Skin Lesions Associated with E. Coli Sepsis in a Patient with Acute Leukemia

The clinical course of a patient with acute leukemia and metastatic intradermal abscesses secondary to Escherichia coli sepsis is described. E. coli organisms, cultured first from the blood and later from the lesions, had an identical antibiotic susceptibility and biotyping profile. This complication has not been previously described. Granulocytopenia and varicose veins may have been critical predisposing factors. With more widespread use of progressive immunosuppressive regimens, unusual manifestations of common infections will be recognized more frequently

The application of deep eutectic solvent ionic liquids for environmentally-friendly dissolution and recovery of precious metals

publisher: Elsevier articletitle: The application of deep eutectic solvent ionic liquids for environmentally-friendly dissolution and recovery of precious metals journaltitle: Minerals Engineering articlelink: http://dx.doi.org/10.1016/j.mineng.2015.09.026 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.© 2015 Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Role of Kindness in Cancer Care

The wonders of high-tech cancer care are best complemented by the humanity of high-touch care. Simple kindnesses can help to diffuse negative emotions that are associated with cancer diagnosis and treatment-and may even help to improve patients\u27 outcomes. On the basis of our experience in cancer care and research, we propose six types of kindness in cancer care: deep listening , whereby clinicians take the time to truly understand the needs and concerns of patients and their families; empathy for the patient with cancer, expressed by both individual clinicians and the care culture, that seeks to prevent avoidable suffering; generous acts of discretionary effort that go beyond what patients and families expect from a care team; timely care that is delivered by using a variety of tools and systems that reduce stress and anxiety; gentle honesty, whereby the truth is conveyed directly in well-chosen, guiding words; and support for family caregivers, whose physical and mental well-being are vital components of the care their loved ones receive. These mutually reinforcing manifestations of kindness-exhibited by self-aware clinicians who understand that how care is delivered matters-constitute a powerful and practical way to temper the emotional turmoil of cancer for patients, their families, and clinicians themselves

The Genetic Basis of Natural Variation in Drosophila melanogaster Immune Defense against Enterococcus faecalis

This work is licensed under a Creative Commons Attribution 4.0 International License.Dissecting the genetic basis of natural variation in disease response in hosts provides insights into the coevolutionary dynamics of host-pathogen interactions. Here, a genome-wide association study of Drosophila melanogaster survival after infection with the Gram-positive entomopathogenic bacterium Enterococcus faecalis is reported. There was considerable variation in defense against E. faecalis infection among inbred lines of the Drosophila Genetics Reference Panel. We identified single nucleotide polymorphisms associated with six genes with a significant (p < 10−08, corresponding to a false discovery rate of 2.4%) association with survival, none of which were canonical immune genes. To validate the role of these genes in immune defense, their expression was knocked-down using RNAi and survival of infected hosts was followed, which confirmed a role for the genes krishah and S6k in immune defense. We further identified a putative role for the Bomanin gene BomBc1 (also known as IM23), in E. faecalis infection response. This study adds to the growing set of association studies for infection in Drosophila melanogaster and suggests that the genetic causes of variation in immune defense differ for different pathogens

Вемурафениб улучшает выживаемость при меланоме кожи с мутацией BRAF V600E

В 40–60% случаев меланомы кожи выявляют мутации онкогена BRAF, следствием которых является конститутивная активация серинтреониновой киназы BRAF и, соответственно, митогенного сигнала по пути MAPK/ERK. Представлены результаты международных рандомизированных исследований I, II, III фазы, в которых оценивали эффективность и токсичность ингибитора RAF-киназной активности вемурафениба (PLX4032, Зелбораф) у больных метастатической меланомой кожи с мутацией BRAF V600E. В исследовании III фазы BRIM3 сравнивали режимы монотерапии вемурафенибом (960 мг перорально 2 раза в сутки — 337 пациентов и дакарбазином (1000 мг/м2 внутривенно каждые 3 нед — 338 пациентов). Первичными точками исследования были общая выживаемость и выживаемость без прогрессирования, вторичными — частота объективного ответа, его длительность, время до развития ответа. Анализ данных после 6 мес наблюдения показал, что применение вемурафениба приводило к относительному снижению риска смерти на 63% и риска прогрессирования заболевания на 74% по сравнению с дакарбазином (р < 0,001 для обоих показателей). Объективный ответ зафиксирован в 48% случаев в группе вемурафениба и в 5% случаев — дакарбазина. Наиболее частыми токсическими эффектами вемурафениба были артралгии, сыпь, общая слабость, алопеция, плоскоклеточная карцинома кожи и кератоакантома, фотосенсибилизация, тошнота, диарея; сокращение дозы, связанное с токсичностью, потребовалось у 38% пациентов. По результатам исследования сделан вывод об эффективности вемурафениба у нелеченных ранее больных метастатической меланомой кожи с мутацией BRAF V600E.40 to 60% of cutaneous melanomas carry mutations in BRAF that lead to constitutive activation of BRAF serine/threonine kinase and downstream signaling through the MAPK/ERK pathway. Phase I and II clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032, Zelboraf) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. In a phase III randomized clinical trial (BRIM-3) comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. At 6 months, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (p < 0,001 for both comparisons). Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation

David Versus Goliath: Strategic Behavior of Small Firms In Consolidated Industries

This study assesses the effect of strategy selection and firm adaptability on small firm performance,  using firm  tenure  as a moderator  variable.  The study  is based  upon interviews with sixteen small firms operating in rapidly changing and consolidating industries. All of the firms in the study pursued a differentiation strategy. Half of the firms  pursued  a  broad product strategy and more than three-quarters pursued a broad service strategy. The study found that small firms adapt by addressing community needs and forming cooperative agreements with other small firms but not larger firms. Variation among the industries studied suggests that the intensity of industry concentration affects firm adaptation decisions. For instance, while the heavily concentrated hardware anti drugstore industries  showed limited adaptation, the unconsolidated bookstore industry showed greater commitment to adaptive strategies. In addition, firm tenure was found to affect the adaptation of the small firms  studied

Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's &lt; .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure