Sympathetic activity in breast cancer and metastasis: partners in crime

The vast majority of patients with advanced breast cancer present skeletal complications that severely compromise their quality of life. Breast cancer cells are characterized by a strong tropism to the bone niche. After engraftment and colonization of bone, breast cancer cells interact with native bone cells to hinder the normal bone remodeling process and establish an osteolytic “metastatic vicious cycle”. The sympathetic nervous system has emerged in recent years as an important modulator of breast cancer progression and metastasis, potentiating and accelerating the onset of the vicious cycle and leading to extensive bone degradation. Furthermore, sympathetic neurotransmitters and their cognate receptors have been shown to promote several hallmarks of breast cancer, such as proliferation, angiogenesis, immune escape, and invasion of the extracellular matrix. In this review, we assembled the current knowledge concerning the complex interactions that take place in the tumor microenvironment, with a special emphasis on sympathetic modulation of breast cancer cells and stromal cells. Notably, the differential action of epinephrine and norepinephrine, through either a- or ß-adrenergic receptors, on breast cancer progression prompts careful consideration when designing new therapeutic options. In addition, the contribution of sympathetic innervation to the formation of bone metastatic foci is highlighted. In particular, we address the remarkable ability of adrenergic signaling to condition the native bone remodeling process and modulate the bone vasculature, driving breast cancer cell engraftment in the bone niche. Finally, clinical perspectives and developments on the use of ß-adrenergic receptor inhibitors for breast cancer management and treatment are discussed.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and Portuguese funds through FCT/ MCTES in the framework of the project “SproutOC” (POCI-01-0145-FEDER-030158, PTDC/MED-PAT/30158/2017). F.C. is a recipient of the Ph.D. fellowship SFRH/BD/ 128771/2017. D.M.S. is a recipient of the postdoctoral fellowship SFRH/BPD/115341/ 2016

The Use of Spikes Protocol in Cancer: an Integrative Review

This is an integrative review which aimed to evaluate the use of the SPIKES protocol in Oncology. We selected articles published in Medline and CINAHL databases between 2005-2015, in English, with the descriptors defined by the Medical Subject Headings (MeSH):cancer, neoplasms, plus the uncontrolled descriptor: protocol spikes. Six articles met the inclusion criteria and were analyzed in full, three thematic categories were established: aspects inherent to the health care professional; Aspects related to the patient and aspects related to the protocol. The main effects of the steps of SPIKES protocol can provide the strengthening of ties between health professionals and patients, and ensure the maintenance and quality of this relationship. The results indicate an important limiting factor for effective doctor-patient relationship, the little training provided to medical professionals communication of bad news, verified by the difficulty reported in this moment through interviews in the analyzed studies

Comparing Visual Search Patterns in Chest X-Ray Diagnostics

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Serum amyloid A proteins reduce bone mass during mycobacterial infections

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFN gamma- and TNF alpha-dependent manner. IFN gamma produced during infection enhanced macrophage TNF alpha secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was supported by KOG-202108-00929 from the European Haematology Society, awarded to AG. Work in the MS lab was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028955 (PTDC/SAU-INF/28955/2017). AG and MS are supported by an Individual Scientific Employment contract (CEECIND/00048/2017; CEECIND/00241/2017 respectively). DS acknowledges the Portuguese Foundation for Science and Technology (FCT) for the Post-Doc fellowship (SFRH/BPD/115341/2016). RP, DS and AF have PhD grants (SFRH/BD/145217/2019; SFRH/BD/143536/2019; 2020.05949.BD, respectively) financed by FCT

Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation

Prova tipográfica (In Press)An important question arising from previous observations in vivo is whether glucocorticoids can directly influence neuronal survival in the hippocampus. To this end, a primary postnatal hippocampal culture system containing mature neurons and expressing both glucocorticoid (GR) and mineralocorticoid (MR) receptors was developed. Results show that the GR agonist dexamethasone (DEX) targets neurons (microtubule-associated protein 2-positive cells) for death through apoptosis. GR-mediated cell death was counteracted by the MR agonist aldosterone (ALDO). Antagonism of MR with spironolactone ([7a-(acetylthio)-3-oxo-17a-pregn- 4-ene,21 carbolactone] (SPIRO)) causes a dose-dependent increase in neuronal apoptosis in the absence of DEX, indicating that nanomolar levels of corticosterone present in the culture medium, which are sufficient to activate MR, can mask the apoptotic response to DEX. Indeed, both SPIRO and another MR antagonist, oxprenoate potassium ((7a,17a)-17-Hydroxy-3-oxo-7- propylpregn-4-ene-21-carboxylic acid, potassium salt (RU28318)), accentuated DEX-induced apoptosis. These results demonstrate that GRs can act directly to induce hippocampal neuronal death and that demonstration of their full apoptotic potency depends on abolition of survival-promoting actions mediated by MR

Massive mortality of invasive bivalves as a potential resource subsidy for the adjacent terrestrial food web

Large-scale mortality of invasive bivalves was observed in the River Danube basin in the autumn of 2011 due to a particularly low water discharge. The aim of this study was to quantify and compare the biomass of invasive and native bivalve die-offs amongst eight different sites and to assess the potential role of invasive bivalve die-offs as a resource subsidy for the adjacent terrestrial food web. Invasive bivalve die-offs dominated half of the study sites and their highest density and biomass were recorded at the warm water effluent. The density and biomass values recorded in this study are amongst the highest values recorded for aquatic ecosystems and show that a habitat affected by heated water can sustain an extremely high biomass of invasive bivalves. These mortalities highlight invasive bivalves as a major resource subsidy, possibly contributing remarkable amounts of nutrients and energy to the adjacent terrestrial ecosystem. Given the widespread occurrence of these invasive bivalves and the predicted increase in the frequency and intensity of extreme climatic events, the ecological impacts generated by their massive mortalities should be taken into account in other geographical areas as well.The authors are grateful to David Strayer for valuable comments on a previous version of the manuscript. Special thanks to the Danube-Ipoly National Park for the help in field work. Ronaldo Sousa was supported by the project "ECOIAS" funded by the Portuguese Foundation for the Science and the Technology and COMPETE funds (contract: PTDC/AAC-AMB/116685/2010)

Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

Distribution of Corbicula fluminea (Müller, 1774) in the invaded range: a geographic approach with notes on species traits variability

Corbicula fluminea is considered one of the most important non-native invasive species (NIS) in aquatic systems mainly due to its widespread distribution and ecological and economic impacts. This species is known to negatively affect native bivalves, also with severe effects on biodiversity and ecosystem functioning. Throughout an exhaustive bibliographic survey and with the aid of Geographic Information Systems tools, this study tracks the species dispersion from its native range, including the description of important physical and environmental barriers. Additional analyses were conducted to examine possible influences of latitudinal/ temperature gradients on important traits (e.g. life span, maximum and mean body length, growth at the end of first year). Altitude and winter minimum temperature appear to be delaying the invasion worldwide, but it seems inevitable that the species will spread across the globe. Latitude and summer temperature show a relationship with growth and life span. Overall, the information gathered in this review may be relevant to forecast future distribution patterns of this NIS, and to anticipate the possible implementation of effective management measures. Moreover, it may constitute a valuabletool inthe prediction of population responses to an increasingly changing environment.This research was supported by FCT (Portuguese Foundation for Science and Technology), through a PhD grant attributed to D. Crespo (SFRH/BD/80252/2011), a post-doc grant attributed to S. Leston (SFRH/BPD/91828/2012) and M Dolbeth (SFRH/BPD/41117/2007) and BIOCHANGED project (PTDC/MAR/111901/2009), subsidized by the European Social Fund and MCTES (Ministério da Ciência, Tecnologia e Ensino Superior) National Funds, through the POPH (Human Potential Operational Programme), QREN (National Strategic Reference Framework) and COMPETE (Programa Operacional Factores de Competitividade).info:eu-repo/semantics/publishedVersio