Descriptive and comparative analysis of mucocutaneous manifestations in patients with dengue fever: A prospective study.

BACKGROUND: Dengue is an arbovirosis affecting nearly 4 billion people worldwide. Since 2018, dengue has been re-emerging in Reunion Island. The incidence of mucocutaneous manifestations varies according to the studies and is generally called 'rash'. OBJECTIVES: To assess the prevalence of different mucocutaneous symptoms and describe the characteristics of patients developing these symptoms and the clinical signs associated with severe dengue. METHODS: A prospective study was conducted in 2019 at the University Hospital of La Réunion, in patients presenting a positive PCR for dengue. Descriptive analyses were performed. All cases in the prospective study were examined by a dermatologist. RESULTS: A total of 163 cases were included. The prevalence of mucocutaneous signs was 80.4%. A pruritus was reported in 33.7% cases, an erythematous rash in 29.4% and a mouth involvement including lip, tongue, cheek, angular cheilitis, pharyngitis, mouth ulcer and gingivitis in 31.3%. Most of symptoms appeared in the first days, but some of them could disappear only after the 3rd week. Mucocutaneous signs were not associated with a severe dengue fever (p = 0.54), but ecchymotic purpura was (p = 0.037). In multivariate analysis, skin involvement was associated with flu-like syndrome (headache, pharyngitis, rachis pain) and patient required rehydration but not invasive reanimation. CONCLUSION: This work confirms the high prevalence of skin symptoms in dengue disease, but also their wide diversity. The mucocutaneous involvement of dengue fever appears to be accompanied by a pronounced flu-like syndrome in people without severity, but careful examination to identify ecchymotic purpura or sign of dehydration in the mucous membranes would better identify cases that may worsen.

[Spontaneous remission of cutaneous myeloid sarcoma]. / Régression spontanée d'un sarcome myéloïde cutané.

INTRODUCTION: Cutaneous myeloid sarcoma is a rare extramedullary tumour of immature myeloid cells. It is most often associated with acute myeloid leukaemia, and more rarely with myelodysplastic/myeloproliferative disease. PATIENTS AND METHODS: Herein we report a case of cutaneous myeloid sarcoma associated with myelodysplastic/myeloproliferative disease in an 84-year-old man with a diffuse purple papular and nodular rash. The disease course was marked by a spontaneous and total regression for two months. Given the patient's age and general condition, chemotherapy could not be given. DISCUSSION: Cutaneous myeloid sarcoma is rare. It is often associated with acute myeloid leukaemia, and more rarely with myelodysplastic/myeloproliferative disease, but it can occur in isolation. Diagnosis is particularly difficult and is based a consistent body of clinical and histological evidence. Spontaneous regression is very rare and involves immunological mechanisms that are still incompletely understood. Recurrence occurs within a variable time frame and is often associated with transformation to acute myeloid leukaemia if this was not already present at the time of diagnosis. CONCLUSION: Herein we report an extremely rare case of spontaneous regression of cutaneous myeloid sarcoma associated with myelodysplastic/myeloproliferative disease.

[Carbon dioxide laser treatment of genital intraepithelial neoplasia: A retrospective study]. / Traitement des néoplasies intraépithéliales génitales par laser CO2 : étude rétrospective.

INTRODUCTION: Genital intraepithelial neoplasias (IEN) are precursors of squamous cell carcinoma. The ideal treatment must be efficacious, conservative and well-tolerated. CO2 laser is one of the recommended therapies, but its efficacy and safety have not been extensively studied. PATIENTS AND METHODS: This was a retrospective single-center study. Sixteen patients (8 women and 8 men) treated with CO2 laser for genital IEN, whether high-grade or differentiated, were included. Surgical lateral margins of 3 to 5mm were taken macroscopically during treatment. The CO2 laser session, assessment of therapeutic response and follow-up were undertaken by a dermatologist at the University Hospital of Caen. RESULTS: The mean patient age was 68.1 years and mean follow-up was 52.7 months (5-130). Lesions were isolated in 87.5% of patients. The recurrence rates of genital intraepithelial neoplasia after CO2 laser treatment were 58% for women and 40% for men. No impact on quality of life or on sexual activity was reported in over 90% of patients. CONCLUSION: Whatever the treatment recommended for intraepithelial neoplasia, recurrence is frequent. CO2 laser is an effective and well-tolerated conservative therapeutic option. It enables rapid clinical remission, but as with all currently available treatments, long-term dermatologic follow-up remains necessary.

Genomic innovations, transcriptional plasticity and gene loss underlying the evolution and divergence of two highly polyphagous and invasive Helicoverpa pest species.

BACKGROUND: Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis for their properties as pests. RESULTS: We find that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had accumulated up to more than 100 more members of specific detoxification and digestion gene families and more than 100 extra gustatory receptor genes, compared to other lepidopterans with narrower host ranges. The two genomes remain very similar in gene content and order, but H. armigera is more polymorphic overall, and H. zea has lost several detoxification genes, as well as about 50 gustatory receptor genes. It also lacks certain genes and alleles conferring insecticide resistance found in H. armigera. Non-synonymous sites in the expanded gene families above are rapidly diverging, both between paralogues and between orthologues in the two species. Whole genome transcriptomic analyses of H. armigera larvae show widely divergent responses to different host plants, including responses among many of the duplicated detoxification and digestion genes. CONCLUSIONS: The extreme polyphagy of the two heliothines is associated with extensive amplification and neofunctionalisation of genes involved in host finding and use, coupled with versatile transcriptional responses on different hosts. H. armigera's invasion of the Americas in recent years means that hybridisation could generate populations that are both locally adapted and insecticide resistant.

A multidimensional approach to impulsivity in Parkinson's disease: measurement and structural invariance of the UPPS Impulsive Behaviour Scale.

BACKGROUND: Poor impulse control is a common feature in patients with Parkinson's disease (PD). However, before testing whether patients with PD and controls differ in impulsivity, one must assess whether impulsivity measures are invariant across groups. Consequently, we examined (a) the measurement and structural invariance of a scale assessing changes in four dimensions of impulsivity (urgency, lack of premeditation, lack of perseverance and sensation seeking) among patients with PD and controls; and (b) whether the four impulsivity traits relate differentially to risky decisions by patients. METHOD: Close relatives of 78 patients with idiopathic PD and 96 control participants were given the short Urgency-Premeditation-Perseverance-Sensation seeking Impulsive Behaviour Scale (UPPS), which assesses changes in four dimensions of impulsivity. Participants also completed the Game of Dice Task (GDT), a laboratory measure of risk taking. RESULTS: Multigroup confirmatory factor analyses supported measurement invariance across groups, whereas structural invariance was not confirmed. Patients with PD showed greater variability and higher impulsivity than controls. Furthermore, patients with impulse control disorders (ICDs) demonstrated even greater levels of sensation seeking than patients without ICDs. Finally, lower premeditation and greater perseverance were significantly associated with greater risk taking in patients with PD, and higher agonist dopaminergic doses with less risky choices on the GDT. CONCLUSIONS: The questionnaire appears to function comparably across patients and controls. Thus, group comparisons on the questionnaire can be considered valid. Mean differences between groups on the dimensions of impulsivity may reflect executive impairments and/or abnormal reward processing in patients with PD, which may lead to risky behaviours.

De novo transcriptome assembly for a non-model species, the blood-sucking bug Triatoma brasiliensis, a vector of Chagas disease.

High throughput sequencing (HTS) provides new research opportunities for work on non-model organisms, such as differential expression studies between populations exposed to different environmental conditions. However, such transcriptomic studies first require the production of a reference assembly. The choice of sampling procedure, sequencing strategy and assembly workflow is crucial. To develop a reliable reference transcriptome for Triatoma brasiliensis, the major Chagas disease vector in Northeastern Brazil, different de novo assembly protocols were generated using various datasets and software. Both 454 and Illumina sequencing technologies were applied on RNA extracted from antennae and mouthparts from single or pooled individuals. The 454 library yielded 278 Mb. Fifteen Illumina libraries were constructed and yielded nearly 360 million RNA-seq single reads and 46 million RNA-seq paired-end reads for nearly 45 Gb. For the 454 reads, we used three assemblers, Newbler, CAP3 and/or MIRA and for the Illumina reads, the Trinity assembler. Ten assembly workflows were compared using these programs separately or in combination. To compare the assemblies obtained, quantitative and qualitative criteria were used, including contig length, N50, contig number and the percentage of chimeric contigs. Completeness of the assemblies was estimated using the CEGMA pipeline. The best assembly (57,657 contigs, completeness of 80 %, <1 % chimeric contigs) was a hybrid assembly leading to recommend the use of (1) a single individual with large representation of biological tissues, (2) merging both long reads and short paired-end Illumina reads, (3) several assemblers in order to combine the specific advantages of each.

[Impact of surgery in the management of pancreatic metastases of renal cell cancer]. / Place de la chirurgie dans la prise en charge des métastases pancréatiques des cancers du rein.

