Plasmodium possesses dynein light chain classes that are unique and conserved across species

Plasmodium belongs to the phylum Apicomplexa. Within the Apicomplexa, Plasmodium, Toxoplasma and Cryptosporidium are parasites of considerable medical importance while Theileria and Eimeria are animal pathogens. P. falciparum is particularly important as it causes malaria, resulting in more than 1 million deaths each year. The malaria parasite actively invades the host cell in which it propagates and several proteins associated with the apical organelles have been implicated to be crucial in the invasion process. The biogenesis of the apical organelles is not well understood, but several studies indicate that microtubule-based vesicular transport is involved. Vesicular transport proteins are also present in Plasmodium and are presumed to be involved in transcellular transport in infected erythrocytes. Dynein is a multi-subunit motor protein involved in microtubule-based vesicular transport. In this study, we analyzed the cytoplasmic dynein light chains (Dlcs) of P. falciparum since they provide adaptor surface to the cargoes and are likely to be involved in differential transport. Dlcs consist of three different families: TcTex1/2, LC8 and LC7/roadblock. The data presented demonstrate that P. falciparum Dlcs sequences and functional domains show high sequence similarity within the species, but that only the Dlc group 1 (LC8) has a high similarity to human orthologues. TcTex1 and LC7/roadblock have low similarity to human orthologues. This sequence variation could be targeted for vaccine or drug development.     

Phylogenetic and structural information on glyceraldehyde-3-phosphate dehydrogenase (G3PDH) in Plasmodium provides functional insights.

Plasmodium is dependent on glycolysis for ATP production. The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (G3PDH) plays an important role in glycolysis and is, therefore, a potential target for antimalarial drug development. The g3pdh gene of nine Plasmodium species was sequenced from genomic DNA and the type and origin determined by phylogenetic analysis. Substitutions were analyzed over a wide phylogenetic spectrum in relation to the known three-dimensional structures of the P. falciparum and human proteins. Substitutions were found within the functional domains (Rossman NAD+-binding and catalytic domains). A number of replacements within the adenosyl-binding surfaces were found to be conserved within the Chromoalveolates, others in the Apicomplexa, and still others within the genus Plasmodium, all of which were different from the human sequence. These sites may prove to be of functional importance and provide insights for drug-targeting studies, as have other regions examined in Leishmania and Toxoplasma G3PDH research.     

Phylogenetic analysis of the genus Plasmodium based on the gene encoding adenylosuccinate lyase.

Phylogenetic studies of the genus Plasmodium have been performed using sequences of the nuclear, mitochondrial and plastid genes. Here we have analyzed the adenylosuccinate lyase (ASL) gene, which encodes an enzyme involved in the salvage of host purines needed by malaria parasites for DNA synthesis. The ASL gene is present in several eukaryotic as well as prokaryotic organisms and does not have repeat regions, which facilitates the accuracy of the alignment. Furthermore, it has been shown that ASL is not subject to positive natural selection. We have sequenced the ASL gene of several different Plasmodium species infecting humans, rodents, monkeys and birds and used the obtained sequences along with the previously known P. falciparum ASL sequence, for structural and phylogenetic analysis of the genus Plasmodium. The genetic divergence of ASL is comparable with that observed in other nuclear genes such as cysteine proteinase, although ASL cannot be considered conserved when compared to aldolase or superoxide dismutase, which exhibit a slower rate of evolution. Nevertheless, a protein like ASL has a rate of evolution that provides enough information for elucidating evolutionary relationships. We modeled 3D structures of the ASL protein based on sequences used in the phylogenetic analysis and obtained a consistent structure for four different species despite the divergence observed. Such models would facilitate alignment in further studies with a greater number of plasmodial species or other Apicomplexa.     

ArtinM, a D-mannose-binding lectin from Artocarpus integrifolia, plays a potent adjuvant and immunostimulatory role in immunization against Neospora caninum

ArtinM and Jacalin (JAC) are lectins from the jackfruit (Artocarpus integrifolia) that have important role in modulation of immune responses to pathogens. Neospora caninum is an Apicomplexa parasite that causes neuromuscular disease in dogs and reproductive disorders in cattle, with economic impact on the livestock industry. Hence, we evaluated the adjuvant effect of ArtinM and JAC in immunization of mice against neosporosis. Six C57BL/6 mouse groups were subcutaneously immunized three times at 2-week intervals with Neospora lysate antigen (NLA) associated with lectins (NLA + ArtinM and NLA + JAC), NLA, ArtinM and JAC alone, and PBS (infection control). Animals were challenged with lethal dose of Nc-1 isolate and evaluated for morbidity, mortality, specific antibody response, cytokine production by spleen cells, brain parasite burden and inflammation. Our results demonstrated that ArtinM was able to increase NLA immunogenicity, inducing the highest levels of specific total IgG and IgG2a/IgG1 ratio, ex vivo Th1 cytokine production, increased survival, the lowest brain parasite burden, along with the highest inflammation scores. In contrast, NLA + JAC immunized group showed intermediate survival, the highest brain parasite burden and the lowest inflammation scores. In conclusion, ArtinM presents stronger immunostimulatory and adjuvant effect than Jacalin in immunization of mice against neosporosis, by inducing a protective Th1-biased pro-inflammatory immune response and higher protection after parasite challenge.     

Zoonotic babesiosis: Overview of the disease and novel aspects of pathogen identity

Babesiosis is a zoonosis caused by tick-transmitted intraerythrocytic protozoa of the Phylum Apicomplexa. The disease mostly occurs in the USA, but cases have also been reported in several European countries, in Egypt, India, Japan, Korea, Taiwan, and South Africa. The main pathological event is lysis of erythrocytes resulting in haemolytic anaemia, which in severe cases may lead to organ failure and death, particularly in immunocompromised patients. The 2 groups of parasites involved, Babesia microti-like and Babesia sensu stricto (s.s.) species, differ in their life cycle characteristics and susceptibility to antibabesial drugs. Molecular taxonomy is now making a major contribution to the identification of novel pathogens within both groups. Effective treatment of severe cases was initially hampered by the lack of specific antibabesial drugs for human use, but increased use of supportive measures and of the recently developed antimalarial, atovaquone, particularly in combination with azithromycin, has improved the prospects for management of acute disease especially when caused by Babesia s.s. species. Prevention should be based primarily on increasing the awareness of physicians and the public to the risks, but infection from blood transfusions is particularly difficult to prevent. Expanding deer populations, resulting in wider distribution and greater abundance of ticks, heightened medical awareness, and growing numbers of immunocompromised patients are likely to result in a continuing rise of reported cases.     

Examining the HIV/AIDS case management process

Eight themes in the HIV/AIDS case management process emerged from a 1998 study of 14 Ryan White Title I-funded case management programs in the New York City tri-county region. For individuals who were struggling with multiple environmental stressors, the diagnosis of HIV or AIDS was merely one of the many pressures that brought them to case management programs. Most came when they were in crisis. Using both chart reviews and focus groups with case managers and supervisors, this article reports that the activities that characterize this region's case management introduce alternative ways of thinking about the HIV/AIDS case management process.     

HIV Case Manager Preparedness for Practice in Ryan White CARE Act Funded Settings

While current research on the factors affecting the HIV epidemic within the general population has considered the role of HIV case managers, much remains to be known about case management effectiveness and how it might be enhanced. This article presents the data from a statewide survey of case management professionals in Florida. The study focused on case managers' preparation for practice and barriers to successful practice. The study results reflect a very broad educational preparation in multiple disciplines with highly varied means of case manager training and orientation at entry to practice. Further, the results highlighted the existence of multiple barriers that challenge the ability of case managers to cope with the demands of case management practice in sites serving people living with HIV/AIDS who are socially and economically challenged. The article concludes with recommendations for changes in the system that would enhance the preparation of case management professionals for entry to practice.     

Gene×Environment Interaction from Case‐Control and Case‐Case Approaches

Using the Genetic Analysis Workshop 12 data, we applied case‐control and case‐case approaches to study the effects of a major gene and its interaction with sex on the disease liability. Although no joint additive effect was simulated, the case‐case approach detected a small but significant multiplicative interaction effect, which could not be explained by the effect of random error. Given that analyses of “real” data will not be made with the knowledge of the true effects a priori, this study showed that the measure of gene×environment interaction is critical and the definition of interaction should be explicit. © 2001 Wiley‐Liss, Inc.     

东阿县新农合单病种限额支付实施效果研究

对2005年和2007年东阿县新型农村合作医疗(新农合)单病种限额支付的相关数据库资料进行分析,结果显示,目前东阿县实行单病种限额支付的病种以手术治疗为主,2005年制度实施尚不充分,病种实际次均医疗费用与支付标准差异较大,2007年实施得比2005年充分,各级别医院的病种实际次均医疗费用基本控制在支付标准以内,表明新农合实施单病种限额支付办法,对医疗费用的控制具有较好的效果。     

An organizational case study of the case manager's role in a client's return-to-work programme in Australia

The purpose of this study was to examine the case manager's role in a return-to-work programme in Sydney, Australia. The investigators examined the case manager's role assumed by occupational therapists, physiotherapists, psychologists and rehabilitation counsellors when providing occupational rehabilitation services. Files of closed cases (n=172) were examined to investigate the relationship between the case manager's profession and return-to-work outcomes. It was found that the provider of occupational rehabilitation examined in this study achieved above-average return-to-work rates (83%), with no significant difference between case managers. There was, however, a significant relationship between the client's type of injury and the case manager (p<0.001), and case length was significantly different between case managers (p=0.004). The occupational therapist had the largest case management load (43%), followed by the rehabilitation counsellor (23%). There were trends (0.05相似文献   

Stories as case knowledge: case knowledge as stories

INTRODUCTION: Every case contains a human story of illness and a medical story of disease, which together cover person management, case management, health system management and self-management. Much of that management can be learned via a thorough set of stories of typical and atypical core cases compiled by clinical teachers. Stories provide a highly flexible framework for illustrating the lessons of experience, the tips and traps for young players, and the dilemmas requiring careful judgement in the trade-offs between benefits and risks. Listening to real stories unfold is much more fun than being lectured (and better remembered). DISCUSSION: Stories illustrate 'what can happen' in a case as a guide to 'what to do'. A story begins with a real world situation with some predicament and a (causal) sequence of events or plot in which things are resolved one way or another. Patients tell their illness story; their clinician translates that into a disease story. Stories sort out what is important in such a predicament, consider the strategy and tactics of what to do, and speak about the outcomes. Each local situation provides relevance, context and circumstantial detail. Stories about case management can encapsulate practical knowledge, logical deduction, judgement and decision making, sharing with the student all the ingredients that develop expertise. Sometimes it is the plot that is important, sometimes the detail, sometimes it is the underlying message, the parable that resonates with the listener's experiences and feelings.1 Stories can also accommodate the complexity of multiple variables and the influence of other stakeholders, the uncertainties and dilemmas within the trade-offs, and the niceties of 'informed judgement'. CONCLUSION: This paper makes four points. First, clinical stories recount pointed examples of 'what happened' that expand our expertise in handling 'a case like that'. Second, cases are the unit of clinical work. Case stories expand the dimensions and details of case knowledge, case-based reasoning and case management. Carefully collated case stories can comprise the 'real life' clinical curriculum. Third, stories provide a framework for 'web' or 'net' thinking that links all the objective and subjective details within the multifaceted complexity of case management. Fourth, personal stories explain how both numerical and non-linear influences determined what decision was actually made in that case.     

The effect of outcome information on health professionals' spontaneous learning

Medical Education 2010: 44 : 962–968 Objectives Previous studies have demonstrated the presence of an outcome bias in medical decision making, which can be represented by a tendency to overweight outcome information when evaluating the quality of a decision. This study investigates whether the outcome of a previous decision on a medical case affects a later decision on a similar case. Methods Thirty‐six practising doctors and 36 nurses were presented with two superficially different but structurally identical dichotomous diagnostic problems, at intervals of about 6 weeks. The first problem was followed by the delivery of information about the outcome that could be either positive or negative. Results Of the doctors, 39% of those who received information indicating an adverse outcome in the first case modified their diagnosis in the second case, whereas none of the doctors who were given information indicating a positive outcome made an alternative diagnosis. Of the nurses, 22% of those given information of a positive outcome and 56% of those given information of a negative outcome in the first case made an alternative decision in the second case. Conclusions The results show that the outcome of a previous single case can be overweighted in the process of making a later decision about a similar case, to the point that information on outcome alone can modify a decision that the health provider originally thought to be optimal, according to his or her experience and the available evidence. Hence, outcome bias not only affects the evaluation of a decision, but can also affect learning by modifying later decisions.     

Out-patient case mix: a survey of user requirements

Research and development of out-patient case mix systems, to plan and monitor resource use in the out-patient sector, has hitherto not been accorded priority in the NHS. As part of an investigation of their usefulness, a survey of NHS professionals' requirements for out-patient case mix was conducted. The results confirmed that there was support for developing out-patient case mix systems, although different users had different requirements. However, a common theme to emerge was the desirability of constructing holistic systems which cover in-patient, day-case and out-patient care. Additionally, development of care packages was seen as a necessary first step in constructing systems for out-patient care. Concludes that visit-based case mix systems are unlikely to fulfil users' requirements and recommends that case mix contracting projects by Healthcare Resource Groups should be extended to the out-patient sector, but must recognize that existing systems do not meet users' requirements.     

