Asymptomatic Leishmania infantum infection in dogs and dog owners in an endemic area in southeast France.

The prevalence of asymptomatic leishmaniasis in dogs and their owners in the main endemic areas of France has not been studied to date. The objective of this study was to quantify asymptomatic Leishmania infantum infection in southeast France in healthy people and their dogs using molecular and serological screening techniques. We examined the presence of parasitic DNA using specific PCR targeting kinetoplast DNA (kDNA) and specific antibodies by serology (ELISA for dogs and Western blot for humans) among immunocompetent residents and their dogs in the Alpes-Maritimes. Results from 343 humans and 607 dogs were included. 46.9% (n = 161/343) of humans and 18.3% (n = 111/607) of dogs were PCR positive; 40.2% of humans (n = 138/343) and 9.9% of dogs (n = 60/607) were serology positive. Altogether, 66.2% of humans (n = 227) and 25.7% of dogs (n = 156) had positive serologies and/or positive PCR test results. Short-haired dogs were more frequently infected (71.8%, n = 112) than long-haired dogs (12.2%, n = 19) (p = 0.043). Dogs seemed to be more susceptible to asymptomatic infection according to their breed types (higher infection rates in scenthounds, gun dogs and herding dogs) (p = 0.04). The highest proportion of dogs and human asymptomatic infections was found in the Vence Region, corresponding to 28.2% (n = 20/71) of dogs and 70.5% (n = 31/44) of humans (4.5/100,000 people). In conclusion, the percentage of infections in asymptomatic humans is higher than in asymptomatic dogs in the studied endemic area. It is questionable whether asymptomatic infection in humans constitutes a risk factor for dogs.

Title: Infection asymptomatique à Leishmania infantum chez les chiens et propriétaires de chiens dans une zone endémique du sud-est de la France. Abstract: La prévalence de la leishmaniose asymptomatique chez les chiens et leurs propriétaires dans les principales zones d'endémie françaises n'a pas été étudiée à ce jour. L'objectif de cette étude était de quantifier l'infection asymptomatique à Leishmania infantum dans le sud-est de la France chez des personnes saines et leurs chiens à l'aide de techniques de dépistage moléculaire et sérologique. Nous avons examiné chez des résidents immunocompétents et leurs chiens dans les Alpes-Maritimes la présence d'ADN parasitaire par PCR spécifique ciblant l'ADN du kinétoplaste (ADNk) et d'anticorps spécifiques par sérologie (ELISA pour le chien et Western Blot pour l'homme). Les résultats de 343 humains et 607 chiens ont été inclus; 46,9 % (n = 161/343) des humains et 18,3 % (n = 111/607) des chiens étaient positifs à la PCR et 40,2 % des humains (n = 138/343) et 9,9 % des chiens (n = 60/607) avaient une sérologie positive. Au total, 66,2 % des humains (n = 227) et 25,7 % des chiens (n = 156) avaient des sérologies positives et/ou des résultats de tests PCR positifs. Les chiens à poils courts étaient plus fréquemment infectés (71,8 %, n = 112) que les chiens à poils longs (12,2 %, n = 19) (p = 0,043). Les chiens semblaient plus sensibles à l'infection asymptomatique selon leurs races (taux supérieurs chez les chiens de chasse et chiens de berger) (p = 0,04). La plus forte proportion d'infections asymptomatiques chez les chiens et les humains a été observée dans la Région de Vence, correspondant à 28,2 % (n = 20/71) des chiens et 70,5 % (n = 31/44) des humains (4,5/100 000). personnes). En conclusion, le pourcentage d'infections chez les humains asymptomatiques est plus élevé que chez les chiens asymptomatiques dans la zone d'endémie étudiée. On peut se demander si une infection asymptomatique chez l'homme constitue un facteur de risque pour les chiens.

Adaptation and validation of the muscle dysmorphic disorder inventory in a population of French athletes (MDDI-Fr).

