Antiemetics: American Society of Clinical Oncology clinical practice guideline update

Purpose: To update the ASCO guideline for antiemetics in oncology. Methods: ASCO convened an Expert Panel and conducted a systematic review of the medical literature for the period of November 2009 to June 2016. Results: Forty-one publications were included in this systematic review. A phase III randomized controlled trial demonstrated that adding olanzapine to antiemetic prophylaxis reduces the likelihood of nausea among adult patients who are treated with high emetic risk antineoplastic agents. Randomized controlled trials also support an expanded role for neurokinin 1 receptor antagonists in patients who are treated with chemotherapy. Recommendation: Key updates include the addition of olanzapine to antiemetic regimens for adults who receive high-emetic-risk antineoplastic agents or who experience breakthrough nausea and vomiting; a recommendation to administer dexamethasone on day 1 only for adults who receive anthracycline and cyclophosphamide chemotherapy; and the addition of a neurokinin 1 receptor antagonist for adults who receive carboplatin area under the curve ≥ 4 mg/mL per minute or high-dose chemotherapy, and for pediatric patients who receive high-emetic-risk antineoplastic agents. For radiation-induced nausea and vomiting, adjustments were made to anatomic regions, risk levels, and antiemetic administration schedules. Rescue therapy alone is now recommended for low-emetic-risk radiation therapy. The Expert Panel reiterated the importance of using the most effective antiemetic regimens that are appropriate for antineoplastic agents or radiotherapy being administered. Such regimens should be used with initial treatment, rather than first assessing the patient’s emetic response with less-effective treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki

Prevention of methamphetamine-induced microglial cell death by TNF-α and IL-6 through activation of the JAK-STAT pathway

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>It is well known that methamphetamine (METH) is neurotoxic and recent studies have suggested the involvement of neuroinflammatory processes in brain dysfunction induced by misuse of this drug. Indeed, glial cells seem to be activated in response to METH, but its effects on microglial cells are not fully understood. Moreover, it has been shown that cytokines, which are normally released by activated microglia, may have a dual role in response to brain injury. This led us to study the toxic effect of METH on microglial cells by looking to cell death and alterations of tumor necrosis factor-alpha (TNF-α) and interleukine-6 (IL-6) systems, as well as the role played by these cytokines.</p> <p><b>Methods</b></p> <p>We used the N9 microglial cell line, and cell death and proliferation were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and incorporation of bromodeoxyuridine, respectively. The TNF-α and IL-6 content was quantified by enzyme-linked immunosorbent assay, and changes in TNF receptor 1, IL-6 receptor-alpha, Bax and Bcl-2 protein levels by western blotting. Immunocytochemistry analysis was also performed to evaluate alterations in microglial morphology and in the protein expression of phospho-signal transducer and activator of transcription 3 (pSTAT3).</p> <p><b>Results</b></p> <p>METH induced microglial cell death in a concentration-dependent manner (EC₅₀ = 1 mM), and also led to significant morphological changes and decreased cell proliferation. Additionally, this drug increased TNF-α extracellular and intracellular levels, as well as its receptor protein levels at 1 h, whereas IL-6 and its receptor levels were increased at 24 h post-exposure. However, the endogenous proinflammatory cytokines did not contribute to METH-induced microglial cell death. On the other hand, exogenous low concentrations of TNF-α or IL-6 had a protective effect. Interestingly, we also verified that the anti-apoptotic role of TNF-α was mediated by activation of IL-6 signaling, specifically the janus kinase (JAK)-STAT3 pathway, which in turn induced down-regulation of the Bax/Bcl-2 ratio.</p> <p><b>Conclusions</b></p> <p>These findings show that TNF-α and IL-6 have a protective role against METH-induced microglial cell death via the IL-6 receptor, specifically through activation of the JAK-STAT3 pathway, with consequent changes in pro- and anti-apoptotic proteins.</p

Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia

Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia

SVILUPPO DI UNA METODOLOGIA DI TRACCIABILITÀ E DEFINIZIONE DELL’IMPRONTA PETROCHIMICA IN SUOLI E VINI DELLA SICILIA OCCIDENTALE NELLA PIANA DI MARSALA (TP).

