The research gap in chronic paediatric pain: A systematic review of randomised controlled trials

Background and Objective: Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. Methods: We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. Results: A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Conclusions: Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. Significance: There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases

The draft genome sequence of the rice weevil Sitophilus oryzae as a model to explore the host-symbiont interactions in a nascent stage of endosymbiosis

International audienceOrganisms across the tree of life are associated with diverse microbial partners that impact host adaptive traits and exhibit phenotypes ranging from parasitism to mutualism. For example, insects thriving on nutritionally unbalanced habitats are prone to house mutualistic intracellular bacteria (endosymbionts) that complement their diet, thus greatly improving their ecological performances. Within insects, endosymbiosis is very common in the Curculionoidea weevils superfamily, which constitutes a group with considerable worldwide biodiversity. Weevils include some of the most invasive insects and cause huge crop damages. Recent phylogenetic and molecular studies have shown that endosymbiosis history has been marked by several symbiotic displacements within this insect group. The most recent event may have occurred less than one million year ago within the cereal weevil Sitophilus clade resulting in the replacement of an ancestral symbiont Candidatus Nardonella by Sodalis pierantonius symbiont. S. pierantonius genome exhibits peculiar molecular features associated with a massive pseudogenization and the occurrence of a huge amount of repeated elements. Whether these phenomena are adaptive, and whether they impact host genome reshaping are puzzling questions that will be addressed thanks to the genome level investigation of the Sitophilus-Sodalis recent association.Here, we present the draft genome sequence of the rice weevil Sitophilus oryzae. The full genome sequence has been obtained through a combination of short-read (Illumina HiSeq and Roche/454 GS FLX) and long-read (Pacific Biosciences PacBio RS) sequencing methods. After error correction, the data were assembled using the Platanus algorithm for an initial scaffolding and gap-filling. These scaffolds were then re-scaffolded several times using PacBio data. The final assembly consisted in 17,365 scaffolds of a total length of 652 Mbp (the S. oryzae genome size was estimated to be about 650 Mbp using flow cytometry), a N50 value of 110 kbp, a coverage of 101X and a GC content of 38.4%. Intriguingly, transposable elements (TE) analysis using both automated tools (dnaPipeTE, RepeatModeler and MITEhunter) and manual annotations revealed an unexpected high amount of repeated DNA (>50%) in this weevil genome. Gene prediction was then performed using a combination of MAKER, GeneMark, Augustus and SNAP algorithms and taking advantage of the available transcriptomic data (EST and RNA-seq data) on S. oryzae to build more accurate gene models. Finally, the official gene set contained 17,026 protein-coding genes. Based on this gene set, the complete catalogue of gene phylogenies (phylome) was predicted through the PhylomeDB pipeline and will be publicly available in this database (www.phylomedb.org). The weevil metabolic and signalling networks were also reconstructed using the CycADS pipeline in order to generate the SitorCyc database (a BioCyc interface of the S. oryzae metabolism). These metabolic pathways were integrated in the ArthropodaCyc database collection dedicated to comparative metabolic analyses among arthropods (http://arthropodacyc.cycadsys.org/). The interdependence of the metabolic networks of S. oryzae and its endosymbiont S. pierantonius will then be characterized thanks to their integration into the ArtSymbioCyc database that is being developed and will be dedicated to arthropod symbioses. All these annotations (TE, phylome and metabolic networks) will be integrated in a comprehensive genome database providing a genome browser with crosslinks to available resources.Altogether, these results are expected to unravel basic molecular mechanisms and evolutionary features associated with the establishment and the maintenance of endosymbiosis in animals, and to permit identifying potential gene targets useful for the development of new ecologically-friendly strategies for pest insects control and management

Evaluating the essentiality of the primary endosymbiont of the rice weevil Sitophilus oryzae through genome analysis

