National Institute of Health Dr. Ricardo Jorge
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Disease similarity network analysis of autism spectrum disorder and comorbid neurological and neuropsychiatric disorders
Get PDFA Perturbação do Espetro do Autismo (PEA) é uma perturbação do neurodesenvolvimento
com apresentação clínica heterogénea, nível de gravidade variável
e ocorrência de múltiplas comorbilidades. A PEA tem uma arquitetura
genética complexa que se reflete na sua heterogeneidade clínica, existindo
evidência de uma sobreposição de genes alterados entre esta condição e
diversas comorbilidades do foro neurológico e neuropsiquiátrico. Neste estudo,
construímos uma rede de interação entre doenças baseada na similaridade
genética, para explorar a componente genética compartilhada entre
a PEA e comorbilidades neurológicas e neuropsiquiátricas. As doenças
analisadas incluem o Défice Intelectual (DI), a Perturbação de Hiperatividade/
Défice de Atenção (PHDA) e a Epilepsia, bem como outras doenças neuropsiquiátricas
como a Esquizofrenia (SCZ) e a Perturbação Bipolar (PB).
Usando a base de dados de doenças da DisGeNET, a similaridade genética
entre as doenças analisadas foi calculada a partir do coeficiente de Jaccard
entre pares de doenças, e o algoritmo de Leiden foi usado para identificar
comunidades de doenças na rede. Identificámos uma comunidade heterogénea
de doenças geneticamente mais semelhantes à PEA, que inclui a Epilepsia,
a PB, a PHDA com apresentação combinada, e algumas perturbações
no espetro da SCZ. Esta abordagem permitiu obter uma maior clarificação
acerca da componente genética compartilhada entre a PEA e comorbilidades
neurológicas e neuropsiquiátricas, com implicações importantes para a
nosologia, fisiopatologia e o tratamento o personalizado da doença.Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with
heterogeneous clinical presentation, var iable sever ity, and multiple
comorbidities. A complex under lying genetic architecture matches the
clinical heterogeneity, and evidence indicates that several co-occur r ing
brain disorders share a genetic component with ASD. In this study, we
established a genetic similar ity disease network approach to explore the
shared genetics between ASD and f requent comorbid brain diseases,
namely Intellectual Disability (ID), At tention-Def ici t /Hyperactivity Disorder
(ADHD), and Epilepsy, as well as other rarely co-occur r ing neuropsychianeuropsychiatr
ic conditions in the Schizophrenia (SCZ) and Bipolar Disease spectrum
(BP). Using sets of disease-associated genes curated by the DisGeNET
database, disease genetic similar ity was estimated f rom the Jaccard
coef f icient between disease pairs, and the Leiden detection algor ithm
was used to identi f y network disease communities. We identi f ied a
heterogeneous brain disease community that is genetically more similar
to ASD, and that includes Epilepsy, BP, ADHD combined type, and some
disorders in the SCZ. This approach enabled fur ther clar i f ication of
genetic shar ing between ASD and brain disorders. Understanding gene
shar ing across disorders has impor tant implications for disease nosology,
pathophysiology, and personalized treatment.info:eu-repo/semantics/publishedVersio
Exposure to methylmercury and fish consumption: issuing national recommendations, 2023
Get PDFConsiderando que o consumo de pescado é uma fonte importante de exposição
ao metilmercúrio, a Comissão Europeia recomendou aos Estados-
-membros que estabelecessem recomendações para o seu consumo. Assim,
tendo sido criado um grupo de trabalho, é objetivo deste artigo apresentar
o trabalho desenvolvido para a elaboração das recomendações de consumo
de pescado adaptadas à população portuguesa, tendo em conta o padrão
nacional de consumo de peixe e as espécies consumidas.
A definição das recomendações assentou na realização de um estudo de
avaliação de risco-benefício associado ao consumo de pescado. Esta metodologia
permitiu identificar dois grupos populacionais sujeitos a recomendações
distintas: para a população em geral recomenda-se uma frequência de
consumo de 4 a 7 vezes por semana e, para a população vulnerável, uma
frequência de 3 a 4 vezes por semana das espécies com médio e baixo teor
de mercúrio, devendo ser evitado o consumo das espécies com elevado teor
de mercúrio.
Estas recomendações foram divulgadas num evento público e deverão ser
alvo de esforços adicionais para chegarem à população vulnerável, constituída
por mulheres grávidas, mulheres a amamentar e crianças até aos 10
anos.Consider ing that fish consumption is an important source of exposure to
methylmercury, the European Commission recommended Member States
to establish recommendations for i ts consumption. Therefore, having
created a working group, the objective of this article is to present the
work developed to prepare fish consumption recommendations adapted
to the Por tuguese population.
The def ini t ion of the recommendat ions was based on car r ying out
a risk-benef it assessment study associated wi th f ish consumpt ion.
This methodology made it possible to identify two populat ion groups
subjected to di f ferent recommendat ions: for the general population, a
frequency of consumpt ion of 4 to 7 times per week is recommended and
for the vulnerable populat ion, a frequency of 3 to 4 t imes per week for species wi th medium and low mercury content and the avoidance of the
consumpt ion of species with high mercury content is advised.
These recommendations were released at a public event and should be the
target of additional efforts to reach the vulnerable population, consisting of
pregnant women, breast feeding women and children up to 10 years of age.info:eu-repo/semantics/publishedVersio
To Correct or not to Correct (for treatment): Estimating Pre-treatment LDL-C Concentrations in Genetically Characterized Patients with Familial Hypercholesterolaemia on Lipid-lowering Medication
No full textBackground and Aims: Pretreatment LDL-C measurements aid familial hypercholesterolaemia (FH) diagnosis, and are crucial in epidemiologic studies investigating FH, but are often unavailable because individuals are already on lipid-lowering medication (LLM). Several formulae have been reported to estimate pre-treatment LDL-C in people on LLM by ‘correcting’ their LDL-C concentrations for LLM type and dosage, based on observational or trial evidence of drug efficacy. We compared 4 published correction factors in estimating pre-treatment LDL-C in patients with FH.
Methods: Cross-sectional analysis of adults with pathogenic/likely-pathogenic FH variants in the EAS-FH Studies Collaboration (FHSC) Registry. At the time of LDL-C measurement, N=3012 participants were not on LLM (Untreated group), and N=3226 were on LLM monotherapy, with information on LLM type and dosage allowing estimation of pre-treatment LDL-C (Corrected group) based on correction factors by Ruel 2018, Ellis 2016, Haralambos 2015 and Besseling 2014. We compared the groups for clinical characteristics and LDL-C by gene and variant.
Results: The Corrected group was older than the Untreated group (median[IQR]: 50[39,63] vs. 38[28,50]y), with similar proportion of women (54.5% vs. 56.8%;p=0.14) but more comorbidities (all pAPOB>PCSK9 gene variants, but Corrected was still higher than Untreated LDL-C within each gene group. The difference in Corrected vs. Untreated LDL-C varied by variant, from +0.6 to +3.5mmol/L (20 commonest variants). The LDL-C differences persisted after adjusting for age, sex and comorbidities.
Conclusions: Application of current LDL-C correction factors appears to overestimate pre-treatment LDL-C in epidemiologic settings, or the Untreated and Corrected groups might have inherently different LDL-C profiles. The accuracy of using LDL-C correction factors in FH therefore warrants further investigation.N/
The key role of Spain in the traffic of West Nile virus lineage 1 strains between Europe and Africa
No full textBackground: West Nile Virus (WNV) is a zoonotic arbovirus worldwide spread. Seasonal WNV outbreaks occur in the Mediterranean basin since the late 1990's with ever-increasing incidence. In Southern Spain WNV is endemic, as disease foci - caused by WNV lineage 1 (WNV-L1) strains - occur every year. On the contrary, WNV-L2 is the dominant lineage in Europe, so most European WNV sequences available belong to this lineage, WNV-L1 sequences being still scarce.
Methods: To fill this gap, this study reports the genetic characterisation of 27 newly described WNV-L1 strains, involved in outbreaks affecting wild birds and horses during the last decade in South-Western Spain.
Results: All strains except one belong to the Western Mediterranean-1 sub-cluster (WMed-1), related phylogenetically to Italian, French, Portuguese, Moroccan and, remarkably, Senegalese strains. This sub-cluster persisted, spread and evolved into three distinguishable WMed-1 phylogenetic groups that co-circulated, notably, in the same province (Cádiz). They displayed different behaviours: from long-term persistence and rapid spread to neighbouring regions within Spain, to long-distance spread to different countries, including transcontinental spread to Africa. Among the different introductions of WNV in Spain revealed in this study, some of them succeeded to get established, some extinguished from the territory shortly afterwards. Furthermore, Spain's southernmost province, Cádiz, constitutes a hotspot for virus incursion.
