Skin microbiota secretomes modulate cutaneous innate immunity against Borrelia burgdorferi s.s.

In Lyme borreliosis, the skin constitutes a major interface for the host, the bacteria and the tick. Skin immunity is provided by specialized immune cells but also by the resident cells: the keratinocytes and the fibroblasts. Discoveries on the role of the microbiome in the modulation of skin inflammation and immunity have reinforced the potential importance of the skin in vector-borne diseases. In this study, we analyzed in vitro the interaction of human primary keratinocytes and fibroblasts with Borrelia burgdorferi sensu stricto N40 in presence or absence of bacterial commensal supernatants. We aimed to highlight the role of resident skin cells and skin microbiome on the inflammation induced by B. burgdorferi s.s.. The secretomes of Staphylococcus epidermidis, Corynebacterium striatum and Cutibacterium acnes showed an overall increase in the expression of IL-8, CXCL1, MCP-1 and SOD-2 by fibroblasts, and of IL-8, CXCL1, MCP-1 and hBD-2 in the undifferentiated keratinocytes. Commensal bacteria showed a repressive effect on the expression of IL-8, CXCL1 and MCP-1 by differentiated keratinocytes. Besides the inflammatory effect observed in the presence of Borrelia on all cell types, the cutaneous microbiome appears to promote a rapid innate response of resident skin cells during the onset of Borrelia infection.

Motor strategies and adiabatic invariants: The case of rhythmic motion in parabolic flights.

The role of gravity in human motor control is at the same time obvious and difficult to isolate. It can be assessed by performing experiments in variable gravity. We propose that adiabatic invariant theory may be used to reveal nearly conserved quantities in human voluntary rhythmic motion, an individual being seen as a complex time-dependent dynamical system with bounded motion in phase space. We study an explicit realization of our proposal: An experiment in which we asked participants to perform ∞- shaped motion of their right arm during a parabolic flight, either at self-selected pace or at a metronome's given pace. Gravity varied between 0 and 1.8 g during a parabola. We compute the adiabatic invariants in the participant's frontal plane assuming a separable dynamics. It appears that the adiabatic invariant in vertical direction increases linearly with g, in agreement with our model. Differences between the free and metronome-driven conditions show that participants' adaptation to variable gravity is maximal without constraint. Furthermore, motion in the participant's transverse plane induces trajectories that may be linked to higher-derivative dynamics. Our results show that adiabatic invariants are relevant quantities to show the changes in motor strategy in time-dependent environments.

Adiabatic invariants drive rhythmic human motion in variable gravity.

Voluntary human movements are stereotyped. When modeled in the framework of classical mechanics they are expected to minimize cost functions that may include energy, a natural candidate from a physiological point of view also. In time-changing environments, however, energy is no longer conserved-regardless of frictional energy dissipation-and it is therefore not the preferred candidate for any cost function able to describe the subsequent changes in motor strategies. Adiabatic invariants are known to be relevant observables in such systems, although they still need to be investigated in human motor control. We fill this gap and show that the theory of adiabatic invariants provides an accurate description of how human participants modify a voluntary, rhythmic, one-dimensional motion of the forearm in response to variable gravity (from 1 to 3g). Our findings suggest that adiabatic invariants may reveal generic hidden constraints ruling human motion in time-changing gravity.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis.

The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline, ceftriaxone, or amoxicillin for 28 days. Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis.

Lyme borreliosis is transmitted en France by the tick Ixodes ricinus, endemic in metropolitan France. In the absence of vaccine licensed for use in humans, primary prevention mostly relies on mechanical protection (clothes covering most parts of the body) that may be completed by chemical protection (repulsives). Secondary prevention relies on early detection of ticks after exposure, and mechanical extraction. There is currently no situation in France when prophylactic antibiotics would be recommended. The incidence of Lyme borreliosis in France, estimated through a network of general practitioners (réseau Sentinelles), and nationwide coding system for hospital stays, has not significantly changed between 2009 and 2017, with a mean incidence estimated at 53 cases/100,000 inhabitants/year, leading to 1.3 hospital admission/100,000 inhabitants/year. Other tick-borne diseases are much more seldom in France: tick-borne encephalitis (around 20 cases/year), spotted-fever rickettsiosis (primarily mediterranean spotted fever, around 10 cases/year), tularemia (50-100 cases/year, of which 20% are transmitted by ticks), human granulocytic anaplasmosis (<10 cases/year), and babesiosis (<5 cases/year). The main circumstances of diagnosis for Lyme borreliosis are cutaneous manifestations (primarily erythema migrans, much more rarely borrelial lymphocytoma and atrophic chronic acrodermatitis), neurological (<15% of cases, mostly meningoradiculitis and cranial nerve palsy, especially facial nerve) and rheumatologic (mostly knee monoarthritis, with recurrences). Cardiac and ophtalmologic manifestations are very rarely encountered.

