Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture

We have recently described a nonnucleoside compound that specifically inhibits the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS. This compound, nevirapine (BI-RG-587), interacts with highly conserved tyrosine residues at positions 181 and 188 in the reverse transcriptase to inhibit the recombinant enzyme and virus replication in cell culture with 50% inhibitory concentrations in the 40 nM range. HIV-1 variants resistant to nevirapine emerged with passage in cell culture in the presence of drug. This resistant phenotype was stable with continued passage in the absence of drug. These mutants had a substitution of cysteine for the tyrosine at position 181. Introduction of this mutation into the recombinant enzyme increased the inhibitory concentration of nevirapine 100-fold. Substitution of cysteine for tyrosine at residue 181 into the wild-type viral genome conferred a similar reduction in susceptibility to nevirapine. Mutants were also resistant to a tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione derivative and two 6-phenylthiouracil derivatives but retained their sensitivity to the other reverse transcriptase inhibitors, 3'-azido-3'-deoxythymidine and foscarnet

Psoriasis Carries an Increased Risk of Venous Thromboembolism: A Danish Nationwide Cohort Study

Psoriasis is an immunoinflammatory disease associated with cardiovascular risk factors, atherothrombotic events, and hypercoagulability. Venous thromboembolism (VTE) is potentially lethal and shares risk factors with psoriasis, but the risk of VTE associated with psoriasis is unknown. The present study investigated the potential association between psoriasis and VTE.Information from nationwide prospectively recorded registers of hospitalization, drug dispensing from pharmacies, socio-economic data, and causes of death was linked on an individual level. In an unselected nationwide cohort, we used multivariate Poisson regression models controlling for age, gender, comorbidity, concomitant medication, socio-economic data, and calendar year, to assess the risk of VTE associated with psoriasis. A total of 35,138 patients with mild and 3,526 patients with severe psoriasis were identified and compared with 4,126,075 controls. Patients with psoriasis had higher incidence rates per 1000 person-years of VTE than controls (1.29, 1.92, and 3.20 for controls, mild psoriasis, and severe psoriasis, respectively). The rate ratio (RR) of VTE was elevated in all patients with psoriasis with RR 1.35 (95% confidence interval [CI] 1.21–1.49) and RR 2.06 (CI 1.63–2.61) for mild and severe psoriasis, respectively. Exclusion of patients with malignancies, and censoring of patients undergoing surgery did not alter the results.This nationwide cohort study indicates that patients with psoriasis are at increased risk of VTE. The risk was highest in young patients with severe psoriasis. Physicians should be aware that patients with psoriasis may be at increased risk of both venous and arterial thromboembolic events

Psoriasis and Hypertension Severity: Results from a Case-Control Study

BACKGROUND: Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized. OBJECTIVE: We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients. APPROACH: We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients. KEY RESULTS: Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p < 0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p < 0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68-13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01-24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58-37.33) in multivariable analysis after adjusting for traditional cardiac risk factors. CONCLUSIONS: Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients

What’s new in psoriasis treatment? An analysis of systematic reviews published in 2015

This review provides a summary of key findings from 27 systematic reviews of 51 articles first published or indexed during 2015, focusing on the treatment of psoriasis as well as precision medicine in psoriasis. Evidence supports weight loss interventions by dieting and exercise for the improvement in disease severity in overweight and obese patients with psoriasis. No significant increased risk of serious infections were reported for the biologic therapies adalimumab, etanercept and ustekinumab when compared with appropriate comparators. Evidence could not provide reliable estimates of rare adverse events, underscoring the need for large prospective registries. Polymorphisms in the tumour necrosis factor (TNF) alpha gene may confer improved responses to TNF inhibitor (TNFI) therapy, but studies to date lack power to detect true association. From limited available evidence, multidisciplinary management is both more effective and more satisfactory for patients with psoriasis and psoriatic arthritis than conventional consultations. This summary of reviews provides a succinct guide for clinicians and patients wishing to remain up‐to‐date with high quality evidence for the treatment of psoriasis

Imágenes arquetipicas del horror en el videojuego Silent Hill

El videojuego como producto cultural ha sufrido una acelerada evolución en los últimos años, consecuencia de las nuevas tecnologías presentes en su desarrollo, las cuáles hacen más complejo el proceso de producción y por lo mismo, sus temáticas también son más elaboradas. En este contexto, la presente investigación está basada en la búsqueda de los símbolos y arquetipos manifiestos en el videojuego Silent Hill, los cuáles son utilizados con el fin de ambientar y dar al jugador una experiencia completa cargada de emociones, a la par de los elementos audiovisuales e interactivos que acompañan al producto. Identificando estos símbolos y arquetipos a través de una metodología de la psicología se podrán obtener conclusiones acerca de si éstos son importantes en la construcción de la narrativa de horror en Silent Hill, o si simplemente su aparición no es intencional y no influyen en la narrativa del juego

Derivatization and Detection of FAMEs in Ancient North American Soapstone Artifacts

Presentation by Natalie Prodanovich ('18) and Stephen Carmody delivered at the Rhodes College Undergraduate Research and Creative Activity Symposium (URCAS).Prior to the production of pottery 3000 years ago, humans would often carve large bowls out of rock, usually soapstone. Samples of such an artifact from the Thrash site, a Late Archaic period (3,000-1000B.P,) site in Pike Country, Alabama, have been subjected to a three step process for identifying fatty acids, the primary substance of foodstuffs. We used gas chromatography/mass spectroscopy (GC/MS) to analyze samples from the artifact along with samples of natural soapstone. The presence of different fatty acids can provide information about prehistoric dietary habits, whether from fish, mammals and/or plants. For the analysis, however, the fatty acids must be converted (derivatized) to fatty acid methyl esters (FAMEs). We used a method that converts triacylglycerides into FAMES in a one step process. These fatty acids will be correlated to a range of plants and animals that came into an extended period of contact with the artifact