Transition from Saltation to Collisional Regime in Windblown Sand.

We report experiments on windblown sand that highlight a transition from saltation to collisional regime above a critical dimensionless mass flux or Shields number. The transition is first seen through the mass flow rate Q, which deviates from a linear trend with the Shields number and seems to follow a quadratic law. Other physical evidences confirm the change of the transport properties. In particular, the particle velocity and the height of the transport layer increases with increasing Shields number in the collisional regime while the latter are invariant with the wind strength in the saltation regime. Discrete numerical simulations support the experimental findings and ascertain that mid-air collisions are responsible for the change of transport regime.

Isolation and characterization of Clostridium difficile from a small survey of wastewater, food and animals in New Zealand.

The objective of this study was to undertake a microbiological survey of foods, animal faeces and wastewater samples for Clostridium difficile, and determine the genotypes and antimicrobial susceptibilities of isolates. A total of 211 samples were tested for C. difficile using culture methods. Thirteen toxigenic C. difficile isolates were obtained; ten from wastewater samples, one each from pig and duck faeces and another from a raw meat product. Eight PCR-ribotypes (RTs) were identified, including two novel RTs (878 and 879). Single-nucleotide polymorphism analysis using WGS data for all isolates provided greater discrimination between C. difficile isolates within the same RT and multilocus sequence typing (MLST) profiles. All C. difficile isolates were found to be susceptible to the first-line human antimicrobials used to treat C. difficile infection. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to report the isolation of Clostridium difficile from animals, food and wastewater in New Zealand (NZ) and provides important data with respect to ribotypes and multilocus sequence typing profiles, whole genome sequence and antimicrobial susceptibilities. The results highlight the need for further investigations into the epidemiology of C. difficile in NZ and to elucidate the role of the environmental and food sources as transmission routes of human infection.

An outbreak of multiple genotypes of Listeria monocytogenes in New Zealand linked to contaminated ready-to-eat meats-a retrospective analysis using whole-genome sequencing.

Four cases of listeriosis in a hospital (A) in New Zealand were identified in 2012. Pulsed-field gel electrophoresis (PFGE) used at the time identified four pulsotypes amongst the clinical isolates. Two of the pulsotypes matched to Listeria monocytogenes isolates obtained from ready-to-eat (RTE) meat samples from a RTE producer tested during a nationwide microbiological survey the month prior. The outbreak investigation confirmed that the RTE producer had supplied product to the hospital and additional testing confirmed the presence of L.  monocytogenes in RTE meats from the hospital kitchen. Two further listeriosis cases presented in another hospital (B) with one clinical isolate identified as the same pulsotype as identified for one case in hospital A, but the epidemiology information concluded that the clinical cases from hospital B were not linked to the outbreak. Retrospective whole-genome sequencing confirmed that epidemiologically linked isolates belonging to three different genotypes for clinical cases from hospital A and RTE meats samples from the hospital kitchen differed by 0-1 core-genome locus or single nucleotide polymorphisms (SNP). The use of core-genome multilocus sequence typing and SNP analysis provided a greater degree of discrimination between isolates compared to PFGE. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes a listeriosis outbreak associated with a hospital in New Zealand and attributed to contaminated ready-to-eat (RTE) meat supplied to the hospital by a single producer. Retrospective whole-genome sequence analysis of outbreak isolates was found to provide a greater degree of discrimination between isolates compared to pulsed-field gel electrophoresis and supported the conclusions made at the time of the outbreak. The multiple genotypes identified from clinical cases and the RTE meats obtained during the outbreak highlight the importance of epidemiological concordance alongside genotyping.

Coordinative task difficulty and behavioural errors are associated with increased long-range beta band synchronization.

