Vitamin D and Biomarkers of Sex Steroid Hormones Are Non-Linearly and Inversely Related to All-Cause Mortality: Results from NHANES III

Background: In men, hypovitaminosis D as well as high and low testosterone levels have been linked to adverse events, including death. A biological interaction has been previously suggested between vitamin D and androgens. In a cohort study using Third National Health and Nutrition Examination Survey data, we simultaneously investigated circulating vitamin D and biomarkers of sex steroid hormones as predictors of all-cause mortality. Methods: Age-adjusted and fully-adjusted Cox regression models were constructed to estimate hazard ratios (HR) and their 95% confidence intervals (CI). Whereas the vitamin D sufficient group (25(OH)D3 ≥30 ng/ml) was selected as a referent, biomarkers of sex steroid hormones (testosterone, estradiol, SHBG) were defined as Loge-transformed continuous variables. Results: Of 1,472 men with a mean age of 42.1 years at baseline, 382 died over a median of 192 months of follow-up. Estradiol levels were significantly higher among vitamin D deficient compared to vitamin D sufficient men and sex hormone binding globulin level was significantly higher in vitamin D sufficient compared to vitamin D insufficient or deficient groups. An inverse non-linear relationship was observed between all-cause mortality rate and levels of testosterone, estradiol and vitamin D, in fully-adjusted models. There were no significant interaction effects between vitamin D and sex steroid hormones in relation to all-cause mortality rate. Conclusions: Vitamin D and sex steroid hormones, but not sex hormone binding globulin, may be inversely and non-linearly related to all-cause mortality among adult men, after adjustment for baseline demographic, socioeconomic, lifestyle and clinical characteristics

Virtual geographic environments in socio-environmental modeling: a fancy distraction or a key to communication?

Modeling and simulation are recognized as effective tools for management and decision support across various disciplines; however, poor communication of results to the end users is a major obstacle for properly using and understanding model output. Visualizations can play an essential role in making modeling results accessible for management and decision-making. Virtual reality (VR) and virtual geographic environments (VGEs) are popular and potentially very rewarding ways to visualize socio-environmental models. However, there is a fundamental conflict between abstraction and realism: models are goal-driven, and created to simplify reality and to focus on certain crucial aspects of the system; VR, in the meanwhile, by definition, attempts to replicate reality as closely as possible. This elevated realism may add to the complexity curse in modeling, and the message might be diluted by too many (background) details. This is also connected to information overload and cognitive load. Moreover, modeling is always associated with the treatment of uncertainty–something difficult to present in VR. In this paper, we examine the use of VR and, specifically, VGEs in socio-environmental modeling, and discuss how VGEs and simulation modeling can be married in a mutually beneficial way that makes VGEs more effective for users, while enhancing simulation models

Monotherapy Trials of New Antiepileptic Drugs

A number of clinical trials that test the efficacy and safety of the newer antiepileptic drugs (AEDs) have recently been concluded. Two dose-response trials in inpatients with refractory partial seizures and outpatients with newly diagnosed partial epilepsy established the efficacy of gabapentin as monotherapy. Lamotrigine was found to have efficacy similar to that of phenytoin and carbamazepine (CBZ) and to be better tolerated than CBZ in patients with newly diagnosed epilepsy. It was also shown to have efficacy as monotherapy in partial seizures, based on the results of an active controlled trial, and in the treatment of absence seizures, based on the results of a responder-enriched study. Topiramate as monotherapy was found to be efficacious for treatment of partial-onset seizures, based on the results of a single-center dose-response trial. A dose-response trial that tested the efficacy of tiagabine monotherapy in patients with refractory partial epilepsy was uninformative. Oxcarbazepine was found to be safe and efficacious in four comparative trials in patients with newly diagnosed epilepsy as well as in one placebo-controlled inpatient trial in patients with refractory partial seizures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65625/1/j.1528-1157.1997.tb05201.x.pd

Value of Inpatient Diagnostic CCTV-EEG Monitoring in the Elderly

Purpose: To examine the outcome of inpatient diagnostic closed circuit TV-EEG (CCTV-EEG) monitoring in a consecutive series of elderly patients admitted to an adult epilepsy-monitoring unit (EMU) over a continuous 6-year period. Methods: Retrospective review of all admissions to a university hospital adult EMU. Those older than 60 years were identified. Patients who were monitored for status epilepticus were excluded. Data on duration of events, frequency of events, physical examination, medications, preadmission EEG, brain imaging, length of stay, and interictal and ictal EEG were obtained. Results: Of the 18 patients admitted for monitoring only, mean age was 69.5 years (range, 60–90 years). Mean length of stay was 4.3 days (range, 2–9 days). Five patients had complex partial seizures recorded. Three patients, all treated with antiepileptic drugs (AEDs), had no spells recorded, and no additional diagnostic information was gained from the admission. The other 10 patients, eight of whom had been treated with AEDs, were symptomatic during their admission, leading to a variety of neurologic but not epileptic, psychiatric, or other medical disorders, and allowing tapering of AEDs. Conclusions: In elderly patients with suspected epilepsy, CCTV-EEG is a very useful diagnostic tool. In this series of 18, 10 patients were diagnosed with potentially treatable medical illnesses not responsive to AEDs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65172/1/j.1528-1157.1999.tb00825.x.pd

SPIRONOLACTONE FOR NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY: A RANDOMIZED CONTROLLED CROSSOVER STUDY.

