Otorhinolaryngological manifestations and delayed diagnosis in Kawasaki disease.

OBJECTIVES: Kawasaki disease (KD) is a febrile multisystemic vasculitis of unknown etiology whose coronary prognosis is improved by early diagnosis and management. The objective of this study was to describe ENT manifestations encountered and to look for a delayed diagnosis associated with these manifestations. METHODS: A retrospective descriptive single-center study was conducted in Lyon between January 2009 and December 2017. All children treated for Kawasaki disease were included in the study. Clinical, biological and cardiac ultrasound data were collected. According to the diagnosis made at the first medical visit, children were classified into two groups: diagnosis of ENT spectrum or non-ENT diagnosis. The diagnostic times were compared by a Student test. RESULTS: 142 patients were included: 64 in the ENT diagnostic group, 78 in the non-ENT diagnostic group. When the initial diagnosis was of ENT spectrum, the diagnostic time of KD was significantly longer: 8.51 days vs 5.77 days - (p < 0.01). The total duration of fever was also longer - 10.92 vs 8.32 days - (p = 0.013) - and the frequency of antibiotics intake more important - 92.2% vs 46.2% - (p < 0.01). Four children underwent surgery in the ENT diagnostic group: two retro-pharyngeal abscesses, one paracentesis and one cervicectomy. CONCLUSIONS: ENT manifestations are frequently at the forefront of KD and constitute a misleading clinical picture responsible for delayed diagnosis and potentially inappropriate medico-surgical management. It is necessary to provide more education to practitioners for earlier recognition of Kawasaki disease.

Climate change is catchy--but when will it really hurt?

Concern and general awareness about the impacts of climate change in all sectors of the social-ecological-economic system is growing as a result of improved climate science products and information, as well as increased media coverage of the apparent manifestations of the phenomenon in our society. However, scales of climate variability and change, in space and time, are often confused and so attribution of impacts on various sectors, including the health sector, can be misunderstood and misrepresented. In this review, we assess the mechanistic links between climate and infectious diseases in particular, and consider how this relationship varies, and may vary according to different time scales, especially for aetiologically climate-linked diseases. While climate varies in the medium (inter-annual) time frame, this variability itself may be oscillating and/or trending on cyclical and long-term (climate change) scales because of regional and global scale climate phenomena such as the El-Nino southern oscillation coupled with global-warming drivers of climate change. As several studies have shown, quantifying and modelling these linkages and associations at appropriate time and space scales is both necessary and increasingly feasible with improved climate science products and better epidemiological data. The application of this approach is considered for South Africa, and the need for a more concerted effort in this regard is supported.

The influence of prior expectations on facial expression discrimination in schizophrenia.

BACKGROUND: Belief inflexibility is a thinking style observed in patients with schizophrenia, in which patients tend to refute evidence that runs counter to their prior beliefs. This bias has been related to a dominance of prior expectations (prior beliefs) over incoming sensory evidence. In this study we investigated the reliance on prior expectations for the processing of emotional faces in schizophrenia. METHOD: Eighteen patients with schizophrenia and 18 healthy controls were presented with sequences of emotional (happy, fearful, angry or neutral) faces. Perceptual decisions were biased towards a particular expression by a specific instruction at the start of each sequence, referred to as the context in which stimuli occurred. Participants were required to judge the emotion on each face and the effect of the context on emotion discrimination was investigated. RESULTS: For threatening emotions (anger and fear), there was a performance cost for facial expressions that were incongruent with, and perceptually close to, the expression named in the instruction. For example, for angry faces, participants in both groups made more errors and reaction times (RTs) were longer when they were asked to look out for fearful faces compared with the other contexts. This bias against sensory evidence that runs counter to prior information was stronger in the patients, evidenced by a group by context interaction in accuracy and RTs for anger and fear respectively. CONCLUSIONS: Overall, the present data suggest an overdependence on prior expectations for threatening stimuli, reflecting belief inflexibility, in schizophrenia.

[Nifurtimox, a bright future for treatment of Chagas disease]. / Le nifurtimox, molécule en plein devenir dans le traitement de la maladie de Chagas.

Nifurtimox is one of the two molecules used for treatment of Chagas disease. Although posology has not yet been clearly defined, nifurtimox is increasingly used, especially in combination with eflonithin. Nifurtimox is perfectly suited to the WHO's Chagas disease eradication program.

[Benzonidazole: one of the rare treatment for Chagas disease]. / Le benznidazole : un des rares traitements de la maladie de Chagas.

Benznidazole is indicated in the treatment of Chagas' disease, which is endemic in Latin America. However, it has numerous adverse effects and is effective only at certain disease stages. Because of these drawbacks and the appearance of resistance to benzinidazole, there is ongoing research for alternative therapeutic strategies and new drugs.

Characterization of a glycosyl transferase inactivating macrolides, encoded by gimA from Streptomyces ambofaciens.

In Streptomyces ambofaciens, the producer of the macrolide antibiotic spiramycin, an open reading frame (ORF) was found downstream of srmA, a gene conferring resistance to spiramycin. The deduced product of this ORF had high degrees of similarity to Streptomyces lividans glycosyl transferase, which inactivates macrolides, and this ORF was called gimA. The cloned gimA gene was expressed in a susceptible host mutant of S. lividans devoid of any background macrolide-inactivating glycosyl transferase activity. In the presence of UDP-glucose, cell extracts from this strain could inactivate various macrolides by glycosylation. Spiramycin was not inactivated but forocidin, a spiramycin precursor, was modified. In vivo studies showed that gimA could confer low levels of resistance to some macrolides. The spectrum of this resistance differs from the one conferred by a rRNA monomethylase, such as SrmA. In S. ambofaciens, gimA was inactivated by gene replacement, without any deleterious effect on the survival of the strain, even under spiramycin-producing conditions. But the overexpression of gimA led to a marked decrease in spiramycin production. Studies with extracts from wild-type and gimA-null mutant strains revealed the existence of another macrolide-inactivating glycosyl transferase activity with a different substrate specificity. This activity might compensate for the effect of gimA inactivation.

Antibiotic resistance gene cassettes derived from the omega interposon for use in E. coli and Streptomyces.

Three antibiotic resistance gene cassettes, derived from the omega interposon (Prentki and Krisch (1984) Gene 29, 303-313) were constructed. These cassettes carry different antibiotic resistance genes, conferring resistance to geneticin, hygromycin or viomycin, flanked by short inverted repeats containing transcription and translation termination signals and synthetic polylinkers. These cassettes were designated omega aac, omega hyg and omega vph. Resistance phenotypes conferred by these constructions are selectable in E. coli and Streptomyces. These cassettes can be used for insertional mutagenesis or for vector construction.

The macrolide-lincosamide-streptogramin B resistance phenotypes characterized by using a specifically deleted, antibiotic-sensitive strain of Streptomyces lividans.

Genes conferring resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics via ribosomal modification are widespread in bacteria, including clinical isolates and MLS-producing actinomycetes. Such erm-type genes encode enzymes that mono- or dimethylate residue A-2058 of 23S rRNA. The different phenotypes resulting from monomethylation (MLS-I phenotype, conferred by erm type I genes) or dimethylation (MLS-II phenotype due to erm type II genes) have been characterized by introducing tlrD or ermE, respectively, into an MLS-sensitive derivative of Streptomyces lividans TK21. This strain (designated OS456) was generated by specific replacement of the endogenous resistance genes lrm and mgt. The MLS-I phenotype is characterized by high-level resistance to lincomycin with only marginal resistance to macrolides such as chalcomycin or tylosin, whereas the MLS-II phenotype involves high-level resistance to all MLS drugs. Mono- and dimethylated ribosomes were introduced into a cell-free protein-synthesizing system prepared from S. lividans and compared with unmodified particles in their response to antibiotics. There was no simple correlation between the relative potencies of MLS drugs at the level of the target site (i.e., the ribosome) and their antibacterial activities expressed as MICs.

Resistance to spiramycin in Streptomyces ambofaciens, the producer organism, involves at least two different mechanisms.

During its stationary phase, Streptomyces ambofaciens produces the macrolide antibiotic spiramycin, and has to protect itself against this antibiotic. Young mycelia, not yet producing spiramycin, are sensitive to it, but they become fully resistant when production begins. In a sensitive mycelium, resistance could be induced by exposure to sub-inhibitory concentrations of spiramycin, and these induced mycelia, like producing mycelia were resistant not only to spiramycin but also to several other macrolide antibiotics. Ribosomes extracted from these resistant mycelia were shown in vitro to be more resistant to spiramycin than ribosomes extracted from sensitive mycelium, indicating that S. ambofaciens possesses a spiramycin-inducible ribosomal resistance to spiramycin and to macrolide antibiotics. Studies with spiramycin non-producing mutants showed that, in these mutants, resistance to spiramycin also varies during cultivation, in that an old culture was much more resistant than a young one. But with these non-producing mutants, the spectrum of resistance was narrower, and in vitro data showed that resistance was not due to ribosomal modification. These results suggest that S. ambofaciens presents at least two distinct mechanisms for spiramycin resistance; a spiramycin-inducible ribosomal resistance, and a second resistance mechanism which might be temporally regulated and which could involve decreased permeability to, or export of, the antibiotic. The two mechanisms are probably at work simultaneously in the producing mycelium, the spiramycin-inducible resistance being induced by endogenous spiramycin. In non-producing mutants, in the absence of self-induction by spiramycin, only the second mechanism is observed.

Resistance to macrolides, lincosamides and streptogramin type B antibiotics due to a mutation in an rRNA operon of Streptomyces ambofaciens.

Streptomyces ambofaciens produces spiramycin, a macrolide antibiotic and expresses an inducible resistance to macrolides, lincosamides and streptogramin B antibiotics (MLS). From a mutant of S.ambofaciens exhibiting a constitutive MLS resistance phenotype a resistance determinant was cloned on a low copy number vector (pIJ61) through its expression in Streptomyces lividans. Further characterization has shown that this determinant corresponded to a mutant rRNA operon with a mutation in the 23S rRNA gene. In different organisms, mutations leading to MLS resistance have been located at a position corresponding to the adenine 2058 of Escherichia coli 23S rRNA. In the 23S rRNA from S.ambofaciens a similar position for the mutation has been postulated and DNA sequencing of this region has shown an adenine to guanine transition at a position corresponding to 2058. S.ambofaciens possesses four rRNA operons which we have cloned. In Streptomyces, contrary to other bacteria, a mutation in one among several rRNA operons confers a selectable MLS resistance phenotype. Possible reasons for this difference are discussed.