The neural network and the task-dependence of (local) activity changes involved in bimanual coordination are well documented. However, much less is known about the functional connectivity within this neural network and its modulation according to manipulations of task complexity. Here, we assessed neural activity via high-density electroencephalography, focussing on changes of activity in the beta frequency band (~15-30Hz) across the motor network in 26 young adult participants (19-29 years old). We investigated how network connectivity was modulated with task difficulty and errors of performance during a bimanual visuomotor movement consisting of dial rotation according to three different ratios of speed: an isofrequency movement (1:1), a non-isofrequency movement with the right hand keeping the fast pace (1:3), and the converse ratio with the left hand keeping the fast pace (3:1). To quantify functional coupling, we determined neural synchronization which might be key for the timing of the activity within brain regions during task execution. Individual source activity with realistic head models was reconstructed at seven regions of interest including frontal and parietal areas, among which we estimated phase-based connectivity. Partial least squares analysis revealed a significant modulation of connectivity with task difficulty, and significant correlations between connectivity and errors in performance, in particular between sensorimotor cortices. Our findings suggest that modulation of long-range synchronization is instrumental for coping with increasing task demands in bimanual coordination.

Evaluation of the safety and adjuvant effect of a detoxified listeriolysin O mutant on the humoral response to dengue virus antigens.

Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination.

Non-Conjugated Chitosan-Based Nanoparticles to Proteic Antigens Elicit Similar Humoral Immune Responses to Those Obtained with Alum.

Biodegradables Chitosan-based Nanoparticles (CS NPs) have been extensively studied as delivery system for therapeutic molecules and as efficient carriers or adjuvants in experimental vaccination. Physicochemical association between CS NPs and antigens is a key step for the biological function as carrier devices. However, for the adjuvant CS NPs property, it is not well known if coupling with vaccine antigens is required or not to potentiate the immune response. To address this issue, in this work, we evaluated the potential adjuvant effect of CS NPs by simply mixing with two different antigens such as Bovine Serum Albumin (BSA) or E protein from Dengue Virus serotype 2 (E protein DENV2). Thus the CS NPs were prepared by ionic gelation with sodium tripolyphosphate, resulting particles among 68 and 188 nm of size. Immunization of 6­8 week old female BALB/c mice, were carried out by intraperitoneal route with a simple combination of CS NPs either with BSA (CS NPs-BSA) at 10 µg or with E protein DENV2 (CS NPs-Protein E) at 5 µg. Combinations with the above antigens with CS NPs elicited robust specific primary and secondary humoral responses comparable to alum, a well-known adjuvant. BSA-specific IgG titers were detectable by day 14 after priming with the CS NPs-BSA formulation, with titers that ranged from 102 to 103 EU ml-. After a second immunization, the anti-BSA titers ranged around 104 EU ml-. In contrast, in the group of mice immunized with the protein alone, BSA-specific serum IgG titers were undetectable at day 14 and 28. For the immunizations with the CS NPs-E protein formulation, we observed also a remarkable specific-antibody production in the primary response, with titers reaching 103 EU ml-. After the booster immunization the anti-E protein DENV2 antibodies titers reached peak values around 104 EU ml-. Interestingly, for both antigens, the combination with CS NPs polarized the immune response to a Th2-like profile, which is characterized mainly by the production of the IgG1 Isotype, confirming that CS NPs can enhance and modulate the humoral immune responses against different antigens independently of physicochemical conjugation. This could represent a simplification in the use of CS NPs as adjuvants in vaccination.

[Social representations of illness: Comparison of "expert" knowledge and "naïve" knowledge]. / Représentations sociales de la maladie : comparaison entre savoirs « experts ¼ et savoirs « profanes ¼.

