Ultrafast 3d spin-echo acquisition improves gadolinium-enhanced mri signal contrast enhancement

Long scan times of 3D volumetric MR acquisitions usually necessitate ultrafast in vivo gradient-echo acquisitions, which are intrinsically susceptible to magnetic field inhomogeneities. This is especially problematic for contrast-enhanced (CE)-MRI applications, where non-negligible T 2 & z.ast; effect of contrast agent deteriorates the positive signal contrast and limits the available range of MR acquisition parameters and injection doses. To overcome these shortcomings without degrading temporal resolution, ultrafast spin-echo acquisitions were implemented. Specifically, a multiplicative acceleration factor from multiple spin echoes (??32) and compressed sensing (CS) sampling (??8) allowed highly-accelerated 3D Multiple-Modulation- Multiple-Echo (MMME) acquisition. At the same time, the CE-MRI of kidney with Gd-DOTA showed significantly improved signal enhancement for CS-MMME acquisitions (??7) over that of corresponding FLASH acquisitions (??2). Increased positive contrast enhancement and highly accelerated acquisition of extended volume with reduced RF irradiations will be beneficial for oncological and nephrological applications, in which the accurate in vivo 3D quantification of contrast agent concentration is necessary with high temporal resolution.open0

The Transcription Factor NFAT5 Is Required for Cyclin Expression and Cell Cycle Progression in Cells Exposed to Hypertonic Stress

Background: Hypertonicity can perturb cellular functions, induce DNA damage-like responses and inhibit proliferation. The transcription factor NFAT5 induces osmoprotective gene products that allow cells to adapt to sustained hypertonic conditions. Although it is known that NFAT5-deficient lymphocytes and renal medullary cells have reduced proliferative capacity and viability under hypertonic stress, less is understood about the contribution of this factor to DNA damage responses and cell cycle regulation. Methodology/Principal Findings: We have generated conditional knockout mice to obtain NFAT5−/− T lymphocytes, which we used as a model of proliferating cells to study NFAT5-dependent responses. We show that hypertonicity triggered an early, NFAT5-independent, genotoxic stress-like response with induction of p53, p21 and GADD45, downregulation of cyclins, and cell cycle arrest. This was followed by an NFAT5-dependent adaptive phase in wild-type cells, which induced an osmoprotective gene expression program, downregulated stress markers, resumed cyclin expression and proliferation, and displayed enhanced NFAT5 transcriptional activity in S and G2/M. In contrast, NFAT5−/− cells failed to induce osmoprotective genes and exhibited poorer viability. Although surviving NFAT5−/− cells downregulated genotoxic stress markers, they underwent cell cycle arrest in G1/S and G2/M, which was associated with reduced expression of cyclins E1, A2 and B1. We also show that pathologic hypertonicity levels, as occurring in plasma of patients and animal models of osmoregulatory disorders, inhibited the induction of cyclins and aurora B kinase in response to T cell receptor stimulation in fresh NFAT5−/− lymphocytes. Conclusions/Significance: We conclude that NFAT5 facilitates cell proliferation under hypertonic conditions by inducing an osmoadaptive response that enables cells to express fundamental regulators needed for cell cycle progression.Molecular and Cellular Biolog

Barriers and Facilitators in Readiness to Adopt Rapid HIV Testing Among Healthcare Workers in Chile

Oral rapid HIV testing (ORT), which is an alternative to the Enzyme-linked Immunosorbent Assay (ELISA) for HIV, has the potential to help Chile meet its national HIV prevention goals of increased testing and early entry into treatment. This study examined individual factors affecting Chilean healthcare providers’ readiness to adopt ORT and their perceived comfort in performing the test. This study used a cross-sectional survey design. A total of 150 nurses, midwives, and physicians participated in the study, and they were all employed at four clinics of the University Católica de Chile health network in Santiago. The participants completed a self-administered survey that included questions about their demographic characteristics, attitudes towards and experience with evidence-based practice (EBP), and AIDS-related attitudes and beliefs, including HIV-related stigmatization, perceived importance of HIV testing, and perceived comfort performing rapid HIV tests. Results showed that providers had a mean Readiness to implement ORT score of 15.1 on a scale of 0-20, with higher scores indicating higher readiness. Educational background, Beliefs about evidence-based practice, Perceived comfort performing rapid HIV test (PCP-ORT), and Perceived importance of HIV testing explained 43.6% of the variance in readiness to adopt ORT. Perceived comfort performing rapid HIV test was the strongest predictor of Readiness to adopt ORT. Developed for this study, this scale asked about level of comfort in performing pre-test counseling, giving an oral test, giving a finger-prick test, giving a positive test and post-counseling, and giving a negative test and post-counseling. Results showed a mean score of 16.21 (range 0-20). Participants felt least comfortable with giving positive test results and providing appropriate post-test counseling to patients. Stigmatizing attitudes were negatively related to Perceived Comfort Performing ORT. This finding highlights the need to address HIV-related stigmatization among healthcare providers and to offer ORT training, focusing on giving positive test results so that they can be truly comfortable performing ORT. This is the first pre-implementation study in anticipation of the possible introduction of ORT in Chile, and the results can guide preparations for ORT implementation by identifying and addressing potential barriers related to individual provider readiness to implement ORT

HIV-Related Stigma and Multidimensional Frailty Among Older Latinos With HIV

Introduction: Frailty is a geriatric syndrome of increased vulnerability to stressors marked by a higher risk for poor health outcomes. HIV-related stigma is a stressor for Latino people with HIV (PWH) and an important barrier to HIV care. This study examines the association between HIV-related stigma and multidimensional frailty among older Latino PWH. Methods: A cross-sectional design with 120 Latino PWH aged 50 and older was used. Self-reported questionnaires were administered to assess multidimensional frailty (Tilburg Frailty Indicator) and HIV-related stigma (HIV stigma scale). Results: Participants were 59.1 ± 7.0 years old, primarily White-Hispanic (85.00%, n = 102), single (48.33%, n = 58), and male (73.30%, n = 88). Nearly half of the participants were frail (45.85%, n = 55). Compared to non-frail, frail individuals had significantly higher scores in the total HIV-related stigma ( M = 98.5 ± 24.7 vs. M = 85.3 ± 25.6, p = .020) and all subscales. The odds of multidimensional frailty were 1.021 times higher for people with higher HIV-related stigma scores ( p = .007). This association remained significant after adjustment for income and comorbidities ( p = .049). Conclusions: HIV-related stigma among older Latino PWH was significantly associated with their odds of being frail. Efforts to prevent multidimensional frailty should consider addressing HIV-related stigma through age-appropriate and culturally tailored resources for this group

Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.

Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16) and pregnant controls (n = 32). The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6) were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels). Aromatase content and estrogens and androgens concentrations were measured.The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic placental ischemia and hypoxia later in gestation.Placental aromatase expression and functionality are diminished in pregnancies complicated by preeclampsia in comparison with healthy pregnant controls