INTRODUCTION: Incidence of renal cell carcinoma (RCC) is increasing over the 25 last years. Pancreatic metastases of RCC are rare. The aim of this work was to study overall survival of patients operated for pancreatic metastases of RCC in Montpellier cancer institute. PATIENTS AND METHODS: Between 2000 and 2012, a retrospective monocentric study was performed at Montpellier cancer institute. We evaluated the outcomes of curative pancreatic metastases from renal primary and the impact of targeted therapies. RESULTS: Thirty-eight patients were treated in our center for pancreatic metastases of RCC. Twelve patients had a curative surgery of metachronous pancreatic metastases. Four patients were without recurrence after pancreatic resection (33.3%). None had adjuvant therapy. Six patients were treated by targeted therapies, because of metastatic progression. Five of 6 died, the sixth evolved with targeted therapies by thyrosine kinase inhibitor. Average deadline between appearance of metastases and death was 89.9 months for operated patients. Average deadline between appearance of c metastases and death was 33.1 months for the others (P=0.004). CONCLUSION: Surgical treatment of pancreatic metastases should increase life expectancy of patients. Others studies are necessary to prove the impact of targeted therapies in metastatics patients in this indication. LEVEL OF EVIDENCE: 5.

Cytochrome P450s and cytochrome P450 reductase in the olfactory organ of the cotton leafworm Spodoptera littoralis.

Cytochrome P450 enzymes (P450s) are involved in many physiological functions in insects, such as the metabolism of signal molecules, adaptation to host plants and insecticide resistance. Several P450s have been reported in the olfactory organs of insects, the antennae, and have been proposed to play a role in odorant processing and/or xenobiotic metabolism. Despite recent transcriptomic analyses in several species, the diversity of antennal P450s in insects has not yet been investigated. Here, we report the identification of 37 putative P450s expressed in the antennae of the pest moth Spodoptera littoralis, as well as the characterization of a redox partner, cytochrome P450 reductase (CPR). Phylogenetic analysis revealed that S. littoralis P450s belong to four clades defined by their conservation with vertebrate P450s and their cellular localization. Interestingly, the CYP3 and CYP4 clans, which have been described to be mainly involved in the metabolism of plant compounds and xenobiotics, were largely predominant. More surprisingly, two P450s related to ecdysteroid metabolism were also identified. Expression patterns in adult and larval tissues were studied. Eight P450s appeared to be specific to the chemosensory organs, ie the antennae and proboscis, suggesting a specific role in odorant and tastant processing. Moreover, exposure of males to a plant odorant down-regulated the transcript level of CPR, revealing for the first time the regulation of this gene by odorants within insect antennae. This work suggests that the antennae of insects are a key site for P450-mediated metabolism of a large range of exogenous and endogenous molecules.

Candidate chemosensory ionotropic receptors in a Lepidoptera.

A new family of candidate chemosensory ionotropic receptors (IRs) related to ionotropic glutamate receptors (iGluRs) was recently discovered in Drosophila melanogaster. Through Blast analyses of an expressed sequenced tag library prepared from male antennae of the noctuid moth Spodoptera littoralis, we identified 12 unigenes encoding proteins related to D. melanogaster and Bombyx mori IRs. Their full length sequences were obtained and the analyses of their expression patterns suggest that they were exclusively expressed or clearly enriched in chemosensory organs. The deduced protein sequences were more similar to B. mori and D. melanogaster IRs than to iGluRs and showed considerable variations in the predicted ligand-binding domains; none have the three glutamate-interacting residues found in iGluRs, suggesting different binding specificities. Our data suggest that we identified members of the insect IR chemosensory receptor family in S. littoralis and we report here the first demonstration of IR expression in Lepidoptera.

A diversity of putative carboxylesterases are expressed in the antennae of the noctuid moth Spodoptera littoralis.

Recent studies have suggested that pheromone-degrading enzymes belonging to the carboxylesterase family could play a role in the dynamics of the olfactory response to acetate sex pheromones in insects. Bioinformatic analyses of a male antennal expressed sequence tag library allowed the identification of 19 putative esterase genes expressed in the antennae of the moth Spodoptera littoralis. Phylogenetic analysis revealed that these genes belong to different insect esterase clades, defined by their putative cellular localization and substrate preferences. Interestingly, two of the 19 genes appeared to be antennal specific, suggesting a specific role in olfactory processing. This high esterase diversity suggested that the antennae are the location for intense esterase-based metabolism, against potentially a large range of exogenous and endogenous molecules.

Islet beta cell failure in the 60% pancreatectomised obese hyperlipidaemic Zucker fatty rat: severe dysfunction with altered glycerolipid metabolism without steatosis or a falling beta cell mass.

