Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of Tie2 signaling in vascular progenitor cells

Inhibition by all-trans retinoic acid (atRA) of the microvasculature formation in chicken chorioallantoic membrane (CAM) accompanied remarkably reduced numbers of endothelial cells (ECs) and increased numbers of mural cells (MCs) under the chorionic epithelial layer. Ro41-5253 (retinoid antagonist) exerted the opposite effect. Although atRA did not affect the differentiation of murine embryonic stem cell-derived vascular progenitor cells (VPCs) into ECs or MCs, atRA suppressed EC-MC interaction, leading to impaired branching. In both atRA-treated VPC cultures and CAM tissues underneath the chorionic epithelial layer, the expression of angiopoietin-2 (Ang-2; competitor for Ang-1) was enhanced, whereas that of Tie2 (a receptor for Angs) was reduced. Simultaneous treatment with Ang-1 partially blocked RA induction of EC-MC malinteraction and reduction in blood vessel formation. These results suggest that retinoid(s) may reduce EC-MC interaction by down-regulating Tie2 signaling as well as decreased EC numbers, which lead to impaired vascular remodeling.     

Predictors of voluntary HIV counselling and testing services utilization among people with disabilities in Addis Ababa,Ethiopia

The study investigated HIV testing prevalence and factors associated with the utilization of voluntary HIV counselling and testing (VCT) services among individuals with disabilities in Addis Ababa. The analysis was based on a survey of 209 men and 203 women with disabilities, aged 15–49, who had ever heard about HIV and AIDS in four sub-cities in Addis Ababa. HIV testing prevalence was 53.2%, with no significant difference between males and females. Comprehensive HIV knowledge, living with spouse, and religious affiliations positively predicted utilization of VCT services among participants. Living with both parents and having physical or mental/intellectual disabilities were negative predictors of VCT services utilization. More research on the predictors of utilization of VCT services by gender and urban/rural divides are needed among people with disabilities.     

Growth of children with end-stage renal disease undergoing daily hemodialysis

Background

The aim of this report is to describe the effect of daily hemodialysis on the growth of children with end-stage renal disease (ESRD).

Methods

We performed a prospective, observational study on 24 children with ESRD undergoing daily hemodialysis (DHD). The control group comprised 26 children on concurrent conventional hemodialysis (CHD), and the follow-up for both groups was 9.3?±?3.0 months. No patient received growth hormone (GH) therapy.

Results

At the onset of the study, the height-for-age Z-score was ?2.12?±?1.54 in the CHD group and ?2.84?±?2.27 in the DHD group (p?=?0.313). Assuming an increase of 0.5 standard deviation scores (SDS) of the height-for-age parameter as an improvement of growth, there were 33 % of patients in the DHD group and 8 % in the CHD group (p?=?0.035). The cumulative probability of gain in height for age at 12 months was 40 % in the DHD group versus 15 % in the CHD group (p?=?0.047). Also, 98 % of patients in the DHD group had an adequate total caloric intake, whereas 38 % in the CHD group reached this goal (p?<?0.001). No patient left the study due to intensification of the dialysis modality.

Conclusions

Our data show that the DHD favored a 0.5 SDS height gain in a third of patients without GH treatment. Dialysis intensification was not a cause for treatment dropouts, and DHD should be considered as a treatment for selected cases, especially small children.     

Highly sensitive detection of GATA1 mutations in patients with myeloid leukemia associated with Down syndrome by combining Sanger and targeted next generation sequencing

Myeloid leukemia associated with Down syndrome (ML‐DS) is characterized by a predominance of acute megakaryoblastic leukemia, the presence of GATA1 mutations and a favorable outcome. Because DS children can also develop conventional acute myeloid leukemia with unfavorable outcome, detection of GATA1 mutations is important for diagnosis of ML‐DS. However, myelofibrosis and the significant frequency of dry taps have hampered practical screening of GATA1 mutations using bone marrow (BM) samples. In response to those problems, 82 patients were enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML‐D11 study. GATA1 mutations were analyzed by Sanger sequencing (SS) using genomic DNA (gDNA) from BM and cDNA from peripheral blood (PB) followed by targeted next‐generation sequencing (NGS) using pooled diagnostic samples. BM and PB samples were obtained from 71 (87%) and 82 (100%) patients, respectively. GATA1 mutations were detected in 46 (56%) and 58 (71%) patients by SS using BM gDNA and PB cDNA, respectively. Collectively, GATA1 mutations were identified in 73/82 (89%) patients by SS. Targeted NGS detected GATA1 mutations in 74/82 (90%) patients. Finally, combining the results of SS with those of targeted NGS, GATA1 mutations were identified in 80/82 (98%) patients. These results indicate that SS using BM gDNA and PB cDNA is a rapid and useful method for screening for GATA1 mutations in ML‐DS patients. Thus, a combination of SS and targeted NGS is a sensitive and useful method to evaluate the actual incidence and clinical significance of GATA1 mutations in ML‐DS patients.     

Significance of mast cells in spermatogenesis,implantation, pregnancy,and abortion: Cross talk and molecular mechanisms

Both subsets of MCs including MC_TC (tryptase‐positive, chymase‐positive) and MC_T (tryptase‐positive, chymase‐negative) are present in the testis and epididymis. Increased number of MCs, higher levels of MC‐released tryptase in testis and seminal plasma of males with fertility problems, and promoting sperm motility in individuals with oligozoospermia after using MC blockers provide evidence that MCs may play a role in male infertility/subfertility disturbances. MC‐released tryptase and histamine contribute to the fibrosis and may disrupt spermatogenesis. MCs not only influence the process of spermatogenesis but also have effects on the function of other testis‐residing cells. MC‐derived histamine may influence the steroidogenesis of Leydig cells by acting through H1R and H2R receptors. Additionally, the interaction between MC‐released ATP and P2X receptors expressed on the peritubular cells may induce the production of the pro‐inflammatory mediators by peritubular cells. Further investigations showed that MCs may be involved in the pathology of female infertility during implantation, pregnancy, and abortion. In the uterus, MC_T subtype is abundant in myometrium and adjacent basal layer while MC_TC subtype is distributed in all layers. MCs in response to hormones mainly estradiol and progesterone become activated and release a wide range of mediators including histamine, VEGF, proteases, and metalloproteinases (MMPs) that have a role in different stages of pregnancy. An increasing influx of MCs to the cervix during the pregnancy occurs that helps to the physiologic cervical ripening. While MMPs degrade the extracellular matrix (ECM), VEGF modulates neovascularization and histamine influences the embryo implantation. MC‐derived histamine may have a positive effect during implantation due to its participation in tissue remodeling. MC proteases including tryptase and chymase activate the precursors of MMP2 and MMP9 to mediate ECM degradation during the physiologic menstrual cycle. There is a line of evidence that MCs have a role in abortion by releasing TNF‐α.