Identification of Cellular Targets of MicroRNA-181a in HepG2 Cells: A New Approach for Functional Analysis of MicroRNAs

<div><p>MicroRNAs (miRNAs) are known to play a part in regulating important cellular processes. They generally perform their regulatory function through their binding with mRNAs, ultimately leading to a repression of target protein expression levels. However, their roles in cellular processes are poorly understood due to the limited understanding of their specific cellular targets. Aberrant levels of miRNAs have been found in hepatocellular carcinoma (HCC) including miR-181a. Using bioinformatics analysis, cyclin-dependent kinase inhibitor 1B (CDKN1β) and transcriptional factor E2F7 were identified as potential targets of miR-181a. Validation analysis using surface plasmon resonance (SPR) showed a positive binding between miR-181a and the 3’UTRs of these two potential mRNA targets. <i>In vivo</i> luciferase assay further confirmed the positive miR-181a:mRNA bindings, where a significant decrease in luciferase activity was detected when HepG2 cells were co-transfected with the 3’UTR-containing reporter plasmids and miR-181a. The potential impact of miR-181a binding to its specific targets on the general cellular behavior was further investigated. Results showed that miR-181a significantly activated the MAPK/JNK pathway which regulates cell proliferation, supporting our recently reported findings. Inhibition of miR-181a, on the other hand, abolished the observed activation. Our findings open up a new approach in designing targeted functional analysis of miRNAs in cellular processes, through the identification of their cellular targets.</p></div

Solution of the natural convection problem by parameter differentiation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22404/1/0000854.pd

Technical Development of a New Semispherical Radiofrequency Bipolar Device (RONJA): Ex Vivo and In Vivo Studies

The aim of this study is to inform about the development of a new semispherical surgical instrument for the bipolar multielectrode radiofrequency liver ablation. Present tools are universal; however they have several disadvantages such as ablation of healthy tissue, numerous needle punctures, and, therefore, longer operating procedure. Our newly designed and tested semispherical surgical tool can solve some of these disadvantages. By conducting an in vivo study on a set of 12 pigs, randomly divided into two groups, we have compared efficiency of the newly developed instrument with the commonly used device. Statistical analysis showed that there were no significant differences between the groups. On average, the tested instrument RONJA had shorter ablation time in both liver lobes and reduced the total operating time. The depth of the thermal alteration was on average 4 mm larger using the newly tested instrument. The new radiofrequency method described in this study could be used in open liver surgery for the treatment of small liver malignancies (up to 2 cm) in a single application with the aim of saving healthy liver parenchyma. Further experimental studies are needed to confirm these results before clinical application of the method in the treatment of human liver malignancies

Unique Localization of Circulating Tumor Cells in Patients With Hepatic Metastases

Purpose There are few data on the impact of immediate and differing surgical interventions on circulating tumor cells (CTCs), nor their compartmentalization or localization in different anatomic vascular sites. Patients and Methods CTCs from consecutive patients with colorectal liver metastases were quantified before and immediately after open surgery, laparoscopic resection, open radiofrequency ablation (RFA), or percutaneous RFA. For individuals undergoing open surgery, either hepatic resections or open RFA, CTCs were examined in both systemic and portal circulation by measuring CTCs in samples derived from the peripheral vein, an artery, the hepatic portal vein, and the hepatic vein. Results A total of 29 consecutive patients with colorectal liver metastases with a median age of 55 years (range, 30 to 88 years) were included. CTCs were localized to the hepatic portosystemic macrocirculation with significantly greater numbers than in the systemic vasculature. Surgical procedures led to a statistically significant fall in CTCs at multiple sites measured. Conversely, RFA, either open or percutaneous, was associated with a significant increase in CTCs. Conclusion Surgical resection of metastases, but not RFA, immediately decreases CTC levels. In patients with colorectal liver metastases, CTCs appear localized to the hepatic (and pulmonary) macrocirculations. This may explain why metastases in sites other than the liver and lungs are infrequently observed in cancer

Perinatal mortality in rural Burkina Faso: a prospective community-based cohort study