International audienceThe rice weevil Sitophilus oryzae is a pest insect responsible for great economic losses to the agriculture, particularly in developing countries where the damage can exceed 40% of the cereal production. This pest harbors an endosymbiont, “Candidatus Sodalis pierantonius” (cited Sodalis hereafter) that improves its fitness and invasive power. It has been demonstrated that Sodalis recently replaced the ancestral endosymbiont “Candidatus Nardonella” (cited Nardonella hereafter), which is still conserved in other members of the Dryophthoridae family. This recent acquisition raises several challenges for the host, given that the genome of Sodalis has not experienced a drastic genome size shrinkage when compared to other old-lasting insect’s endosymbionts. While the genomes of Sodalis and several strains of Nardonella are available, the insect’s genome is still needed to perform a full study of the system. To this end, we have sequenced and assembled the full genome of the weevil S. oryzae using a combination of Next Generation Sequencing data. Additionally, we have compared this genome with other available insect genomes. We found that the genome of S. oryzae encodes immune elements similar to those of other holometabolous insects, including those living without endosymbionts. Remarkably, an impressive amount of repeated elements was identified, similar to what was previously described in the Sodalis endosymbiont, suggesting the occurrence of gene rearrangement processes at this early phase of symbiogenesis. We concluded that while Sodalis is completely dependent on its host, the insect can survive without its endosymbiont

Evaluating the essentiality of the primary endosymbiont of the rice weevil Sitophilus oryzae through genome analysis

International audienceThe rice weevil Sitophilus oryzae is a pest insect responsible for great economic losses to the agriculture, particularly in developing countries where the damage can exceed 40% of the cereal production. This pest harbors an endosymbiont, “Candidatus Sodalis pierantonius” (cited Sodalis hereafter) that improves its fitness and invasive power. It has been demonstrated that Sodalis recently replaced the ancestral endosymbiont “Candidatus Nardonella” (cited Nardonella hereafter), which is still conserved in other members of the Dryophthoridae family. This recent acquisition raises several challenges for the host, given that the genome of Sodalis has not experienced a drastic genome size shrinkage when compared to other old-lasting insect’s endosymbionts. While the genomes of Sodalis and several strains of Nardonella are available, the insect’s genome is still needed to perform a full study of the system. To this end, we have sequenced and assembled the full genome of the weevil S. oryzae using a combination of Next Generation Sequencing data. Additionally, we have compared this genome with other available insect genomes. We found that the genome of S. oryzae encodes immune elements similar to those of other holometabolous insects, including those living without endosymbionts. Remarkably, an impressive amount of repeated elements was identified, similar to what was previously described in the Sodalis endosymbiont, suggesting the occurrence of gene rearrangement processes at this early phase of symbiogenesis. We concluded that while Sodalis is completely dependent on its host, the insect can survive without its endosymbiont

Evaluating the essentiality of the primary endosymbiont of the rice weevil Sitophilus oryzae through genome analysis

International audienceThe rice weevil Sitophilus oryzae is a pest insect responsible for great economic losses to the agriculture, particularly in developing countries where the damage can exceed 40% of the cereal production. This pest harbors an endosymbiont, “Candidatus Sodalis pierantonius” (cited Sodalis hereafter) that improves its fitness and invasive power. It has been demonstrated that Sodalis recently replaced the ancestral endosymbiont “Candidatus Nardonella” (cited Nardonella hereafter), which is still conserved in other members of the Dryophthoridae family. This recent acquisition raises several challenges for the host, given that the genome of Sodalis has not experienced a drastic genome size shrinkage when compared to other old-lasting insect’s endosymbionts. While the genomes of Sodalis and several strains of Nardonella are available, the insect’s genome is still needed to perform a full study of the system. To this end, we have sequenced and assembled the full genome of the weevil S. oryzae using a combination of Next Generation Sequencing data. Additionally, we have compared this genome with other available insect genomes. We found that the genome of S. oryzae encodes immune elements similar to those of other holometabolous insects, including those living without endosymbionts. Remarkably, an impressive amount of repeated elements was identified, similar to what was previously described in the Sodalis endosymbiont, suggesting the occurrence of gene rearrangement processes at this early phase of symbiogenesis. We concluded that while Sodalis is completely dependent on its host, the insect can survive without its endosymbiont

The research gap in chronic paediatric pain : A systematic review of randomised controlled trials

Background and Objective: Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. Methods: We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. Results: A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Conclusions: Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. Significance: There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases