Ministere De Research Articles

Individual right to clean air including compensation for health damage – comment on JP v Ministre de la Transition écologique, C-61/21

Abstract On the one hand, the EU member states are to manage ambient air quality in line with the Air Quality Directive (dir. 2008/50/EC) provisions that put forward local air quality targets. On the other hand, EU citizens have their right to demand that their local authorities pass ‘air quality plans’ for towns or districts where air quality standards were below the so-called limit values. In 2008, in the Janecek Judgement of the Court of Justice of 25.07.2008, C-237/07 Dieter Janecek v. Freistaat Bayern EU:C:2008:447. case the Court of Justice of the EU (the CJEU) for the first time recognised the direct effect of Articles 13 and 23 of this directive, and in this way granted rights to individuals to challenge local air quality plans for their inefficiency. The main point of this article is to prove that EU citizens have a subjective, justiciable right to clean and healthy air, and to examine whether this right entitles them to compensation for health damage due to air pollution, as was the subject matter of the commented case: JP v Ministre de la Transition écologique. Therefore, it is necessary to examine the three conditions of the Francovich rule for state liability established in the Brasserie du Pêcheur case: ‘1. the rule of law infringed must be intended to confer rights on individuals; 2. the breach must be sufficiently serious, 3. and there must be a direct causal link between the breach of the obligation resting on the state and the damage sustained by the injured parties’ Judgement of the Court of Justice of 5.03.1996, C-46/93 and 48/93 Brasserie du Pêcheur EU:C:1996:79. .

Group Taxation Regimes Across the European Union: A Domestic Tax Regime Beyond Borders?

In this note, the author discusses the impact of the freedom of establishment on group taxation rules across several EU Member States (France, Luxembourg and the Netherlands), The selection of these Member States was linked to the fact that they were involved in the ECJ case law highlighted as part of this note. in light of the recent ECJ decision in Manitou BF (C-407/22), FR: ECJ, 11 May 2023, Case C-407/22, Ministre de l’Economie, des Finances et de la Relance v. Manitou BF SA, ECLI:EU:C:2023:392, Case Law IBFD. as well as older ECJ case law. It also discusses practical examples that demonstrate the value of group taxation rules for taxpayers amid European and international tax developments.

C-61/21 Ministre de la Transition Écologique: Putting the Individual-centered CJEU Case Law on Air Quality on Hold

In its judgment in C-61/21 Ministre de la Transition écologique rendered on 22 December 2022, the Grand Chamber of the CJEU decided, against the Opinion of Advocate General Kokott, that Articles 13(1) and 23(1) of Directive 2008/50/EC on air quality did not give rise to individual rights. This decision implies that these articles cannot be invoked to request compensation for health damage suffered as a result of a breach of obligations by Member States. The CJEU came to this conclusion by arguing that the Directive only serves a general purpose of protection of human health and the environment, which does not satisfy the conditions for State liability established in Francovich. This judgment seems to put a stop to the trend observed in earlier case law on air quality, rather focusing on individuals. This case note aims at reflecting upon this judgment in light of previous case law, and in the context of the revision of the Directive on air quality.

The first Choosing Wisely Africa conference: a roadmap to value-based cancer care in Africa (16th December 2022, Senegal).

The Choosing Wisely campaign was formally launched in 2012 and a decade later, the inaugural Choosing Wisely Africa conference was held in Dakar, Senegal on 16 December 2022 supported by ecancer. Academic partners included Ministere de la Sante et de I'Action Sociale, Senegalese Association of Palliative Care, Federation Internationale des Soins Palliatifs, Universite Cheikh Anta diop de Dakar, Societe Senegalaise de Cancerologie and King's College London. There were around 70 delegates attending in person mostly from Senegal and a further 30 joining virtually. Ten speakers gave insight into Choosing Wisely from an African perspective and Dr's Fabio Moraes and Frederic Ivan Ting shared the Choosing Wisely experience from Brazil and the Philippines, respectively. This report therefore shares the highlights of the first Choosing Wisely Africa conference guided by topics discussed.

Pravci razvoja univerzalnog ljudskog prava na zdravu životnu sredinu

The process of political shaping of the right to a healthy environment, started with the adoption of the Stockholm Declaration in 1972, basically ended only fifty years later, when the United Nations Assembly adopted the Resolution declaring access to a clean, healthy and sustainable environment as a universal human right. At the beginning of the long journey, the responsibilities for implementing the decisions expressed in the Stockholm Declaration were divided between the member states, on the one hand, and the international community, on the other.The dominant position was given to state authorities. It was agreed that they must be entrusted with the task of planning, managing and controlling ecological resources, in order to improve the quality of the environment, and that states have the right to sovereignly exploit their own resources in accordance with their environmental protection policy. On the other hand, the belief was expressed that the international community will find a source of strength for later concrete action in the Stockholm Declaration. Since then, very modest progress has been made at international level. Official UN statements noted that the 2022 Resolution is not legally binding for 193 member states, but that its proponents hope it will encourage countries to enshrine the right to a healthy environment in national constitutions and regional treaties and encourage them to implement laws that relate to that right, and that it will help people fight for their right to a safe climate, their right to breathe clean air and their rights to access clean and safe water, adequate food, healthy ecosystems and a non-toxic environment. In the global context, the right to a healthy environment is still aspirational (imperfect, unfinished), something that still needs to be fought for at the national level. It will remain so until the consumer society model is replaced by a new form of social organization, which will be based on a different value system. Such a conclusion is also indicated by the reasonable, well-balanced judgement of the Court of Justice of the European Union at the end of 2022, in the case of JP v. Ministre de la Transition écologique (C-61/21). It stated that the provisions of the directives related to air quality must be interpreted in the sense that they do not aim to give individuals the right to seek compensation from the member state for loss and damage caused by the state's violation of EU law, but that it does not excludes the possibility of an individual claiming compensation from the state on the basis of national law. During the past half century, about 150 countries around the world have constitutionalized the right to a healthy environment. It thus, at the national level, gained a significantly different physiognomy and more effective protection not only before the courts of general jurisdiction, but also before the constitutional courts, in proceedings regarding constitutional appeals. However, some new problems arise here. Among them, the competition (conflict) of property rights and certain sectoral rights included (integrated) within universal human right to a healthy environment, such as the right to water, which is discussed in this paper, is particularly significant. In conditions where it is not possible to satisfy the interests of everyone, states will be forced to prioritize their own citizens, and that means civil (private) rights, over universal human rights for the sake of social stability and the preservation of internal order. The process of constitutionalization will be slowed down, and it is possible that in some countries a kind of deconstitutionalization will be carried out, by amending the constitution or informally, through a more restrictive application of universal human rights and more restrictive decision-making regarding constitutional appeals. In the final part of the paper, it was stated that the boundaries between traditional subjects and objects of law are gradually being erased and that the environment must eventually be understood as a community of all living beings, which has a specific legal subjectivity and the right to be healthy.

A Clinically Validated Genetic Screening for Familial Hypercholesterolemia in Quebec

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis Familial Hypercholesterolemia (FH) is the most common genetic disorder in humans with an estimated prevalence of 1/311. In geographic regions with founder effect mutations, such as the province of Quebec, Canada, prevalence is as high as 1/80. FH is associated with premature atherosclerotic cardiovascular disease (ASCVD) caused by elevated low-density lipoprotein cholesterol (LDL-C). Although early diagnosis and therapy of FH can normalize life expectancy, less than 15% of cases are diagnosed. Cascade screening and genetic testing aim to improve diagnosis, treatment, and outcomes in FH. Objective/Purpose Determine the impact of unbiased genetic testing in re-classification of patients with a clinical diagnosis of FH in Quebec, in comparison with the existing genetic panel offered by Quebec's Ministry of Health and Social Services (Ministere de la Sante et des Services Sociaux (MSSS)). Methods A retrospective cohort study was conducted on patients seen in the Preventive Cardiology/Lipid Clinic of the McGill University Health Center (MUHC) at the Royal Victoria Hospital in Montreal, Quebec, Canada, between September 2017 to September 2021. The MUHC Preventive Cardiology/Lipid clinic is one of the 19 academic FH Canada Registry participating sites. Here, we report a single-center experience with the only clinically validated molecular genetic screening for FH (CLIA compliant) in Canada. We performed next-generation sequencing of the LDLR, APOB, and PCSK9 genes and multiplex ligation-dependent probe amplification (MLPA) of the LDLR gene to detect genetic mutations and copy number variants. All mutations were reviewed by a geneticist and cross-referenced in ClinVar. Results Between 2018-2021, we examined 369 FH cases (57% males, 43% females) based on the Canadian FH definition clinical criteria. For index patients, mean age at diagnosis was 40+/- 16 years, while 30+/-16 years was for cascade screening patients. Baseline (untreated) LDL-C was 6.5+/-2.0 mmol/L. In 224 patients who underwent genetic testing, a pathogenic mutation was identified in 167 (75%) individuals, in keeping with ∼20% of FH patients with a polygenic form. A majority of affected patients had mutations in the LDLR (87%) or APOB (13%) genes. Interestingly, the genetic panel offered by Quebec's Health Ministry, which includes 10 common mutations in French Canadians, only accounted for 46% of identified mutations. Even in patients self-describing as French Canadians, more than 20% did not have a common mutation. We subsequently examined the impact of genetic testing in re-classification of patients' FH diagnosis. Interestingly, genetic screening identified a genetic variant in 26% of patients initially classified as 'severe hypercholesterolemia' and allowed for 85 (75%) of patients initially diagnosed as 'probable FH' to be re-classified as 'definite FH'. Conclusions Genetic testing in patients suspected of having FH provides diagnostic certainty and permits re-classification of individuals with a diagnosis of 'severe hypercholesterolemia' or 'probable FH' according to current definitions. Furthermore, the limited genetic panel offered by the province of Quebec, focusing on common French-Canadian mutations, provides incomplete data in the majority of cases. We therefore propose that most patients with a presumptive diagnosis of FH undergo an unbiased genetic analysis. This allows for increased identification of FH patients and can help reduce burden of ASCVD and death in Canadians with FH. Furthermore, this study has important implications on cascade screening, public health policies and reimbursement of drugs such as PCSK9 inhibitors. Nothing to disclose.

Particularités de la 3e vague de la pandémie à COVID-19 en Afrique sub-Saharienne, cas de la République Démocratique du Congo comme exemple

Particularités de la 3e vague de la pandémie à COVID-19 en Afrique sub-Saharienne, cas de la République Démocratique du Congo comme exemple

Beyond Food Safety – EU Food Information Standards as a Facilitator of Political Consumerism and International Law Enforcement Mechanism

In Case C-363/18 Organisation juive europeenne, Vignoble Psagot Ltd v Ministre de l’Economie et des Finances (“Occupied Territories case”), the Court of Justice of the European Union (CJEU or Court) was tasked with deciding what information on its country of origin or place of provenance is mandatory for business according to existing European legislation. This casenote summarizes the interpretative decisions taken by the Advocate General Hogan (Advocate General or AG) and the Court in their opinion and judgment, respectively. It then considers the broader implications of this case from several perspectives: first, from the perspective of political consumerism and its (potential) role in EU internal market law; second, from the perspective of the enforcement of international law; and third, from the perspective of the coherence of EU food and consumer law including its behavioural dimension.

Can local risk of West Nile virus infection be predicted from previous cases? A descriptive study in Quebec, 2011-2016.

This study aimed at (1) describing the local risk of West Nile virus (WNV) infection in humans based on previous case reports and (2) investigating the spatial clustering of cases in the five most affected administrative regions of Quebec, Canada, for the 2011-2016 period. Human WNV cases declared to the Ministry of Health and Social Services of Quebec(Ministère de la santé et des services sociaux, MSSS) were retrieved. Incidence risk by age and sex was calculated for the study period. The yearly and monthly occurrence of cases in geographical units (GUs) was described and the probability of observing cases in a GU with cases reported in the previous year or month was assessed. Moran's I was used to assess global clustering across the study area. Spatial clusters were identified by the Kulldorff scan statistic. A total of 261 WNV cases were declared to the MSSS between 2011 and 2016 in the study area. Overall, a low percentage of GU with cases reported had additional cases reported over the next month or year. Global spatial clustering was weak but statistically significant (p < 0.05) for 2012 and 2015. For these two years, spatial clusters of high-risk GUs were identified. Results underline the challenge of predicting the distribution of WNV incidence risk in Quebec based on previous occurrence of human cases. Ongoing research with high spatial resolution entomological data is still necessary to understand the spatial distribution of risk at a local scale.

Vitamin D Deficiency in Young African Children

Background: Vitamin D deficiency is linked to infections, rickets, and poor child development. However, data on the vitamin D status of African children are limited. We examined the prevalence and predictors of low vitamin D status in young African children. Methods: We measured 25-hydroxyvitamin D (25OHD), C-reactive protein (CRP), malaria parasitaemia, and anthropometry among 3880 children aged 0-8 years living in Kenya, Uganda, Burkina Faso, and South Africa. We evaluated associations between vitamin D status and country, age, sex, anthropometric indices, inflammation and malaria parasitaemia in regression analyses and structural equation models. Findings: The overall prevalence of vitamin D deficiency using 25OHD cut-offs of <30 nmol/L and <50 nmol/L was 0·7% (95% CI 0·5, 1·0) and 7·4% (95% CI 6·6, 8·3) respectively, while 35·4% (95% CI 33·9, 36·9) of children had levels between 50–75 nmol/L. Overall geometric mean 25OHD level was 78·1 nmol/L (95% CI 77·3, 78·9) and median age was 22·1 months (interquartile range 12·1, 25·2). Vitamin D deficiency was more prevalent in South African and in older children. 25OHD levels were lower in children with malaria parasitaemia and higher in those with inflammation, but were not associated with sex, stunting, underweight or wasting. Interpretation: Only 1% and 7% of children were vitamin D deficient as defined by 25OHD levels <30 nmol/L and <50 nmol/L, respectively. Latitude, age and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa. Funding Statement: This work was funded by Wellcome [grant numbers SHA 110255, TNW 202800, AJM 106289 and AME 064693, 079110, 095778], and with core awards to the KEMRI-Wellcome Trust Research Programme [203077]. AA is supported by the Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH (1ZIAHG200362) is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health. RMM and JMM are supported through the Developing Excellence in Leadership, Training and Science (DELTAS) Africa Initiative [DEL-15-003]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from Wellcome [107769] and the UK government. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: Informed written consent was obtained from all children’s parents or guardians before inclusion in the study. Ethical approvals were granted by the Scientific Ethics Review Unit of the Kenya Medical Research Institute (KEMRI/SERU/CGMR-C/046/3257) in Kenya, the Uganda Virus Research Institute (GC/127/12/07/32) and Uganda National Council for Science and Technology (MV625) in Uganda, by Ministere de la Recherche Scientifique et de l’Innovation (reference 2014-12-151) in Burkina Faso, the University of Witwatersrand Human Research (M130714) in South Africa and in the UK by the London School of Hygiene and Tropical Medicine (A340) and the Oxford Tropical Research Ethics Committees (39-12, 41-12, 42-14, and 1042-13).

ALEXANDRE DUMAS AND A GOTHIC NOVEL (DEDICATED TO 150TH ANNIVERSARY OF THE WRITER’S DEATH)

The article considers the characteristics of interpretation by Alexandre Dumas père of a genre of gothic fiction based on the writer’s less popular works: Le Château d’Eppstein, 1843 and Le Pasteur d’Ashbourn,1853. Alexandre Dumas père deviates from the genre’s traditional surrounding, i.e. the southern France, Italy, Spain. Le Château d’Eppstein is set in Germany; by connecting the legendary past with the historical time, Dumas enhances one of the genre’s inherent features, at the same time enriching the narrative with a dense intertextual component. The events of Le pasteur d’Ashbourn happen in England. The first part of the book is a rescript of a sentimental novel Leben Eines Armen Landpredigers by August Heinrich Julius Lafontaine (1801; translated in French by Isabelle de Montolieu as Nouveaux Tableaux De Famille Ou La Vie D’un Pauvre Ministre De Village Allemand Et De Ses Enfants – 1802; translated in English as The Village Pastor and His Children – 1803), which beautifully contrasts with a traditional gothic plot of the second part and an extensive ironic epilogue. Both novels demonstrate that Dumas did not intend to imitate the gothic fiction, but rather to transform it by means of witty genre and stylistic experiments.

Disharmonization in the Regulation of Transgenic Plants in Europe

Disharmonization in the Regulation of Transgenic Plants in Europe

Second Sahelian amphibian endemism suggested by phylogeography of Groove crowned Bullfrog ( Hoplobatrachus occipitalis ) in western Sahel and hints of polyploid species formation

D. Gower and A. Ohler provided access to samples under the scope of a Synthesys 3 grant (FR‐TAF‐4220/GB‐TAF‐3882). P.A. Crochet provided valuable comments. This work was also funded by National Geographic Society (CRE 7629‐04/8412‐08), MBZ Species Conservation Fund (11052499), FCT (PTDC/BIA‐BEC/099934/2008, PTDC/BIA‐BIC/2903/2012), and by ERDF through COMPETE (FCOMP‐01‐0124‐FEDER‐008917/028276). Individual support was given by FCT (SFRH/BD/78402/2011, IF/00459/2013) within QREN‐POPH‐T4.1 funded by ESF and Portuguese MEC. Logistic support for fieldwork was given by Pedro Santos Lda (Trimble GPS), Off Road Power Shop, P.N. Banc d'Arguin (Mauritania), and Ministere de l'Environnement et du Developpement Durable of Mauritania.

Potentially Life-Threatening Emergencies and Near-Misses as a Framework for Quality and Safety Measurement in Gynaecological Emergency Care: Results of the URGO Multicentre Prospective Study

Several acute gynaecological (including pelvic or early pregnancy-related) conditions may be responsible for severe complications or death. Accordingly, a precise list of these conditions might be provide relevant outcomes for measuring processes and their relation to diagnostic errors in gynaecological emergencies. Methods: This multicentre study including 21 gynaecological emergency departments (G-EDs) in France and Belgium began with a modified Delphi procedure (in 2014) among health-care providers to define relevant combinations of gynaecological potentially life-threatening emergencies (G-PLEs) and near-misses. A prospective case-cohort study (March 9-April 13, 2015) then assessed their relative frequencies and analysed the risks among women of reproductive age with acute pelvic pain (APP) consulting at these G-EDs. Findings: Delphi procedure identified eight G-PLEs, defined as painful conditions at high risk of rapid deterioration and potentially threatening to life or fertility, and 17 near-miss criteria (adapted from similar obstetric standards). Among the 3825 women with APP, 130 (3*5%, 95% CI [3*0-4*1]) were diagnosed with a G-PLE. most common G-PLEs were complicated ectopic pregnancies with severe bleeding, complicated pelvic inflammatory disease, adnexal torsion, haemorrhagic miscarriage, and complicated appendicitis. Controls were the 225 women hospitalised for a non-G-PLE condition and a random sample of 381 outpatients. Diagnostic errors occurred more frequently among women with G-PLEs than among controls. Of the women with G-PLEs, 26 (20*6%) met near-miss criteria, compared with 6 with non-G-PLE conditions (1*6%), OR 25*6 (95% CI [10*9-70*7]). Interpretation: G-PLEs are a group of frequently encountered and serious conditions that may present diagnostic challenges in women consulting for APP at G-EDs. Routine tracking of G-PLEs and near-miss is feasible and may serve as a useful framework for research and actions to improve quality of care in this setting. Funding Statement: study was funded by a grant from the Programme de Recherche sur la Performance du systeme des Soins - PREPS 2012 (Ministere de la Sante, 12-002-0081 Prof. Fauconnier). sponsor was Assistance Publique - Hopitaux de Paris (Shoreh Azimi, Departement de la Recherche Clinique et du Developpement). URGO Study was also supported by Versailles-Saint399 Quentin University and its Institut de Recherche en Sante de la Femme (IRSF). Declaration of Interests: authors declare: The authors did not report any disclosure of interest for the present study. Ethics Approval Statement: No written informed consent was required by French law for this observational, non-interventional study 242 (Huriet-Serusclat law, 20 December 1998). However, all women received information about it study and 243 could decline to participate. Ethics Committee of Ile-de-France, VII approved the study.

EU Labelling Practices for Products Imported from Disputed Territories

On 13 June 2019, Advocate General Hogan issued his opinion on Case C-363/18 Organisation juive europeenne, Vignoble Psagot Ltd v Ministre de l'Economie et des Finances, currently pending with the Court of Justice. In this case, referred by the Conseil d’Etat, the Court was invited to rule whether EU law requires for products originating in a territory occupied by Israel since 1967 (“Israeli settlements”), an indication that the product comes from that territory. While this question was answered affirmatively by the Advocate General, it remains unclear if the Court’s forthcoming decision, whether or not it will follow Mr. Hogan’s opinion, will have consequences on EU trade policy for occupied, disputed or annexed territories other than Israeli settlements. This paper aims to review TBT measures adopted by the EU against the territories whose military and economic occupation was openly condemned by international arena. By examining the EU’s trade agreements with States that claim sovereignty over the disputed territories, it reveals which rules of origin apply to products imported into the EU from the Israeli settlements, Turkish Republic of Northern Cyprus, Western Sahara and Crimea. In particular, this paper focuses on conditions that exporters have to fulfil to bring their product into the EU under preferential trading rules. The findings suggest that the EU lacks coherence both in its policy and practice towards trade with disputed territories, which in turn undermines the effectiveness of its measures and weakens the EU’s position in international arena.

Vaccine Deployment and Ebola Transmission Dynamics Estimation in Eastern DR Congo

Background. Over the last 19 months, the Democratic Republic of the Congo has reported approximately 3000 cases of Ebola virus disease (EVD). Since August 2018, an experimental vaccine has been deployed to curb transmission. Methods. A generalizable data assembly algorithm was developed to automatically curate publicly available cumulative reported case count and vaccine deployment data from the Ministere de la Sante. The Incidence Decay and Exponential Adjustment model was then used to estimate basic and observed reproduction numbers associated with the outbreak for three health zones that have been most affected as well as for the country as a whole. Reproduction number estimates at the national level were paired with a sensitivity analysis to assess immunization rates and to project end-of-year case counts under three different transmission scenarios. Findings. Basic and observed reproduction number estimates at the national level range from 1.13 to 1.99 and from 1.06 to 1.34, respectively. These estimates suggest that approximately 2% to 20% of the affected population across the country has thus far been effectively immunized against EVD and that the outbreak would likely be 4–34 times greater in size today had the vaccine not been deployed. Assuming no changes in transmission dynamics, we estimate that the expected cumulative case count will range between 3479 and 4249 by late December 2019; alternative transmission dynamics scenarios result in lesser and greater case count estimates. Interpretation. Transmission dynamics associated with the outbreak suggest that though the experimental vaccine has likely helped curb the spread of EVD, the outbreak may continue into 2020. Data assembly algorithms like the one presented here will continue to prove useful as this outbreak and others like it persist. Funding. Research reported in this work was supported by the National Institutes of Health through an NIH Director’s New Innovator Award DP2-MD012722.

Corrigendum: Probing the Surface of a Laccase for Clues towards the Design of Chemo-Enzymatic Catalysts.

The authors of this Full Paper wish to correct the acknowledgements as below, and apologize for this oversight. “L.S. was the recipient of a Ministre de l'Education Nationale fellowship. This study was supported by grants from the Agence Nationale de la Recherche (ANR-09-BLANC-0176 and ANR-15-CE07-0021-01) and from the Ministerio de Economa, Industria y Competitividad (CTQ2016-79138-R). We thank Elise Courvoisier–Dezord from the Plateforme AVB (AMU): Analyse et Valorisation de la Biodiversit and Yolande Charmasson for help in the production of the recombinant enzymes, as well as Pascal Mansuelle and Régine Lebrun from the Plateforme Protéomique, MaP IBiSA Labelled, Institut de Microbiologie de la Méditerranée, CNRS, Aix-Marseille Univ, for performing N-Terminal sequencing and for help in acquiring MALDI-TOF mass spectrometry data.”

The Origin of Microglia Determines the Content of Exosomes and Biological Function

Background: It is interesting to know whether microglia cells migrating in different central brain system components, i.e. cortex or in the spinal cord, are subjected to the same maturation processes and share similar functional phenotypes which could account with peculiar pathologies. Methods: We used a combination of pan proteomic platform associated with systemic biology analyses, in order to investigate that microglial cells derived from cortex and spinal cord expressed different phenotypes upon the physiological or pathological conditions Findings: This difference was found in cells and in their secreted exosomes. Cortical microglia showed neurogenesis/tumorigenesis characteristics, the spinal cord microglia revealed mostly involvement in the modulation of the inflammatory response to injury. We confirmed these results by performing functional testing including neurite outgrowth assays, and 3D spheroid cultures, which was used for glioma proliferation analysis. Results indicated that microglia located at different CNS areas reveal not only diverse content but also differential biological functions. Thus, the origin of microglia affected the physio-pathological function. These results also indicate differences in which the glioma is more prevalent in the brain than in spinal cord. Conclusion: Taken together, we demonstrated that microglia cells produce exosomes which can be used as therapeutic nanoparticles in translational medicine either in cancer treatment or in regenerative medicine. In fact, exosomes issued from spinal cord microglia can be addressed for glioma treatment and the ones from cortex microglia for spinal cord or brain traumatic injuries. Microglia exosomes are clearly a new source of therapeutic agents. Funding Statement: This research was supported by a collaboration between the Fundamental and Applied Biology Mass Spectrometry Laboratory (MS) and grants from Ministere de L’Education Nationale, L’Enseignement Superieur et de la Recherche, INSERM, SIRIC ONCOLille Grant INCD) a-DGOS-Inserm 6041aa (IF) and Universite de Lille (AM), APVV 15-0613 (DC), Stefanik SK-FR-2015-0018 (DC, MS), ERANET Axon Repair (DC). Declaration of Interests: The authors declare no competing financial interests in this work. Ethics Approval Statement: The study was performed with the approval and according to the guidelines of the Institutional Animal Care and Use Committee of the Slovak Academy of Sciences and with the European Communities Council Directive (2010/63/EU) regarding the use of animals in Research, Slovak Law for Animal Protection No. 377/2012 and 436/2012.

SoS Back-and-Forth? Minimum v. Exhaustive Harmonization of Entitled Protected Customers In Gas Supply Crises: Eni and Others

The Russian-Ukraine gas supply crisis in January 2009 brought an unprecedented disruption for the gas supply in Europe. As a response, the SoS Regulation put in place an ambitious plan to mitigate not only the risks of another gas supply crisis, but also to protect a defined group of customers in case of unavoidable gas shortage – households, small and medium enterprises, institutions providing essential social services among others. While it was thought the SoS Regulation had pursued exhaustive harmonization standards in the definition of protected costumers, the ECJ’s judgement in Eni and Others reopened the question. This article, instead, argues that the Court got it wrong. Neither the judgment nor the opinion of the Advocate General paid attention to the legal content of the provision that defined protected customers. If the Court had done so, the judgement would have likely taken additional linguistic, systemic, and teleological arguments into account. The analyses and comments on Eni and Others here offered focus on the first referred question about whether Member States could impose additional obligation on gas undertakings by reviewing the definition of protected customer. Case C-226/16, Eni and Others v Premier Ministre and Ministre de l’Environnement, de l’Energie et de la Mer, Judgement of the Court (First Chamber) of 20 December 2017, EU:C:2017:1005

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

Background: The receptor for advanced glycation end products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition was recently associated with attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will first require assessment of this strategy in larger animals. Methods: Forty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid i) alone; ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), a S100P-derived peptide that prevents activation of RAGE by its ligands, or iii) in combination with intravenous administration of recombinant soluble (s)RAGE that acted as a decoy receptor. The primary outcome measure was net AFC at 4 h. Arterial oxygenation was assessed hourly for 4 h and alveolar-capillary permeability, alveolar inflammation, lung histology and lung mRNA expression of the epithelial sodium channel (α1-ENaC), α1-Na,K-ATPase and aquaporin (AQP)-5 were assessed at 4 h. Findings: Treatment with either RAP or sRAGE improved net AFC rates (median [interquartile range], 21.2 [18.8-21.7] and 19.5 [17.1-21.5] %/h, respectively, versus 12.6 [3.2-18.8] %/h in injured, untreated controls), improved oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after acid-induced ARDS. RAGE inhibition also restored lung mRNA expression of α1-Na, K-ATPase and AQP-5. Interpretation: RAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS. Funding: Auvergne Regional Council, Agence Nationale de la Recherche, Direction Generale de l'Offre de Soins. Declaration of Interest: No conflict of interest, other source of financial support, corporate involvement, patent holdings, etc. is to be declared for all authors. Ethical Approval: Animals were maintained and all procedures were performed with the approval of the ethics committee of the French Ministere de l’Education Nationale, de l’Enseignement Superieur et de la Recherche in the Centre International de Chirurgie Endoscopique, School of Medicine - University of Clermont-Ferrand (approval number 01505.03). All experiments were performed in accordance with the “Animal Research: Reporting In Vivo Experiments” (ARRIVE) guidelines.