As stroke related functional measures mRS and BI

As stroke-related functional measures, mRS and BI similarly deteriorated in both groups (Fig. 4A,B), with no apparent difference. Also, given the studies suggesting favorable effects of statin on cognitive function, whether change of CDR and MMSE score differs between the two groups was of interest. In the current study, CDR score similarly deteriorated during the time course in both groups (Fig. 4C). However, decline of MMSE score tended to be less in the pravastatin group although the change was not significant (Fig. 4D), which may be in line with a previous meta-analysis, suggesting an effect of statins for mitigating decline of MMSE score (McGuinness et al., 2014). Additionally, incidence of newly diagnosed dementia was relatively low as in prior studies (Forette et al., 1998; Tzourio et al., 2003), with no significant difference between the groups. Further studies are required to define the impact of statin on cognitive function and dementia. The current study has certain limitations. First, in part because of the restriction of national health insurance system, this pim kinase inhibitor study was conducted by the PROBE method, potentially allowing for arbitrariness in the endpoint evaluation. Under such condition, we made every effort to increase accuracy of event adjudication. Particularly, all stroke and other vascular events were reviewed by the dedicated central event evaluation committees in a strictly blinded manner. Also, all events were adjudicated precisely in accordance with the predefined definition (Nagai et al., 2014), to prevent inconsistent judgment between committee members and between occasions. Second, although all stroke and other vascular events were cautiously reviewed and adverse events were eagerly collected, how lack of blinding impacted on reporting from the local centers is not known. Third, because this study was conducted as part of the clinical practice, we could not strictly prohibit the use of statins in the control group. Indeed, in part because of the study demonstrating favorable effects of statins for stroke prevention (Amarenco et al., 2006), more than 10% of patients in the control group took some kinds of statins. Inversely, nearly 20% of patients in the pravastatin group did not take pravastatin or took less than 1/4 of prescribed pravastatin. However, such protocol violations would dilute intrinsic differences between the groups and decrease the likelihood of achieving statistical significance. Under such conditions, the robustness of our analyses was tested for the per protocol analysis set (Fig. 1). By such sensitivity analysis, intergroup difference in the occurrence of atherothrombotic infarction persisted (0.15 vs. 0.55%/year, p=0.0047, adjusted HR 0.26 [95%CI 0.10 to 0.71]), supporting the reliability of our finding.
Conclusion
Author\'s Contributions The following are the supplementary data related to this article
Acknowledgments
Introduction Parasitic nematodes comprise a major group of pathogens that infect nearly one third of the human population, and compromise, or threaten, the health and productivity of most agricultural animals and plants throughout the world. The selection of anthelmintics (nematicides) that can be used for treatment and control of these pathogens is relatively limited, and acquired resistance to anthelmintics by parasitic nematodes is a growing problem (Albonico et al., 2004; Awadzi et al., 2004; Bourguinat et al., 2008; Osei-Atweneboana et al., 2007; Vercruysse et al., 2012). Consequently, a need exists to identify new parasite targets for therapeutic intervention and the nematode intestine provides a tissue to investigate for this purpose. The intestine of parasitic nematodes, and nematodes in general, is sited at an internal interface that is continuous with the outside environment. As such, the intestine is accessible to anthelmintics that can interfere with intestinal cell functions essential for survival of nematodes. The intestine has a relatively simple tubular design formed by a single cell layer of intestinal cells that resemble polarized epithelial cells (Yin et al., 2008). This single cell layer serves as a physical separation between the environment and the pseudocoelomic body cavity. Evidence indicates that a wide range of functions involved in nutrient acquisition (McGhee, 2007; Yin et al., 2008; Jasmer et al., 2015; Rosa et al., 2015), physiological homeostasis and basic defense against environmental toxins (Park et al., 2001) are all sited at the apical intestinal membrane. Intestinal cells are also a primary site for synthesis of yolk proteins that are eventually incorporated into ova (Chotard et al., 2010). Nematode intestinal cells Protein families (orthologous groups) were defined utilizing the Markov cluster algorithm (Enright et al., 2002) using the OrthoMCL also have clear importance as targets for anthelmintic therapies related to vaccines (Jasmer et al., 1993; Smith, 1993; Pearson et al., 2010), contemporary anthelmintics (Jasmer et al., 2000) and biotoxins (Wei et al., 2003). Nevertheless, the limited knowledge on biological properties of nematode intestinal cells and the extent to which those properties are conserved among parasitic species has impeded research aimed at developing new therapeutic methods directed at this tissue. Indeed, the challenges related to research on the nematode intestine extend to virtually every tissue in parasitic nematodes. Hence, methods related to solving challenges related to the intestine have application to other tissues of nematode pathogens.