Conclusion: Southern Spain seems a likely scenario for emergence of exotic pathogens of African origin. Therefore, circulation of diverse WNV-L1 variants in Spain prompts for an extensive surveillance under a One Health approach.This work was supported by the Spanish INIA-MAPA agreements EG17-141 and AEG21-198, by the INIA grant E-RTA2015-00002-C02-00, AEI grant PID2020-116768RR-C21 and by Extremadura regional project IB16135. Pilar Aguilera-Sepúlveda was funded by a FPI predoctoral fellowship from INIA. Vítor Borges work was co-financed through the DURABLE project. The DURABLE project has been co-funded by the European Union, under the EU4Health Programme (EU4H), Project no. 101102733
Impacts of land-use and land-cover changes on temperature-related mortality
No full textMulti-Country Multi-City (MCC) Collaborative Research Network: Susana das Neves Pereira da Silva, Joana Madureira, Instituto Nacional de Saúde Dr Ricardo Jorge, Portugal.Background: Land-use and land-cover change (LULCC) can substantially affect climate through biogeochemical and biogeophysical effects. Here, we examine the future temperature-mortality impact for two contrasting LULCC scenarios in a background climate of low greenhouse gas concentrations. The first LULCC scenario implies a globally sustainable land use and socioeconomic development (sustainability). In the second LULCC scenario, sustainability is implemented only in the Organisation for Economic Cooperation and Development countries (inequality).
Methods: Using the Multi-Country Multi-City (MCC) dataset on mortality from 823 locations in 52 countries and territories, we estimated the temperature-mortality exposure-response functions (ERFs). The LULCC and noLULCC scenarios were implemented in three fully coupled Earth system models (ESMs): Community Earth System Model, Max Planck Institute Earth System Model, and European Consortium Earth System Model. Next, using temperature from the ESMs' simulations and the estimated location-specific ERFs, we assessed the temperature-related impact on mortality for the LULCC and noLULCC scenarios around the mid and end century.
Results: Under sustainability, the multimodel mean changes in excess mortality range from -1.1 to +0.6 percentage points by 2050-2059 across all locations and from -1.4 to +0.5 percentage points by 2090-2099. Under inequality, these vary from -0.7 to +0.9 percentage points by 2050-2059 and from -1.3 to +2 percentage points by 2090-2099.
Conclusions: While an unequal socioeconomic development and unsustainable land use could increase the burden of heat-related mortality in most regions, globally sustainable land use has the potential to reduce it in some locations. However, the total (cold and heat) impact on mortality is very location specific and strongly depends on the underlying climate change scenario due to nonlinearity in the temperature-mortality relationship.What this study adds: Numerous environmental epidemiological studies have investigated the temperature-related mortality impact of changes in global greenhouse gas concentrations. However, more scientific evidence is needed on the temperature-related impacts of land-use and land-cover change (LULCC) on human health. An effective climate policy to achieve the targets of the 2015 Paris Agreement requires a substantial transformation in the land sector. Based on recently developed land-use scenarios, this interdisciplinary study contributes to the literature by assessing the temperature-related mortality impacts induced by LULCC using three Earth system models and the most comprehensive exposure–response functions
Temporal variations in the short-term effects of ambient air pollution on cardiovascular and respiratory mortality: a pooled analysis of 380 urban areas over a 22-year period
No full textBackground: Ambient air pollution, including particulate matter (such as PM10 and PM2·5) and nitrogen dioxide (NO2), has been linked to increases in mortality. Whether populations' vulnerability to these pollutants has changed over time is unclear, and studies on this topic do not include multicountry analysis. We evaluated whether changes in exposure to air pollutants were associated with changes in mortality effect estimates over time.
Methods: We extracted cause-specific mortality and air pollution data collected between 1995 and 2016 from the Multi-Country Multi-City (MCC) Collaborative Research Network database. We applied a two-stage approach to analyse the short-term effects of NO2, PM10, and PM2·5 on cause-specific mortality using city-specific time series regression analyses and multilevel random-effects meta-analysis. We assessed changes over time using a longitudinal meta-regression with time as a linear fixed term and explored potential sources of heterogeneity and two-pollutant models.
Findings: Over 21·6 million cardiovascular and 7·7 million respiratory deaths in 380 cities across 24 countries over the study period were included in the analysis. All three air pollutants showed decreasing concentrations over time. The pooled results suggested no significant temporal change in the effect estimates per unit exposure of PM10, PM2·5, or NO2 and mortality. However, the risk of cardiovascular mortality increased from 0·37% (95% CI -0·05 to 0·80) in 1998 to 0·85% (0·55 to 1·16) in 2012 with a 10 μg/m3 increase in PM2·5. Two-pollutant models generally showed similar results to single-pollutant models for PM fractions and indicated temporal differences for NO2.