Research studies carried out on a vineyard, selected on the basis of the bio-agronomic factors’ homogeneity (age, cultivation techniques, production capability…), in the Marsala Plain (TP) Sicily, have permitted to define geochemical fingerprints inherited by grapes and wines. 24 soil’s samples (gathered in correspondence of the root system) of 4 different cultivar types (6 from Nero D’Avola, 6 from Refosco dal peduncolo rosso, 6 from Fiano and 6 from Verdicchio) were collected. The soil samples were characterized by XRF chemical analysis and the wine samples were analysed by ICP-MS technique. The Marsala Plain is test site both for soils and for the presence of an aquifer characterized by good quality of water and lack of salinisation processes. These pilot site is located in an area currently interested by desertification phenomena and for this reason carefully monitored. This situation can be helpful in order to characterize the features of grapes and wines in several vintage years contributing on the comprehension of the effects of desertification on the production of wine. Analysis of different cultivar were focused on the definition of particular grapevine varieties less sensitive to climatic stress conditions, in order to plan suitable qualification actions to face the impact of climatic changes foreseen in the Mediterranean area. The aim of this study is to define the background standard values for inorganic macro and micronutrients, acquiring the essential data set useful for the evaluation of climatic changes and desertification effects on the wine quality

Sex-biased dispersal obscures species boundaries in integrative species delimitation approaches

Accurate delimitation of species is crucial for a stable taxonomy, which provides the foundation for the study of evolutionary biology, ecology, and essentially all biological disciplines. Several approaches toward impartial and repeatable taxonomic practices are available but all existing methods have potentially unacceptable shortcomings. In particular, problems can arise when the underlying model assumptions are violated, for instance, in the presence of reduced gene flow. This is observed in the context of sex-biased dispersal, which is a common but underappreciated feature in many groups of organisms. Previously, simulations have indicated that sex-biased dispersal may lead to erroneous estimations of the true species numbers. However, this phenomenon has never been examined using empirical data. We evaluate the bias introduced by extreme female philopatry on a range of de novo [GMYC, PTP, ABGD, statistical parsimony, trinomial distribution of triplets model (tr2)] and validation (STACEY, iBPP) approaches to species delimitation in the scarab beetle genus Pachypus. Since female philopatry exhibitedinthis genusinparticular can affectmitochondrial geneflow, wecompared the results from analyses of single loci, mitochondrial loci, nuclear loci and combined data, as well as the performance of morphometric data as a secondary data source in a fully integrative Bayesian framework. Large overestimation of species numbers was observed across all analyses of combined and mitochondrial DNA data sets, suggesting specimens from nearly every sampling location as separate species. The use of nuclear data resulted in more reasonable estimations of species boundaries, which were largely supported by morphometrics of linear measurements, while geometric morphometrics of body outlines resulted in stronger splitting. Simulations of population divergence with migration, corresponding to the biology of Pachypus, showed that female philopatry strongly increases reciprocal monophyly of mitochondrial markers and may substantially contribute to over-splitting in species delimitation. Robust results recovered using nuclear DNA and morphological data nevertheless enabled us to reach novel conclusions about species boundaries in Pachypus. Our findings suggest that mitochondrial DNA will be less suited to species delimitation in many cases, in particular in the presence of sex-biased dispersal

Self-administered mindfulness interventions reduce stress in a large, randomized controlled multi-site study

Mindfulness witnessed a substantial popularity surge in the past decade, especially as digitally self-administered interventions became available at relatively low costs. Yet, it is uncertain whether they effectively help reduce stress. In a preregistered (OSF https://doi.org/10.17605/OSF.IO/UF4JZ; retrospective registration at ClinicalTrials.gov NCT06308744) multi-site study (nsites = 37, nparticipants = 2,239, 70.4% women, Mage = 22.4, s.d.age = 10.1, all fluent English speakers), we experimentally tested whether four single, standalone mindfulness exercises effectively reduced stress, using Bayesian mixed-effects models. All exercises proved to be more efficacious than the active control. We observed a mean difference of 0.27 (d = −0.56; 95% confidence interval, −0.43 to −0.69) between the control condition (M = 1.95, s.d. = 0.50) and the condition with the largest stress reduction (body scan: M = 1.68, s.d. = 0.46). Our findings suggest that mindfulness may be beneficial for reducing self-reported short-term stress for English speakers from higher-income countries