The Impact of COVID-19 on doctors well-being: Results of a web survey during the lockdown in Italy

OBJECTIVE: On March 12, 2020, the World Health Organization (WHO) declared the outbreak of a new Coronavirus disease (COVID-19), to be a pandemic. From the be- ginning, Italy (in particular the Northern re- gions) was the first large European country to be hit and one of the most affected coun- tries worldwide. This had a significant impact on the workload and psychological health of health workers. The aim of this web-based cross-sectional study is to assess the con- sequences of the COVID-19 pandemic on Ital- ian doctors’ well-being and psychological dis- tress, in respect of demographic and occu- pational characteristics, lifestyle and habits during the lockdown period.PATIENTS AND METHODS: We conducted a web-based cross-sectional survey based on Google® Forms to collect data. The participa- tion was available during the lockdown period that started in Italy on March 9, 2020 and it was voluntary and anonymous. The question- naire explored demographic and occupational variables, lifestyle and habits during the lock- down, perceived well-being and psychological distress. Multivariate logistic regression models were fitted. RESULTS: Our study reported the very alarm- ing psychological conditions of Italian doctors, especially among those who worked in the most affected regions, where a level of psychological distress of 93.8% and poor well-being of 58.9% were registered. These percentages were even higher in the case of female hospital workers with low job seniority, and those caring for COVID-19 patients. CONCLUSIONS: Our findings reported a sig- nificant psychosocial impact of the COVID-19 outbreak on Italian doctors, particularly among those working in the most affected regions of the country. Further studies are necessary to better understand the effects of the COVID-1

Pharmacists' mental health during the SARS-CoV-2 pandemic in Italy

OBJECTIVE: The year 2020 was characterized by the outbreak of a new pandemic caused by a novel coronavirus named SARSCoV- 2. To face the pandemic, many countries worldwide imposed general lockdowns, closing all non-essential businesses. As primary care services, pharmacies had to remain open, thus putting pharmacy staff at significant risk of viral infection and overwork. This study aimed to assess the mental health of Italian Pharmacists, considering demographic and occupational characteristics, lifestyle, and habits, during the SARS-CoV-2 outbreak and the subsequent lockdown period (March-May 2020). MATERIALS AND METHODS: A web-based survey was created using Google® Forms to collect data from March 30, 2020, to June 1, 2020. The questionnaire consisted of three sections investigating: (1) demographic and occupational variables, (2) lifestyle and habits variables, (3) psychological distress and perceived well-being. RESULTS: A total of 401 participants completed the questionnaire. Older workers and those with more work experience reported more psychological stress. Older and female workers, who felt lonely at home and reported psychological stress, perceived poor well-being. CONCLUSIONS: Our findings demonstrate that the Sars-CoV-2 outbreak and subsequent lockdown rules affected pharmacists' mental health and that it is important to put in place preventive measures against the occurrence of mental disorders among them

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

Taphonomic phenomenon of ancient hair from Glacial Beringia:perspectives for palaeoecological reconstructions

An accumulation of mammoth hair, discovered in the Bol'shaya Chukochya River valley (northeast Yakutia, Russia), was found to contain remains of terrestrial and aquatic organisms, including plants, insects, crustaceans, birds and mammals. Radiocarbon dating indicated that this post-mortem taphocoenosis represented multiple time periods. The mammoth hair was dated to older than 45 ka BP, the plants were dated to 12 750 +/- 50 a BP (which corresponds to a shift in the environmental conditions and landscapes during the formation of thermokarst in northeastern Russia) and the bird feathers were dated to 4115 +/- 40 a BP. A scenario of the formation of this fossil assemblage is proposed, covering the MIS 3-1 time range. The hair also yielded various Arctic branchiopod crustaceans, which inhabit shallow temporary water bodies and therefore are important for reconstruction of palaeoenvironments. The cladoceran subgenus Daphnia (Ctenodaphnia), currently absent from the Asian part of Beringia, is reported from this region for the first time. The study demonstrates that the discovered permafrostpreserved hair is a unique repository of Ice Age organisms.</p

Optimization of intravascular volume determination in patients with acute decompensated heart failure