Interpretation: Although air pollution levels decreased during the study period, the effect sizes per unit increase in air pollution concentration have not changed. This observation might be due to the composition, toxicity, and sources of air pollution, as well as other factors, such as socioeconomic determinants or changes in population distribution and susceptibility.Questions answered in this article: - How do the findings from different countries regarding air pollution effects on mortality vary?; - What is the significance of this multicountry, multicity study in understanding air pollution effects over time?; -
What exploratory secondary analyses were conducted to investigate the effects of air pollution on mortality?; - How many cities and countries were included in the analysis of air pollution effects on mortality?; - Why is it important to understand temporal trends in air pollution effects for future health estimates?AG was supported by the European Union's Horizon 2020 Project Exhaustion (grant number 820655). FS was supported by the Italian Ministry of University and Research, Department of Excellence project 2023–2027 ReDS “Rethinking Data Science”—Department of Statistics, Computer Science and Applications, University of Florence. AMV-C acknowledges funding from the Swiss National Science Foundation (grant number TMSGI3_211626). JJKJ was supported by the Academy of Finland (grant number 310372; Global Health Risks Related to Atmospheric Composition and Weather Consortium).info:eu-repo/semantics/publishedVersio
Improving quality and patient safety in surgical care through standardisation and harmonisation of perioperative care (SAFEST project): A research protocol for a mixed methods study
No full textIntroduction: Adverse events in health care affect 8% to 12% of patients admitted to hospitals in the European Union (EU), with surgical adverse events being the most common types reported.
Aim: SAFEST project aims to enhance perioperative care quality and patient safety by establishing and implementing widely supported evidence-based perioperative patient safety practices to reduce surgical adverse events.
Methods: We will conduct a mixed-methods hybrid type III implementation study supporting the development and adoption of evidence-based practices through a Quality Improvement Learning Collaborative (QILC) in co-creation with stakeholders. The project will be conducted in 10 hospitals and related healthcare facilities of 5 European countries. We will assess the level of adherence to the standardised practices, as well as surgical complications incidence, patient-reported outcomes, contextual factors influencing the implementation of the patient safety practices, and sustainability. The project will consist of six components: 1) Development of patient safety standardised practices in perioperative care; 2) Guided self-evaluation of the standardised practices; 3) Identification of priorities and actions plans; 4) Implementation of a QILC strategy; 5) Evaluation of the strategy effectiveness; 6) Patient empowerment for patient safety. Sustainability of the project will be ensured by systematic assessment of sustainability factors and business plans. Towards the end of the project, a call for participation will be launched to allow other hospitals to conduct the self-evaluation of the standardized practices.
Discussion: The SAFEST project will promote patient safety standardized practices in the continuum of care for adult patients undergoing surgery. This project will result in a broad implementation of evidence-based practices for perioperative care, spanning from the care provided before hospital admission to post-operative recovery at home or outpatient facilities. Different implementation challenges will be faced in the application of the evidence-based practices, which will be mitigated by developing context-specific implementation strategies. Results will be disseminated in peer-reviewed publications and will be available in an online platform.European Union under the Horizon Europe Research and Innovation Programme under the grant agreement n˚ 101057825info:eu-repo/semantics/publishedVersio
Phenotypic and Genotypic Characterization of Escherichia coli and Salmonella spp. Isolates from Pigs at Slaughterhouse and from Commercial Pork Meat in Portugal
No full text(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)Background: Foodborne diseases are a serious public health concern, and food-producing animals are a major source of contamination. Methods: The present study analysed Escherichia coli and Salmonella spp. isolated from faecal samples of 100 fattening pigs and from 52 samples of pork meat. Results: The results showed that the majority of the analysed meat samples were considered satisfactory in terms of microbiological quality (92.3% for E. coli and 94.2% for Salmonella spp.). Salmonella spp. was identified in 5.8% of the meat samples, whereas E. coli was detected in 89.5% of all samples (69.2% in meat and 100% in faecal samples). Furthermore, 1.9% of the faecal samples contained Shiga-toxin-producing E. coli and 3.9% contained enterotoxigenic E. coli. All sequenced isolates presented virulence genes for extraintestinal pathogenic