Nunavimmi puvakkut kaggutimik aanniaqarniq: Qanuilirqitaa? Lung cancer in Nunavik: How are we doing? A retrospective matched cohort study.

BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.

Predictors of clinical deterioration and intensive care unit admission in trauma patients transferred from northern Quebec to a level 1 trauma centre: a retrospective cohort study.

BACKGROUND: Trauma care in Nunavik, Quebec, is highly challenging. Geographic distances and delays in transport can translate into precarious patient transfers to tertiary trauma care centres. The objective of this study was to identify predictors of clinical deterioration during transport and eventual intensive care unit (ICU) admission for trauma patients transferred from Nunavik to a tertiary trauma care centre. METHODS: This is a retrospective cohort study using the Montreal General Hospital (MGH) trauma registry. All adult trauma patients transferred from Nunavik and admitted to the MGH from 2010 to 2019 were included. Main outcomes of interest were hemodynamic and neurologic deterioration during transport and ICU admission. RESULTS: In total, 704 patients were transferred from Nunavik and admitted to the MGH during the study period. The median age was 33 (interquartile range [IQR] 23-47) years and the median Injury Severity Score was 10 (IQR 5-17). On multiple regression analysis, transport time from site of injury to the MGH (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.01-1.06), thoracic injuries (OR 1.75, 95% CI 1.03-2.99), and head and neck injuries (OR 3.76, 95% CI 2.10-6.76) predicted clinical deterioration during transfer. Injury Severity Score (OR 1.04, 95% CI 1.01-1.08), abnormal local Glasgow Coma Scale score (OR 2.57, 95% CI 1.34-4.95), clinical deterioration during transfer (OR 4.22, 95% CI 1.99-8.93), traumatic brain injury (OR 2.44, 95% CI 1.05-5.68), and transfusion requirement at the MGH (OR 4.63, 95% CI 2.35-9.09) were independent predictors of ICU admission. CONCLUSION: Our study identified several predictors of clinical deterioration during transfer and eventual ICU admission for trauma patients transferred from Nunavik. These factors could be used to refine triage criteria in Nunavik for more timely evacuation and higher level care during transport.

Surgical, trauma and telehealth capacity in Indigenous communities in Northern Quebec: a cross-sectional survey.

BACKGROUND: Delivering trauma and surgical care to Northern Quebec presents unique challenges owing to the region's remoteness, extreme weather and limited transport; the expansion of telehealth could help address these difficulties. We aimed to evaluate current surgical, trauma and telemedicine capacity in Nunavik, Quebec. METHODS: We used validated assessment tools, including the Personnel, Infrastructure, Procedures, Equipment and Supplies survey, the International Assessment of Capacity for Trauma index and the Maryland Health Care Commission Telemedicine Readiness tool to evaluate surgical, trauma and telemedicine capacity, respectively. We adapted these tools to the Northern Quebec context through discussions with local leadership. Data were collected in 2 regional hospitals - the Ungava Tulattavik Health Centre (UTHC) and the Inuulitsivik Health Centre (IHC) - and 12 Centres locaux de services communautaires (CLSCs; local community services centres) in 6 villages along the Hudson Bay coast and 6 villages along the Ungava Bay coast through iterative discussions with 4 chief nurses from each regional hospital and set of CLSCs; resources were confirmed through on-site evaluation by the respondents. We performed a descriptive analysis of the data. RESULTS: Surgical capacity was highest in the IHC (6.76) and lowest in the Ungava Bay CLSCs (5.52). Personnel (0%-0%) and procedures (13%-33%) were the least available resources. Trauma capacity was highest in the IHC (7.25) and lowest in the Hudson Bay CLSCs (5.58). Although equipment (90%-100%) and supplies (100%-100%) were readily available, personnel (0%-0%) and procedures (25%-56%) were lacking. The UTHC was most prepared for telehealth (67.80%), and the Ungava Bay CLSCs achieved a lower score (51.13%). Underdeveloped telehealth criteria included funding, administrative support, quality improvement and physical spaces (all 33%-67%). CONCLUSION: Acute care capacity in Nunavik appears heterogeneous, with readily available equipment and supplies, but a lack of personnel capable of performing lifesaving procedures. To address the need for telemedicine, future initiatives should focus on improving funding, administrative support, physical spaces and quality-improvement initiatives.

