Attorney advertising: The effect on juror perceptions and verdicts

This study examined the effect of attorney television advertising on jurors. Southern Nevada jurors who had served on personal injury and malpractice trials were sent survey questionnaires designed to elicit juror attitudes about attorneys and attorney advertising. The response rate was 53.3%; The major finding was that although respondents generally do not like lawyer television advertising, it does not affect their trial verdicts unless jurors are actually confronted with a plaintiff\u27s lawyer who advertises on television; then, jurors tend to vote for the defense. There is strong sentiment that the law should be changed to limit jury awards. Advertising lawyers become the focus of this perception and therefore jurors tend to vote against the plaintiff in these trials, voting their perceived economic self-interest. Jurors who have more positive opinions of lawyers in general and those in current working relationships with lawyers also have more positive opinions about legal service advertising

Pyrrolcarboxamide derivatives for the inhbition of erk5

The invention provides compounds of formula (I) or a tautomer, stereoisomer, N-oxide, pharmaceutically acceptable salt or solvate thereof. The compounds are useful for the prophylaxis or treatment of a disease state or condition mediated by ERK5 in particular cancers

Discovery and optimisation of small-molecule ERK5 inhibitors as cancer therapeutics

PhD ThesisExtracellular signal-regulated kinase 5 (ERK5) is a member of the protein kinase superfamily, which plays an essential role in the transduction of extracellular signals to intracellular effectors. Activation of the ERK5 signalling pathway is associated with cell survival, proliferation, and differentiation, and thus ERK5 over-expression may have implications in carcinogenesis. Therefore, the discovery and development of small molecule inhibitors of ERK5 may offer a novel therapeutic intervention for cancer. High throughput screening (HTS) of chemical libraries, conducted by Cancer Research Technology, revealed three distinct chemical series as moderate inhibitors of ERK5. Two of these series are described herein i.e.: 3-cyanopyridines (IC50 = 0.5 – 31.3 μM); and pyrrolecarboxamides (IC50 = 0.66 – 3.5 μM). Two 3-cyanopyridine based hits (2-(2-((3-cyano-4-(4-fluorophenyl)-6-phenylpyridin-2- yl)thio)acetamido)acetic acid, 68 and 2-((3-cyano-4-(4-fluorophenyl)-6-phenylpyridin-2- yl)thio)-N-(2-oxopropyl)acetamide, 67; IC50 values = 1.6 and 0.5 μM, respectively) were resynthesised and were slightly less active at 4.9 and 20.5 μM. The 3-cyanopyridine scaffold was deemed a valid starting point for initiating structure activity relationship (SAR) studies. Three areas were identified for further investigation i.e.: modification to the thioether sidechain; modification to the aryl substituent; and isosteric replacement of the 3-cyano motif. Structure-activity studies did not result in improved potency over the initial hits. Previously, the pyrrole-carboxamide series has been validated successfully. Hit-to-lead studies around the aroyl ring highlighted the importance of substitution pattern for potency, with 2,6-difluoro (or 2,3-dichloro) substituents conferring the greatest potency (4-(2,6- difluorobenzoyl)-N-(pyridin-4-ylmethyl)-1H-pyrrole-2-carboxamide, 144; IC50 = 2.3 μM) initially. Truncation of the carboxamide side-chain resulted in improved activity (IC50 = 0.9 4 μM) and crucially, ≥100-fold selectivity for ERK5 over the closely related kinase p38α was also achieved e.g. 4-(2,6-difluorobenzoyl)-N-(pyridin-4-yl)-1H-pyrrole-2-carboxamide, 256.. Tuning of the aroyl substituents and pyridyl groups resulted in discovery of 4-(2-bromo-6- fluorobenzoyl)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide, 278 a potent and selective ERK5 inhibitor with excellent drug-like properties (i.e.: MW = 388; cLogP = 3.2; LE = 0.35; Aqueous solubility = >100 μM; PPB = 94%). Preliminary in vivo studies of lead compound 4-(2-bromo-6-fluorobenzoyl)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide have confirmed efficacy in xenograft tumour models, and satisfactory pharmacokinetic properties in mice. The pyrrole-carboxamide series has now entered the lead optimisation phase of drug discovery, focussing on improvement of cellular activity, and eliminating CYP inhibition, with the aim of providing compounds with suitable potency and properties for clinical trials.Cancer Research U

Providing Preventive Health Education and Developing a Referral Policy and Toolkit to Increase Access to Primary Care for Individuals with Mental Illness

Treatment rates in primary care for the mental health population is traditionally low. Individuals with mental illnesses were at a higher risk for the development of chronic health problems (Ross et al., 2015). Substance Abuse and Mental Health Services Administration (SAMHSA) indicated that many people with serious mental illness die from preventable diseases. People with serious mental illness also have a higher mortality rate than those in the general population (SAMHSA, 2017b). The purpose of this Doctor of Nursing Practice (DNP) project was to determine if educational training regarding specific chronic disease conditions influenced the attitude and knowledge of the Community Health Workers (CHWs) in the day treatment program. The project was also to determine if the development and utilization of the referral policy and toolkit would assist CHWs in referring clients to primary care. There were a total of eight participants. A pretest and survey were administered to the CHW followed by an educational presentation. A posttest and survey were administered. The means of the post-test and post surveys increased. The pre/posttest and survey results supported the incorporation of education regarding the importance of preventive health and wellness to the CHW. The Director of Adult Services of the mental health facility assembled a focus group of mental health providers. The referral policy and toolkit was introduced to the CHWs and the focus group. Following the introduction of the referral policy and toolkit, the focus group completed a questionnaire. The purpose of the questionnaire was to determine the ease of use and the overall usefulness of the toolkit. Overall the staff thought the toolkit was useful in assisting with referrals

β-funaltrexamine effects on lipopolysaccharide-induced behavior deficits and inflammation in mice

Inflammation plays a pivotal role in neurological and peripheral disorders. Specifically, inflammation is one of the common factors in diseases such as anxiety, depression, Alzheimer’s disease (AD), Parkinson’s disease (PD), inflammatory bowel disease (IBD), and many others that have all been linked to inflammatory changes in our central or peripheral systems. Thus, exploring potential treatments geared toward the abatement of inflammation is crucial to the continuation of treatment development. One pharmacological agent researched for its anti-inflammatory effects is β-funaltrexamine (β-FNA), a selective mu-opioid receptor (MOR) antagonist. Preclinical studies using in vitro human astroglial cells showed that β-FNA inhibited inflammatory signaling, NF-κB signaling, and chemokine expression in a mechanism unrelated to MOR. Also, the neuroprotective effects of β-FNA were discovered in a preclinical model of lipopolysaccharide (LPS)-induced neuroinflammation and sickness-like behavior when administered before LPS. This study determines the effects of β-FNA (50 mg/kg, i.p.) on LPS-induced (0.83 mg/kg i.p.) sickness-like behavior using a 10 min open field test and anxiety-like behavior using a 5 min elevated plus maze in male and female C57BL/6J mice. Depending on the study, it also assesses the effects on LPS-induced neuro and peripheral inflammation when β-FNA is administered immediately, 4 h or 10 h post-LPS. Tissue collected included the whole brain, hippocampus, prefrontal cortex, cerebellum/brain stem, spleen, liver, small intestine, large intestine, and plasma. Levels of inflammatory cytokines/chemokines (TNF-α, IL-6, IL-1β, CXCL10, CCL2) were measured using an enzyme-linked immunosorbent assay (ELISA), and inflammatory factors (NF-κB-p65, TAK1, p38 MAPK, GFAP) were measured using a western blot analysis. Also, to our knowledge, this is the first time the effects of β-FNA on female mice has been assessed. Differential effects of β-FNA were found between the whole brain vs. brain regions, central vs. peripheral nervous system, inflammatory factors, sexes, and temporal differences. Overall, this study will provide insight into the protection offered by β-FNA in both the central and peripheral systems and provides further exploration into additional therapeutic options for neurological disorders

Regional Corn Re-plant Recommendations for Iowa

Each year in areas where corn (Zea mays L.) is grown, biotic and abiotic (living and nonliving) factors can prevent timely planting or reduce stands so severely that yield potential may be reduced to unsatisfactory levels. Once these threats are realized, producers must make quick and accurate decisions. Careful evaluation of the current situation in terms of projected yields and profitability is crucial. If projected profitability is not acceptable, replant options should be considered