Resilience after a nuclear accident: readiness in using mobile phone applications to measure radiation and health indicators in various groups (SHAMISEN SINGS project).

An anonymous web-based survey was developed to check different aspects (SHAMISEN SINGS project): stakeholder awareness and perceptions of available mobile applications (apps) for measuring ionising radiation doses and health/well-being indicators; whether they would be ready to use them in the post-accidental recovery; and what are their preferred methodologies to acquire information etc. The results show that participation of the citizens would be most beneficial during post-accident recovery, providing individual measurements of external ionizing dose and health/well-being parameters, with possible follow-up. Also, participants indicated different preferences for sources to gain knowledge on ionising radiation and for the functions that an ideal app should have. The level of awareness and readiness to use apps to measure ionising radiation dose depended on two main aspects: individual differences (age & gender) and whether people were from countries affected by the previous major accidents. We concluded that stakeholders could have benefits from the data management plan: (1) it potentiates resilience at individual and community level; (2) citizens' measurements contribute to environmental monitoring and public health screening; (3) linkages between different types of data (environmental exposure, individual behavioural diaries, and measurements of health indicators) allow to perform more rigorous epidemiological studies.

No evidence of false-negative Plasmodium falciparum rapid diagnostic results in Monrovia, Liberia.

BACKGROUND: Malaria diagnosis in many malaria-endemic countries relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia. METHODS: PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n = 951) and pregnant women at first antenatal care (ANC) visit (n = 87) enrolled in the Saint Joseph's Catholic Hospital (Monrovia) from March to July 2019 were used to assess the frequency of false-negative RDT results. True-false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy results. Samples that were positive by 18S rRNA qPCR but negative by PfHRP2-RDT were subjected to multiplex qPCR assay for detection of pfhrp2 and pfhrp3. RESULTS: One-hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum-positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and decreased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n = 5) and 8% (n = 7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the 16 RDT-negative but microscopy-positive samples which were available for molecular testing. Among the 14 samples that were positive by qPCR but negative by RDT and microscopy, 3 only amplified pfldh, and among these 3 all were positive for pfhrp2 and pfhrp3. CONCLUSION: There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates that these deletions are not expected to affect the performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.

Monocytic myeloid-derived suppressor cells home to tumor-draining lymph nodes via CCR2 and locally modulate the immune response.

Efficient priming of anti-tumor T cells requires the uptake and presentation of tumor antigens by immunogenic dendritic cells (DCs) and occurs mainly in lymph nodes draining the tumor (tdLNs). However, tumors expand and activate myeloid-derived suppressor cells (MDSCs) that inhibit CTL functions by several mechanisms. While the immune-suppressive nature of the tumor microenvironment is largely documented, it is not known whether similar immune-suppressive mechanisms operate in the tdLNs. In this study, we analyzed MDSC characteristics within tdLNs. We show that, in a metastasis-free context, MO-MDSCs are the dominant MDSC population within tdLNs, that they are highly suppressive and that tumor proximity enhances their recruitment to tdLN via a CCR2/CCL2-dependent pathway. Altogether our results uncover a mechanism by which tumors evade the immune system that involves MDSC-mediated recruitment to the tdLN and the inhibition of T-cell activation even before reaching the highly immunosuppressive tumor microenvironment.

The SHAMISEN Recommendations on preparedness and health surveillance of populations affected by a radiation accident.

This paper, the last in the Special Issue (SI) on the SHAMISEN project, presents an overview of the SHAMISEN Recommendations for Preparedness and Health Surveillance of Populations Affected by a Radiation Accident. The recommendations are based on the lessons learnt from previous nuclear accidents, and the engagement activities with different stakeholder groups, described in the other papers of this SI. The SHAMISEN project developed a total of 28 recommendations. They include general recommendations, applicable across all phases of an accident, and specific recommendations for each of the three main phases: preparedness, early and intermediate, and long-term recovery. The recommendations are subdivided by topic: health surveillance, epidemiological studies, dose reconstruction, evacuation, and training of and communication with health personnel and other actors involved in liaising with affected populations. Each recommendation is divided into 3 sections - why, how and who - thus providing background and concrete advice as to how each SHAMISEN recommendation should be implemented and by whom. It is notable that many recommendations are also applicable to other disaster types, including the current SARS-CoV-2 pandemic.