INTRODUCTION: Muscle dysmorphia, a theme mainly investigated by Anglo-Saxon research, is a specific body dysmorphic disorder that characterizes individuals who think they are insufficiently muscular and lean. Understudied in francophone countries, tools translated and validated in French to measure the symptomatology of muscle dysmorphia remain rare. OBJECTIVES: The aim of this study was the translation into French and the psychometric validation of a tool evaluating muscle dysmorphia, the Muscle Dysmorphic Disorder Inventory (MDDI-Fr), through 13 items divided into three dimensions: the "Drive For Size" (DFS), the "Appearance Intolerance" (AI) and the "Functional Impairment" (FI). METHODOLOGY: A first translation step was conducted, followed by two cross-sectional studies conducted in France. In both of the latter studies, a sociodemographic questionnaire and the Muscle Dysmorphic Disorder Inventory - French version (MDDI-Fr) were administered. The first study included 342 university students (Mage=20.9; SDage=2.9), and 1822 athletes for the second study (Mage=23.9; SDage=5.9). Validation was performed using internal consistency measures and confirmatory factor analysis. RESULTS: The correlation matrices showed good significant results between items and dimensions. The three dimensions appeared distinct from each other with significant intra-dimension correlations. The internal consistency of the tool and its three dimensions show valid Cronbach's alphas (study 1: DFS=0.79, AI=0.74, FI=0.75, MDDI=0.74; study 2: DFS=0.72, AI=0.75, FI=0.83, MDDI=0.75). In addition, the tri-factor analysis shows significant and promising scores for the tool in three dimensions and 13 items for study 1 (χ2/df=4.67, CFI=0.85, TLI=0.83, RMSEA=0.10, SRMR=0.00), as for study 2 (χ2/df=16.08, CFI=0.87, TLI=0.84, RMSEA=0.09, SRMR=.06). Gender analyses were conducted on study 2, which showed that the DFS subscale (items 1, 4, 5) and the AI subscale (items 6 and 9) presented the greatest differences in factor loadings between genders. CONCLUSION: The translation, as well as the validation of the MDDI-Fr structured with 13 items and three dimensions, showed significantly satisfying results for its adaptation in French in a population of French men and women practicing weight training. However, the "Appearance Intolerance" dimension shows moderate links with the global tool, which should be investigated in future studies. Although the psychometric properties of the MDDI-Fr are promising, additional research is needed to gain a better understanding of gender differences in the results, especially for the DFS dimension.

Performance of five serological tests in the diagnosis of visceral and cryptic leishmaniasis: a comparative study.

INTRODUCTION: Leishmaniasis is a major health problem and its diagnosis still represents a challenge. Since consistent evidence on the comparison of serological methods is lacking, our work aims to compare five serological tests for the diagnosis of visceral and asymptomatic leishmaniasis in southern France, a region where leishmaniasis is endemic. METHODOLOGY: Serum samples from 75 patients living in Nice, France were retrospectively analyzed. They included patients affected by visceral leishmaniasis (VL; n = 25), asymptomatic carriers (AC; n = 25) and negative controls (n = 25). Each sample was tested using two immunochromatographic tests (ICT; IT LEISH® and TruQuick IgG/IgM®), an indirect fluorescent antibody test (IFAT) and two Western Blotting (WB; LDBio BIORAD® and an in-house method). RESULTS: Diagnosis of VL with IFAT and TruQuick® showed the highest diagnostic performance parameters. IFAT had 100% sensitivity and specificity, while TruQuick had 96% sensitivity and 100% specificity. Finally, the two tests showed high accuracy (100% for IFAT and 98% for TruQuick) for the AC group. WB LDBio® was the only method able to detect Leishmania latent infection, with a sensitivity of 92%, and a specificity of 100%, with a Negative Predictive Value (NPV) of 93%. This performance is reflected in the high accuracy of the test. CONCLUSIONS: The data obtained with TruQuick® supports its application in the rapid diagnosis of leishmaniasis in endemic areas, a feature not shown by IFAT despite its high diagnostic performance. Regarding the diagnosis of asymptomatic leishmaniasis, the best results were obtained with WB LDBio®, confirming previous studies.