Trauma in northern Quebec, 2005-2014: epidemiologic features, transfers and patient outcomes.

BACKGROUND: The Inuit people residing in Nunavik, Quebec, are vulnerable to major trauma owing to environmental and social factors; however, there is no systematic data collection for trauma in Nunavik, and, apart from data regarding patients who are transferred to tertiary care centres, no data enter the Quebec trauma registry directly from Nunavik. We performed a study to characterize the epidemiologic features of trauma in Nunavik, and describe indications for transfer and outcomes of patients referred to the tertiary trauma centre. METHODS: We collected data retrospectively for all patients with trauma admitted to the Centre de santé Tulattavik de l'Ungava in Kuujjuaq from 2005 to 2014. Sociodemographic, injury and health services data were extracted. The data were analyzed in conjunction with coroners' reports on death from trauma in Nunavik. RESULTS: A total of 797 trauma cases were identified. The most common causes of injury were motor vehicle collisions (258 cases [32.4%]), falls (137 [17.2%]) and blunt assault (95 [11.9%]). One-third of patients (262 [32.9%]) were transferred to the tertiary care centre in Montréal. The incidence rate of major trauma (Injury Severity Score > 12) was 18.1 and 21.7 per 10 000 person-years in the Kuujjuaq region and the Puvirnituq region, respectively, which translates to a relative risk (RR) of 4 compared to the Quebec population. The disparity observed in trauma mortality rate was even greater, with an RR of 47.6 compared to the Quebec population. CONCLUSION: The study showed major disparity in trauma incidence and mortality rate between Nunavik and the province of Quebec. Our findings allow for a better understanding of the burden of injury and regional trauma mortality in Nunavik, and recommendations for optimization of the trauma system in this unique setting.

Molecular identification of Trichophyton benhamiae in Strasbourg, France: a 9-year retrospective study.

Trichophyton benhamiae is a zoophilic dermatophyte transmitted to humans mostly from guinea pigs and occasionally other animals. It presents two distinct phenotypes: yellow and white. T. benhamiae was formerly known as Trichophyton species of Arthroderma benhamiae; it was considered part of the T. mentagrophytes species complex, and some authors have incorrectly described the yellow phenotype of T. benhamiae as T. mentagrophytes var. porcellae. Identification of T. benhamiae has been difficult, as it was described under more than three names, two phenotypes, and in several different possible host species. During the past 15 years, human infections due to this dermatophyte have been increasingly reported all over the world. In order to better understand the local epidemiology of T. benhamiae and to compare it to other European countries, we performed a 9-year retrospective study in the Strasbourg University Hospital. We studied 41 dermatophytes (38 isolated from humans and 3 from guinea pigs) identified as T. mentagrophytes var. porcellae or A. benhamiae from January 2008 to December 2016 and verified their identification by ITS (Internal Transcribed Spacer) sequencing. ITS sequencing was performed in 35 of the 41 strains, and they were identified as T. benhamiae (33), T. bullosum (1), and T. eriotrephon (1). The other six remaining strains were identified according to morphology as T. mentagrophytes var. porcellae, name incorrectly used since 2010 for the yellow phenotype of T. benhamiae. ITS sequencing is recommended for accurate identification of this dermatophyte and the culture phenotype (yellow or white) should be specified.

Discovery and targeted proteomics on cutaneous biopsies infected by borrelia to investigate lyme disease.

Lyme disease is the most important vector-borne disease in the Northern hemisphere and represents a major public health challenge with insufficient means of reliable diagnosis. Skin is rarely investigated in proteomics but constitutes in the case of Lyme disease the key interface where the pathogens can enter, persist, and multiply. Therefore, we investigated proteomics on skin samples to detect Borrelia proteins directly in cutaneous biopsies in a robust and specific way. We first set up a discovery gel prefractionation-LC-MS/MS approach on a murine model infected by Borrelia burgdorferi sensu stricto that allowed the identification of 25 Borrelia proteins among more than 1300 mouse proteins. Then we developed a targeted gel prefractionation-LC-selected reaction monitoring (SRM) assay to detect 9/33 Borrelia proteins/peptides in mouse skin tissue samples using heavy labeled synthetic peptides. We successfully transferred this assay from the mouse model to human skin biopsies (naturally infected by Borrelia), and we were able to detect two Borrelia proteins: OspC and flagellin. Considering the extreme variability of OspC, we developed an extended SRM assay to target a large set of variants. This assay afforded the detection of nine peptides belonging to either OspC or flagellin in human skin biopsies. We further shortened the sample preparation and showed that Borrelia is detectable in mouse and human skin biopsies by directly using a liquid digestion followed by LC-SRM analysis without any prefractionation. This study thus shows that a targeted SRM approach is a promising tool for the early direct diagnosis of Lyme disease with high sensitivity (<10 fmol of OspC/mg of human skin biopsy).

