A Comparative Study of Dihydroartemisin in Compounds in Treatment of Uncomplicated Falciparum Malaria in Kampong of Cambodia

Objective: To compare the safety and efficacy of two compounds of dihydroartemisinin(DHA) -Artekin and Artekin (T) in the treatment of uncomplicated falciparum malaria. Methods:The regimen of 8-tablet for 2 days of Artekin and Artekin (T) were applied to 100 patients with uncomplicated falciparum malaria, who were randomly divided into two groups. Each group contained 50 cases. The cure rate, the mean parasites clearance time, the mean fever clearance and side-effects were observed to assess the safety and efficacy of the compounds used. Results: The mean parasites clearance time was 31. 7±9.0 hours in the Artekin group and 32. 8±8. 8 hours in Artekin (T) group respectively; the mean fever clearance time was 12. 7±7. 2 hours in Artekin group and 16. 5±7. 9 hours in Artekin (T) group; there were no recrudescence case in both groups within the 28 days of follow-up, the cure rates in Artekin group and Artekin (T) groups were 100%. It indicated that the tolerability of both compounds were very good, the     

The Socioeconomic Impacts of Clinically Diagnosed Haemorrhagic Septicaemia on Smallholder Large Ruminant Farmers in Cambodia

Haemorrhagic septicaemia (HS) is an acute fatal infectious disease of mainly cattle and buffalo and outbreaks occur commonly in Cambodia. Disease outbreak reports were examined to select five villages from three provinces for a retrospective investigation of HS epidemiology and socioeconomic impact on smallholders, with an aim of identifying potential benefits from improving disease prevention through biosecurity and vaccination. The Village Animal Health Worker (VAHW) or Chief in each village and 66 affected smallholders were surveyed. At the village level, 24% of all households were affected with an estimated mean village herd morbidity of 10.1% and mortality of 28.8%. Affected farmers reported HS disease morbidity and mortality at 42.7% and 63.6% respectively. Buffalo had a higher morbidity (OR = 2.3; P = 0.003) and mortality (OR = 6.9; P < 0.001) compared with cattle, and unvaccinated large ruminants a higher morbidity (OR = 2.9; P = 0.001). The financial impact varied depending on whether the animal survived, provision of treatment, draught replacement and lost secondary income. The mean cost per affected household was USD 952.50 based on ownership of five large ruminants. The impact per affected animal was USD 375.00, reducing the pre‐disease value by 66.1%. A partial budget revealed an overwhelming incentive for farmers to practice biannual vaccination, with a net benefit of USD 951.58 per household based on an annual disease incidence rate of 1. Sensitivity analysis showed that a net benefit of USD 32.42 remained based on an outbreak every 20 years. This study indicates HS can cause a catastrophic financial shock to smallholders and remains a critical constraint to improving large ruminant productivity and profitability. Addressing HS disease control requires a focus on improving smallholder farmer knowledge of biosecurity and vaccination and should be priority to stakeholders interested in addressing regional food insecurity and poverty reduction.     

高度疟疾流行区快速控制疟疾试验

[目的]探索在高度疟疾流行区快速控制疟疾的策略与方法.[方法]2004-2005两年期间,选择柬埔寨石居省疟疾高度流行区及其周边地带作为灭源灭疟试验区,共62个自然村21 343人口.在对当地疟疾流行情况进行了细致调查的基础上,采取三项主要灭源措施:①疟疾现症病人采用复方青蒿素(Artequick,ATQ)方案治疗,发热病人亦以此作假定性治疗;②儿童带虫率≥20%的17个村采用ATQ方案进行一次全民治疗;③儿童带虫率≥6%的27个村采用低剂量伯氨喹全民服药,每10d 1次,连续6个月.组织村抗疟员执行以上灭源措施.监测17个疫源村的人群带虫率,每6个月监测1次.[结果]采取灭源措施2年后,儿童带虫率从55.8%下降为5.3%:其中恶性疟带虫率由37.0%下降为2.3%;间日疟加三日疟带虫率由18.9%下降为3.0%;儿童恶性疟配子体带虫率由13.1%下降为1.2%.有8个村儿童恶性疟带虫率由采取措施前的平均46.5%下降至0.成人带虫率的改变与儿童带虫率改变相似,由46.5%降为6.3%;恶性疟带虫率由采取措施前的平均34.2%下降为2.5%,间日疟加三日疟带虫率由12.3%降为3.8%.[结论]灭源灭疟法有别于以控制蚊媒为主的传统方法,是一种又快又省钱的新方法和新策略,可在较短时间内扭转疟疾的高度流行,直至彻底消灭疟疾,值得在广大高疟区推广应用.     