The global impact of adverse childhood experiences on criminal behavior: A cross-continental study.

BACKGROUND: Adverse Childhood Experiences (ACEs) have been associated with a greater risk of later criminal offending. However, existing research in this area has been primarily conducted in Western developed countries and cross-cultural studies are rare. OBJECTIVES: This study examined the relationship between ACEs and criminal behaviors in young adults living in 10 countries located across five continents, after accounting for sex, age, and cross-national differences. PARTICIPANTS AND SETTING: In total, 3797 young adults aged between 18 and 20 years (M = 18.97; DP = 0.81) were assessed locally in community settings within the 10 countries. METHOD: The ACE Questionnaire was used to assess maltreatment and household dysfunction during childhood and a subset of questions derived from the Deviant Behavior Variety Scale (DBVS) was used to determine past-year criminal variety pertaining to 10 acts considered crime across participating countries. RESULTS: Physical and sexual abuse, physical neglect, and household substance abuse were related to criminal variety, globally, and independently across sexes and countries ranked differently in the United Nations Human Development Index (HDI). In addition, three out of five experiences of household dysfunction were related to criminal variety, but subsequent analyses indicate that some forms of household dysfunction only hold statistical significance among males or females, or in countries ranking lower in the HDI. CONCLUSIONS: This research strengthens the finding that there are cross-cultural mechanisms perpetuating the cycle of violence. It also indicates that forms of household dysfunction have an impact on criminal behavior that is shaped by gender and the country's levels of social well-being.

New method for screening anti-Leishmania compounds in plants extracts by HPTLC-bioautography.

Leishmania genus is responsible for leishmaniasis, a group of diseases affecting 12 million people in the tropical and subtropical zone. Currently, the few drugs that are available to treat this disease are expensive and cause many side effects. Searching for new therapeutics from plant species seems to be a promising path. This work proposes an original HPTLC test against parasites, in particular on Leishmania infantum, to screen new molecules from plant extracts. The technique uses protozoa transformed to express the luciferase gene to observe the bioautogram in bioluminescence. We have developed two different test protocols based on the two dimorphic stages of the parasite. The free promastigote stage, and an intracellular stage parasitizing macrophage cells called the amastigote stage. These two stages only survive under extremely different conditions which required the development of two very different test protocols. For the promastigote free stage of the protozoa, the direct bioautography technique was chosen while for the intracellular amastigote stage, bioautography by immersion (agar overlay) was required. Amphotericine B was chosen as the reference compound for this assay. The development of each of these two tests made it possible to clearly detect areas of activity on the bioautogram, allowing a rapid and inexpensive screening of the antiparasitic properties of molecules in natural extracts.

The C-terminal segment of Leishmania major HslU: Toward potential inhibitors of LmHslVU activity.

It is urgent to develop less toxic and more efficient treatments for leishmaniases and trypanosomiases. We explore the possibility to target the parasite mitochondrial HslVU protease, which is essential for growth and has no analogue in the human host. For this, we develop compounds potentially inhibiting the complex assembly by mimicking the C-terminal (C-ter) segment of the ATPase HslU. We previously showed that a dodecapeptide derived from Leishmania major HslU C-ter segment (LmC12-U2, Cpd 1) was able to bind to and activate the digestion of a fluorogenic substrate by LmHslV. Here, we present the study of its structure-activity relationships. By replacing each essential residue with related non-proteinogenic residues, we obtained more potent analogues. In particular, a cyclohexylglycine residue at position 11 (cpd 24) allowed a more than three-fold gain in potency while reducing the size of compound 24 from twelve to six residues (cpd 50) without significant loss of potency, opening the way toward short HslU C-ter peptidomimetics as potential inhibitors of HslV proteolytic function. Finally, conjugates constituted of LmC6-U2 analogues and a mitochondrial penetrating peptide were found to penetrate into the promastigote form of L. infantum and to inhibit the parasite growth without showing toxicity toward human THP-1 cells at the same concentration (i.e. 30 µM).

Identification of adipocytes as target cells for Leishmania infantum parasites.

Leishmania infantum is the causative agent of visceral leishmaniasis transmitted by the bite of female sand flies. According to the WHO, the estimated annual incidence of leishmaniasis is one million new cases, resulting in 30,000 deaths per year. The recommended drugs for treating leishmaniasis include Amphotericin B. But over the course of the years, several cases of relapses have been documented. These relapses cast doubt on the efficiency of actual treatments and raise the question of potential persistence sites. Indeed, Leishmania has the ability to persist in humans for long periods of time and even after successful treatment. Several potential persistence sites have already been identified and named as safe targets. As adipose tissue has been proposed as a sanctuary of persistence for several pathogens, we investigated whether Leishmania infantum could be found in this tissue. We demonstrated both in cell cultures and in vivo that Leishmania infantum was able to infect adipocytes. Altogether our results suggest adipocytes as a 'safe target' for Leishmania infantum parasites.

A comparative study of cognitive and socio-emotional development in children with Rubinstein-Taybi syndrome and children with Autism Spectrum Disorder associated with a severe intellectual disability, and in young typically developing children with matched developmental ages.

BACKGROUND: Cognitive and socio-emotional profiles of children with CREBBP-related Rubinstein-Taybi syndrome (RSTS 1), children with Autism Spectrum Disorder (ASD) with severe intellectual disability and developmental ages (DA) under 24 months, and typically developing (TD) children with similar DA were compared. PARTICIPANTS: Thirty-one children with RSTS 1 (mean chronological age, CA = 59,8 months; 33-87) and thirty children with ASD, matched on CA and DA and developmental quotients (DQ), were compared to thirty TD children (CA ranged from 12 to 24 months). METHODS: Cognitive and socio-emotional developmental levels, DA and DQ were assessed with appropriated tests. RESULTS: More socio-emotional developmental similarities were observed between TD and RSTS 1 than between TD and ASD children. Clinical groups displayed similar developmental delays in cognitive (self-image, symbolic play, means-ends, and object permanence) and socio-emotional domains (language and imitation). Children with RSTS 1 exhibited higher developmental levels in behavior regulation, joint attention, affective relations, emotional expression domains, and a lower developmental level in spatial relations domain. CONCLUSIONS: Common interventions centered on symbolic play, self-image, language, and imitation for both clinical groups, and differentiated interventions centered on spatial abilities for RSTS 1 children and on social abilities for ASD could be used by caregivers were suggested.

Escherichia coli Rho GTPase-activating toxin CNF1 mediates NLRP3 inflammasome activation via p21-activated kinases-1/2 during bacteraemia in mice.

Inflammasomes are signalling platforms that are assembled in response to infection or sterile inflammation by cytosolic pattern recognition receptors. The consequent inflammasome-triggered caspase-1 activation is critical for the host defence against pathogens. During infection, NLRP3, which is a pattern recognition receptor that is also known as cryopyrin, triggers the assembly of the inflammasome-activating caspase-1 through the recruitment of ASC and Nek7. The activation of the NLRP3 inflammasome is tightly controlled both transcriptionally and post-translationally. Despite the importance of the NLRP3 inflammasome regulation in autoinflammatory and infectious diseases, little is known about the mechanism controlling the activation of NLRP3 and the upstream signalling that regulates the NLRP3 inflammasome assembly. We have previously shown that the Rho-GTPase-activating toxin from Escherichia coli cytotoxic necrotizing factor-1 (CNF1) activates caspase-1, but the upstream mechanism is unclear. Here, we provide evidence of the role of the NLRP3 inflammasome in sensing the activity of bacterial toxins and virulence factors that activate host Rho GTPases. We demonstrate that this activation relies on the monitoring of the toxin's activity on the Rho GTPase Rac2. We also show that the NLRP3 inflammasome is activated by a signalling cascade that involves the p21-activated kinases 1 and 2 (Pak1/2) and the Pak1-mediated phosphorylation of Thr 659 of NLRP3, which is necessary for the NLRP3-Nek7 interaction, inflammasome activation and IL-1ß cytokine maturation. Furthermore, inhibition of the Pak-NLRP3 axis decreases the bacterial clearance of CNF1-expressing UTI89 E. coli during bacteraemia in mice. Taken together, our results establish that Pak1 and Pak2 are critical regulators of the NLRP3 inflammasome and reveal the role of the Pak-NLRP3 signalling axis in vivo during bacteraemia in mice.

Emotional lability and irritability have specific associations with symptomatology in children with attention deficit hyperactivity disorder.

Irritability and emotional lability have been shown to be severity and impairment factors in community and clinical sample studies and are frequent comorbid features of Attention Deficit Hyperactivity Disorder (ADHD). However, while irritability and emotional lability seem to be closely linked, the differential effect of these two features has received little attention. This study assessed the distinct associations of irritability and emotional lability on symptomatology in children with ADHD. One hundred and eight children diagnosed with ADHD participated in the study. Children were rated by parents on ADHD and comorbid symptomatology with the Conners Rating Scale - Revised. Irritability was the most significant predictive factor of the severity of anxiety and oppositional symptoms. Regarding emotional lability, it was significantly predictive of the severity of hyperactivity symptoms. While emotional lability shares common theoretical characteristics with irritability, each seems to be associated with specific areas. Irritability is a symptom of Oppositional Defiant Disorder, a frequent ADHD comorbidity, and also seems to be related to internalizing disorder (e.g. anxiety). Emotional lability seems to be related to ADHD severity symptoms per se. Both could be clinically informative in the diagnosis of ADHD and its comorbidities.

Association between adolescent rough-and-tumble play and conduct problems, substance use, and risk-taking behaviors: Findings from a school-based sample.

Rough-and-tumble play (RTP), also known as play fighting, is a common form of play frequently reported and studied by researchers. However, one important limitation of past research in the area of RTP has been the neglect of the adolescence period. Consequently, little is known about the function of adolescent RTP as well as about clinical characteristics of youth who engage in this activity after childhood. In a school-based sample of 1,771 middle school students (ages 9-16 years), the current study sought to address this gap by examining, via bivariate and multivariate logistic regression analyses, the potential cross-sectional associations of adolescent RTP with (a) selected demographic variables, (b) conduct problem symptoms, (c) substance use, and (d) risk-taking behaviors, including adjustment for several demographic confounders. Results indicated that adolescents reporting higher rates of conduct problem symptoms were more likely to report a recent participation in RTP. In addition, substance use (experimentation and current consumption of tobacco, alcohol, and marijuana) and risk behaviors assessed all were strongly associated with an increased likelihood of reporting an engagement in RTP. This finding suggests that participation in this activity probably implicates particular phenotypic characteristics including the propensity to engage in health-damaging behaviors. But the most profound issue raised by this research concerns the strong relationship between RTP and great levels of conduct disorder symptoms, suggesting a possible significant change in the functional significance of RTP in the adolescence period.

The relation between ADHD symptoms, perceived stress and binge drinking in college students.

