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  • RNA seq results also support the similarity between ESC and


    RNA-seq results also support the similarity between ESC- and YS-derived B-1 progenitors. Bmi1 expression, known as an important gene for self-renewal ability in stem cells, was reduced in ESC-derived B cells compared with YS-derived B cells, and Bmi1 overexpression improved the engraftment of ESC-derived B cells in the recipient mice. Our result is similar to the report that inducing Bmi1 into adult BM erythroblasts enhanced self-renewal ability extensively (Kim et al., 2015). Thus, Bmi1 may also play a role in the self-renewal ability of B-1 cells. Of note, there was a variation of engraftment efficiency among B cells derived from regular ESCs (Figures 1C, 5B, and 5C ES total). Since B-progenitors differentiate into mature IgM+ cells by interacting stromal cells and cytokines in the BM and spleen, the differentiation capacity and characteristics of each ESC line could be important factors for the engraftment, and Bmi1-overexpression may have helped this differentiation process as was seen in vitro experiments (Figure 5F). The clinical importance of human B-1 cells has attracted attention based on the methods to isolate the human counterpart of mouse B-1 cells (Griffin et al., 2011, Griffin and Rothstein, 2011). Since BM HSCs do not reconstitute B-1a cells, patients after BM transplantation may lack B-1 cells if human B-1 cells have similar characteristics with mouse B-1 cells. Indeed, it has been reported that patients who develop graft versus host disease following stem cell transplantation are at high risk for developing sepsis from encapsulated bacteria, associated with deficiency of human B-1-like cells that normally produce natural PHA-665752 to these bacteria (Moins-Teisserenc et al., 2013). Therefore, PSC-derived B-1 cells could theoretically be an important source of cell therapy for these patients in the future.
    Experimental Procedures
    Author Contributions
    Introduction Hypertension is the most prevalent cardiovascular risk factor worldwide. Despite its prevalence, evaluation and management are rather erratic among physicians worldwide. Guidelines from scientific societies aim to provide standardized recommendations based on the scientific evidence available. In addition, several expert-based recommendations are provided in these documents, a situation that can lead to confusion. The scope of this article is to briefly compare the American College of Cardiology (ACC) /American Heart Association (AHA) guidelines and the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines for the management of arterial hypertension (HT).Fortunately, ESC classes of recommendation (I, IIa, IIb, III) and levels of evidence (A, B, C) are the same as in the American guidelines.
    Definition of Hypertension Blood pressure (BP) is a continuous variable. Even from low levels, there is a linear relation with cardiovascular and renal adverse events. We should define arterial hypertension as the point where lowering BP treatment (not only with drugs) outweighs the risks of that treatment. For practical reasons, this definition relies on an arbitrary cut-off value of both systolic and diastolic blood pressures (SBP and DBP, respectively). The selection of this appropriate cut-off value is controversial, considering that higher or lower values have profound consequences in an individual and population level. Reasons that favour a higher cut-off value: Reasons that favour a lower cut-off value: In the 2018 ESC/ESH guidelines, HT cut-off is set to SBP ≥140 mmHg and/or DBP ≥90 mmHg. Therefore, it remains unchanged from the former European document (see Table 1).
    Blood Pressure Measurement Out-of-office BP measurements are an alternative to conventional office-BP and consist of home BP monitoring (HBPM) and ambulatory BP monitoring (ABPM). Both methods provide a larger number of measurements and are thought to be more representative of the patient's true daily BP. Values of BP in HBPM and ABPM trend to be lower than office BP, so thresholds to consider HT are different (see Table 2). Both guidelines recommend the use of out-of-office BP measurements to confirm the diagnosis of HT. They also support its use to appraise BP response to treatment, in the evaluation of resistant HT, and when there is considerable variability in office BP measurements.