Ticks and tick-borne diseases.

Ticks are a major group of arthropod vectors, characterized by the diversity of pathogens they transmit, by their impact on human and animal health, and by their socioeconomic implication especially in countries of the Southern Hemisphere. In Europe, Ixodes is the most important tick due to its wide distribution in the ecosystems and the variety of transmitted pathogens, in particular Borrelia (responsible for Lyme borreliosis), but also the tick-borne encephalitis virus. Their increased presence in the environment since the beginning of the 20th century is undeniable, because of major modifications in the biodiversity caused by humans. Increasing the awareness of health professionals and the general population is required to achieve better control of these infections. Thus, "a better understanding of these tick-borne diseases for a better control" is a simple but effective approach, considering their ubiquity in the environment and their particular mode of pathogen transmission (long-lasting blood meal for hard ticks and delayed transmission for bacteria and parasites). Finally, these ectoparasites are problematic due to the potential allergic reactions and other damages caused by their saliva, in humans and animals.

Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders.

With an onset under the age of 3 years, autism spectrum disorders (ASDs) are now understood as diseases arising from pre- and/or early postnatal brain developmental anomalies and/or early brain insults. To unveil the molecular mechanisms taking place during the misshaping of the developing brain, we chose to study cells that are representative of the very early stages of ontogenesis, namely stem cells. Here we report on MOlybdenum COfactor Sulfurase (MOCOS), an enzyme involved in purine metabolism, as a newly identified player in ASD. We found in adult nasal olfactory stem cells of 11 adults with ASD that MOCOS is downregulated in most of them when compared with 11 age- and gender-matched control adults without any neuropsychiatric disorders. Genetic approaches using in vivo and in vitro engineered models converge to indicate that altered expression of MOCOS results in neurotransmission and synaptic defects. Furthermore, we found that MOCOS misexpression induces increased oxidative-stress sensitivity. Our results demonstrate that altered MOCOS expression is likely to have an impact on neurodevelopment and neurotransmission, and may explain comorbid conditions, including gastrointestinal disorders. We anticipate our discovery to be a fresh starting point for the study on the roles of MOCOS in brain development and its functional implications in ASD clinical symptoms. Moreover, our study suggests the possible development of new diagnostic tests based on MOCOS expression, and paves the way for drug screening targeting MOCOS and/or the purine metabolism to ultimately develop novel treatments in ASD.

[Protection against tick bites]. / Protection contre les piqûres de tiques.

There are numerous tick-borne infections, which include viral (TBE), parasitic (babesiosis) and bacterial diseases. Lyme disease (Lyme borreliosis) is the most common tick-borne disease in France. In temperate climates such as in France, ticks bite humans between March and October. Prevention relies on adequate clothing and on repellents. The latter are reviewed in this work. Repellents may be natural, made from eucalyptus, tomato and coconut, or synthetic, among which the most widely used is DEET (N,N,-Diethyl-m-toluamide). Newer, synthetic repellents exist such as IR3535 which, as well as being less toxic, also exhibits greater efficacy against ticks. Some repellents are used on the skin, while others, like permethrin, which is actually an insecticide, may be applied to clothing.

Septorhinoplasty by disarticulation: early assessment of a new technique for morphological correction of crooked noses.