Acute decompensated heart failure (ADHF) is based on multilevel pathological pathways, which include hemodynamic overload and venous stasis. Determination of the volemic status is one of the most important tasks in managing such patients. Despite the availability of modern diagnostic markers (physical examination, chest x-ray, and brain natriuretic peptide (BNP) assessment), they do not accurately assess the degree of fluid overload, and therefore there remains a need to find a new, accurate and simple technology for assessing pulmonary congestion. The urgency of this problem has led to the development of a novel non-invasive remote dielectric sensing (ReDS) technology, which is a quantitative method for measuring the total volume of lung fluid by determining the tissue dielectric properties. The use of this technology makes it possible to quickly, non-invasively and quantitatively measure the fluid content in the lungs, makes it possible to optimize the treatment regimen and reduces the number of readmissions. This article presents the results of studies on the efficacy, safety and prospects for using a ReDS technology for the quantitative measurement of total lung fluid in patients with ADHF

The diacylglycerol kinase α/Atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness

Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells

ERS statement: A core outcome set for clinical trials evaluating the management of COPD exacerbations

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use

Nuclear Localization of CXCR4 Determines Prognosis for Colorectal Cancer Patients

Chemokines and their receptors are implicated in formation of colorectal cancer metastases. Especially CXCR4 is an important factor, determining migration, invasiveness, metastasis and proliferation of colorectal cancer cells. Object of this study was to determine expression of CXCR4 in tumor tissue of colorectal cancer patients and associate CXCR4 expression levels to clinicopathological parameters. Levels of CXCR4 expression of a random cohort of patients, who underwent primary curative resection of a colorectal carcinoma, were retrospectively determined by quantitative real-time RT-PCR and semi-quantitative analyses of immunohistochemical stained paraffin sections. Expression levels were associated to clinicopathological parameters. Using RT-PCR we found that a high expression of CXCR4 in the primary tumor was an independent prognostic factor for a poor disease free survival (p = 0.03, HR: 2.0, CI = 1.1–3.7). Immunohistochemical staining showed that nuclear distribution of CXCR4 in the tumor cells was inversely associated with disease free and overall survival (p = 0.04, HR: 2.6, CI = 1.0–6.2), while expression in the cytoplasm was not associated with prognosis. In conclusion, our study showed that a high expression of nuclear localized CXCR4 in tumor cells is an independent predictor for poor survival for colorectal cancer patients

Mesenchymal Stem Cells in Early Entry of Breast Cancer into Bone Marrow

BACKGROUND: An understanding of BC cell (BCC) entry into bone marrow (BM) at low tumor burden is limited when compared to highly metastatic events during heavy tumor burden. BCCs can achieve quiescence, without interfering with hematopoiesis. This occurs partly through the generation of gap junctions with BM stroma, located close to the endosteum. These events are partly mediated by the evolutionary conserved gene, Tac1. METHODOLOGY/PRINCIPAL FINDINGS: This study focuses on the role of mesenchymal stem cells (MSCs), Tac1, SDF-1 and CXCR4 in BCC entry into BM. The model is established in studies with low numbers of tumor cells, and focuses on cancer cells with low metastatic and invasion potential. This allowed us to recapitulate early event, and to study cancer cells with low invasive potential, even when they are part of larger numbers of highly metastatic cells. A novel migration assay showed a facilitating role of MSCs in BCC migration across BM endothelial cells. siRNA and ectopic expression studies showed a central role for Tac1 and secondary roles for SDF-1alpha and CXCR4. We also observed differences in the mechanisms between low invasive and highly metastatic cells. The in vitro studies were verified in xenogeneic mouse models that showed a preference for low invasive BCCs to BM, but comparable movement to lung and BM by highly metastatic BCCs. The expressions of Tac1 and production of SDF-1alpha were verified in primary BCCs from paired samples of BM aspirates and peripheral blood. CONCLUSIONS/SIGNIFICANCE: MSC facilitate BCC entry into BM, partly through Tac1-mediated regulation of SDF-1alpha and CXCR4. We propose a particular population of BCC with preference for BM could be isolated for characterization. This population might be the subset that enter BM at an early time period, and could be responsible for cancer resurgence and resistance to current therapies