E. coli. Moreover, 75.0% of E. coli isolates from meat and 71.8% from faeces samples showed antibiotic resistance, with 40.7% and 51.4%, respectively, being multidrug-resistant (MDR). The most prevalent resistances were to tetracycline, ampicillin, and sulfamethoxazole, and one E. coli isolate showed resistance to extended-spectrum β-lactamase. Conclusions: This study highlights the role of pigs as a potential source of human contamination and the importance of a One Health approach to ensure food safety and to promote public health.This research was funded by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 773830: One Health European Joint Programme, as part of the DiSCoVeR project (Discovering the sources of Salmonella, Campylobacter, VTEC and Antimicrobial Resistance), as well as developed under the project “FMVULusófona_ResisCampyOH”, funded by the Faculty of Veterinary Medicine from Lusófona University
Safety evaluation of curdlan as a food additive
No full textEFSA Panel on Food Additives and Flavourings (FAF) Members: Henriqueta Louro, Departamento de Genética Humana, INSA.The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of curdlan as a new food additive used as firming and gelling agent, stabiliser, thickener. Curdlan is a high molecular weight polysaccharide consisting of β-1,3-linked glucose units, produced by fermentation from Rhizobium radiobacter biovar 1 strain NTK-u. The toxicological dataset consisted of sub-chronic, chronic and carcinogenicity, reproductive and developmental toxicity studies as well as genotoxicity. In vivo data showed that curdlan is not absorbed as such but is extensively metabolised by the gut microbiota into CO2 and other innocuous compounds. Curdlan was not genotoxic and was well-tolerated with no overt organ-specific toxicity. Effects observed at very high doses of curdlan, such as decreased growth and increased cecum weight, are common for indigestible bulking compounds and therefore considered physiological responses. In a combined three-generation reproductive and developmental toxicity study, decreased pup weight was observed during lactation at 7500 mg curdlan/kg body weight (bw) per day, the highest dose tested. The Panel considered the observed effects as treatment-related and adverse, although likely secondary to nutritional imbalance and identified a conservative no observed adverse effect level (NOAEL) of 2500 mg/kg bw per day. Despite the limitations noted in the dataset, the Panel was able to conclude applying the margin of exposure (MOE) approach. Given that curdlan and its break-down products are not absorbed and that the identified adverse effect is neither systemic nor local, no adjustment factor was deemed necessary. Thus, an MOE of at least 1 was considered sufficient. The highest exposure estimate was 1441 mg/kg bw per day in toddlers at the 95th percentile of the proposed maximum use level exposure assessment scenario. The Panel concluded that there is no safety concern for the use of curdlan as a food additive at the proposed uses and use levels.info:eu-repo/semantics/publishedVersio
Challenges of the Application of In Vitro Digestion for Nanomaterials Safety Assessment
No full textThis article belongs to the Special Issue Prospects for Risks and Benefits in the Context of Food and Health.Considering the increase in the production and use of nanomaterials (NM) in food/feed and food contact materials, novel strategies for efficient and sustainable hazard characterization, especially in the early stages of NM development, have been proposed. Some of these strategies encompass the utilization of in vitro simulated digestion prior to cytotoxic and genotoxic assessment. This entails exposing NM to fluids that replicate the three successive phases of digestion: oral, gastric, and intestinal. Subsequently, the resulting digestion products are added to models of intestinal cells to conduct toxicological assays, analyzing multiple endpoints. Nonetheless, exposure of intestinal cells to the digested products may induce cytotoxicity effects, thereby posing a challenge to this strategy. The aim of this work was to describe the challenges encountered with the in vitro digestion INFOGEST 2.0 protocol when using the digestion product in toxicological studies of NM, and the adjustments implemented to enable its use in subsequent in vitro biological assays with intestinal cell models. The adaptation of the digestion fluids, in particular the reduction of the final bile concentration, resulted in a reduced toxic impact of digestion products.This research was funded by the Portuguese Fundação para a Ciência e a Tecnologia, I.P., through national funds PTDC/SAU-PUB/32587/2017 and PTDC/SAU-PUB/29481/2017. Research was co-funded by UIDB/00009/2020 (https://doi.org/10.54499/UIDP/00009/2020) and UIDP/00009/2020 (https://doi.org/10.54499/UIDB/00009/2020), both for the Centre for Toxicogenomics and Human Health—ToxOmics, FCT— Fundação para a Ciência e a Tecnologia. N.V. work was funded by Fundação para a Ciência e a Tecnologia, I.P PhD grant number 2020.07168.BD (https://doi.org/10.54499/2020.07168.BD). Thanks are due to CESAM by FCT/MCTES (UIDP/50017/2020+ UIDB/50017/2020 + LA/P/0094/2020), through national funds