OBJECTIVE: This study was aimed to assess the early morphological results of a new septorhinoplasty technique based on disarticulation (SRD) between bony and cartilaginous nose structures. METHODOLOGY: A retrospective, multi-judge, blind comparison of pre- and post-operative photographs displayed on Google documents was designed. A nasal morphology analysis grid based on 10 items was fulfilled independently by 6 judges to assess pre- and post-operatively, two times with a 15 day interval, the severity of each deformity by a score between 0 and 2. The sum of all deformities in a single patient produced the individual global score of nasal deformity, which was set between 0 and 20 for each patient. Pre- and post-operative individual global scores were compared using Student`s t test on paired samples. Percentages of post-operative improvement and deterioration were calculated for each item. RESULTS: Thirty-five SRD were analyzed. Before surgery, 80% of noses were humped and 86% were crooked; three months after surgery, 64% of noses had a rectilinear nasal crest on profile and 57% on facial view. The mean global score of deformities drop- ped from 11.1 before surgery to 5.8 after surgery, an improvement of 47% . Improvement rates of 82% and 74.3% were obtained, respectively, for hump profiles and orbitonasal lines. DISCUSSION: The early morphological results of SRD allow to propose this technique as a possible solution to correct crooked noses with humps.

Pathology of tumours originating in the olfactory cleft.

UNLABELLED: PROBLEMS/OBJECTIVE: This study describes the variety of tumours originating in the olfactory cleft which have been treated with endonasal endoscopic surgery. METHODOLOGY: The study is a retrospective review covering a seven-year period (2004-2010) of the medical records of all patients in whom a tumour originating in the olfactory cleft was excised (72 patients: 63 men and 9 women; age: average of 61 years; range, 19 to 90 years). RESULTS: The most common tumours in the series were adenocarcinoma (43 [60%] patients), inverted papilloma (7 [10%] patients), respiratory epithelial adematoid hamartoma (6 [8%] patients) and olfactory neuroblastoma (5 [7%] patients). CONCLUSIONS: The olfactory cleft can be identified as a new surgical field for endonasal endoscopic surgery. This anatomic region is amenable to endoscopic evaluation and the excision of tumours. Exenteration of the olfactory cleft appears to be a key technique for removing adenocarcinoma and can be extended to exenteration of the olfactory groove in cases with intracranial extension. Partial exenteration of the olfactory cleft would seem to be a suitable way of removing benign tumours like inverted papilloma or respiratory epithelial adematoid hamartoma.

[What primary prevention should be used to prevent Lyme disease?]. / Quelles mesures de prévention primaire peut-on proposer pour éviter une borréliose de Lyme?

Arthropod-borne diseases are a real public health problem. One of these, Lyme disease, is a bacterial infection due to Borrelia spp., transmitted by a hard tick, Ixodes spp.. The infection is particularly prevalent in the Northern Hemisphere and primary prevention relies on the use of repellents for cloth impregnation (pyrethroids) or for skin application (DEET). Pyrethroids and DEET are the two most studied repellents. The concentration of the active principle is essential to get a real repellent efficiency. The most efficient are: DEET at 30-50%, picaridin or KBR3023 at 20%, citriodiol at 30-50%, and IR35/35 at 20-35%. These molecules may induce adverse-effects. Considered for some time as cosmetics, a new European regulation now defines these molecules as biocides.

Immunopeptides in the defense reactions of Glossina morsitans to bacterial and Trypanosoma brucei brucei infections.

Several dipteran insects are vectors of parasites causing major human infectious diseases. Among these, the tsetse fly, Glossina spp., is responsible for the transmission of trypanosomes, the pathogens responsible for sleeping sickness in Africa. A better understanding of insect-parasite interactions will help establish new strategies to fight this important often fatal disease. Antimicrobial peptides (AMPs) are part of the humoral immune response in insects during bacterial, fungal and parasitic infections. Here, we studied the immune response of Glossina morsitans to bacteria and to Trypanosoma brucei brucei by analyzing the synthesis of AMPs as markers of the humoral immune response. By reversed-phase chromatography, mass spectrometry analysis, Edman degradation and in vitro antimicrobial assays of the hemolymph of immune-challenged adults of G. morsitans, we identified three AMPs: a cecropin, an attacin and a defensin. These three AMPs were found to be induced upon systemic bacterial infection and also after per os infections by bacteria and parasites.

Immune response of Drosophila melanogaster to infection with the flagellate parasite Crithidia spp.