Binge drinking is a major public health problem associated with various negative short-term and long-term clinical and social outcomes. If there is evidence to suggest a relationship between ADHD and alcohol use in college students, no study has investigated the role of ADHD symptomatology in binge drinking. Thus, this research was designed to explore the relative contributions of inattention and hyperactivity/impulsivity symptoms to binge drinking in a sample of French college students while controlling for effects of perceived stress. Participants (N = 7011; mean age = 20.9; 74.9% of females) completed self-report surveys assessing ADHD symptoms, perceived stress, sociodemographic characteristics, and binge drinking frequency. Multinomial logistic regression revealed significant associations between higher levels of ADHD symptoms in general, but not perceived stress, and increasing frequency of binge drinking. Moreover, higher levels of inattention and hyperactivity/impulsivity symptoms were independently associated with greater frequency of binge drinking. The association was stronger between high rates of binge drinking and inattention than for hyperactivity/impulsivity. These findings, which remained statistically significant after adjusting for a range of potential confounders (including perceived stress), suggest that the presence of ADHD symptoms may be an important factor related to binge drinking.

Is self-esteem associated with self-rated health among French college students? A longitudinal epidemiological study: the i-Share cohort.

OBJECTIVES: The aim of the study was to estimate the association between self-esteem and subsequent self-rated health during college years, taking into account a wide range of potential confounders. DESIGN: Prospective longitudinal study. SETTING: The French i-Share cohort. PARTICIPANTS: The sample consisted of 1011 college students. PRIMARY AND SECONDARY OUTCOME MEASURES: The association between self-esteem and later self-rated health was evaluated using multivariate modelling.Data regarding self-rated health, global self-esteem and demographic, educational, social, behavioural, environmental and financial characteristics were collected through an internet-based questionnaire. RESULTS: The 1011 participants had a median age of 21.9 years and 79% (795/1011) were females. Self-rated health was assessed a median of 8 months after the self-esteem measurement. Twenty per cent of the students declared average to very poor health (203/1011). Students with higher levels of self-esteem were more likely to declare good or very good self-rated health (adjusted OR=1.40, 95% CI 1.15 to 1.72, p value=0.001). Other factors associated with good or very good self-rated health were low body mass index, a comfortable financial situation during childhood and three personality traits (low persistence and harm avoidance and high cooperativeness). CONCLUSIONS: This study offers novel findings on the impact of self-esteem on self-rated health among college students. Interventions targeting self-esteem should be experimented during university years in order to improve health outcomes.

Adolescent Mental Health and the Choking Game.

OBJECTIVES: To examine the demographic and health risk factors associated with participation in the choking game (CG), a dangerous and potentially fatal strangulation activity in which pressure is applied to the carotid artery to temporarily limit blood flow and oxygen. METHODS: We obtained data from 2 cross-sectional studies realized respectively in 2009 and 2013 among French middle school students. The 2009 (n = 746) and 2013 (n = 1025) data sets were merged (N = 1771), and multivariate modeling was conducted to examine demographic and clinical characteristics of youth reporting a lifetime participation in the CG. The 2 studies included questions about risk-taking behaviors and substance use, and standardized assessments were used to collect conduct disorder symptoms and depressive symptoms. RESULTS: In the merged 2009 and 2013 data set, the lifetime prevalence of CG participation was 9.7%, with no statistically significant differences between boys and girls. A multivariate logistic regression revealed that higher levels of conduct disorder symptoms (odds ratio: 2.33; P < .001) and greater rates of depressive symptoms (odds ratio: 2.18; P < .001) were both significantly associated with an increased likelihood of reporting CG participation. CONCLUSIONS: The significant relationship between elevated levels of depressive symptoms and participation in the CG sheds new light on the function of self-asphyxial activities. However, with the finding that higher rates of conduct disorder symptoms were the most important predictor of CG participation, it is suggested that the profile and the underlying motivations of youth who engage in this activity should be reexamined.

ADHD Symptomatology and Perceived Stress Among French College Students.

Objective: The objective of this study was to examine the independent association between inattention and hyperactivity/impulsivity symptoms and perceived stress among French college students. Method: Participants (N = 6,951) completed self-report surveys assessing ADHD symptoms, perceived stress, and sociodemographic characteristics. Multinomial logistic regression models were used to evaluate the association between ADHD symptoms and perceived stress. Results: Participants had a mean age of 20.8 years, and 75.6% were female. We found significant associations between increasing levels of inattention and hyperactivity/impulsivity symptoms and high level of perceived stress after adjustment for confounding variables. The association was stronger for inattention (odds ratio [OR] = 4.58, 95% confidence interval [CI] = [4.02, 5.22]) than for hyperactivity/impulsivity symptoms (OR = 1.21, 95% CI = [1.05 to 1.39]). Conclusion: Higher levels of inattention and hyperactivity/impulsivity were independently associated with perceived stress in French college students. This association was mainly driven by inattention. Screenings to better detect ADHD symptoms should be implemented in universities.

Leishmania infection: Misdiagnosis as cancer and tumor-promoting potential.

Given the prevalence of cancer and leishmaniasis worldwide, the presence of these two pathologies in the same tissue sample may be merely fortuitous. The clinical outcome of both diseases is under the control of innate and adaptive immunity, and in both cases these progressive diseases are characterized by an impaired host Th1 response. As a consequence, the Th2 cytokine microenvironment occurring in progressive leishmaniasis may potentially promote tumor cell proliferation and vice versa. On the other hand, clinical aspects of subclinical cutaneous or visceral leishmaniasis sometimes closely resemble those observed in various neoplasms thus leading to misdiagnosis. In this review, we present recent findings on the association between leishmaniasis and malignant disorders. Our review includes HIV positive, HIV negative subjects and patients whose HIV status has not been established. Leishmaniasis mimicking a malignant disorder was confirmed and extended to unreported neoplastic disorders including squamous cell carcinoma, T-cell and B-cell lymphoma, oral and intranasal tumors and granulomas. Thus, leishmaniasis should be considered in the differential diagnosis and course of various cancers in Leishmania endemic areas or in patients with travel history to these areas. We also listed recent reports showing that Leishmania can promote cancer development in immunocompromised as well as in immunocompetent patients. The potential mechanisms supporting this promoting effect are discussed.

Subclinical Leishmania infection in patients with rheumatic diseases under biological drugs.

PURPOSE: Climate changes and immunosuppression are influencing the spread of leishmaniasis and re-emergence in Northern Italy, respectively. We evaluated the prevalence of subclinical leishmaniasis in patients from a Northern Italian region with chronic inflammatory rheumatism (CIRD) receiving biological drugs (BD) and correlated it to the area of residence. METHODS: DNA from PBMC of patients affected by CIRD treated with either BD for at least 5 years (Group A) or other immunosuppressive drugs (Group B) was investigated by a qPCR for Leishmania infantum kDNA and compared to healthy subjects (Group C). Variables such as sex and age, rural areas, dog ownership, type of BD administered and association between BD and steroids, were evaluated by statistical analysis. RESULTS: A higher proportion of L. infantum DNA positivity was found in Group A than in Group C (p < 0.05), while no parasite DNA was detected in Group B. In Group A, 18/50 patients (36%) had higher rates of parasite DNA (from 1 to 136 to 1.000.000 copies/ml) than Group C (from 1 to 10 copies/ml). 14/18 (77.7%) of positive patients from Group A lived in rural areas, but no statistical differences occurred in relation to dog ownership or BD type (p < 0.0003). CONCLUSIONS: We can speculate that exposure to rural areas appears to be a factor closely linked with the risk of developing Leishmania subclinical infection. A screening with molecular methods in patients with CIRD treated with BD living in these areas and monitoring Leishmania DNA during such therapies, would be mandatory to prevent delay in diagnosis should VL symptoms appear.

UHPLC-HRMS/MS Based Profiling of Algerian Lichens and Their Antimicrobial Activities.

