Neonatal Morbi-Mortality in Very Low Birth Weight in Europe: the Portuguese Experience

The aim of this study was to access evolution in care of very low birth weight (VLBW) infants after the implementation of a regionalization policy in Portugal. The data of the National Portuguese Network of VLBW infants are analyzed concerning mortality, morbidity, and quality of regionalization. A total of 12,826 VLBW infants born from 1 January 1994 to 31 December 2008 were enrolled, with a prevalence of 0.66%-0.99% of all live born. The global mortality was 11%. The major improvement in survival is in the babies more than 1000 g. Since 2004, the threshold of viability is 25 weeks, but the intact survival is around 28 weeks. In the last 10 years with more efficient regionalization more VLBW babies are born in the right place. The improvement in neonatal mortality rate was determinant in the good evolution of perinatal and infant mortalities. After reinforcement of regionalization policies, we found improvements in mortality for VLBW infants. The aims of regionalization were achieved. The reform of perinatal care in Portugal is an example of how a good diagnosis and adequate proposals combined with a strong political will is crucial for changing.info:eu-repo/semantics/publishedVersio

Broadening Risk Factor or Disease Definition as a Driver for Overdiagnosis: A Narrative Review

Medical overuse-defined as the provision of health services for which potential harms exceed potential benefits-constitutes a paradigm of low-value care and is seen as a threat to the quality of care. Value in healthcare implies a precise definition of disease. However, defining a disease may not be straightforward since clinical data do not show discrete boundaries, calling for some clinical judgment. And, if in time a redefinition of disease is needed, it is important to recognize that it can induce overdiagnosis, the identification of medical conditions that would, otherwise, never cause any significant symptoms or lead to clinical harm. A classic example is the impact of recommendations from professional societies in the late 1990s, lowering the threshold for abnormal total cholesterol from 240 mg/dl to 200 mg/dl. Due to these changes in risk factor definition, literally overnight there were 42 million new cases eligible for treatment in the United States. The same happened with hypertension-using either the 2019 NICE guidelines or the 2018 ESC/ECC guidelines criteria for arterial hypertension, the proportion of people overdiagnosed with hypertension was calculated to be between 14% and 33%. In this review, we will start by discussing resource overuse. We then present the basis for disease definition and its conceptual problems. Finally, we will discuss the impact of changing risk factor/disease definitions in the prevalence of disease and its consequences in overdiagnosis and overtreatment (a problem particularly relevant when definitions are widened to include earlier or milder disease).info:eu-repo/semantics/publishedVersio

Broadening Risk Factor or Disease Definition as a Driver for Overdiagnosis: A Narrative Review

Medical overuse-defined as the provision of health services for which potential harms exceed potential benefits-constitutes a paradigm of low-value care and is seen as a threat to the quality of care. Value in healthcare implies a precise definition of disease. However, defining a disease may not be straightforward since clinical data do not show discrete boundaries, calling for some clinical judgment. And, if in time a redefinition of disease is needed, it is important to recognize that it can induce overdiagnosis, the identification of medical conditions that would, otherwise, never cause any significant symptoms or lead to clinical harm. A classic example is the impact of recommendations from professional societies in the late 1990s, lowering the threshold for abnormal total cholesterol from 240 mg/dl to 200 mg/dl. Due to these changes in risk factor definition, literally overnight there were 42 million new cases eligible for treatment in the United States. The same happened with hypertension-using either the 2019 NICE guidelines or the 2018 ESC/ECC guidelines criteria for arterial hypertension, the proportion of people overdiagnosed with hypertension was calculated to be between 14% and 33%. In this review, we will start by discussing resource overuse. We then present the basis for disease definition and its conceptual problems. Finally, we will discuss the impact of changing risk factor/disease definitions in the prevalence of disease and its consequences in overdiagnosis and overtreatment (a problem particularly relevant when definitions are widened to include earlier or milder disease).info:eu-repo/semantics/publishedVersio

Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

New Emigration and Portuguese Society: Transnationalism and Return

This chapter addresses the theme of transnationalism and return in recent Portuguese emigration, namely the flows that occurred after the turn of the century. It starts with a brief theoretical overview on those topics, which constitute two relatively neglected characteristics of Portuguese emigration. Next, based on a survey carried out in 2014–2015 to more than 6000 recent emigrants, it reveals some of the links that they maintain with their home country, as well as their plans for the future, which include settlement in the destination country, return and re-emigration. Lastly, it examines data on returning emigrants – especially those that returned between 2001 and 2011 – extracted from the 2011 Census. The evidence reveals a significant number of returns, including individuals at both working and retirement ages and at all skill levels, thus exposing the unexpected complexity of movements. The results are based on the research project “Back to the future: new emigration and links with Portuguese society” (REMIGR), which aimed to ascertain the extent and characteristics of the new emigration wave. The project included an overview of emigration and return to and from all regions of the world, as well as case studies in UK, France, Luxembourg, Angola, Mozambique and Brazil.info:eu-repo/semantics/publishedVersio

The fourth wave of Portuguese emigration: Austerity policies, European peripheries and postcolonial continuities

Little is known about emigration in European countries. Migratory pressure and the recent refugee crisis have helped keep academic attention over the last few decades focused on immigration, asylum and integration in Europe. However, these dynamics promoting entries into European countries coexist with other fair-ly significant dynamics promoting departures from these countries. The sovereign debt crisis coupled with austerity policies that asymmetrically affected Europe’s peripheral countries have increased emigration in various European countries. Our book aims to counter the invisibility of emigration from European countries in the literature by examining the particularities of the Portuguese case. In methodological terms, the book compiles the work of authors from different academic backgrounds who have conducted empirical research using a wide vari-ety of extensive and intensive methods. It is argued that when analysing recent Portuguese emigration it is important to examine in further detail: i) the impact of the 2008 economic and financial crisis and the austerity policies that followed in its wake; ii) south-north emigration in Europe; iii) north-south emigration outside Europe and post-colonial continuities; iv) the importance of reassessing the exist-ing model of Southern European migration; v) highly skilled and less skilled mi-gration; and finally, vi) emigrants’ and their descendants’ identities.info:eu-repo/semantics/publishedVersio

Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs).

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c. − 124 and c. − 146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c. − 124C4T mutation was the most common event, present in 2.3% (3/130), and the c. − 146C4T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient’s clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.This project was partially supported by Barretos Cancer Hospital internal research funds (PAIP) and CNPq Universal Grant (476192/2013-7) to RMR. NCC is a recipient of an FAPESP Doctoral Fellowship (2013/25787-3). Further funding from the project ‘Microenvironment, metabolism and cancer’ that was partially supported by Programa Operacional Regional do Norte (ON.2—O Novo Norte) under the Quadro de Referência Estratégico Nacional (QREN) and the Fundo Europeu de Desenvolvimento Regional (FEDER). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education that is partially supported by the FCT

Cell-to-Cell Interactions and Signals Involved in the Reconstitution of Peripheral CD8+ TCM and TEM Cell Pools

We here describe novel aspects of CD8+ and CD4+ T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8+ T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naïve CD8+ T cells and their differentiation of effector functions is limited, but both dramatically increase upon the co-transfer of CD4+ T cells. This helper effect is complex and determined by multiple factors. It was directly correlated to the number of helper cells, required the continuous presence of the CD4+ T cells, dependent on host antigen-presenting cells (APCs) expressing CD40 and on the formation of CD4/CD8/APC cell clusters. By comparing the recovery of (CD44+CD62Lhigh) TCM and (CD44+CD62Llow) TEM CD8+ T cells, we found that the accumulation of TCM and TEM subsets is differentially regulated. TCM-cell accumulation depended mainly on type I interferons, interleukin (IL)-6, and IL-15, but was independent of CD4+ T-cell help. In contrast, TEM-cell expansion was mainly determined by CD4+ T-cell help and dependent on the expression of IL-2Rβ by CD8 cells, on IL-2 produced by CD4+ T-cells, on IL-15 and to a minor extent on IL-6