Classifying disease chromosomes arising from multiple founders, with application to fine-scale haplotype mapping

The availability of high-density haplotype data has motivated several fine-scale linkage disequilibrium mapping methods for locating disease-causing mutations. These methods identify loci around which haplotypes of case chromosomes exhibit greater similarity than do those of control chromosomes. A difficulty arising in such mapping is the possibility that case chromosomes have inherited disease-causing mutations from different ancestral chromosomes (founder heterogeneity). Such heterogeneity dilutes measures of case haplotype similarity. This dilution can be mitigated by separating case chromosomes into subsets according to their putative mutation origin, and searching for an area with excessive haplotype similarity within each subset. We propose a nonparametric method for identifying subsets of case chromosomes likely to share a common ancestral progenitor. By simulation studies and application to published data, we show that the method accurately identifies relatively large subsets of chromosomes that share a common founder. We also show that the method allows more precise estimates of the disease mutation loci than obtained by other fine-scale mapping methods.     

北京市首例人禽流感H5N1病例的感染来源调查

目的 调查北京市首例人禽流感(H5N1)病例的感染来源.方法 通过对患者家属和其他关键人物访谈,检测患者标本以及流行病学关联的环境标本,对患者可能的感染来源进行追踪调查.结果 该患者在其发病前5天曾经接触过宰杀的鸭子(购自河北省燕郊某市场活禽摊位),采集该摊位及邻近活禽摊位的环境标本10份,经PCR方法检测有6份标本为H5N1亚型病毒核酸阳性,并通过鸡胚分离出5株H5N1亚型病毒.将从环境标本中分离的H5N1亚型病毒与患者体内分离的H5N1亚型病毒(禽源、属于Clade 2.3.4)进行全基因组序列比对,氨基酸同源性高达99.8%～100%.结论 流行病学和病原学双重证据表明,北京市首例人禽流感H5N1病例的感染来源为接触携带H5N1亚型禽流感病毒的鸭子.     

Analysis of secondary outcomes in nested case‐control study designs

One of the main perceived advantages of using a case‐cohort design compared with a nested case‐control design in an epidemiologic study is the ability to evaluate with the same subcohort outcomes other than the primary outcome of interest. In this paper, we show that valid inferences about secondary outcomes can also be achieved in nested case‐control studies by using the inclusion probability weighting method in combination with an approximate jackknife standard error that can be computed using existing software. Simulation studies demonstrate that when the sample size is sufficient, this approach yields valid type 1 error and coverage rates for the analysis of secondary outcomes in nested case‐control designs. Interestingly, the statistical power of the nested case‐control design was comparable with that of the case‐cohort design when the primary and secondary outcomes were positively correlated. The proposed method is illustrated with the data from a cohort in Cardiovascular Health Study to study the association of C‐reactive protein levels and the incidence of congestive heart failure. Copyright © 2014 John Wiley & Sons, Ltd.     

Strength of association for incident diabetes risk factors according to diabetes case definitions: the Atherosclerosis Risk in Communities Study

Prospective epidemiologic studies have characterized major risk factors for incident diabetes by a variety of diabetes case definitions. Whether different definitions alter the association of diabetes with risk factors is largely unknown. Using 1987-1998 data from the ongoing Atherosclerosis Risk in Communities (ARIC) Study, the authors assessed the relation of traditional risk factors with 3 different diabetes case definitions and 4 fasting glucose categories. They compared the study protocol case definition with 2 nested case definitions, self-reported diabetes and a multiple-evidence definition. Significant differences in risk factor associations by case definition and by screening cutpoints were observed. Specifically, the magnitude of the association between the risk factors (baseline metabolic syndrome, fasting glucose, blood pressure, body mass index, and serum insulin) and incident diabetes differed by case definition. Associations with these risk factors were weaker with a case definition based on self-report compared with other definitions. These results illustrate the potential limitations of case definitions that rely solely on self-report or those that incorporate measured glucose values to ascertain undiagnosed cases. Although the ability to identify risk factors of diabetes was consistent for the case definitions studied, tests of novel risk factors may result in different estimates of effect sizes depending on the definition used.