Evidence against stabilization of the transition state oxyanion by a pKa-perturbed RNA base in the peptidyl transferase center

The crystal structure of the ribosomal 50S subunit from Haloarcula marismortui in complex with the transition state analog CCdA-phosphate-puromycin (CCdApPmn) led to a mechanistic proposal wherein the universally conversed A2451 in the ribosomal active site acts as an "oxyanion hole" to promote the peptidyl transferase reaction [Nissen, P., Hansen, J., Ban, N., Moore, P.B., and Steitz, T.A. (2000) Science 289, 920-929]. In the model, close proximity (3 A) between the A2451 N3 and the nonbridging phosphoramidate oxygen of CCdApPmn suggested that the carbonyl oxyanion formed during the tetrahedral transition state is stabilized by hydrogen bonding to the protonated A2451 N3, the pKa of which must be perturbed substantially. We characterize the contribution of the putative hydrogen bond between the N3 of A2451 and the nonbridging phosphoramidate oxygen by using chemical protection and peptidyl transfer inhibition assays. If this putative hydrogen bond makes a significant thermodynamic contribution, then CCdApPmn-binding affinity to the 50S ribosomal subunit should be strongly pH-dependent, with affinity increasing as the pH is lowered. We report that CCdApPmn binds 50S ribosomes with essentially equal affinity at all pH values between 5.0 and 8.5. These data argue against a mechanism for peptidyl transfer in which a residue with near neutral pKa stabilizes the transition-state oxyanion, at least to the extent that CCdApPmn accurately mimics the transition state.     

A protocol for the differentiation of human embryonic stem cells into dopaminergic neurons using only chemically defined human additives: Studies in vitro and in vivo

Our ability to use human embryonic stem (hES) cells in cell replacement therapy for Parkinson's disease depends on the discovery of ways to simply and reliably differentiate a dopaminergic (DA) phenotype in these cells. Although several protocols exist for the differentiation of DA traits in hES, they involve the prolonged use of complex media with undefined components, cell conditioned media and/or co-culture with various cells, usually of animal origin. In this study, several well-characterized (H9, BG01) and several new uncharacterized (HUES7, HUES8) hES cell lines were studied for their capacity to differentiate into DA neurons in culture using a novel rapid protocol which uses only chemically-defined human-derived media additives and substrata. Within 3 weeks, cells from all 4 cell lines progressed from the undifferentiated state to beta-tubulin III positive cells expressing DA markers in vitro. Moreover, transplantation of these cells into the striata of 6-hydroxydopamine-treated rats at the neuronal progenitor stage resulted in the appearance of differentiated DA traits in vivo 2-3 weeks later.     

Improvement in Smallholder Farmer Knowledge of Cattle Production,Health and Biosecurity in Southern Cambodia between 2008 and 2010