PURPOSE: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy. METHODS: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity. RESULTS: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0-Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed. CONCLUSION: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo

MicroRNA-135a regulates NHE9 to inhibit proliferation and migration of glioblastoma cells

Abstract Background Glioblastoma multiformae (GBM) is the most aggressive type of malignant brain tumor with complex molecular profile. Overexpression of Na+/H+ Exchanger isoform 9 (NHE9) promotes tumor progression and correlates positively with insensitivity to radiochemotherapy and poor prognosis. However, molecular mechanisms responsible for increase in NHE9 levels beyond a critical threshold have not been identified. Methods Bioinformatics analysis, luciferase reporter assays, real-time PCR and western blotting were conducted to examine the expression profiles and identify microRNAs (miRNA) that target NHE9. Cell proliferation and migration assays were conducted in U87 glioblastoma cells to determine the consequence of miRNA mediated targeting of NHE9. Endosomal pH measurements, immunofluorescence microscopy and surface biotinylation experiments were conducted to characterize the mechanistic basis of regulation. Results We show that microRNA 135a (miR-135a) targets NHE9 to downregulate its expression in U87 cells. MiR-135a levels are significantly lower in glioblastoma cells compared to normal brain tissue. Downregulation of NHE9 expression by miR-135a affects proliferative and migratory capacity of U87 cells. Selectively increasing NHE9 expression in these cells restored their ability to proliferate and migrate. We demonstrate that miR-135a takes a two-pronged approach affecting epidermal growth factor receptors (EGFRs) to suppress tumor cell growth and migration. EGFR activity is a potent stimulator of oncogenic signaling. While miR-135a targets EGFR transcripts to decrease the total number of receptors made, by targeting NHE9 it routes the few EGFRs made away from the plasma membrane to dampen oncogenic signaling. NHE9 is localized to sorting endosomes in glioblastoma cells where it alkalinizes the endosome lumen by leaking protons. Downregulation of NHE9 expression by miR-135a acidifies sorting endosomes limiting EGFR trafficking to the glioblastoma cell membrane. Conclusions We propose downregulation of miR-135a as a potential mechanism underlying the high NHE9 expression observed in subset of glioblastomas. Future studies should explore miR-135a as a potential therapeutic for glioblastomas with NHE9 overexpression.https://deepblue.lib.umich.edu/bitstream/2027.42/140393/1/12964_2017_Article_209.pd

A survey of security issue in multi-agent systems

Multi-agent systems have attracted the attention of researchers because of agents' automatic, pro-active, and dynamic problem solving behaviors. Consequently, there has been a rapid development in agent technology which has enabled us to provide or receive useful and convenient services in a variety of areas such as banking, transportation, e-business, and healthcare. In many of these services, it is, however, necessary that security is guaranteed. Unless we guarantee the security services based on agent-based systems, these services will face significant deployment problems. In this paper, we survey existing work related to security in multi-agent systems, especially focused on access control and trust/reputation, and then present our analyses. We also present existing problems and discuss future research challenges. © Springer Science+Business Media B.V 2011

Bilateral dilation of the urinary tract due to iliopsoas pyomyositis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pyomyositis is an acute bacterial infection of the skeletal muscles that arises from hematogenous spread and is caused predominantly by Gram-positive cocci.</p> <p>Case presentation</p> <p>We report a case of iliopsoas pyomyositis in a 25-year-old Greek Caucasian woman with a history of intravenous drug use. Her condition was complicated by bilateral dilation of the ureters and renal calyces as a result of mechanical pressure from inflammation and edema of the involved muscle. The patient did not present aggravation of renal function and was treated successfully solely with intravenous antibiotics, without surgical intervention. This is the first case report describing iliopsoas pyomyositis with reversible bilateral dilation of the urinary tract that was treated successfully with intravenous antibiotics, without surgical intervention.</p> <p>Conclusion</p> <p>We present the first described case of iliopsoas pyomyositis with reversible bilateral hydroureteronephrosis that was treated successfully with intravenous antibiotics, without the necessity of surgical intervention. To our knowledge, this is the first report of its kind in the literature regarding an unexpected event in the course of treating a patient with iliopsoas pyomyositis, and it should be of particular interest to different clinical medical specialties such as internal medicine, infectious disease and urology.</p