BACKGROUND: There is a scarcity of reliable data on perinatal mortality (PNM) in Sub-Saharan Africa. The PROMISE-EBF trial, during which we promoted exclusive breastfeeding, gave us the opportunity to describe the epidemiology of PNM in Banfora Health District, South-West in Burkina Faso. STUDY OBJECTIVES: To measure the perinatal mortality rate (PNMR) in the PROMISE-EBF cohort in Banfora Health District and to identify potential risk factors for perinatal death. METHODS: We used data collected prospectively during the PROMISE-EBF-trial to estimate the stillbirth rate (SBR) and early neonatal mortality rate (ENMR). We used binomial regression with generalized estimating equations to identify potential risk factors for perinatal death. RESULTS: 895 pregnant women were enrolled for data collection in the EBF trial and followed-up to 7 days after birth. The PNMR, the SBR and the ENMR, were 79 per 1000 (95% CI: 59-99), 54 per 1000 (95% CI: 38-69) and 27 per 1000 (95% CI: 9-44), respectively. In a multivariable analysis, nulliparous women (RR = 2.90, 95% CI: 1.6-5.0), primiparae mothers (RR = 2.20, 95% CI: 1.2-3.9), twins (RR = 4.0, 95% CI: 2.3-6.9) and giving birth during the dry season (RR = 2.1 95% CI: 1.3-3.3) were factors associated with increased risk of perinatal death. There was no evidence that risk of perinatal death differed between deliveries at home and at a health centre CONCLUSION: Our study observed the highest PNMR ever reported in Burkina. There is an urgent need for sustainable interventions to improve maternal and newborn health in the country

Causes of Perinatal Death at a Tertiary Care Hospital in Northern Tanzania 2000-2010: A Registry Based Study.

Perinatal mortality reflects maternal health as well as antenatal, intrapartum and newborn care, and is an important health indicator. This study aimed at classifying causes of perinatal death in order to identify categories of potentially preventable deaths. We studied a total of 1958 stillbirths and early neonatal deaths above 500 g between July 2000 and October 2010 registered in the Medical Birth Registry and neonatal registry at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. The deaths were classified according to the Neonatal and Intrauterine deaths Classification according to Etiology (NICE). Overall perinatal mortality was 57.7/1000 (1958 out of 33 929), of which 1219 (35.9/1000) were stillbirths and 739 (21.8/1000) were early neonatal deaths. Major causes of perinatal mortality were unexplained asphyxia (n=425, 12.5/1000), obstetric complications (n=303, 8.9/1000), maternal disease (n=287, 8.5/1000), unexplained antepartum stillbirths after 37 weeks of gestation (n= 219, 6.5/1000), and unexplained antepartum stillbirths before 37 weeks of gestation (n=184, 5.4/1000). Obstructed/prolonged labour was the leading condition (251/303, 82.8%) among the obstetric complications. Preeclampsia/eclampsia was the leading cause (253/287, 88.2%) among the maternal conditions. When we excluded women who were referred for delivery at KCMC due to medical reasons (19.1% of all births and 36.0% of all deaths), perinatal mortality was reduced to 45.6/1000. This reduction was mainly due to fewer deaths from obstetric complications (from 8.9 to 2.1/1000) and maternal conditions (from 8.5 to 5.5/1000). The distribution of causes of death in this population suggests a great potential for prevention. Early identification of mothers at risk of pregnancy complications through antenatal care screening, teaching pregnant women to recognize signs of pregnancy complications, timely access to obstetric care, monitoring of labour for fetal distress, and proper newborn resuscitation may reduce some of the categories of deaths

[(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma

BACKGROUND: To compare morphological gross tumor volumes (GTVs), defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of (18)F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning. METHODS: Nineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV union or logical sum BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed. RESULTS: Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (p = 0.9), CTVs (mean 57.8 +/- 30.4 cm(3)) were significantly larger than BTVs (mean 42.1 +/- 24.4 cm(3); p &lt; 0.01) or GTVs (mean 38.7 +/- 25.7 cm(3); p &lt; 0.01). In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended &gt;or= 10 and 20 mm from the margin of the gadolinium enhancement. CONCLUSION: Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients