•The 28 SHAMISEN Recommendations are based on lessons from past accidents.•They cover all phases of an accident and multiple relevant fields of expertise.•The motivation, strategy and responsibility ...for implementation is described.•The approach was holistic covering doses, health, socio-economic & ethical issues.•Many recommendations are applicable to other disaster types (e.g. COVID19).
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.
•SHAMISEN built upon the experience of past nuclear accidents.•It aimed to develop holistic recommendations to limit impact of nuclear accidents.•SHAMISEN drew lessons about preparedness, response ...and health surveillance.•SHAMISEN aimed to build resilience/improve well-being in affected populations.
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.
Inflammatory CC chemokines have long been associated with cancer, but unequivocal evidence of a role in clinically relevant models of carcinogenesis is lacking. D6, a promiscuous decoy receptor that ...scavenges inflammatory CC chemokines, plays a non-redundant role in reducing the inflammatory response in various organs. As inflammation is a key player in the development of inflammatory bowel disease (IBD) and IBD-associated colorectal cancer, we investigated D6 expression in human colitis and colon cancer, and its role in experimental colitis and inflammation-associated colon cancer.
In humans, D6 was mainly expressed by lymphatic vessels and leukocytes in the mucosa of individuals with IBD and colon cancer, as well as the mucosa of control individuals. Mice lacking expression of D6 were significantly more susceptible to experimental colitis than wild-type mice and failed to resolve colitis, with significantly higher levels of several pro-inflammatory chemokines. In bone marrow chimeric mice, the ability of D6 to regulate colitis was tracked to the stromal/lymphatic compartment, with no contribution of haemopoietic cells. Finally, after administration of the carcinogen azoxymethane, D6(-/-) mice showed increased susceptibility to colitis-associated cancer in the distal segment of the colon compared with wild-type mice.
D6 expressed on lymphatic vessels plays a key role in the control of intestinal inflammation and the development of inflammation-associated colon cancer. Our results reveal a new unexpected role for the lymphatic system in the pathogenesis of IBD and intestinal cancer, and candidate chemokines as novel players in tumour promotion and progression.
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 NPPs
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. NGOs
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 CIEMAT
, UPM
and ISGlobal
) 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.
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.
Abstract
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.
The versatility and plasticity of myeloid cell polarization/differentiation has turned out to be crucial in health and disease, and has become the subject of intense investigation during the last ...years. On one hand, myeloid cells provide a critical contribution to tissue homeostasis and repair. On the other hand, myeloid cells not only play an important role as first line defense against pathogens but also they are involved in a broad array of inflammation-related diseases such as cancer. Recent studies show that macrophages can exist in different activation states within the same tumor, underlining their plasticity and heterogeneity. In this review, we will discuss recent evidence on how the tumor microenvironment, as it evolves, shapes the recruitment, function, polarization and differentiation of the myeloid cell compartment, leading to the selection of myeloid cells with immunosuppressive and angiogenic functions that facilitate tumor progression and dissemination.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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