INTRODUCTION: The link between social practices and representations is now well known. But while many studies have focused on the social representation of mental illness, in various populations, few studies have focused on the notion of disease/illness by comparing professionals and non-professionals health workers representations. Indeed, the disease is both a reality described, explained and treated by medicine; for those who are affected by a disease, it is an individual experience with psychological, social and cultural impacts. The social representation is determined by the structure of the social groups in which it develops; therefore, it is a form of knowledge socially shaped and shared by the members of a social group. Several theoretical extensions have been elaborated and particularly, the structural approach and the central core theory. These approaches sustain the arguments of a hierarchical organization of a social representation with a central core surrounded by peripheral zones. The central core is common and shared by the majority of the members of a given group, whereas the peripheral zones provide space for the individualization of the social knowledge. PURPOSE: The main goal of our study is to highlight the social representations of disease in health professionals (HP) and in non-health professionals (NHP). The group of HP has been differentiated into three subgroups: "medical doctors", "nurses" and "pharmacists", while that of NHP in two subgroups: those submitted to a "long period medical treatment" and those "without treatment". Our aim is to show that there are different social and professional Representations of disease. The professional representations are specific social representations related to professional contexts. We formulate the following assumptions (a) that the social representations of HP and NHP will be articulated around a common central core. Nevertheless, we expect to find specific peripheral elements related to professional status, based on different knowledge and a differentiated "practice"; (b) the HP should refer to more descriptive aspects of the disease and monitoring of patients, while (c) NHP should refer more to the experience of illness around emotional aspects. METHOD: Our sample is composed of 270 participants (135 HP and 135 HNP). Representations are measured by a free association task based on the target term: disease. The data have been submitted to prototypical and categorical analyses in agreement with the central core theory. RESULTS AND DISCUSSION: The results confirm that there is a common social representation of disease shared by the two groups, which refers essentially to suffering and pain. The analysis of each group brings to light two different registers: the one of the HP with more descriptive words referring to the nature and the illness's characteristics, and the other ones of the HNP with more words connected to emotions and referring to personal real experience of the illness. As expected, the social representation of the HP is referring to the "professional representations" of the disease, while the one for the HNP is linked to "practices" of an illness. An analysis of intra-group differences shows specificities for each of the questioned subgroups. In the HP, medical doctors focus on the diagnosis and consequences of the disease, pharmacists refer to the treatment of the disease and its management, while nurses focus on the treatment and on the relation while monitoring patients. In the NHP, people submitted to a "long period medical treatment" refer to the emotional aspects and to the consequences of the illness on their live, while those without treatment use more descriptive and formal terms. These results suggest to the PS to expand exchanges related to the disease in order to facilitate communication centered on taking care of the patient, considered in its wholeness and not only as an actual or potential patient. This is an important step in improving the health of the patient.

ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients.

BACKGROUND: Lymphopenia is a predictive factor for hematological toxicity, progression and early death in advanced cancers including metastatic breast cancer (MBC). CYT107 is a recombinant interleukin 7 (IL-7) (Cytheris, now Revimmune), well tolerated and able to expand lymphocyte pool in humans. The aims of this study were to determine the optimal schedule to deliver CYT107 and to assess its effect on clinical end points. PATIENT AND METHODS: This placebo-controlled, double blind, phase IIa was conducted in MBC patients with <1500/µl lymphocytes treated with capecitabine. Using a 2-by-2 factorial design, 20 patients were randomly allocated to four arms to receive (i) before chemotherapy: CYT107 or placebo; then (ii) during chemotherapy: CYT107 or placebo. The primary end point was CD4+ count changes before and during chemotherapy. Secondary end points were hematological toxicity, safety, overall response, progression-free survival (PFS) and overall survival (OS). Quantification and functional competence of circulating immune cells were also assessed. RESULTS: When administered before chemotherapy, CYT107 induced a significant increase of CD4+ [+148.1% in CYT107 versus +9.9% in placebo groups, (Wilcoxon, P = 0.002)] and CD8+ T-cell counts, including both naïve and memory subsets. When CYT107 was administered during chemotherapy, the magnitude of CD4+ and CD8+ increase was less important. No modulation of immune cell functional competence was observed. CYT107 was well tolerated with no related ≥grade 3 adverse events except 1 fatal suspected unexpected serious adverse reaction (SUSAR) of uncertain relationship. Of the 12 cases evaluable for response, 6 of 7 patients (86%) receiving CYT107 before chemotherapy achieved a response or stabilization, whereas two of five patients (40%) receiving placebo achieved the same result. No significant difference was observed for PFS or OS. CONCLUSION: In lymphopenic MBC, CYT107 increases CD4+ and other T-cell subset counts without altering their function. A larger clinical trial to demonstrate its impact on clinical outcome is warranted. CLINICALTRIALSGOV IDENTIFIER: NCT01362107.

Voxel-based comparison of state-of-the-art reconstruction algorithms for 18F-FDG PET brain imaging using simulated and clinical data.

UNLABELLED: The resolution of a PET scanner (2.5-4.5mm for brain imaging) is similar to the thickness of the cortex in the (human) brain (2.5mm on average), hampering accurate activity distribution reconstruction. Many techniques to compensate for the limited resolution during or post-reconstruction have been proposed in the past and have been shown to improve the quantitative accuracy. In this study, state-of-the-art reconstruction techniques are compared on a voxel-basis for quantification accuracy and group analysis using both simulated and measured data of healthy volunteers and patients with epilepsy. METHODS: Maximum a posteriori (MAP) reconstructions using either a segmentation-based or a segmentation-less anatomical prior were compared to maximum likelihood expectation maximization (MLEM) reconstruction with resolution recovery. As anatomical information, a spatially aligned 3D T1-weighted magnetic resonance image was used. Firstly, the algorithms were compared using normal brain images to detect systematic bias with respect to the true activity distribution, as well as systematic differences between two methods. Secondly, it was verified whether the algorithms yielded similar results in a group comparison study. RESULTS: Significant differences were observed between the reconstructed and the true activity, with the largest errors when using (post-smoothed) MLEM. Only 5-10% underestimation in cortical gray matter voxel activity was found for both MAP reconstructions. Higher errors were observed at GM edges. MAP with the segmentation-based prior also resulted in a significant bias in the subcortical regions due to segmentation inaccuracies, while MAP with the anatomical prior which does not need segmentation did not. Significant differences in reconstructed activity were also found between the algorithms at similar locations (mainly in gray matter edge voxels and in cerebrospinal fluid voxels) in the simulated as well as in the clinical data sets. Nevertheless, when comparing two groups, very similar regions of significant hypometabolism were detected by all algorithms. CONCLUSION: Including anatomical a priori information during reconstruction in combination with resolution modeling yielded accurate gray matter activity estimates, and a significant improvement in quantification accuracy was found when compared to post-smoothed MLEM reconstruction with resolution modeling. AsymBowsher provided the most accurate subcortical GM activity estimates. It is also reassuring that the differences found between the algorithms did not hamper the detection of hypometabolic regions in the gray matter when performing a voxel-based group comparison. Nevertheless, the size of the detected clusters differed. More elaborated and application-specific studies are required to decide which algorithm is best for a group analysis.

Celiac disease seroprevalence in subjects with dyspeptic symptoms. A study on a Mexican population.

INTRODUCTION AND AIMS: Celiac disease (CD) is an autoimmune enteropathy that develops in genetically susceptible individuals. The typical gastrointestinal manifestation is diarrhea but symptoms of dyspepsia, such as epigastric pain, nausea, or satiety, can sometimes appear. Previous studies have reported that the prevalence of CD in patients with dyspepsia can be as high as 7%. The aim of the present study was to evaluate CD seroprevalence in subjects with dyspeptic symptoms and a control group in a Mexican population. MATERIAL AND METHODS: A case-control study was conducted on blood donors that answered the PAGI-SYM questionnaire for dyspepsia and in whom IgA antibodies to tissue transglutaminase 2 (IgA anti-tTG2) and IgG antibodies to deamidated gliadin peptide (IgG anti-DGP) were determined. CD seroprevalence in subjects with dyspeptic symptoms and in asymptomatic subjects was compared. RESULTS: A total of 427 subjects (76.3% men), with a mean patient age of 34 years (range of 18-65 years) were included. Of those participants, 87 (20.3%) had symptoms of dyspepsia (group A) and 340 (79.6%) were asymptomatic (group B). Antibodies were positive in one (1.15%) of the group A subjects (1/87, 95% CI 0.2-6 %), whereas they were positive in 4 (1.18%) of the group B subjects (4/340, 95% CI 0.4-2.9%, p = 0.59). CONCLUSIONS: CD seroprevalence in the study population with dyspeptic symptoms (1%) was not different from that of the control population. Thus, CD screening in Mexican patients with dyspepsia is not justified.

Motor learning-induced changes in functional brain connectivity as revealed by means of graph-theoretical network analysis.