Ixodes tick saliva suppresses the keratinocyte cytokine response to TLR2/TLR3 ligands during early exposure to Lyme borreliosis.

Ixodes hard tick induces skin injury by its sophisticated biting process. Its saliva plays a key role to enable an efficient blood meal that lasts for several days. We hypothesized that this feeding process may also be exploited by pathogens to facilitate their transmission, especially in the context of arthropod-borne diseases. To test this, we used Lyme borreliosis as a model. This bacterial infection is caused by Borrelia burgdorferi sensu lato transmitted by Ixodes. We co-incubated Borrelia with human keratinocytes in the presence of poly (I: C), a dsRNA TLR3 agonist generated by skin injury. This induced a strong cytokine response from human primary keratinocytes that was much greater than that induced by Borrelia alone. OspC, a TLR2/1 agonist and a major surface lipoprotein of Borrelia also amplified the process. Interestingly, tick saliva inhibited cytokine responses by keratinocytes to these TLR agonists. We propose that Borrelia uses the immunoprivileged site produced by tick saliva to facilitate its transmission.

Proteomic analysis of three Borrelia burgdorferi sensu lato native species and disseminating clones: relevance for Lyme vaccine design.

Lyme borreliosis is the most important vector-borne disease in the Northern hemisphere. It is caused by Borrelia burgdorferi sensu lato bacteria transmitted to humans by the bite of hard ticks, Ixodes spp. Although antibiotic treatments are efficient in the early stage of the infection, a significant number of patients develop disseminated manifestations (articular, neurological, and cutaneous) due to unnoticed or absence of erythema migrans, or to inappropriate treatment. Vaccine could be an efficient approach to decrease Lyme disease incidence. We have developed a proteomic approach based on a one dimensional gel electrophoresis followed by LC-MS/MS strategy to identify new vaccine candidates. We analyzed a disseminating clone and the associated wild-type strain for each major pathogenic Borrelia species: B. burgdorferi sensu stricto, B. garinii, and B. afzelii. We identified specific proteins and common proteins to the disseminating clones of the three main species. In parallel, we used a spectral counting strategy to identify upregulated proteins common to the clones. Finally, 40 proteins were found that could potentially be involved in bacterial virulence and of interest in the development of a new vaccine. We selected the three proteins specifically detected in the disseminating clones of the three Borrelia species and checked by RT-PCR whether they are expressed in mouse skin upon B. burgdorferi ss inoculation. Interestingly, BB0566 appears as a potential vaccine candidate. All MS data have been deposited in the ProteomeXchange with identifier PXD000876 (http://proteomecentral.proteomexchange.org/dataset/PXD000876).

[Anthropization and tick-borne diseases: the example of Lyme borreliosis]. / Anthropisation et maladies à tique : l'exemple de la borréliose de Lyme.

Ticks and tick-borne diseases are on the rise throughout the world. The reasons are multifactorial but all associated with human practices, including climate change and socio-economic and eco systemic changes. In the northern hemisphere, Lyme borreliosis and its vector, the tick belonging to the Ixodes ricinus complex, are particularly studied. Changes in forestry and the expansion of certain wild ungulates since the Second World War could explain the increasing presence of this tick in our environment. As it is likely to transmit other microorganisms potentially pathogenic to humans, an integrated multidisciplinary approach to identify human practices promoting its expansion is critical to control the (re)emergence of infectious diseases. Other ticks also benefit from the same anthropised context to increase their numbers in the environment.

Les tiques et maladies à tiques sont en expansion à travers le monde. Les raisons sont multifactorielles mais toutes associées aux pratiques humaines, notamment les modifications climatiques et les changements socio-économiques et écosystémiques. Dans l'hémisphère nord, la borréliose de Lyme et son vecteur, la tique appartenant au complexe Ixodes ricinus sont particulièrement étudiés. Les modifications de sylviculture et l'expansion de certains ongulés sauvages depuis la seconde guerre mondiale pourraient expliquer la présence de plus en plus importante de la tique dans notre environnement. Cette tique étant susceptible de transmettre d'autres microorganismes potentiellement pathogènes pour l'homme, une approche multidisciplinaire intégrée afin d'identifier les pratiques humaines qui favorisent son expansion est essentielle afin de contrôler la (ré)-émergence de maladies infectieuses. D'autres tiques bénéficient du même contexte anthropisé pour augmenter leur nombre dans l'environnement.

Multiple factors affecting Ixodes ricinus ticks and associated pathogens in European temperate ecosystems (northeastern France).

In Europe, the main vector of tick-borne zoonoses is Ixodes ricinus, which has three life stages. During their development cycle, ticks take three separate blood meals from a wide variety of vertebrate hosts, during which they can acquire and transmit human pathogens such as Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis. In this study conducted in Northeastern France, we studied the importance of soil type, land use, forest stand type, and temporal dynamics on the abundance of ticks and their associated pathogens. Negative binomial regression modeling of the results indicated that limestone-based soils were more favorable to ticks than sandstone-based soils. The highest tick abundance was observed in forests, particularly among coniferous and mixed stands. We identified an effect of habitat time dynamics in forests and in wetlands: recent forests and current wetlands supported more ticks than stable forests and former wetlands, respectively. We observed a close association between tick abundance and the abundance of Cervidae, Leporidae, and birds. The tick-borne pathogens responsible for Lyme borreliosis, anaplasmosis, and hard tick relapsing fever showed specific habitat preferences and associations with specific animal families. Machine learning algorithms identified soil related variables as the best predictors of tick and pathogen abundance.

Vaccines against tick-borne diseases: a big step forward?

Ticks and tick-borne diseases are on the rise due to socioecosystemic changes and climate modification and are affecting human and animal health. Few vaccines are available. Two recent articles from Matias et al. and Pine et al. used mRNA technology to explore tick and pathogen proteins as vaccine candidates.

Cross-alteration of murine skin and tick microbiome concomitant with pathogen transmission after Ixodes ricinus bite.

BACKGROUND: Ticks are major vectors of diseases affecting humans such as Lyme disease or domestic animals such as anaplasmosis. Cross-alteration of the vertebrate host skin microbiome and the tick microbiome may be essential during the process of tick feeding and for the mechanism of pathogen transmission. However, it has been poorly investigated. METHODS: We used mice bitten by field-collected ticks (nymphs and adult ticks) in different experimental conditions to investigate, by 16S rRNA gene metabarcoding, the impact of blood feeding on both the mouse skin microbiome and the tick microbiome. We also investigated by PCR and 16S rRNA gene metabarcoding, the diversity of microorganisms transmitted to the host during the process of tick bite at the skin interface and the dissemination of the pathogen in host tissues (blood, heart, and spleen). RESULTS: Most of the commensal bacteria present in the skin of control mice were replaced during the blood-feeding process by bacteria originating from the ticks. The microbiome of the ticks was also impacted by the blood feeding. Several pathogens including tick-borne pathogens (Borrelia/Borreliella, Anaplasma, Neoehrlichia, Rickettsia) and opportunistic bacteria (Williamsia) were transmitted to the skin microbiome and some of them disseminated to the blood or spleen of the mice. In the different experiments of this study, skin microbiome alteration and Borrelia/Borreliella transmission were different depending on the tick stages (nymphs or adult female ticks). CONCLUSIONS: Host skin microbiome at the bite site was deeply impacted by the tick bite, to an extent which suggests a role in the tick feeding, in the pathogen transmission, and a potentially important impact on the skin physiopathology. The diversified taxonomic profiles of the tick microbiome were also modified by the blood feeding. Video Abstract.

Diversity and phylogeny of the tick-borne bacterial genus Candidatus Allocryptoplasma (Anaplasmataceae).

The family Anaplasmataceae includes tick-borne bacteria of major public and veterinary health interest, as best illustrated by members of the genera Anaplasma and Ehrlichia. Recent epidemiological surveys have also reported on the presence of a novel putative genus in the Anaplasmataceae, Candidatus Allocryptoplasma, previously described as Candidatus Cryptoplasma in the western black-legged tick, Ixodes pacificus. However, the genetic diversity of Ca. Allocryptoplasma and its phylogenetic relationship with other Anaplasmataceae remain unclear. In this study, we developed a multi-locus sequence typing approach, examining the DNA sequence variation at five genes of Ca. Allocryptoplasma found in ticks. Combining this multi-locus sequence typing and genetic data available on public databases, we found that substantial genetic diversity of Ca. Allocryptoplasma is present in Ixodes, Amblyomma and Haemaphysalis spp. ticks on most continents. Further analyses confirmed that the Ca. Allocryptoplasma of ticks, the Ca. Allocryptoplasma of lizards and some Anaplasma-like bacteria of wild mice cluster into a monophyletic genus, divergent from all other genera of the family Anaplasmataceae. Candidatus Allocryptoplasma appears as a sister genus of Anaplasma and, with the genera Ehrlichia and Neoehrlichia, they form a monophyletic subgroup of Anaplasmataceae associated with tick-borne diseases. The detection of genetically distinct Ca. Allocryptoplasma in ticks of significant medical or veterinary interest supports the hypothesis that it is an emergent genus of tick-borne pathogens of general concern.

Title: Diversité et phylogénie du genre bactérien transmis par les tiques Candidatus Allocryptoplasma (Anaplasmataceae). Abstract: La famille des Anaplasmataceae comprend des bactéries transmises par les tiques qui présentent un intérêt majeur pour la santé publique et vétérinaire, comme les membres des genres Anaplasma et Ehrlichia. Des surveillances épidémiologiques récentes ont également signalé la présence d'un nouveau genre putatif dans les Anaplasmataceae, Candidatus Allocryptoplasma, initialement décrit comme Ca. Cryptoplasma chez une tique nord-américaine, Ixodes pacificus. Cependant, la diversité génétique des bactéries Ca. Allocryptoplasma et leurs relations phylogénétiques avec d'autres Anaplasmataceae restent méconnues. Dans cette étude, nous avons développé une approche de typage génétique multi-locus, en examinant la variation nucléotidique pour cinq gènes de bactéries Ca. Allocryptoplasma détectées chez les tiques. En combinant ce typage génétique multi-locus et les données génétiques disponibles dans les bases de données publiques, nous avons mis en évidence qu'une diversité génétique substantielle des bactéries Ca. Allocryptoplasma est présente chez les tiques des genres Ixodes, Amblyomma et Haemaphysalis sur la plupart des continents. Des analyses complémentaires confirment que les bactéries Ca. Allocryptoplasma des tiques, les bactéries Ca. Allocryptoplasma de lézards et des bactéries Anaplasma-like de souris sauvages se regroupent dans un genre monophylétique, divergent de tous les autres genres de la famille Anaplasmataceae. Candidatus Allocryptoplasma apparaît comme un genre frère d'Anaplasma et, avec les genres Ehrlichia et Neoehrlichia, ces trois genres forment un sous-groupe monophylétique d'Anaplasmataceae associé aux maladies transmises par les tiques. La détection de Ca. Allocryptoplasma dans des tiques d'intérêt médical et vétérinaire soutient l'hypothèse qu'il s'agit d'un genre émergent d'agents pathogènes majeurs.

Phylogenetic evidence for a clade of tick-associated trypanosomes.

BACKGROUND: Trypanosomes are protozoan parasites of vertebrates that are of medical and veterinary concern. A variety of blood-feeding invertebrates have been identified as vectors, but the role of ticks in trypanosome transmission remains unclear. METHODS: In this study, we undertook extensive molecular screening for the presence and genetic diversity of trypanosomes in field ticks. RESULTS: Examination of 1089 specimens belonging to 28 tick species from Europe and South America led to the identification of two new trypanosome strains. The prevalence may be as high as 4% in tick species such as the castor bean tick Ixodes ricinus, but we found no evidence of transovarial transmission. Further phylogenetic analyses based on 18S rRNA, EF1-α, hsp60 and hsp85 gene sequences revealed that different tick species, originating from different continents, often harbour phylogenetically related trypanosome strains and species. Most tick-associated trypanosomes cluster in a monophyletic clade, the Trypanosoma pestanai clade, distinct from clades of trypanosomes associated with transmission by other blood-feeding invertebrates. CONCLUSIONS: These observations suggest that ticks may be specific arthropod hosts for trypanosomes of the T. pestanai clade. Phylogenetic analyses provide further evidence that ticks may transmit these trypanosomes to a diversity of mammal species (including placental and marsupial species) on most continents.

First Expert Elicitation of Knowledge on Possible Drivers of Observed Increasing Human Cases of Tick-Borne Encephalitis in Europe.

Tick-borne encephalitis (TBE) is a viral disease endemic in Eurasia. The virus is mainly transmitted to humans via ticks and occasionally via the consumption of unpasteurized milk products. The European Centre for Disease Prevention and Control reported an increase in TBE incidence over the past years in Europe as well as the emergence of the disease in new areas. To better understand this phenomenon, we investigated the drivers of TBE emergence and increase in incidence in humans through an expert knowledge elicitation. We listed 59 possible drivers grouped in eight domains and elicited forty European experts to: (i) allocate a score per driver, (ii) weight this score within each domain, and (iii) weight the different domains and attribute an uncertainty level per domain. An overall weighted score per driver was calculated, and drivers with comparable scores were grouped into three terminal nodes using a regression tree analysis. The drivers with the highest scores were: (i) changes in human behavior/activities; (ii) changes in eating habits or consumer demand; (iii) changes in the landscape; (iv) influence of humidity on the survival and transmission of the pathogen; (v) difficulty to control reservoir(s) and/or vector(s); (vi) influence of temperature on virus survival and transmission; (vii) number of wildlife compartments/groups acting as reservoirs or amplifying hosts; (viii) increase of autochthonous wild mammals; and (ix) number of tick species vectors and their distribution. Our results support researchers in prioritizing studies targeting the most relevant drivers of emergence and increasing TBE incidence.

Update on the proteomics of major arthropod vectors of human and animal pathogens.

Vector-borne diseases (VBDs) are defined as infectious diseases of humans and animals caused by pathogenic agents such as viruses, protists, bacteria, and helminths transmitted by the bite of blood-feeding arthropod (BFA) vectors. VBDs represent a major public health threat in endemic areas, generally subtropical zones, and many are considered to be neglected diseases. Genome sequencing of some arthropod vectors as well as modern proteomic and genomic technologies are expanding our knowledge of arthropod-pathogen interactions. This review describes the proteomic approaches that have been used to investigate diverse biological questions about arthropod vectors, including the interplay between vectors and pathogens. Proteomic studies have identified proteins and biochemical pathways that may be involved in molecular crosstalk in BFA-pathogen associations. Future work can build upon this promising start and functional analyses coupled with interactome bioassays will be carried out to investigate the role of candidate peptides and proteins in BFA-human pathogen associations. Dissection of the host-pathogen interactome will be key to understanding the strategies and biochemical pathways used by BFAs to cope with pathogens.

"Laurin-Sandrow Syndrome - a review of the literature and classification system".

INTRODUCTION: Laurin-Sandrow syndrome also known as tetramelic mirror-image polydactyly is a rare congenital disorder characterized classically by polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella) often associated with ulnar and/or fibular duplication. As a pathologic entity, it is heterogeneous, the patients displaying a variety of symptoms. This review aims to analyze the different aspects of the condition, such as clinical findings and methods of treatment to summarize the principal features of Laurin-Sandrow syndrome. MATERIALS AND METHODS: The review is based on searches on PubMed, Web of Science and Researchgate of the following terms: "Laurin-Sandrow syndrome", "mirror hands", "mirror feet", "tetramelic mirror-image polydactyly", "fibular dimelia" and "ulnar dimelia". Clinical cases, reviews and original articles were included. RESULTS: As a consequence of our findings, we suggest a modification of the Al-Qattan classification system for Mirror Hand-Multiple Hand Spectrum. CONCLUSION: Even though it has an extremely low incidence, a thorough understanding of the syndrome enables the surgeon to choose the appropriate treatment with the ultimate goal to improve the patient's life quality.

Impact of Different Anthropogenic Environments on Ticks and Tick-Associated Pathogens in Alsace, a French Region Highly Endemic for Tick-Borne Diseases.

Ticks and tick-borne diseases have spread over the last decades. In parallel, the incidence in humans, accidental hosts for most of these zoonotic diseases, has increased. This epidemiological intensification can be associated with anthropogenic alterations of forest ecosystems and animal biodiversity, but also with socioeconomic changes. Their proliferation is largely due to human-induced effects on the factors that favor the circulation of these infectious agents. We selected different types of anthropogenic environments in Alsace, a region endemic for tick-borne diseases in France, to better understand the impact of human interventions on tick populations and tick-borne disease incidence. Ticks were collected in one golf course, three urban parks, one mid-mountain forest, and one alluvial forest that is currently part of a protected natural area. Ixodes ricinus was found primarily in humid vegetation, which is favorable for tick survival, such as grounds populated with trees and covered with leaf litter. We also observed that reforestation and high animal biodiversity in a protected area such as the alluvial forest led to a greater number of ticks, including both Ixodes ricinus and Dermacentor reticulatus, as well as to a higher prevalence of pathogens such as Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Borrelia miyamotoi, and Rickettsia raoulti.

Clobetasol increases the abundance of Borrelia burgdorferi in the skin 70 times more in male mice compared to female mice.

Lyme borreliosis is caused by the spirochete Borrelia burgdorferi and is transmitted among vertebrate hosts by Ixodes scapularis ticks in eastern North America. Treatment with topical corticosteroids increases the abundance of B. burgdorferi in the skin of lab mice that have been experimentally infected via needle inoculation. In the present study, female and male C3H/HeJ mice were infected with B. burgdorferi via nymphal tick bite. Infected mice were treated with clobetasol on the skin of the right hindleg on days 35 and 36 post-infection and euthanized at days -2, 1, 3, 5, and 7 post-treatment; a group of control mice was infected but not treated with clobetasol. The spirochete abundance was quantified in 8 mouse tissues including bladder, heart, left hindleg skin, right hindleg skin, dorsal skin, ventral skin, left ear and right ear. Averaged across the 8 mouse tissues, the abundance of B. burgdorferi on days 3 and 5 were 21.4x and 14.4x higher in mice treated with clobetasol compared to the untreated control mice, but there were large differences among tissues. There was a dramatic sex-specific effect of the clobetasol treatment; the peak abundance of B. burgdorferi in the skin (left hindleg, right hindleg, dorsal, ventral) was 72.6x higher in male mice compared to female mice. In contrast, there was little difference between the sexes in the tissue spirochete load in the ears, bladder, and heart. Topical application of clobetasol could increase the sensitivity of direct diagnostic methods (e.g., culture, PCR) to detect B. burgdorferi in host skin biopsies.

Antialarmin effect of tick saliva during the transmission of Lyme disease.

Tick saliva has potent immunomodulatory properties. In arthropod-borne diseases, this effect is largely used by microorganisms to increase their pathogenicity and to evade host immune responses. We show that in Lyme borreliosis, tick salivary gland extract and a tick saliva protein, Salp15, inhibit in vitro keratinocyte inflammation induced by Borrelia burgdorferi sensu stricto or by the major outer surface lipoprotein of Borrelia, OspC. Chemokines (interleukin-8 [IL-8] and monocyte chemoattractant protein 1 [MCP-1]) and several antimicrobial peptides (defensins, cathelicidin, psoriasin, and RNase 7) were downregulated. Interestingly, antimicrobial peptides (AMPs) transiently inhibited bacterial motility but did not kill the organisms when tested in vitro. We conclude that tick saliva affects the chemotactic properties of chemokines and AMPs on immune cells and has an antialarmin effect on human primary keratinocytes. Alarmins are mediators that mobilize and activate antigen-presenting cells. Inhibition of cutaneous innate immunity and of the migration of immune cells to the site of the tick bite ensures a favorable environment for Borrelia. The bacterium can then multiply locally and, subsequently, disseminate to the target organs, including joints, heart, and the central nervous system.