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Background There are a large number of assessment tools for tinnitus, with little consensus on what it is important to measure and no preference for a minimum reporting standard. The item content of tinnitus assessment tools should seek to capture relevant impacts of tinnitus on everyday life, but no-one has yet synthesised information about the range of tinnitus complaints. This review is thus the first comprehensive and authoritative collection and synthesis of what adults with tinnitus and their significant others report as problems in their everyday lives caused by tinnitus. Methods Electronic searches were conducted in PubMed, Embase, CINAHL, as well as grey literature sources to identify publications from January 1980 to June 2015 in which participants were enrolled because tinnitus was their primary complaint. A manual search of seven relevant journals updated the search to December 2017. Of the 3699 titles identified overall, 84 records (reporting 86 studies) met our inclusion criteria and were taken through to data collection. Coders collated generic and tinnitus-specific complaints reported by people with tinnitus. All relevant data items were then analyzed using an iterative approach to narrative synthesis to form domain groupings representing complaints of tinnitus, which were compared patients and significant others. Results From the 86 studies analyzed using data collected from 16,381 patients, 42 discrete complaints were identified spanning physical and psychological health, quality of life and negative attributes of the tinnitus sound. This diversity was not captured by any individual study alone. There was good convergence between complaints collected using open- and closed-format questions, with the exception of general moods and perceptual attributes of tinnitus (location, loudness, pitch and unpleasantness); reported only using closed questions. Just two studies addressed data from the perspective of significant others ( n  = 79), but there was substantial correspondence with the patient framework, especially regarding relationships and social life. Conclusions Our findings contribute fundamental new knowledge and a unique resource that enables investigators to appreciate the broad impacts of tinnitus on an individual. Our findings can also be used to guide questions during diagnostic assessment, to evaluate existing tinnitus-specific HR-QoL questionnaires and develop new ones, where necessary. Trial Registration PROSPERO registration number: CRD42015020629 . Protocol published in BMJ Open. 2016;6e009171.

Background During COVID-19 pandemic, healthcare workers (HCWs) have had high workload and have been exposed to multiple psychosocial stressors. The aim of this study was to evaluate HCWs in terms of the relative contributions of socio-demographic and mental health variables on three burnout dimensions: personal, work-related, and client-related burnout. Methods A cross-sectional study was performed using an online questionnaire spread via social networks. A snowball technique supported by health care institutions and professional organizations was applied. Results A total of 2008 subjects completed the survey. Gender, parental status, marriage status, and salary reduction were found to be significant factors for personal burnout. Health problems and direct contact with infected people were significantly associated with more susceptibility to high personal and work-related burnout. Frontline working positions were associated with all three dimensions. Higher levels of stress and depression in HCWs were significantly associated with increased levels of all burnout dimensions. Higher levels of satisfaction with life and resilience were significantly associated with lower levels of all burnout dimensions. Conclusions All three burnout dimensions were associated with a specific set of covariates. Consideration of these three dimensions is important when designing future burnout prevention programs for HCWs.

Cell competition is an emerging principle underlying selection for cellular fitness during development and disease. Competition may be relevant for cancer, but an experimental link between defects in competition and tumorigenesis is elusive. In the thymus, T lymphocytes develop from precursors that are constantly replaced by bone-marrow-derived progenitors. Here we show that in mice this turnover is regulated by natural cell competition between ‘young’ bone-marrow-derived and ‘old’ thymus-resident progenitors that, although genetically identical, execute differential gene expression programs. Disruption of cell competition leads to progenitor self-renewal, upregulation of Hmga1 , transformation, and T-cell acute lymphoblastic leukaemia (T-ALL) resembling the human disease in pathology, genomic lesions, leukaemia-associated transcripts, and activating mutations in Notch1 . Hence, cell competition is a tumour suppressor mechanism in the thymus. Failure to select fit progenitors through cell competition may explain leukaemia in X-linked severe combined immune deficiency patients who showed thymus-autonomous T-cell development after therapy with gene-corrected autologous progenitors. T cells develop from thymic precursor cells that are constantly replaced with newly arriving bone marrow progenitor cells, and the ‘old’ and ‘new’ cells are shown here to compete; in the absence of cell competition, when the influx of new bone marrow progenitor cells is blocked, the old cells acquire the ability to self-renew and eventually become transformed, leading to the development of a form of leukaemia. New T cells for old in the thymus In the thymus, T cells develop from precursor cells that are constantly replaced by newly arriving bone marrow progenitor cells. Hans-Reimer Rodewald and colleagues show that this is the result of competition between the 'old' and 'new' cells. In the absence of cell competition, when the influx of new bone marrow progenitor cells is blocked in mice, old cells reacquire the ability to self-renew and eventually become transformed, leading to the development of T-cell acute lymphoblastic leukaemia (T-ALL) resembling the human disease. At the same time there are changes in gene expression and the appearance of genetic mutations often also found in human T-ALL. Thus cell competition can act as a tumour-suppressor mechanism. This work may also help to explain the widely discussed T-cell leukaemia seen in X-linked severe combined immune deficiency patients after therapy with gene-corrected autologous progenitors.

Epidermal wound healing is a complex and highly coordinated process where several different cell types and molecules, such as growth factors and extracellular matrix (ECM) components, play an important role. Among the many proteins that are essential for the restoration of tissue integrity is the metalloproteinase (MMP) family. MMPs can act on ECM and non-ECM components affecting degradation and modulation of the ECM, growth-factor activation and cell–cell and cell–matrix signalling. MMPs are secreted by different cell types such as keratinocytes, fibroblasts and inflammatory cells at different stages and locations during wound healing, thereby regulating this process in a very coordinated and controlled way. In this article, we review the role of MMPs and their inhibitors (TIMPs), as well as the disintegrin and metalloproteinase with the thrombospondin motifs (ADAMs) family, in epithelial wound repair.

In a time marked by the development of innovative treatments in healthcare and the need for health professionals to deal with resulting ethical dilemmas in clinical practice, this study was developed to determine the influence of the bioethics teaching on the moral competence of medical and nursing students. The authors conduct a longitudinal study using the Moral Competence Test extended version before and after attending the ethics curricular unit, in three nursing schools and three medical schools of Portugal. In this questionnaire the participant is confronted with three ethical dilemmas (related to theft, euthanasia and the torture of a terrorist) and asked to evaluate arguments for and against the attitude of the main character (Worker, doctor and judge). For both nursing and medical students, C-score was lower after the attendance of the ethics curricular units, with a statistically significant decrease in the total score (from 21 to 19.5 on average; p = 0.046) for nursing students and a decrease not statistically significant for medical students (from 23.2 to 22 on average; p = 0.358). A multivariate analysis did not find any association between this decrease and gender, course, or age. The phenomenon of moral segmentation was observed, with better performance in the worker and judge dilemma, than in the doctor dilemma. These results highlight the need to reflect on the curricular strategies that can be implemented for health professionals to better develop moral competence and decision-making, allowing for the provision of humanized health care.

PurposeTo explore the relationship between sustainability and the complexity of the food supply chain (FSC) and to promote adopting a sustainable approach that balances financial growth, environmental preservation and social well-being.Design/methodology/approachAquantitative method approach was employed using a survey of 379 respondents. Principal component analysis (PCA) was employed to evaluate the factors contributing to sustainability and their impact on the complexity of the FSC.FindingsSustainability amplifies the complexity of the FSC. Several factors that influence the complexity attributes were identified, including clean technologies, stakeholder engagement and supply chain coordination.Research limitations/implicationsHighlights the importance of adopting a sustainable approach that balances financial growth, environmental preservation and social well-being in FSCs. It also suggests the need for further research to improve understanding of the factors influencing the complexity of the FSC.Practical implicationsCompanies operating in the FSC should invest in control measures, risk identification and prevention, employee training and awareness and policies and procedures for waste management and environmental sustainability.Social implicationsHighlights the importance of social responsibility in the FSC, including all stakeholders. It also emphasizes the need to minimize negative impacts on the environment and ensure the preservation of natural resources.Originality/valueProvides a comprehensive analysis of the complexity attributes of the FSC and their relationship with sustainability factors. It offers practical and theoretical insights for companies to sustainably manage the FSC.

Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α ( ESR1 ) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance. ESR1 mutations occur in endocrine-resistant patients but have not yet been reported in in vitro models of breast cancer. Here, the authors report the discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in two breast cancer cell lines after acquisition of resistance to long-term-estrogen-deprivation.

Background The COVID-19 pandemic had a large consequence on healthcare systems, increasing the risks of psychological issues in health professionals. Nurses, in particular, have been exposed to multiple psychosocial stressors and struggled with intensive work, insufficiency of resources and uncertainty in the face of an unknown disease. Life satisfaction might protect nurses from the consequences of chronic stress. The aim of this study was to explore the mediating role of satisfaction with life in the relationship between depression, stress, anxiety and burnout (personal, work-related, and client-related). Methods A cross-sectional, descriptive, correlational study design was performed, using an online questionnaire distributed via social networks. A total of 379 nurses completed the survey, comprising standardized measures of satisfaction with life, resilience (Resilience Scale), depression, anxiety, stress (Depression Anxiety Stress Scales), and burnout (Copenhagen Burnout Inventory Scale). A hierarchical regression model was estimated for each burnout dimension. Results Participants showed high levels of work, personal and client-related burnout, 57.3%, 57%, and 35.1%, respectively. More than 70% of the respondents had a normal level of depressive symptoms, 66.8% presented normal level of anxiety and 33.5% of the respondents reported mild, moderate, severe or extremely severe symptoms of stress. The results revealed that life satisfaction partially mediated the association between stress and personal burnout, depression and work-related burnout, and the association between anxiety and client-related burnout in nurses. Conclusions The COVID-19 pandemic brought added difficulties for nurses’ work conditions, whereby it became necessary to develop adaptative measures that reduce stressors in work environment and promote nurses’ life satisfaction.

ObjectivesThe COVID-19 pandemic has had a negative impact on the mental health of healthcare workers (HCWs) worldwide. This study aims to identify the degree to which sociodemographic variables and indicators of subjective well-being and psychological resilience are associated, positively and negatively, with the outcomes of burnout, stress, depression and anxiety among Portuguese HCWs observed during the first wave. It also aims to evaluate the strength of association of these variables and indicators with each outcome.DesignCross-sectional quantitative study. The statistical methods used are simple logistic model, multiple logistic regression model and −2*log-likelihood statistic.SettingPortuguese HCWs living in Portugal and working in the Portuguese healthcare system.ParticipantsThe study included 1535 professionals, with a mean age of 38 years.Primary and secondary outcomes measuresPsychological variables were measured by Copenhagen Burnout Inventory, the Resilience Scale, the Depression, Anxiety and Stress Scales and the Satisfaction with Life Scale.ResultsHigh levels of personal (55%; n=844), work-related (55.1%; n=846) and client-related burnout (35.4%; n=543) were found. Additionally, participants expressed substantial levels of depression (28.7%; n=441), stress (36.4%; n=558) and anxiety (33.1%; n=508). About 1202 participants (78.3%) demonstrated moderate-to-high levels of resilience. Profession, work regime during the pandemic, having a health problem, resilience and satisfaction with life are independent variables significantly associated with the outcomes of burnout, stress, depression and anxiety. Satisfaction with life was the independent variable that had a major association with all outcomes.ConclusionsGovernments and hospital administrations should take action to promote resilience and satisfaction with life as these variables are protective relating to mental health problems. Interventions as educational sessions, psychological support at work, programmes promoting resilience and coping mechanisms and better work conditions may improve mental health. The implementation of measures to protect healthcare students from developing prejudicial outcomes seams very adequate and important.

Purpose This study aims to identify the appropriate combination of attributes that must be present to deliver value in a new product for a pharmaceutical enterprise. Design/methodology/approach The application object was the Metronidazole analytical standard, using choice experiments to product attributes and price. Findings The practical results indicate that consumer value anticipation allows entry into the market with higher competitiveness. Originality/value Conceptually, it uses a value delivery approach, generally applied to large companies, in a case aimed at enterprises. In practice, for the enterprise studied, the value anticipation by the consumer allows entry into the market with higher competitiveness.