Complex bimanual motor learning causes specific changes in activation across brain regions. However, there is little information on how motor learning changes the functional connectivity between these regions, and whether this is influenced by different sensory feedback modalities. We applied graph-theoretical network analysis (GTNA) to examine functional networks based on motor-task-related fMRI activations. Two groups learned a complex 90° out-of-phase bimanual coordination pattern, receiving either visual or auditory feedback. 3T fMRI scanning occurred before (day 0) and after (day 5) training. In both groups, improved motor performance coincided with increased functional network connectivity (increased clustering coefficients, higher number of network connections and increased connection strength, and shorter communication distances). Day×feedback interactions were absent but, when examining network metrics across all examined brain regions, the visual group had a marginally better connectivity, higher connection strength, and more direct communication pathways. Removal of feedback had no acute effect on the functional connectivity of the trained networks. Hub analyses showed an importance of specific brain regions not apparent in the standard fMRI analyses. These findings indicate that GTNA can make unique contributions to the examination of functional brain connectivity in motor learning.

Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers.

BACKGROUND: This phase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinum-based therapy. PATIENTS AND METHODS: Thirty-seven patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity. The primary end point was the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. Angiogenesis-related proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control. RESULTS: Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with noncontrolled disease, we observed in patients with controlled disease a significant higher baseline level of angiopoietin-1 and a significant early plasma decrease in angiopoietin-1, endoglin, and platelet-derived growth factor-AB. PTEN loss was observed only in patients with PD. CONCLUSIONS: Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.

Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram.

Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using (123)I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects' Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.

[Stress and smoking in treatment-seeking smokers]. / Stress et tabagisme des consultants en tabacologie.

Fear of not controlling stress is the most frequently reported obstacle to smoking cessation. We report a retrospective study involving 70 smokers whose files were randomly selected from a smoking cessation clinic's recruitment. Stress management as a motive to smoke (SMMS) was systematically explored at the first visit, before quit date. SMMS mean score was 7.36 (+/- 2.4) on a 10 point scale. The score was higher in females than in males (p = 0,048). A multivariate logistic regression showed that SMMS was explained by two variables: physical dependence as measured with the FTND score (OR = 1.7, 95% CI = 1.18-2.46), and anxiety as measured with the HAD scale (OR = 1.27, 95% CI = 1.03-1.56). In conclusion, the high frequency and impact of perceived stress on smoking behavior call for a systematic clinical evaluation of perceived stress when engaging a treatment for smoking dependence. Our work has confirmed the importance for the smokers of perceived stress on their smoking behavior, particularly in females. Perceived stress showed a strong relationship with nicotine dependence and anxiety. Further investigation is warranted for a better understanding of the relationship between perceived stress and anxiety in smokers.

Particle impact on a cohesive granular media.

We investigate numerically the impact process of a particle of diameter d and velocity V_{i} onto a cohesive granular packing made of similar particles via two-dimensional discrete element method simulations. The cohesion is ensured by liquid bridges between neighboring particles and described by short range attraction force based on capillary modeling. The outcome of the impact is analyzed through the production of ejected particles from the packing, referred to as the splash process. We quantify this production as a function of the impact velocity for various capillary strength Γ and liquid content Ω. The numerical data indicate that the splash process is modified when the dimensionless cohesion number Co=6Γ/ρ_{p}gd^{2} (where ρ_{p} is the particle density, d its diameter, and g the gravitational acceleration) exceeds a critical value of the order of the unity. Above this value, we highlight that the ejection process is triggered above a threshold impact Froude number, Fr=V_{i}/sqrt[gd], which depends both on Γ and Ω and scales as Γ^{ß}Ω^{δ}, where the values of the exponents are found close to 1/2 and 1/6, respectively, and can be derived from rational physical arguments. Importantly, we show that, above the threshold, the number of splashed particles follows a linear law with the impact Froude number as in the cohesionless case.

Scaling laws in aeolian sand transport.