Insects are able to recognize invading microorganisms and to mount an immune response to bacterial and fungal infections. Recently, the fruitfly Drosophila melanogaster has emerged as a promising invertebrate model to investigate innate immunity because of its well-characterized genetics. Insects are also vectors of numerous parasites which can trigger an immune response. We have investigated the interaction of Drosophila melanogaster with the flagellate protozoan Crithidia spp. We show that a per os parasitic infection triggers the synthesis of several antimicrobial peptides. By reverse phase HPLC and mass spectrometry, peptides were shown to be present in the hemolymph and not in the gut tissue, suggesting the presence of immune messengers between the site of the infection, namely the gut, and the fat body, the main site of synthesis for antimicrobial peptides. Interestingly, we have identified one molecule which is specifically induced in the hemolymph after infection with Crithidia, but not with bacteria, suggesting that Drosophila can discriminate between pathogens. When flagellates were injected into the hemolymph, a low synthesis of antimicrobial peptides was observed together with phagocytosis of parasites by circulating hemocytes. The data presented here suggest that Drosophila-Crithidia spp. represents an interesting model to study host defense against protozoan parasites.

[Evaluation of the psychological consequences of environmental catastrophes: a feasibility study based on the 1992 floods in the Vaucluse]. / Evaluation des conséquences psychologiques des catatrophes environnementales: une étude de faisabilité à partir des inondations de 1992 dans le Vaucluse (France).

Scientific studies of environmental disasters, whether human or natural in origin, have shown that the psychological impact of such events may be considerable and long-lasting. Several natural disasters have occurred in France, but their impact on public psychological health has not been assessed. In September 1992, there was a major flood in southeast France (Vaucluse), which caused 38 deaths. Four years later, we performed a pilot cross-sectional study to assess the feasibility of a larger epidemiological study to assess the psychological impact of this flood. Two affected towns were chosen for this study: Vaison-la-Romaine (VLR), where the flood was very sudden and 29 people were killed, and Bédarrides, where the water level rose more slowly. In Bédarrides, households were randomly selected from a list of victims (n = 100) and in Vaison-la-Romaine, households were randomly selected from the telephone directory (n = 140). Exposure to the flood was assessed by a series of questions, the answers to which were used to calculate an exposure score. The questionnaire also included psychometric scales for post-traumatic stress disorder (QE-PTSD), anxiety (Spielberger State-Trait Anxiety Inventory) and depression (Beck Depression Inventory). In Bédarrides, the participation rate was high: 69% of the selected households were successfully contacted and found to be eligible for inclusion and 74% agreed to a face-to-face interview. In Vaison-la-Romaine, 51% of the selected households were contacted and eligible and 50% agreed to the face-to-face interview. Our survey showed that exposure was multidimensional and that it was possible to calculate an exposure score suitable for the analysis of exposure-effect relationships. The PTSD scale was completed well by the interviewees, several of whom did not fill in the depression and anxiety scales correctly. However, analysis of the responses obtained showed that these tools had a high level of internal consistency. Cross-correlations between the various psychological scales used in this study were highly significant (p < 10-4). There was some degree of association between some psychometric scales and exposure. This pilot study shows that a cross-sectional study of the long-term psychological consequences of an environmental disaster could be carried out several years after the event but that the feasibility of such a study depends ultimately on its acceptance by the public and the relevant authorities. It underlines the need to collect exposure data immediately after the event and enabled us to identify and to adapt the tools required for this kind of evaluation. It should encourage public health decision-makers to support such evaluation and to improve the psychological and social support available to people exposed to floods.

A comparison of the prosodic characteristics of the speech of people with Parkinson's disease and Friedreich's ataxia with neurologically normal speakers.

The realization of prosody (speech rate, fundamental frequency, intonation) was investigated in a group of 10 individuals with Parkinson's disease and a group of 10 individuals with Friedreich's ataxia. Data from these two neurologically disordered groups were compared to individuals without neurological impairment. Both neurologically impaired groups retained some aspects of normal speech prosody, while other aspects were affected to a significant degree. The prosodic characteristics of speakers with Parkinson's disease were distinct from those of speakers with Friedreich's ataxia. These results were interpreted in terms of prosodic competence and prosodic performance.