Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials

Colonoscopy: Advanced and Emerging Techniques-A Review of Colonoscopic Approaches to Colorectal Conditions.

A complete colonoscopy is key in the diagnostic and therapeutic approaches to a variety of colorectal diseases. Major challenges are incomplete polyp removal and missed polyps, particularly in the setting of a difficult colonoscopy. There are a variety of both well-established and newer techniques that have been developed to optimize polyp detection, perform complete polypectomy, and endoscopically treat various complications and conditions such as strictures and perforations. The objective of this article is to familiarize the colorectal surgeon with techniques utilized by advanced endoscopists

Coverage of obesity treatment: A state-by-state analysis of Medicaid and state insurance laws

Objectives. We determined whether state Medicaid programs cover recommended treatments for adult and pediatric obesity and to what extent states regulate the treatment and coverage of obesity by private insurers. Methods. We conducted a state-by-state document review of Medicaid manuals and private insurance laws and regulations. Results. Eight state Medicaid programs appear to cover all recommended obesity treatment modalities for adults. Only 10 states appear to reimburse for obesity-related treatment in children. In the small-group insurance market, 35 states expressly allow obesity to be used for rate adjustments, while 10 states do so in the individual market. Two states expressly allow obesity to be used in eligibility decisions in the individual market. Five states provide for coverage of one or more treatments for obesity in both small-group and individual markets. Conclusions. Very few states ensure coverage of recommended treatments for adult and pediatric obesity through Medicaid or private insurance. Most states allow obesity to be used to adjust rates in the small-group and individual markets and to deny coverage in the individual market

Motor deficits in schizophrenia quantified by nonlinear analysis of postural sway.

Motor dysfunction is a consistently reported but understudied aspect of schizophrenia. Postural sway area was examined in individuals with schizophrenia under four conditions with different amounts of visual and proprioceptive feedback: eyes open or closed and feet together or shoulder width apart. The nonlinear complexity of postural sway was assessed by detrended fluctuation analysis (DFA). The schizophrenia group (n = 27) exhibited greater sway area compared to controls (n = 37). Participants with schizophrenia showed increased sway area following the removal of visual input, while this pattern was absent in controls. Examination of DFA revealed decreased complexity of postural sway and abnormal changes in complexity upon removal of visual input in individuals with schizophrenia. Additionally, less complex postural sway was associated with increased symptom severity in participants with schizophrenia. Given the critical involvement of the cerebellum and related circuits in postural stability and sensorimotor integration, these results are consistent with growing evidence of motor, cerebellar, and sensory integration dysfunction in the disorder, and with theoretical models that implicate cerebellar deficits and more general disconnection of function in schizophrenia

The use of complementary and alternative medicine among california adults with and without cancer.

This article examines the extent and correlates of complementary and alternative medicine (CAM) use among a population-based sample of California adults that is highly diverse in terms of sociodemographic characteristics and health status. As a follow-up to a state-wide health survey of 55,428 people, 9187 respondents were interviewed by phone regarding their use of 11 different types of CAM providers, special diets, dietary supplements, mind-body interventions, self-prayer and support groups. The sample included all participants in the initial survey who reported a diagnosis of cancer, all the non-white respondents, as well as a random sample of all the white respondents. The relation of CAM use to the respondents' demographic characteristics and health status is assessed. CAM use among Californians is generally high, and the demographic factors associated with high rates of CAM use are the same in California as have been found in other studies. Those reporting a diagnosis of cancer and those who report other chronic health problems indicate a similar level of visits to CAM providers. However, those with cancer are less likely to report using special diets, and more likely to report using support groups and prayer. Health status, gender, ethnicity and education have an independent impact upon CAM use among those who are healthy as well as those who report suffering from chronic health problems, although the precise relation varies by the type of CAM used

Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.

Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5) (n = 18) vs. 5.98 ± 1.3 × 10(5) (n = 13), P<0.05) and eosinophils (1.09 ± 0.28 × 10(5) (n = 18) vs. 2.94 ± 0.6 × 10(5) (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11) vs. 8.56 ± 2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1 ± 3.6 (n = 8) vs. 28.8 ± 8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma

MF2294

The information in this document has been funded wholly or in part by the United States Environmental Protection Agency.Jennifer R. Weins, Christopher S. Guy & Charles D. Lee, Streambank revetment, Kansas State University, September 1997

The first international workshop on the role and impact of mathematics in medicine: a collective account

The First International Workshop on The Role and Impact of Mathematics in Medicine (RIMM) convened in Paris in June 2010. A broad range of researchers discussed the difficulties, challenges and opportunities faced by those wishing to see mathematical methods contribute to improved medical outcomes. Finding mechanisms for inter- disciplinary meetings, developing a common language, staying focused on the medical problem at hand, deriving realistic mathematical solutions, obtainin