Lichens are complex symbiotic organisms able to produce a vast array of compounds. The Algerian lichen diversity has only prompted little interest even given the 1085 species listed. Herein, the chemodiversity of four Algerian lichens including Cladonia rangiformis, Ramalina farinaceae, R. fastigiata, and Roccella phycopsis was investigated. A dereplication strategy, using ultra high performance liquid chromatography-high resolution-electrospray ionization-mass spectrometry (UHPLC-HRMS/MS), was carried out for a comprehensive characterization of their substances including phenolics, depsides, depsidones, depsones, dibenzofurans, and aliphatic acids. Some known compounds were identified for the first time in some species. Additionally, the lichenic extracts were evaluated for their antifungal and antimicrobial activities on human pathogenic strains (Candida albicans, C. glabrata, Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli). Cyclohexane extracts were found particularly active against human pathogenic fungi with MIC80 values ranging from 8 to 62.5 µg/mL, without cytotoxicity. This study highlights the therapeutic and prophylactic potential of lichenic extracts as antibacterial and antifungal agents.

Childhood trajectories of peer victimization and prediction of mental health outcomes in midadolescence: a longitudinal population-based study.

BACKGROUND: Exposure to peer victimization is relatively common. However, little is known about its developmental course and its effect on impairment associated with mental illnesses. We aimed to identify groups of children following differential trajectories of peer victimization from ages 6 to 13 years and to examine predictive associations of these trajectories with mental health in adolescence. METHODS: Participants were members of the Quebec Longitudinal Study of Child Development, a prospective cohort of 2120 children born in 1997/98 who were followed until age 15 years. We included 1363 participants with self-reported victimization from ages 6 to 13 years and data available on their mental health status at 15 years. RESULTS: We identified 3 trajectories of peer victimization. The 2 prevailing groups were participants with little or moderate exposure to victimization (441/1685 [26.2%] and 1000/1685 [59.3%], respectively); the third group (244 [14.5%]) had been chronically exposed to the most severe and long-lasting levels of victimization. The most severely victimized individuals had greater odds of reporting debilitating depressive or dysthymic symptoms (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.27-5.17), debilitating generalized anxiety problems (OR 3.27, CI 1.64-6.51) and suicidality (OR 3.46, CI 1.53-7.81) at 15 years than those exposed to the lowest levels of victimization, after adjustment for sex, childhood mental health, family hardship and victimization perpetration. The association with suicidality remained significant after controlling for concurrent symptoms of depression or dysthymia and generalized anxiety problems. INTERPRETATION: Adolescents who were most severely victimized by peers had an increased risk of experiencing severe symptoms consistent with mental health problems. Given that peer victimization trajectories are established early on, interventions to reduce the risk of being victimized should start before enrolment in the formal school system.

Calcium supplementation decreases BCP-induced inflammatory processes in blood cells through the NLRP3 inflammasome down-regulation.

Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis. Our data showed for the first time that calcium supplementation of BCP microparticles had anti-inflammatory properties compared to BCP alone that induced an inflammatory response in blood cells. Our results strongly suggest that the anti-inflammatory property of calcium supplemented-BCP results from its down-modulating effect on P2X7R gene expression and its capacity to inhibit ATP/P2X7R interactions, decreasing the NLRP3 inflammasome activation. Considering that monocytes have a vast regenerative potential, and since the excessive inflammation often observed after bone substitutes implantation limits their performance, our results might have great implications in terms of understanding the mechanisms leading to an efficient bone reconstruction. STATEMENT OF SIGNIFICANCE: Although scaffolds and biomaterials unavoidably come into direct contact with blood during bone defect filling, whole blood-biomaterials interactions have been poorly explored. By studying in 3D the interactions between biphasic calcium phosphate (BCP) in microparticulate form and blood, we showed for the first time that calcium supplementation of BCP microparticles (BCP/Ca) has anti-inflammatory properties compared to BCP-induced inflammation in whole blood cells and provided information related to the molecular mechanisms involved. The present study also showed that BCP, as well as BCP/Ca particles stimulate monocyte proliferation. As monocytes represent a powerful target for regenerative therapies and as an excessive inflammation limits the performance of biomaterials in bone tissue engineering, our results might have great implications to improve bone reconstruction.