Reasonably Accommodating Nonmitigating Plaintiffs After the ADA Amendments Act of 2008

The passage of the ADA Amendments Act of 2008 ( ADAAA ) has significantly changed the landscape of disability law in the United States. Prior to the ADAAA, the Supreme Court narrowed the definition of disability under the ADA in the landmark case Sutton v. United Air Lines, Inc. Superseding Sutton, the ADAAA broadens the definition of disability by indicating that measures used to successfully mitigate a plaintiff\u27s impairment may not be considered when determining whether a plaintiff is disabled. The ADAAA does not, however, expressly address plaintiffs who fail to use these mitigating measures, and there has been confusion among district courts on how to address these nonmitigating plaintiffs. Because the ADAAA expands the definition of disability, it will shift the focus of many ADA cases to the subsequent determination of whether a plaintiff, who could perform his job with or without a reasonable accommodation, is a qualified individual under the ADA. This Note proposes that a nonmitigating plaintiff must establish that the burdens imposed on the plaintiff to mitigate the effects of his disability are not substantially less than the burdens imposed on the employer to accommodate the plaintiffs disability in order to show that an accommodation is reasonable. This proposal screens out cases where a plaintiffs decision not to mitigate is plainly unreasonable, yet allows most nonmitigating plaintiffs to survive summary judgment. In providing coverage in most cases, this proposal comports with the spirit of ADAAA to broaden coverage under the ADA

Effectiveness of Ezetimibe in Reducing the Estimated Risk for Fatal Cardiovascular Events in Hypercholesterolaemic Patients with Inadequate Lipid Control While on Statin Monotherapy as Measured by the SCORE Model

Objectives. The aim of this prospective cohort, multicentre study was to assess the effect of coadministrating ezetimibe 10 mg/day with an ongoing statin on the estimated risk for Cardiovascular (CVD) mortality in patients with persistently elevated LDL-C after statin monotherapy. Methods. The Systematic Coronary Risk Evaluation (SCORE) function was used to estimate the 10-year risk for cardiovascular mortality at baseline and 6 weeks. Primary outcome measures were absolute and percent changes in estimated Coronary Heart Disease (CHD) Mortality Risk, and general CVD Mortality Risk (Total CVD Mortality Risk). Results. 825 patients were included in the analysis. Mean (SD) age was 62 (10.5) years and 62.3% were males. The mean (SD) estimated Total CVD Mortality Risk decreased from 0.068 (0.059) at baseline to 0.053 (0.046) at 6 weeks (RR = 0.77; 95% CI:0.689–0.867), while the estimated CHD Mortality Risk decreased from 0.047 (0.040) at baseline to 0.034 (0.029) at 6 weeks (RR = 0.72; 95% CI:0.624–0.826). Conclusions. Co-administration of ezetimibe with a statin is effective in significantly reducing the estimated risk for cardiovascular mortality as measured by the SCORE model

Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic AhR modulating agent (TAMA)

Tapinarof, a novel, first-in-class small-molecule topical therapeutic aryl hydrocarbon receptor (AhR) modulating agent (TAMA), is in clinical development for the treatment of psoriasis and atopic dermatitis. The efficacy of tapinarof in psoriasis is attributed to its specific binding and activation of AhR, a ligand-dependent transcription factor, leading to the downregulation of pro-inflammatory cytokines, including interleukin-17, and regulation of skin barrier protein expression to promote skin barrier normalization. AhR signaling regulates gene expression in immune cells and skin cells, and has critical roles in the regulation of skin homeostasis. Tapinarof-mediated AhR signaling underlies the mechanistic basis for the significant efficacy and acceptable tolerability observed in early phase clinical trials of tapinarof cream in the treatment of psoriasis

