 163 of them. Furthermore, we estimate that for the same flux limit of 10 −12 erg cm −2 s −1 , the energy range above 10 GeV has twice as many sources as above 50 GeV, highlighting the importance, for future Cherenkov telescopes, of lowering the energy threshold as much as possible.

Molecular and Pharmacological Determinants of the Therapeutic Response to Artemether-Lumefantrine in Multidrug-Resistant Plasmodium falciparum Malaria

Abstract: The emergence of drug resistance in Plasmodium falciparum has significantly undermined malaria-control programs in countries where it is endemic [1]. To ensure high cure rates and to combat this threat, the World Health Organization (WHO) has recommended the use of artemisinin combination therapy (ACT), although debate regarding the most suitable combination and how ACTs should be deployed and funded still continues. Artemisinins ensure rapid reduction of the initial infecting biomass, with the residual parasites being removed by a more slowly eliminated component usually included in combination therapy. The rationale supporting the use of ACT is improvement of anti-malarial efficacy, facilitation of adherence to a full treatment course, and minimization of selection of drug-resistant parasites. Artemether-lumefantrine (AL) is currently the only combination therapy widely available that is manufactured to Good Manufacturing Practice standards in a fixed-dose preparation (each tablet contains 20 mg of artemether and 120 mg of lumefantrine). The fixed-dose regimen ensures that malaria parasites always encounter artemether and metabolites in the presence of lumefantrine and provides protection against the emergence of resistance to both components, but absorption of the lipophilic lumefantrine is erratic, and the drug needs to be administered twice per day [2]. Therapeutic levels are more reliably achieved by coadministration with a fatty meal and by extending the treatment course from 4 to 6 doses [3-5]. The WHO now advocates the higher, 6-dose regimen for the treatment of P. falciparum malaria in all areas, irrespective of the levels of host immunity or prevalence of multidrug resistance. On the western border of Thailand, P. falciparum has become resistant to chloroquine, sulfadoxine-pyrimethamine, mefloquine, and halofantrine [6], although there have been no convincing reports of clinical resistance to the artemisinin derivatives. In studies conducted to determine the molecular basis of mefloquine resistance, we have highlighted a central role of amplification of pfmdr1 [7]. In vitro cross-resistance has been observed between lumefantrine, mefloquine, and halofantrine, and subsequent molecular studies have suggested a common mechanism of resistance [8]. We hypothesized that pfmdr1 polymorphisms would also contribute to treatment failure following AL treatment. To investigate the relative contributions of host, pharmacokinetic, and parasitological factors in determining therapeutic outcome following treatment with AL, we analyzed the cumulative AL experience at the Shoklo Malaria Research Unit (SMRU; Mae Sod, Tak Province, Thailand) between 1995 and 2002.

A variant in the CD209 promoter is associated with severity of dengue disease.

Abstract: Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells. Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 x 10(-7)) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 x 10(-6)). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies.

Role of the Acetabular Labrum and the Iliofemoral Ligament in Hip Stability: An in vitro Biplane Fluoroscopy Study

Abstract: BackgroundRecent biomechanical reports have described the function of the acetabular labrum and iliofemoral ligament in providing hip stability, but the relative stability provided by each structure has not been well described.HypothesisBoth the iliofemoral ligament and acetabular labrum are important for hip stability by limiting external rotation and anterior translation, with increased stability provided by the iliofemoral ligament compared with the acetabular labrum.Study DesignControlled laboratory study.MethodsFifteen fresh-frozen male cadaveric hips were utilized for this study. Each specimen was selectively skeletonized down to the hip capsule. Four tantalum beads were embedded into each femur and pelvis to accurately measure hip translations and rotations using biplane fluoroscopy while either a standardized 5 N·m external or internal rotation torque was applied. The hips were tested in 4 hip flexion angles (10° of extension, neutral, and 10° and 40° of flexion) in the intact state and then by se...

Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications.

Abstract: Malaria is associated with a reduction in the systemic clearance and apparent volume of distribution of the cinchona alkaloids; this reduction is proportional to the disease severity. There is increased plasma protein binding, predominantly to alpha 1-acid glycoprotein, and elimination half-lives (in healthy adults quinine t1/2z = 11 hours, quinidine t1/2z = 8 hours) are prolonged by 50%. Systemic clearance is predominantly by hepatic biotransformation to more polar metabolites (quinine 80%, quinidine 65%) and the remaining drug is eliminated unchanged by the kidney. Quinine is well absorbed by mouth or following intramuscular injection even in severe cases of malaria (estimated bioavailability more than 85%). Quinine and chloroquine may cause potentially lethal hypotension if given by intravenous injection. Chloroquine is extensively distributed with an enormous total apparent volume of distribution (Vd) more than 100 L/kg, and a terminal elimination half-life of 1 to 2 months. As a consequence, distribution rather than elimination processes determine the blood concentration profile of chloroquine in patients with acute malaria. Parenteral chloroquine should be given either by continuous intravenous infusion, or by frequent intramuscular or subcutaneous injections of relatively small doses. Oral bioavailability exceeds 75%. Amodiaquine is a pro-drug for the active antimalarial metabolite desethylamodiaquine. Its pharmacokinetic properties are similar to these of chloroquine although the Vd is smaller (17 to 34 L/kg) and the terminal elimination half-life is 1 to 3 weeks.