Search

Background: Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population. Patients and methods: In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs. Results: A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001). Conclusions: MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A c

Polyamory is an umbrella term denoting the practice of having multiple romantic and intimate relationships with the consent of everyone involved. Within a mononormative culture, becoming polyamorous may be associated with uncertainty and a feeling of being suspended. Moreover, the preferential attitude towards monogamy marginalises polyamory as indecent and corrupt, creating feelings of shame and social isolation. Our research explored the discursive construction of polyamory in Italy by identifying the strategies used to deal with such identity construction and social recognition issues. We conducted 15 semistructured interviews with people who defined themselves as polyamorous. Our discourse analysis identified a narrative that overturns the dominant hegemonic perspective; this narrative presented monogamy as a practice generating difficulties and problems and polyamory as a thoroughly satisfying and adequate relational modality. This narrative was constructed using six discursive strategies, allowing participants to achieve three discursive purposes. By naturalising polyamory and constructing it as a stable trait, participants essentialised polyamory; by providing a normative definition of polyamory and identifying with the polyamorous community, they set up the boundaries of polyamory; finally, by moralising polyamory and attributing transformative power to it, they valorised polyamory. Overall, the definition of a polyamorous order allows for the integration of polyamory into one’s life, even if polyamorists remain a minority group trapped in the public liminality brought about by a mononormative culture.

Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph-chromosome and the BCR-ABL tyrosine-kinase (TK). Target-therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second-generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin−Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in-vivo activity and timecourse of first-line Nilotinib therapy on BM CD34+/lin−Ph+ cells clearance. Eighty-seven CP-CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin− cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per-Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin− cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK-STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed.

Background: Illness expectations are cognitive schemas, both explicit and implicit, describing how symptoms are expected to be in the future. They can be particularly relevant to disease in a mind/body framework. Asthma is a condition in which the psychological aspects can highly influence the body, but no study has directly explored these specific expectations, and no dedicated assessment tools are available. Methods: We developed a questionnaire to assess the illness expectations, together with an ad hoc version of the Implicit Association Test (IAT). We tested its factorial structure, and the internal and test–retest validity, recruiting a sample of 183 asthmatic people. We also explored the convergent validity and the correlations with objective and subjective clinical assessments. Results: Data suggested a three-factorial structure of the questionnaire into expectations about future symptoms, change in current health status, and rigidity of these expectations. The questionnaire showed good psychometric properties and strong associations with the other considered outcomes, including implicit expectations. The implicit evaluation, however, lacked test–retest reliability. Conclusion: The questionnaire is a valid tool to assess illness expectations in people with asthma. The two expectation scales are highly related, and the implicit expectations are moderately associated with the explicit ones. The lack of stability related to IAT results may reflect a lack of stability of the implicit expectations. The implications for the mind/body framework still need to be fully explored.

The safety and activity of immune checkpoint inhibitors have been characterized in interventional and observational studies. However, only small studies have specifically investigated these agents in patients who are excluded or underrepresented in clinical trials, frequently referred to as “special populations” or “underrepresented populations.” These include older adults, those with dysregulated immune activation, patients with a compromised immune function, and those carrying major viral infections, lymphoproliferative diseases, and major organ dysfunctions. Therefore, there remains substantial uncertainty regarding the use of immune checkpoint inhibitors in these specific settings. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project, with the contribution of oncologists and other specialists, to retrieve the existing evidence on the use of immunotherapy in patients with solid and hematological cancers with the final aim to provide an expert guidance. The results of this effort are presented in this article, which is focused on patients with major viral infections or those with immune dysregulation/autoimmune diseases, and could be useful to guide decisions in clinical practice and to design prospective clinical trials focusing on the use of immunotherapy in these populations. Implications for Practice: Substantial uncertainty remains regarding the use of immune checkpoint inhibitors in “underrepresented” patients, such as older adults, those with dysregulated immune activation, and patients with a compromised immune function, major viral infections, lymphoproliferative diseases or major organ dysfunctions. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project to retrieve the existing evidence on the use of immunotherapy in underrepresented patients with cancer in order provide an expert guidance. The results of this effort, with a focus on patients with major viral infections or

Transiting species, phenologies and their trends. In order to contribute to the knowledge of the spatio-temporal pro­gression of post-nuptial migration of birds across the Italian Alps, we present in detail the results of the analysis carried out for 69 species (4 non-Passeriformes; 65 Passeriformes) of the 191 ringed within the Progetto Alpi. Data were collected in 40 ringing stations located in different habi­tats and at different altitudes (mountain passes, slopes and valley floors) and active in the post-breeding migratory period (1 August - 30 Novem­ber). Among these, those (n=15) with continuous activity (at least one month) and known sampling effort (daily capture effort described as product of net area in square meters by operating time in hours) were selected. Data from the 6 stations that operated continuously over the years (2001-2017) and with standardised capture effort were used for trend analyses. Species covered refer to those with more than 100 birds ringed within the first eight hours after sunrise (excluding local retraps). Species accounts contain detailed data from datasets from all stations participating in the Alps Project (1997-2017).

Marmora’s Warbler (Curruca sarda) and Balearic Warbler (C. balearica) are allopatric sibling species and were recently split mostly based on morphological and ethological characteristics. Here we provide the first phylogenetic and phylogeographic analyses of this species complex to support the taxonomic status of C. sarda and C. balearica in light of integrative taxonomy. We sampled the two taxa in most of their breeding ranges and we sequenced three mitochondrial and one nuclear gene region. All C. balearica individuals had private haplotypes for the four markers and formed monophyletic clades. Genetic distances between the two taxa were comparable with those found between other species belonging to the Curruca genus. Furthermore, most of the genetic variance was expressed at the interspecific level, rather than between different populations within taxa or between individuals within populations. Our results strongly support the current taxonomic status of these two warblers as distinct species.

A key goal of conservation is to protect biodiversity by supporting the long-term persistence of viable, natural populations of wild species. Conservation practice has long been guided by genetic, ecological and demographic indicators of risk. Emerging evidence of animal culture across diverse taxa and its role as a driver of evolutionary diversification, population structure and demographic processes may be essential for augmenting these conventional conservation approaches and decision-making. Animal culture was the focus of a ground-breaking resolution under the Convention on the Conservation of Migratory Species of Wild Animals (CMS), an international treaty operating under the UN Environment Programme. Here, we synthesize existing evidence to demonstrate how social learning and animal culture interact with processes important to conservation management. Specifically, we explore how social learning might influence population viability and be an important resource in response to anthropogenic change, and provide examples of how it can result in phenotypically distinct units with different, socially learnt behavioural strategies. While identifying culture and social learning can be challenging, indirect identification and parsimonious inferences may be informative. Finally, we identify relevant methodologies and provide a framework for viewing behavioural data through a cultural lens which might provide new insights for conservation management.

The microbial community of a plastic-polluted landfill soil was described. Among the isolated fungi, some of them showed important degradation skills against polyethylene.

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin-cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib.