Factors Associated with HIV-1 Proviral DNA Loads in Patients with Undetectable Plasma RNA Load

To evaluate factors associated with human immunodeficiency virus type 1 (HIV-1) proviral DNA load, we conducted a cross-sectional study of 36 chronically HIV-1-infected individuals with undetectable plasma viral RNA. We used real-time polymerase chain reaction to determine the number of HIV-1 proviral DNA copies per 106 peripheral blood mononuclear cells. The mean level of plasma viral RNA when the CD4+ T cell count was above 500 cells/µL without highly active antiretroviral therapy (HAART) was significantly associated with proviral DNA load at the time of undetectable plasma HIV RNA with HAART. Strategies to reduce the level of plasma viral RNA when patients' CD4+ T cell counts are above 500 cells/µL without HAART could help reduce HIV-1 proviral DNA load

Regulation of Pituitary Adenylate Cyclase-activating Polypeptide Gene Transcription by TTF-1, a Homeodomain-containing Transcription Factor

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an important hypophysiotrophic factor as well as a regulator for immune, reproductive, and neural tissues. We recently found that TTF-1, a homeodomain-containing transcription factor essential for the development of the fetal diencephalon, is postnatally expressed in the hypothalamic area and plays a transcription regulatory role for certain neurohormones. Based on the similarity of synthesis sites between PACAP and TTF-1 and, moreover, on the presence of conserved core TTF-1 binding motifs in the 5′-flanking region of the PACAP gene, we sought to uncover a regulatory role of TTF-1 in PACAP gene transcription. The TTF-1 homeodomain binds to six of the seven putative binding domains observed in the 5′-flanking region of the PACAP gene. In the C6 glioma cell-line, TTF-1 activates the PACAP promoter in a dose-dependent manner. This transactivation of PACAP by TTF-1 was totally removed when the core TTF-1 binding motif at −369 was deleted. RNase protection assays showed that TTF-1 and PACAP mRNAs have daily fluctuations in the rat hypothalamus. They both were at low levels during the day and high levels during the night. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased the PACAP mRNA level as well as TTF-1 protein content in the rat hypothalamus, suggesting that TTF-1 also regulates PACAP transcription in vivo. Moreover, the TTF-1 promoter was inhibited by molecular oscillators of CLOCK and BMAL-1. Taken together, these data suggest that TTF-1 plays an important regulatory role in the gene transcription for PACAP, which may be important for the generation of a daily rhythm of hypothalamic PACAP gene expression

Estimating contact-adjusted immunity levels against measles in South Korea and prospects for maintaining elimination status.

Measles has been reemerging in South Korea since December 2018 resulting in 185 cases by September 2019. We calculated contact-adjusted immunity levels against measles in South Korea using national seroprevalence data in 2014, vaccination uptake rates, and an age-specific contact matrix. We further explored options to achieve a contact-adjusted immunity level of 93% for herd immunity. The assessed contact-adjusted immunity level has increased from 86% in 2014 to 92% in 2018. Herd immunity could be achieved with immunizing 50% of susceptibles among birth cohorts 1999-2003 in 2018. Contact-adjusted immunity levels against measles have increased recently in South Korea, although they might not yet be high enough to guarantee herd immunity

Cardiodynamics and Infarct Size in Regional and Global Ischemic Isolated Heart Model: Comparison of 1 Hour and 2 Hours Reperfusion

Background and ObjectivesWe investigated whether 1 hour reperfusion is enough to assess cardiodynamics and infarct size in both regional ischemia (RI) and global ischemia (GI) in isolated rat heart models.Materials and MethodsHearts were randomly assigned to one of the following groups (each n=14): 1) Sham hearts for 1 hour; 2) Sham hearts for 2 hours; 3) 30 minutes RI followed by 1 hour reperfusion; 4) 30 minutes of RI followed by 2 hours reperfusion; 5) 30 minutes GI followed by 1 hour reperfusion; and 6) 30 minutes GI followed by 2 hours reperfusion.ResultsThere were no significant differences in infarct size between 1 hour and 2 hours reperfusion in both RI and GI. Left ventricular developed pressure was significantly decreased at both 1 hour and 2 hours reperfusion in groups of RI and GI compared to baseline (p<0.01). Rate-pressure product and +dP/dtmax also significantly decreased compared to baseline level at both 1 hour and 2 hours reperfusion in groups of RI and GI (p<0.05).ConclusionThere was no significant difference in infarct size between 1 hour and 2 hours reperfusion in groups of RI and GI. Cardiodynamic variables measured at 1 hour and 2 hours reperfusion significantly decreased compared to baseline level. Our data suggests that reperfusion of 1 hour is sufficient to assess cardiodynamics in both regional and global ischemic isolated hearts model

MMP9 Processing of HSPB1 Regulates Tumor Progression

Matrix metalloproteinases regulate pathophysiological events by processing matrix proteins and secreted proteins. Previously, we demonstrated that soluble heat shock protein B1 (HSPB1) is released primarily from endothelial cells (ECs) and regulates angiogenesis via direct interaction with vascular endothelial growth factor (VEGF). Here we report that MMP9 can cleave HSPB1 and release anti-angiogenic fragments, which play a key role in tumorprogression. We mapped the cleavage sites and explored their physiological relevance during these processing events. HSPB1 cleavage by MMP9 inhibited VEGF-induced ECs activation and the C-terminal HSPB1 fragment exhibited more interaction with VEGF than did full-length HSPB1. HSPB1 cleavage occurs during B16F10 lung progression in wild-type mice. Also, intact HSPB1 was more detected on tumor endothelium of MMP9 null mice than wild type mice. Finally, we confirmed that secretion of C-terminal HSPB1 fragment was significantly inhibited lung and liver tumor progression of B16F10 melanoma cells and lung tumor progression of CT26 colon carcinoma cells, compared to full-length HSPB1. These data suggest that in vivo MMP9-mediated processing of HSPB1 acts to regulate VEGF-induced ECs activation for tumor progression, releasing anti-angiogenic HSPB1 fragments. Moreover, these findings potentially explain an anti-target effect for the failure of MMP inhibitors in clinical trials, suggesting that MMP inhibitors may have pro-tumorigenic effects by reducing HSPB1 fragmentation

The impact of transferring patients with ST-segment elevation myocardial infarction to percutaneous coronary intervention-capable hospitals on clinical outcomes

Background: Primary percutaneous coronary intervention (PCI) is recommended for ST-segment elevation myocardial infarction (STEMI) patients even when the patient must be transported to a PCI-capable hospital. This study aimed to evaluate the long-term clinical outcomes of STEMI patients who were transferred for primary PCI compared to patients who arrived directly to PCI-capable hospitals. Methods: A total of 3,576 STEMI patients with less than 12 h of symptom onset-to-door time from the Korea Acute Myocardial Infarction Registry were divided into transfer (n = 2,176) and direct-arrival (n = 1,400) groups according to their status. The primary outcome was the composite of major adverse cardiac event (MACE), defined as death, non-fatal myocardial infarction, and revascularization at 1 year. Results: In the transfer vs. the direct-arrival group, the median symptom onset-to-firstmedical contact time was significantly shorter (60 vs. 80 min, p &lt; 0.001), but the median symptom onset-to-door time was significantly longer (194 vs. 90 min, p &lt; 0.001). The median door-to-balloon time was significantly shorter in the transfer group vs. the direct-arrival group (75 vs. 91 min, p &lt; 0.001). Total death and the composite of MACE were not significantly different during hospitalization (5.1 vs. 3.9%, p = 0.980; 5.4 vs. 4.8%, p = 0.435, respectively) and at 1-year (8.2 vs. 6.6%, p = 0.075; 13.7 vs. 13.9%, p = 0.922, respectively). Conclusions: Transferring STEMI patients to PCI-capable hospitals with a time delay did not affect clinical outcomes after 1 year. This study suggests that inter-hospital transfer should be encouraged even with delay for STEMI patients who require primary PCI in areas with a similar geographic accessibility