AIMS/HYPOTHESIS: The Zucker fatty (ZF) rat subjected to 60% pancreatectomy (Px) develops moderate diabetes by 3 weeks. We determined whether a progressive fall in beta cell mass and/or beta cell dysfunction contribute to beta cell failure in this type 2 diabetes model. METHODS: Partial (60%) or sham Px was performed in ZF and Zucker lean (ZL) rats. At 3 weeks post-surgery, beta cell mass and proliferation, proinsulin biosynthesis, pancreatic insulin content, insulin secretion, and islet glucose and lipid metabolism were measured. RESULTS: ZL-Px rats maintained normal glycaemia and glucose-stimulated insulin secretion (GSIS) despite incomplete recovery of beta cell mass possibly due to compensatory enhanced islet glucose metabolism and lipolysis. ZF-Px rats developed moderate hyperglycaemia (14 mmol/l), hypertriacylglycerolaemia and relative hypoinsulinaemia. Despite beta cell mass recovery and normal arginine-induced insulin secretion, GSIS and pancreatic insulin content were profoundly lowered in ZF-Px rats. Proinsulin biosynthesis was not reduced. Compensatory increases in islet glucose metabolism above those observed in ZF-Sham rats were not seen in ZF-Px rats. Triacylglycerol content was not increased in ZF-Px islets, possibly due to lipodetoxification by enhanced lipolysis and fatty acid oxidation. Fatty acid accumulation into monoacylglycerol and diacylglycerol was increased in ZF-Px islets together with a 4.5-fold elevation in stearoyl-CoA desaturase mRNA expression. CONCLUSIONS/INTERPRETATION: Falling beta cell mass, reduced proinsulin biosynthesis and islet steatosis are not implicated in early beta cell failure and glucolipotoxicity in ZF-Px rats. Rather, severe beta cell dysfunction with a specific reduction in GSIS and marked depletion of beta cell insulin stores with altered lipid partitioning underlie beta cell failure in this animal model of type 2 diabetes.

Viral persistence in neurons explained by lack of major histocompatibility class I expression.

Viruses frequently persist in neurons, suggesting that these cells can evade immune surveillance. In a mouse model, 5 x 10(6) cytotoxic T lymphocytes (CTLs), specific for lymphocytic choriomeningitis virus (LCMV), did not lyse infected neurons or cause immunopathologic injury. In contrast, intracerebral injection of less than 10(3) CTL caused disease and death when viral antigens were expressed on leptomeningeal and choroid plexus cells of the nervous system. The neuronal cell line OBL21 expresses little or no major histocompatibility (MHC) class I surface glycoproteins and when infected with LCMV, resisted lysis by virus-specific CTLs. Expression of MHC heavy chain messenger RNA was limited, but beta 2-microglobulin messenger RNA and protein was made normally. OBL21 cells were made sensitive to CTL lysis by transfection with a fusion gene encoding another MHC class I molecule. Hence, neuronal cells probably evade immune surveillance by failing to express MHC class I molecules.

Neuronal cells are deficient in loading peptides onto MHC class I molecules.

Virally infected neurons avoid destruction by cytotoxic T lymphocytes (CTLs) by failing to express major histocompatibility complex (MHC) class I molecules. Like neurons in vivo and in primary culture, the OBL21 neuronal cell line expressed barely detectable levels of MHC class I molecules. This correlated with very low levels of mRNAs for the MHC class I heavy chains (alpha C). OBL21 cells also fail to provide MHC class I molecules with the peptides necessary for their efficient assembly and transport to the cell surface. This function can be restored by treatment with interferon-gamma (IFN-gamma). The mRNA for peptide transporters HAM1 and HAM2 was not detectable in OBL21 neuronal cells, but was induced by IFN-gamma treatment. Hence, the ability of neurons to evade CTL-mediated killing results from expression at low levels of the MHC class I alpha C, the peptide transporters HAM1 and HAM2, and possibly other genes of the peptide-loading machinery.

Molecular identification and characterization of two new Lepidoptera chemoreceptors belonging to the Drosophila melanogaster OR83b family.

In insect antennae, olfaction depends on olfactory receptors (ORs) that function through heterodimerization with an unusually highly conserved partner orthologue to the Drosophila melanogaster DOR83b. Here, we report the identification of two cDNAs encoding new DOR83b orthologues that represent the first members, although nonconventional, of the OR families of two noctuid crop pests, the cotton leafworm Spodoptera littoralis and the cabbage armyworm Mamestra brassicae. They both displayed high protein sequence conservation with previously identified DOR83b orthologues. Transcripts were abundantly detected in adult chemosensory organs as well as in fifth instar larvae heads. In adult antennae, the expression patterns of both genes revealed common features with other members of the OR83b subfamily: they appeared to be expressed at the bases of numerous olfactory sensilla belonging to different functional categories, suggesting that both receptors may be co-expressed with yet unidentified conventional ORs. Bioinformatic analyses predicted the occurrence of seven transmembrane domains and an unusual topology with intracellular N-termini and extracellular C-termini, extending to Lepidoptera the hypothesis of an inverted topology for DOR83b orthologues, demonstrated to date only in D. melanogaster.