The role of Bicoid Stability Factor in oskar mRNA function and regulation, and the mechanisms for oskar mRNA transport to the oocyte

My dissertation is separated into two subjects. First, I examined the role of Bicoid Stability Factor (BSF) in oskar (osk) regulation. Second, I studied cis-acting elements involved in osk mRNA transport to the oocyte during early oogenesis. Oskar (Osk) is a body patterning determinant in Drosophila and is highly concentrated at the posterior pole of the oocyte. This spatially-restricted deployment relies on a coordinated program of osk mRNA localization and translational regulation, all dependent on cis-acting regulatory elements located primarily in the 3’ UTR of the mRNA. Notably, some of these elements, as well as sequences required for a noncoding role of osk mRNA, are clustered in a short region (the C region) near the 3’ end of the osk mRNA. To better understand the role of the C region, I searched for proteins that bind specifically to this region and I found BSF. Binding assays to mutant RNAs suggested that BSF does not act in the noncoding function of osk mRNA. To test for a role for BSF in regulation of Osk protein expression, I used two complementary approaches, reducing the BSF level or disrupting BSF binding to the osk mRNA. Both generated similar results: a reduction or loss of posterior Osk protein and osk mRNA in late oogenesis and early embryogenesis, while the level of osk mRNA was not affected. My work suggests that BSF could act in a late phase of osk mRNA localization or translational activation. Localization of osk mRNA to the posterior pole of the oocyte is achieved by multiple transport steps. One is mRNA transport from the nurse cells to the oocyte. Although cis-acting elements including the oocyte entry signal (OES) in the osk mRNA 3’ UTR have been implicated in mRNA oocyte transport, the precise mechanisms remain unknown. Here, I show that the clusters of Bru binding sites in the osk mRNA 3’ UTR required for translational regulation confer oocyte transport on a reporter mRNA. However, neither Bru sites nor the OES are essential for oocyte transport of osk mRNA. This suggests that there are multiple mechanisms redundantly acting in oocyte transport.Cellular and Molecular Biolog

Psychometric properties of a short self-reported measure of medication adherence among patients with hypertension treated in a busy clinical setting in Korea.

BackgroundWe examined the psychometric properties of the Korean version of the 8-item Morisky Medication Adherence Scale (MMAS-8) among adults with hypertension.MethodsA total of 373 adults with hypertension were given face-to-face interviews in 2 cardiology clinics at 2 large teaching hospitals in Seoul, South Korea. Blood pressure was measured twice, and medical records were reviewed. About one-third of the participants (n = 109) were randomly selected for a 2-week test-retest evaluation of reliability via telephone interview.ResultsInternal consistency reliability was moderate (Cronbach α = 0.56), and test-retest reliability was excellent (intraclass correlation = 0.91; P < 0.001), although a ceiling effect was detected. The correlation of MMAS-8 scores with scores for the original 4-item scale indicated that convergent validity was good (r = 0.92; P < 0.01). A low MMAS-8 score was significantly associated with poor blood pressure control (χ(2) = 29.86; P < 0.001; adjusted odds ratio = 5.08; 95% CI, 2.56-10.08). Using a cut-off point of 6, sensitivity and specificity were 64.3% and 72.9%, respectively. Exploratory factor analysis identified 3 dimensions of the scale, with poor fit for the 1-dimensional construct using confirmatory factory analysis.ConclusionsThe MMAS-8 had satisfactory reliability and validity and thus might be suitable for assessment and counseling regarding medication adherence among adults with hypertension in a busy clinical setting in Korea

Calcific Myonecrosis of the Antetibial Area

Calcific myonecrosis is a rare late post-traumatic condition, in which a single muscle is replaced by a fusiform mass with central liquefaction and peripheral calcification. Compartment syndrome is suggested to be the underlying cause. The resulting mass may expand with time due to recurrent intralesional hemorrhage into the chronic calcified mass. A diagnosis may be difficult due to the long time between the original trauma and the symptoms of calcific myonecrosis. We encountered a 53-year-old male patient diagnosed with calcific myonecrosis in the lower leg. We report the case with a review of the relevant literature

Association of neuromuscular reversal by sugammadex and neostigmine with 90-day mortality after non-cardiac surgery

Abstract Background Reversing a neuromuscular blockade agent with sugammadex is known to lessen postoperative complications by reducing postoperative residual curarization. However, its effects on 90-day mortality are unknown. Therefore, this study aimed to compare the effects of sugammadex and neostigmine in terms of 90-day mortality after non-cardiac surgery. Methods This retrospective cohort study analyzed the medical records of adult patients aged 18 years or older who underwent non-cardiac surgery at a single tertiary care hospital between 2011 and 2016. Propensity score matching and Cox regression analysis were used to investigate the effectiveness of sugammadex and neostigmine in lowering 90-day mortality after non-cardiac surgery. Results A total of 65,702 patients were included in the analysis (mean age: 52.3 years, standard deviation: 15.7), and 23,532 of these patients (35.8%) received general surgery. After propensity score matching, 14,179 patients (3906 patients from the sugammadex group and 10,273 patients from the neostigmine group) were included in the final analysis. Cox regression analysis in the propensity score-matched cohort showed that the risk of 90-day mortality was 40% lower in the sugammadex group than in the neostigmine group (hazard ratio: 0.60, 95% confidence interval: 0.37, 0.98; P = 0.042). These results were similar in the multivariable Cox regression analysis of the entire cohort (hazard ratio: 0.62, 95% confidence interval: 0.39, 0.96; P = 0.036). Conclusions This retrospective cohort study suggested that reversing rocuronium with sugammadex might be associated with lower 90-day mortality after non-cardiac surgery compared to neostigmine. However, since this study did not evaluate quantitative neuromuscular function in the postoperative period due to its retrospective design, the results should be interpreted carefully. Future prospective studies with quantitative neuromuscular monitoring in the postoperative period should be performed to confirm these results

Neuropeptides SP and CGRP Underlie the Electrical Properties of Acupoints

Electrical skin measurements at acupuncture points (acupoints) have been utilized as a diagnostic and therapeutic aid for more than 50 years. Although acupoints are described as having distinct electrical properties, such as high conductance and low impedance, the underlying mechanisms are currently unknown. The present study investigated in a rat model of hypertension whether the high conductance at acupoints is a result of the release of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) during neurogenic inflammation in the referred pain area. When plasma extravasation from neurogenic inflammation was examined by exploring the leakage of intravenously injected Evans blue dye (EBD) to the skin, extravasated EBD was found most frequently in acupoints on the wrist. The increased conductance and temperature at these acupoints occurred during the development of hypertension. The increase in conductance and plasma extravasation at acupoints in hypertensive rats was ablated by cutting median and ulnar nerves, blocking small diameter afferent fibers with resiniferatoxin (RTX) injection into median and ulnar nerves, or antagonizing SP or CGRP receptors in acupoints. In turn, intradermal injection of SP or CGRP resulted in increased conductance and plasma extravasation in naïve rats. Elevated levels of SP and CGRP were found in the acupoints of hypertensive rats. These findings suggest that the high conductance at acupoints is due to vascular leakage following local release of SP and CGRP during neurogenic inflammation