Farmer knowledge surveys were conducted in 2008 and 2010 in Cambodia to evaluate the impact of a research project studying interventions that can improve cattle production and health, including biosecurity and practices relating to risks of transmission of transboundary diseases. The project hypothesis is that by increasing the value of smallholder‐owned large ruminants through nutritional interventions and improved marketing, knowledge‐based interventions including risk management for infectious diseases such as foot‐and‐mouth disease (FMD) can be implemented into a more sustainable pathway for rural development. Between 2008 and 2010, significant improvements in farmer knowledge and attitudes were recorded in three villages in three provinces of southern Cambodia. This was achieved through participatory ‘applied field research’, ‘on the job’ training plus ‘formal’ training programmes. No cases of FMD were recorded during the study period in the ‘high‐intervention’ (HI) villages despite the common occurrence of the disease in a nearby ‘low‐intervention’ and many other villages in the three provinces. Whilst it is likely that protection of these villages from FMD infection was from increasing the herd immunity by vaccination, it could also have been partly because of a decrease in risk behaviours by farmers as a result of their increasing knowledge of biosecurity. The research indicates that smallholder farmers are motivated by nutritional interventions that improve the value of their cattle ‘bank’ and offer better marketing opportunities. This provides a more receptive environment for introduction of disease risk management for infectious and other production limiting diseases, best implemented for smallholder farmers in Cambodia by intensive training programmes. In lieu of a widespread public awareness programme to deliver mass education of smallholder farmers in disease prevention and biosecurity, livestock development projects in South‐East Asia should be encouraged to include training in disease risk management as an important intervention if the current momentum for trade in large ruminant livestock and large ruminant meat is to continue to progress and contribute to addressing global food security concerns.     

Magnetopneumography: a general review

Magnetopneumography is the study of the remanent magnetism of foreign intrathoracic ferromagnetic particles after magnetization by an external magnetic field. Given knowledge of the magnetic characteristics of the inhaled particles, this highly sensitive and non-invasive technique allows the measurement of lung dust loads. Many groups of workers have been examined in this way, e.g. welders, coalminers, asbestos, foundry and steel workers. Magnetopneumography also allows analysis of the distribution of aerocontaminants in the different anatomical structures and, when repeated, the study of clearance speeds and migration from site to site of such particles. Emphasis has been laid on the importance of study of the fading of the remanent magnetic signal as time elapses. This short-term phenomenon, called relaxation, seems highly significant for the study of the dynamic properties of the immediate environment of extra pulmonary particles and especially for the study of macrophage activity.     

RNA sequence analysis defines Dicer's role in mouse embryonic stem cells

Short RNA expression was analyzed from Dicer-positive and Dicer-knockout mouse embryonic [corrected] stem (ES) cells, using high-throughput pyrosequencing. A correlation of miRNA quantification with sequencing frequency estimates that there are 110,000 miRNAs per ES cell, the majority of which can be accounted for by six distinct miRNA loci. Four of these miRNA loci or their human homologues have demonstrated roles in cell cycle regulation or oncogenesis, suggesting that a major function of the miRNA pathway in ES cells may be to shape their distinct cell cycle. Forty-six previously uncharacterized miRNAs were identified, most of which are expressed at low levels and are less conserved than the set of known miRNAs. Low-abundance short RNAs matching all classes of repetitive elements were present in cells lacking Dicer, although the production of some SINE- and simple repeat-associated short RNAs appeared to be Dicer-dependent. These and other Dicer-dependent sequences resembled miRNAs. At a depth of sequencing that approaches the total number of 5' phosphorylated short RNAs per cell, miRNAs appeared to be Dicer's only substrate. The results presented suggest a model in which repeat-associated miRNAs serve as host defenses against repetitive elements, a function canonically ascribed to other classes of short RNA.     

Purified mouse dopamine neurons thrive and function after transplantation into brain but require novel glial factors for survival in culture

Cell replacement therapy in Parkinson's disease depends on a reliable source of purified dopamine (DA) neurons (PDN) and the identification of factors relevant to their survival. Our goal was to genetically tag and purify by flow cytometry embryonic midbrain DA neurons from a transgenic mouse line carrying 11 kb of human tyrosine hydroxylase promoter driving expression of the enhanced green fluorescent protein(GFP) for studies in vivo and in vitro. A 99% purification of GFP+ cells was achieved. When transplanted into 6-hydroxydopamine-treated rat striatum, PDN survived, became well-integrated and produced recovery from amphetamine-induced motor behaviors. However, when grown in culture, PDN died within days of plating. No known growth factors prevented PDN death as did incubation with novel factors in glia/glial-conditioned media. We conclude that GFP-tagged DA neurons can be purified to homogeneity and can survive and function when grown with glial factors in vitro or after transplantation in vivo.