We report on wind tunnel measurements on saltating particles in a turbulent boundary layer and provide evidence that over an erodible bed the particle velocity in the saltation layer and the saltation length are almost invariant with the wind strength, whereas over a nonerodible bed these quantities vary significantly with the air friction speed. It results that the particle transport rate over an erodible bed does not exhibit a cubic dependence with the air friction speed, as predicted by Bagnold, but a quadratic one. This contrasts with saltation over a nonerodible bed where the cubic Bagnold scaling holds. Our findings emphasize the crucial role of the boundary conditions at the bed and may have important practical consequences for aeolian sand transport in a natural environment.

Urinary tract infections in dogs with spontaneous hypercortisolism - frequency, symptoms and involved pathogens.

INTRODUCTION: Dogs with hypercortisolism are predisposed to developing bacteriuria associated either with clinical signs of cystitis or without clinical signs (subclinical bacteriuria). Based on current guidelines, dogs with subclinical bacteriuria should not be treated with antibiotics because there is no evidence that treatment improves outcome and because unnecessary treatments should be avoided. Before these guidelines were published in 2019, dogs with hypercortisolism and bacteriuria were commonly treated with antibiotics irrespective of clinical signs. Comprehensive data on the frequency of bacterial cystitis, subclinical bacteriuria and the outcome of antimicrobial treatment in dogs with hypercortisolism is sparse. The aims of this study were to investigate dogs with hypercortisolism for the presence of bacterial cystitis and subclinical bacteriuria, to address the pathogens involved, and to assess the outcome of antibiotic treatment. Dogs newly diagnosed with hypercortisolism between 2005 and 2015 from which a urine bacterial culture was available were included. Statistical analysis was performed with non-parametric tests. Of the 161 client-owned dogs included, 29 (18%) showed bacteriuria, which was subclinical in 24 (83%) cases. Escherichia coli was the most commonly isolated pathogen (58%). Bacteriuria was not associated with sex or neutering status. In 14 dogs, follow-up data was available, of which 13 (93%) were treated with antimicrobials for 14 to 28 days. Follow-up bacterial culture (1 to 118 days after cessation of therapy) was negative in 10 (77%) treated dogs; a negative follow-up culture was not associated with gender, age or duration of treatment. Bacteriuria persisted in three treated dogs and the one untreated dog. The prevalence of positive bacterial urinary culture in dogs with hypercortisolism was lower than previously reported. In the majority of dogs, bacteriuria was subclinical. Most dogs had a negative bacterial culture result after antimicrobial treatment; however, more resistant bacteria were detected in persistently positive urine.

INTRODUCTION: Les chiens atteints d'hypercortisolisme ont tendance à développer une bactériurie associée avec ou sans signes cliniques de cystite. Selon les recommandations de traitement actuelles, les chiens atteints de bactériurie subclinique ne doivent pas être traités avec des antibiotiques, car il n'y a aucune preuve d'une amélioration du succès du traitement et des traitements inutiles doivent être évités. Avant la publication de ces lignes directrices en 2019, les chiens atteints de hypercortisolisme et de bactériurie étaient traités de façon standard avec des antibiotiques, quels que soient les symptômes cliniques. Les données sur la fréquence de la cystite bactérienne, de la bactériurie subclinique et du résultat du traitement antimicrobien chez les chiens atteints d'hypercortisolisme sont rares. Le but de cette étude était d'examiner des chiens souffrant d'hypercortisolisme quant à la présence d'une cystite bactérienne et d'une bactériurie subclinique, d'identifier les agents pathogènes impliqués et d'évaluer le succès thérapeutique du traitement antibiotique. Cent soixante et un chiens, diagnostiqués avec hypercortisolisme entre 2005 et 2015 et chez qui une culture bactérienne urinaire était disponible, ont été utilisés. L'analyse statistique a été réalisée avec des tests non paramétriques. Une bactériurie a été diagnostiquée chez 29 (18%) des chiens avec hypercortisolisme, de façon subclinique dans 24 (83%) cas. Escherichia coli était le pathogène le plus fréquemment isolé (58%). Il n'y avait aucune association entre la bactériurie et le sexe ou le statut de castration. Des données de suivi étaient disponibles chez 14 chiens, dont 13 (93%) ont été traités avec des antibiotiques pendant 14 à 28 jours. La culture bactérienne (1 à 118 jours après la fin du traitement) a été négative chez 10 chiens (77%) traités. Il n'y avait aucune différence entre le sexe, l'âge ou la durée du traitement. Une bactériurie persistante a été observée chez trois chiens traités et un chien non traité. La prévalence de la culture bactérienne d'urine positive chez les chiens atteints d'hypercortisolisme était moins fréquente que celle publiée précédemment. Chez la majorité des chiens, la bactériurie était subclinique. La plupart des chiens avaient une culture bactérienne négative après un traitement antimicrobien; cependant, les cultures d'urine positives persistantes ont démontré des germes plus résistants aux antibiotiques.

The impact of cancer and chemotherapy during pregnancy on child neurodevelopment: A multimodal neuroimaging analysis.

BACKGROUND: This study applies multimodal MRI to investigate neurodevelopment in nine-year-old children born to cancer-complicated pregnancies. METHODS: In this cohort study, children born after cancer-complicated pregnancies were recruited alongside 1:1 matched controls regarding age, sex and gestational age at birth (GA). Multimodal MRI was used to investigate whole-brain and subcortical volume, cortical structure (using surface-based morphometry), white matter microstructure (using fixel-based analysis) and functional connectivity (using resting-state blood-oxygen-level-dependant signal correlations). Graph theory probed whole-brain structural and functional organization. For each imaging outcome we conducted two group comparisons: 1) children born after cancer-complicated pregnancies versus matched controls, and 2) the subgroup of children with prenatal chemotherapy exposure versus matched controls. In both models, we used the covariate of GA and the group-by-GA interaction, using false-discovery-rate (FDR) or family-wise-error (FWE) correction for multiple comparisons. Exploratory post-hoc analyses investigated the relation between brain structure/function, neuropsychological outcome and maternal oncological/obstetrical history. FINDINGS: Forty-two children born after cancer-complicated pregnancies were included in this study, with 30 prenatally exposed to chemotherapy. Brain organization and functional connectivity were not significantly different between groups. Both cancer and chemotherapy in pregnancy, as compared to matched controls, were associated with a lower travel depth, indicating less pronounced gyrification, in the left superior temporal gyrus (pFDR ≤ 006), with post-hoc analysis indicating platinum derivatives during pregnancy as a potential risk factor (p = .028). Both cancer and chemotherapy in pregnancy were related to a lower fibre cross-section (FCS) and lower fibre density and cross-section (FDC) in the posterior corpus callosum and its tapetal fibres, compared to controls. Higher FDC in the chemotherapy subgroup and higher FCS in the whole study group were observed in the anterior thalamic radiations. None of the psycho-behavioural parameters correlated significantly with any of the brain differences in the study group or chemotherapy subgroup. INTERPRETATION: Prenatal exposure to maternal cancer and its treatment might affect local grey and white matter structure, but not functional connectivity or global organization. While platinum-based therapy was identified as a potential risk factor, this was not the case for chemotherapy in general. FUNDING: This project has received funding from the European Union's Horizon 2020 research and innovation program (European Research council, grant no 647,047), the Foundation against cancer (Stichting tegen kanker, grant no. 2014-152) and the Research Foundation Flanders (FWO, grants no. 11B9919N, 12ZV420N).

Detection of inter-hemispheric metabolic asymmetries in FDG-PET images using prior anatomical information.

[(18)F] FDG positron emission tomography (PET) is commonly used to highlight brain regions with abnormal metabolism. Correct interpretation of FDG images is important for investigation of diseases. When the FDG uptake is compared between hemispheres, confusion can arise because it might be difficult to determine whether an observed asymmetry is physiological and due to normal anatomical variation or pathological. In this paper we propose a new method, which calculates an anatomy-corrected asymmetry index (ACAI), to highlight inter-hemispheric metabolic asymmetry in FDG images without the influence of anatomical asymmetry. Using prior anatomical information from MRI, the ACAI method only takes into account voxels that belong to a certain anatomical class. For the evaluation of detection performance, this method is applied on homogeneous brain phantoms and realistic analytical simulated FDG-PET images with known asymmetries. Results from these simulations demonstrated the validity of ACAI and its potential perspective in the future.