Association of genetic polymorphisms related to Johne’s disease with estimated breeding values of Holstein sires for milk ELISA test scores

peer-reviewedBackground Johne’s disease (JD) is a chronic intestinal inflammatory disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection in ruminants. Since there are currently no effective vaccine or treatment options available to control JD, genetic selection may be an alternative strategy to enhance JD resistance. Numerous Single Nucleotide Polymorphisms (SNPs) have been reported to be associated with MAP infection status based on published genome-wide association and candidate gene studies. The main objective of this study was to validate these SNPs that were previously identified to be associated with JD by testing their effect on Holstein bulls’ estimated breeding values (EBVs) for milk ELISA test scores, an indirect indicator of MAP infection status in cattle. Results Three SNPs, rs41810662, rs41617133 and rs110225854, located on Bos taurus autosomes (BTA) 16, 23 and 26, respectively, were confirmed as significantly associated with Holstein bulls’ EBVs for milk ELISA test score (FDR < 0.01) based on General Quasi Likelihood Scoring analysis (GQLS) analysis. Single-SNP regression analysis identified four SNPs that were associated with sire EBVs (FDR < 0.05). This includes two SNPs that were common with GQLS (rs41810662 and rs41617133), with the other two SNPs being rs110494981 and rs136182707, located on BTA9 and BTA16, respectively. Conclusions The findings of this study validate the association of SNPs with JD MAP infection status and highlight the need to further investigate the genomic regions harboring these SNPs

Transcriptomic signature of Bexarotene (Rexinoid LGD1069) on mammary gland from three transgenic mouse mammary cancer models

Background: The rexinoid bexarotene (LGD1069, Targretin) is a highly selective retinoid × receptor (RXR) agonist that inhibits the growth of pre-malignant and malignant breast cells. Bexarotene was shown to suppress the development of breast cancer in transgenic mice models without side effects. The chemopreventive effects of bexarotene are due to transcriptional modulation of cell proliferation, differentiation and apoptosis. Our goal in the present study was to obtain a profile of the genes modulated by bexarotene on mammary gland from three transgenic mouse mammary cancer models in an effort to elucidate its molecular mechanism of action and for the identification of biomarkers of effectiveness. Methods: Serial analysis of gene expression (SAGE) was employed to profile the transcriptome of p53-null, MMTV-ErbB2, and C3(1)-SV40 mammary cells obtained from mice treated with bexarotene and their corresponding controls. Results: This resulted in a dataset of approximately 360,000 transcript tags representing over 20,000 mRNAs from a total of 6 different SAGE libraries. Analysis of gene expression changes induced by bexarotene in mammary gland revealed that 89 genes were dysregulated among the three transgenic mouse mammary models. From these, 9 genes were common to the three models studied. Conclusion: Analysis of the indicated core of transcripts and protein-protein interactions of this commonly modulated genes indicate two functional modules significantly affected by rexinoid bexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targeting of cancer-causing genes related with cell proliferation, differentiation and apoptosis.Centro de Investigaciones Inmunológicas Básicas y Aplicada

Commercial Vegetable Weed, Insect, and Disease Control Guide: Beets, Carrots, Lettuce, Onions, Parsnips, Radishes, Rutabagas, Turnips, Spinach (Revised 1983)

This archival publication may not reflect current scientific knowledge or recommendations. Current information available from the University of Minnesota Extension: https://www.extension.umn.edu

Abdominal wall and labial edema presenting in a girl with Henoch-Schönlein purpura: a case report

<p>Abstract</p> <p>Introduction</p> <p>Henoch-Schönlein purpura is a common immunoglobulin A-mediated vasculitic syndrome in children, characterized by purpuric rash, arthritis and abdominal pain. Renal involvement, manifested by the presence of hematuria and/or proteinuria, is also frequently seen. In most cases, patients with this disease achieve complete recovery, but some progress to renal impairment. Gastro-intestinal manifestations are present in two-thirds of affected patients and range from vomiting, diarrhea, and peri-umbilical pain to serious complications such as intussusception and gastrointestinal hemorrhage.</p> <p>Case presentation</p> <p>We report the case of a 7-year-old Caucasian girl who presented with abdominal pain, labial swelling, and a large abdominal ecchymosis two weeks after having been diagnosed with Henoch-Schönlein purpura. A computed tomography scan revealed abdominal wall edema extending to the groin, without any intra-abdominal pathology. She was successfully treated with intravenous steroids.</p> <p>Conclusion</p> <p>Circumferential anterior abdominal wall edema and labial edema have never been reported previously, to the best of our knowledge, as a complication of Henoch-Schönlein purpura. These findings further contribute to the wide spectrum of manifestations of this disorder in the literature, aiding in its recognition and management.</p