The SHAMISEN Project: Challenging historical recommendations for preparedness, response and surveillance of health and well-being in case of nuclear accidents: Lessons learnt from Chernobyl and Fukushima.

Experience suggests that current nuclear accident response planning in European countries mostly has a technical focus, with less attention paid to social, psychological and ethical issues. Information provided tends to be directed towards decisions made by experts, rather than for the support of affected populations. The SHAMISEN (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) consortium, composed of close to 50 experts from 10 countries, performed a critical review of current recommendations and experiences regarding dose assessment and reconstruction, evacuation decisions, long-term health surveillance programmes and epidemiological studies. The review included case studies and lessons drawn from the living conditions and health status of populations affected by the Chernobyl and Fukushima accidents, taking an integrative approach to health and well-being. Based on this work, SHAMISEN developed a series of comprehensive recommendations aimed at improving the preparedness, response, long-term surveillance and living conditions of populations affected by past or future radiation accidents, in a manner responding to their needs, while minimising unnecessary anxiety.

Stakeholder participation in nuclear and radiological emergency preparedness and recovery in Spain: benefits and challenges of working together.

Emergency preparedness and response (EP&R) to radiological or nuclear accidents depends on many different stakeholder groups: nuclear and radiological regulators and authorities; institutions and ministries concerned by health, environment and consumption; first-line responders including the police, military, firefighters and health workers; as well as local authorities and nuclear industries. Stakeholders also include the general public, such as people living near NPPs8 or affected by previous nuclear or radiological accidents and incidents. Teachers and journalists, bloggers and other social media figures would play a key role in effective dissemination of knowledge and information. NGOs9 or civil associations/societies can also be involved in radiation monitoring and protection. The present study describes the role of different research institutions (such as CIEMAT10, UPM11 and ISGlobal12) and of the Spanish Society of Radiological Protection (SEPR) in bringing together the above-listed stakeholders in Spain to discuss EP&R and identify benefits and challenges of working together. Stakeholder opinions on EP&R, collected mainly in the framework of several European-funded projects, are provided. Remaining barriers and examples of good practices in radiation protection are discussed, as well as recommendations for improving nuclear and radiological emergency preparedness in Spain. The conclusions may be useful for other countries.

Training through malaria research: building capacity in good clinical and laboratory practice in Liberia.

BACKGROUND: Limited health research capacities (HRC) undermine a country's ability to identify and adequately respond to local health needs. Although numerous interventions to strengthen HRC have been conducted in Africa, there is a need to share the lessons learnt by funding organizations, institutes and researchers. The aim of this report is to identify best practices in HRC strengthening by describing a training programme conducted between 2016 and 2017 at the Saint Joseph's Catholic Hospital (SJCH) in Monrovia (Liberia). METHODS: A call for trainees was launched at the SJCH, the Liberia Medicines and Health Products Regulatory Authority (LMHRA), the Ministry of Health and Social Welfare, the Mother Pattern College of Health Sciences (MPCHS) and community members. Selected trainees participated in four workshops on Good Clinical Laboratory Practice (GCLP), standard operating procedures (SOP) and scientific communication, as well as in a 5-months eLearning mentoring programme. After the training, a collectively-designed research project on malaria was conducted. RESULTS: Twenty-one of the 28 trainees (14 from the SJCH, 3 from LMHRA, one from MPCHS, and 10 community representatives) completed the programme satisfactorily. Pre- and post-training questionnaires completed by 9 of the trainees showed a 14% increase in the percentage of correct answers. Trainees participated in a mixed-methods cross-sectional study of Plasmodium falciparum infection among pregnant women at the SJCH. Selected trainees disseminated activities and research outcomes in three international meetings and three scientific publications. CONCLUSION: This training-through-research programme successfully involved SJCH staff and community members in a practical research exercise on malaria during pregnancy. The challenge is to ensure that the SJCH remains active in research. Harmonization of effectiveness indicators for HRC initiatives would strengthen the case for investing in such efforts.

Community-informed research on malaria in pregnancy in Monrovia, Liberia: a grounded theory study.

BACKGROUND: Liberia is a West African country that needs substantial investment to strengthen its National Malaria Control Programme (NMCP), which was disrupted during the 2014-2016 Ebola epidemic. As elsewhere, Liberian pregnant women are especially vulnerable to malaria. Understanding prevention and treatment-seeking behaviours among the population is crucial to strategize context-specific and women-centred actions, including locally-led malaria research, to improve women's demand, access and use of NMCP strategies against malaria in pregnancy. METHODS: In 2016, after the Ebola crisis, a qualitative inquiry was conducted in Monrovia to explore populations' insights on the aetiology, prevention and therapeutics of malaria, as well as the community and health workers' perceptions on the utility of malaria research for pregnant women. In-depth interviews and focus group discussions were conducted among pregnant women, traditional community representatives and hospital staff (n = 38), using a feminist interpretation of grounded theory. RESULTS: The narratives indicate that some Liberians believed in elements other than mosquito bites as causes of malaria; many had a low malaria risk perception and disliked current effective prevention methods, such as insecticide-treated nets; and some would resort to traditional medicine and spiritual care to cure malaria. Access to clinic-based malaria care for pregnant women was reportedly hindered by lack of financial means, by unofficial user fees requested by healthcare workers, and by male partners' preference for traditional medicine. The participants suggested that malaria research in Liberia could help to design evidence-based education to change current malaria prevention, diagnostic and treatment-seeking attitudes, and to develop more acceptable prevention technologies. CONCLUSION: Poverty, insufficient education on malaria, corruption, and poor trust in healthcare establishment are structural factors that may play a greater role than local traditional beliefs in deterring Liberians from seeking, accessing and using government-endorsed malaria control strategies. To increase access to and uptake of preventive and biomedical care by pregnant women, future malaria research must be informed by people's expressed needs and constructed meanings and values on health, ill health and healthcare.

Prevalence of Plasmodium falciparum infection among pregnant women at first antenatal visit in post-Ebola Monrovia, Liberia.

BACKGROUND: Disruption of malaria control strategies during the West African 2014-2016 Ebola epidemic led to an increase in malaria-attributable mortality. However, recent data on malaria infection in vulnerable groups, such as pregnant women, are lacking in this post-Ebola scenario. This cross-sectional study aimed to assess the prevalence of Plasmodium falciparum infection and of molecular markers of drug resistance among pregnant women attending antenatal care in Monrovia, capital of Liberia. METHODS: From October 2016 to June 2017, all pregnant women attending their first antenatal care visit at the Saint Joseph's Catholic Hospital, Monrovia, were invited to participate in the study. In addition to their routine antenatal care tests, capillary blood spotted onto filter papers were collected from all consenting participants to determine presence of P. falciparum by real-time quantitative PCR. Molecular markers of anti-malarial drug resistance were assessed through Sanger sequencing and quantitative PCR in specimens positive for P. falciparum analysis. RESULTS: Of the 195 women participants, 24 (12.3%) were P. falciparum-positive by qPCR. Infected women tended to be more commonly primigravidae and younger than uninfected ones. Parasite densities were higher in primigravidae. Fever was more frequently detected among the infected women. No statistically significant association between P. falciparum infection and haemoglobin levels or insecticide-treated net use was found. While high prevalence of genetic polymorphisms associated with chloroquine and amodiaquine resistance were detected, no molecular markers of artemisinin resistance were observed. CONCLUSION: Plasmodium falciparum infections are expected to occur in at least one in every eight women attending first ANC at private clinics in Monrovia and outside the peak of the rainy season. Young primigravidae are at increased risk of P. falciparum infection. Molecular analyses did not provide evidence of resistance to artemisinins among the P. falciparum isolates tested. Further epidemiological studies involving pregnant women are necessary to describe the risk of malaria in this highly susceptible group outside Monrovia, as well as to closely monitor the emergence of resistance to anti-malarials, as recommended by the Liberian National Malaria Control Programme.

'Researchers have love for life': opportunities and barriers to engage pregnant women in malaria research in post-Ebola Liberia.

BACKGROUND: Adoption of prevention and therapeutic innovations to ensure that National Malaria Control Programmes meet their incidence reduction targets is highly dependent on the conduct of rigorous clinical trials. In Liberia, malaria control virtually halted during the recent Ebola epidemic, and could enormously benefit from innovations to protect its most vulnerable populations, including pregnant women, against malaria. Health policy-planners could feel more inclined to adopt novel interventions with demonstrated safety and efficacy when trialled among their women population. However, pregnant women are especially vulnerable when targeted as research participants. Whilst some studies in the region attempted to understand the ethical issues around the conduct of clinical research, there is need of such information from Liberia to inform future malaria research. METHODS: This is a grounded theory study that aims to understand the barriers and opportunities for pregnant women to consent to participate in malaria research in Liberia. The study was conducted between November 2016 and May 2017 at the St Joseph's Catholic Hospital, Monrovia. In-depth interviews and focus group discussions were held with hospital staff, traditional community representatives, and pregnant women. RESULTS: According to the participants, useful strategies to motivate pregnant women to consent to participate in malaria research could be providing evidence-based education on malaria and research to the general population and encouraging engagement of traditional leaders in research design and community mobilization. Fears and suspicions towards research and researchers, which were amplified during the conduct of Ebola vaccine and drug clinical trials, may influence women's acceptance and willingness to engage in malaria research. Population's mistrust in the public healthcare system might hinder their acceptance of research, undermining the probability of their benefiting from any improved malaria control intervention. CONCLUSION: Benchmarking for acceptable practices from previous public health interventions; building community discussion and dissemination platforms; and mapping communication and information errors from how previous research interventions were explained to the Liberian population, are strategies that might help ensure a safe and fully informed participation of pregnant women in malaria research. Inequity issues impeding access and use of biomedical care for women must be tackled urgently.

Human CD6 Down-Modulation following T-Cell Activation Compromises Lymphocyte Survival and Proliferative Responses.

Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i) concomitant to increased levels of soluble CD6 (sCD6) in culture supernatants, (ii) partially reverted by protease inhibitors, (iii) not associated to CD6 mRNA down-regulation, and (iv) reversible by stimulus removal. CD6 down-modulation inversely correlated with the upregulation of CD25 in both FoxP3- (Tact) and FoxP3+ (Treg) T-cell subsets. Furthermore, ex vivo analysis of peripheral CD4+ and CD8+ T cells with activated (CD25+) or effector memory (effector memory T cell, CD45RA-CCR7-) phenotype present lower CD6 levels than their naïve or central memory (central memory T cell, CD45RA-CCR7+) counterparts. CD6lo/- T cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6hi T cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of sCD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses.

CD6 modulates thymocyte selection and peripheral T cell homeostasis.

The CD6 glycoprotein is a lymphocyte surface receptor putatively involved in T cell development and activation. CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), and physically associates with the T cell receptor (TCR) at the center of the immunological synapse. However, its precise role during thymocyte development and peripheral T cell immune responses remains to be defined. Here, we analyze the in vivo consequences of CD6 deficiency. CD6(-/-) thymi showed a reduction in both CD4(+) and CD8(+) single-positive subsets, and double-positive thymocytes exhibited increased Ca(2+) mobilization to TCR cross-linking in vitro. Bone marrow chimera experiments revealed a T cell-autonomous selective disadvantage of CD6(-/-) T cells during development. The analysis of TCR-transgenic mice (OT-I and Marilyn) confirmed that abnormal T cell selection events occur in the absence of CD6. CD6(-/-) mice displayed increased frequencies of antigen-experienced peripheral T cells generated under certain levels of TCR signal strength or co-stimulation, such as effector/memory (CD4(+)TEM and CD8(+)TCM) and regulatory (T reg) T cells. The suppressive activity of CD6(-/-) T reg cells was diminished, and CD6(-/-) mice presented an exacerbated autoimmune response to collagen. Collectively, these data indicate that CD6 modulates the threshold for thymocyte selection and the generation and/or function of several peripheral T cell subpopulations, including T reg cells.

Pattern Recognition by CD6: A Scavenger-Like Lymphocyte Receptor.

CD6, one of the first antigens to be identified on T cells, is a membrane glycoprotein that physically associates with the antigen receptor complex. Because of this, its main function seems to involve the modulation of TCR-mediated signaling pathways. However, growing evidence indicates that this ancient and conserved scavenger-like receptor may also play a role as pattern recognition receptor (PRR), similar to other members of the scavenger receptor cysteine rich superfamily (SRCR-SF). Here, we discuss the functional interactions of CD6 with microbe- and damage-associated signals and the potential use of soluble forms of CD6 in the therapeutic treatment of bacterial infections, in particular multi-drug resistant bacterial strains. Importantly, microbe recognition by CD6 may also have functional consequences on T cell activation and differentiation, which remain to be explored.

Mesenchymal stem cells: myths and reality.

Mesenchymal stem cells (MSCs; also called mesenchymal stromal cells) have received much attention during the last two decades, at first because of their regeneration capacity and poor immunogenicity and, more recently, because of their proved immunomodulatory function. Consequently, the number of studies addressing MSC biology and their capacity to treat a broad range of human diseases at the preclinical and clinical level has grown exponentially, with often confusing and conflicting results. The use of poorly defined cell preparations and experimental models, many of them in vitro, has added to such confusion. In this review, we identify what in our opinion remain the main open questions on MSC biology and we attempt to distinguish the facts from the myths concerning endogenous and therapeutic MSC.

CD5 as a Target for Immune-Based Therapies.

CD5 was one of the first surface receptors described for mouse and human T lymphocytes. Since then, it has been found to be highly expressed by regulatory T cells and a subpopulation of regulatory B cells, to be physically associated with the T- and B-cell antigen receptors, to negatively modulate TCR- and BCR-mediated signals, and to bind certain pathogen-associated molecular patterns. These findings position CD5 as an attractive target for developing immunotherapies aimed at either boosting or dampening ongoing immune responses. Here the available data on the function of CD5 and its involvement in the regulation of immune responses in health and disease are reviewed, as well as the evidence for and future challenges in developing therapeutic strategies aimed at targeting CD5 for autoimmune diseases, cancer, and infections.

[The intestinal microbiota: a boost for antitumor treatments]. / Nos bactéries commensales - un coup de pouce pour les thérapies antitumorales.

Two new studies in mice, published in Science, show that the commensal bacteria populations in the gut play a key role in boosting responses to different antitumor regimens. These results argue for a rational use of antibiotics when managing infections in patients undergoing cancer therapies.

Adenosine triphosphate acts as a paracrine signaling molecule to reduce the motility of T cells.

Organization of immune responses requires exchange of information between cells. This is achieved through either direct cell-cell contacts and establishment of temporary synapses or the release of soluble factors, such as cytokines and chemokines. Here we show a novel form of cell-to-cell communication based on adenosine triphosphate (ATP). ATP released by stimulated T cells induces P2X4/P2X7-mediated calcium waves in the neighboring lymphocytes. Our data obtained in lymph node slices suggest that, during T-cell priming, ATP acts as a paracrine messenger to reduce the motility of lymphocytes and that this may be relevant to allow optimal tissue scanning by T cells.

Mechanisms driving macrophage diversity and specialization in distinct tumor microenvironments and parallelisms with other tissues.

Macrophages are extremely versatile cells that adopt a distinct phenotype in response to a changing microenvironment. Consequently, macrophages are involved in diverse functions, ranging from organogenesis and tissue homeostasis to recognition and destruction of invading pathogens. In cancer, tumor-associated macrophages (TAM) often contribute to tumor progression by increasing cancer cell migration and invasiveness, stimulating angiogenesis, and suppressing anti-tumor immunity. Accumulating evidence suggests that these different functions could be exerted by specialized TAM subpopulations. Here, we discuss the potential underlying mechanisms regulating TAM specialization and elaborate on TAM heterogeneity in terms of their ontogeny, activation state, and intra-tumoral localization. In addition, parallels are drawn between TAM and macrophages in other tissues. Together, a better understanding of TAM diversity could provide a rationale for novel strategies aimed at targeting the most potent tumor-supporting macrophages.