The effects of collaborative care versus consultation liaison for anxiety disorders and depression in Denmark: two randomised controlled trials.

BACKGROUND: Collaborative care (CC) and consultation liaison (CL) are two conceptual models aiming to improve mental healthcare in primary care. The effects of these models have not been compared in a Danish setting. AIMS: To examine the effects of CC versus CL for persons with anxiety and depression in Danish general practices (trial registration: NCT03113175 and NCT03113201). METHOD: Two randomised parallel superiority trials for anxiety disorders and depression were carried out in 2018-2019. In the CC-group, care managers collaborated with general practitioners (GPs) to provide evidence-based treatment according to structured treatment plans. They followed up and provided psychoeducation and/or cognitive-behavioural therapy. The GPs initiated pharmacological treatment if indicated, and a psychiatrist provided supervision. In the CL-group, the intervention consisted of the GP's usual treatment. However, the psychiatrist and care manager could be consulted. Primary outcomes were depression symptoms (Beck Depression Inventory-II, BDI-II) in the depression trial and anxiety symptoms (Beck Anxiety Inventory, BAI) in the anxiety trial at 6-month follow-up. RESULTS: In total, 302 participants with anxiety disorders and 389 participants with depression were included. A significant difference in BDI-II score was found in the depression trial, with larger symptom reductions in the CC-group (CC: 12.7, 95% CI 11.4-14.0; CL: 17.5, 95% CI 16.2-18.9; Cohen's d = -0.50, P ≤ 0.001). There was a significant difference in BAI in the anxiety trial (CC: 14.9, 95% CI 13.5-16.3; CL: 17.9, 95% CI 16.5-19.3; Cohen's d = -0.34, P ≤ 0.001), with larger symptom reductions in the CC-group. CONCLUSIONS: Collaborative care was an effective model to improve outcomes for persons with depression and anxiety disorders.

Isolation and characterization of multidrug resistant Gallibacterium anatis biovar haemolytica strains from Polish geese and hens.

Gallibacterium anatis biovar haemolytica is a bacterium that is frequently associated with infections of the reproductive tract and respiratory system in poultry. To assess the current prevalence and resistance profile of these bacteria in Poland, we collected and investigated 63 strains of Gallibacterium from diseased domestic poultry flocks including geese, laying hens, breeding hens and an ornamental hen. Detailed characterization of the isolates included the analysis of phenotypic antimicrobial resistance profiles and biofilm formation ability. Furthermore, the genetic background of 40 selected isolates regarding the presence of virulence and antimicrobial resistance genes and mobile genetic elements was determined. All investigated isolates were multidrug resistant, most prominently to ß-lactams, fluoroquinolones, sulfonamides and macrolides. A total of 48 different resistance profiles were detected. Of all isolates, 50.8% formed a strong biofilm, where strains isolated from geese appeared to be better at biofilm formation than strains isolated from laying and breeding hens. Single-nucleotide polymorphism genotyping revealed that G. anatis bv. haemolytica strains are restricted in host and geographical distribution, and the geese isolates showed greater phylogenetic similarity. Whole genome sequencing enabled identification of 25 different antimicrobial resistance determinants. The most common resistance genes were tetB, blaROB-1, and blaTEM-1 which may be located on mobile genetic elements. All isolates possessed the toxin gene gtxA, and the fimbrial gene flfA was identified in 95% of strains. Our results indicated that all G. anatis bv. haemolytica isolates showed multidrug resistant phenotypes. Strains isolated from geese were characterized by the highest percentage of isolates resistant to selected antimicrobials, probably reflecting host-related adaptations.

Predictors of return to work for people on sick leave with depression, anxiety and stress: secondary analysis from a randomized controlled trial.

PURPOSE: Knowledge about predictors of return to work (RTW) in people on sick leave with common mental disorders (CMDs) may inform the development of effective vocational rehabilitation interventions for this target group. In this study, we investigated predictors of RTW at 6 and 12 months in people on sick leave with depression, anxiety disorders or stress-related disorders. METHODS: We have performed a secondary analysis, utilizing data from two RCTs that evaluated the efficacy of an integrated health care and vocational rehabilitation intervention. Data were obtained from mental health assessments, questionnaires and registers. Using Cox regression analysis, the relationship between baseline variables and RTW was analysed at 6 and 12 months after randomization within the group of CMD as a whole and within the subgroups of depression, anxiety and stress-related disorders. RESULTS: Symptom burden and employment status at baseline predicted RTW in the CMD group (n = 1245) and in the three diagnostic subgroups at both time points. RTW self-efficacy predicted RTW in the depression group but not in the anxiety or stress subgroups. CONCLUSION: Many predictors of RTW were similar over time and, to some extent, across the CMD subgroups. Findings highlight the need not only to take health-related and psychological factors into account when developing vocational rehabilitation interventions but also to consider workplace strategies and options for support.

Predictors of Return to Work for People with Anxiety or Depression Participating in a Randomized Trial Investigating the Effect of a Supported Employment Intervention.

Purpose Common mental disorders have a severe impact on society and individuals; rates of unemployment and disability pensions are high. Knowing which factors facilitate or hinder people's return to work is important when designing effective vocational rehabilitation interventions. Methods We conducted secondary analyses on data from 289 participants with depression or anxiety included in the Individual Placement and Support modified for people with mood and anxiety disorders (IPS-MA) trial. Associations of baseline characteristics and employment or education after 24 months were tested in univariate logistic regression analyses, variables with a p-value below 0.1 were included in multivariate analyses. Results In the univariate analyses, self-reported level of functioning (p = 0.032), higher age (p = 0.070), and higher level of readiness to change (p = 0.001) were associated with the outcome and included in the multivariate analysis. Only age (p = 0.030) and readiness to change (p = 0.003) remained significantly associated with return to work or education after 24 months in the multivariate analysis. Conclusion Higher age and lower readiness to change were associated with a lower chance of having returned to work or education. Factors modifying the effect of higher age should be identified, just as vocational rehabilitation should focus on improving factors related to people's readiness to change.

Integrated Mental Healthcare and Vocational Rehabilitation for People on Sick Leave with Anxiety or Depression: 24-Month Follow-up of the Randomized IBBIS Trial.

Integration of vocational rehabilitation and mental healthcare has shown some effect on work participation at 1-year follow-up after sick leave with depression and anxiety. We aimed to study the effect on work and health outcomes at 2-year follow-up, why we performed a randomized trial was conducted to study the effectiveness of integrated intervention (INT) compared to service as usual (SAU) and best practice mental healthcare (MHC). We included 631 participants, and at 24-month follow-up, we detected no differences in effect between INT and SAU. Compared to MHC, INT showed faster return-to-work (RTW) rates (p = 0.044) and a higher number of weeks in work (p = 0.024). No symptom differences were observed between the groups at 24 months. In conclusion, compared to SAU, INT was associated with a slightly higher work rate reaching borderline statistical significance at 12-month follow-up and lower stress levels at 6-month follow-up. The disappearance of relative effect between 12 and 24 months may be explained by the fact that the intervention lasted less than 12 months or by delayed spontaneous remission in the SAU group after 12 months. Despite the lack of effect at long-term follow-up, INT still performed slightly better than SAU overall. Moderate implementation difficulties, may partly explain the absence of the hypothesized effect. Integrated intervention, as implemented in this trial, showed some positive effects on mid-term vocational status and short-term stress symptom levels. However, these effects were not sustained beyond the duration of the intervention.

Recurring outbreaks by the same Escherichia coli ST10 clone in a broiler unit during 18 months.

The current investigation aimed at characterizing the cause of multiple disease outbreaks in the same broiler production unit during a course of 18 months. The outbreaks had mortality rates of up to 22%. Escherichia coli was diagnosed as the responsible agent. Multiple-locus variable-number tandem-repeat analysis showed that all chicken isolates had identical band patterns. Core genome comparisons demonstrated that the 36 chicken isolates differed with maximum of nine nucleotides indicating that the same E. coli clone was responsible for all seven disease outbreaks despite adherence to the all-in-all production principle and rigorous cleaning and disinfection procedures.

Assessment of automated assays for serum amyloid A, haptoglobin (PIT54) and basic biochemistry in broiler breeders experimentally infected with Escherichia coli.

Biomarkers of inflammation are valuable tools for health status evaluation in numerous species. However, in poultry, methods for measuring acute phase proteins (APP) are sparse and rely on manual laboratory labour reserving these parameters mainly for research studies with APP as a focus point. To extend the use of APP beyond tightly focused research studies, blood from experimentally infected and control hens was analysed using equipment available in many veterinary clinics in order to identify easily accessible biomarkers of infection. Blood samples from broiler breeders (n = 30) inoculated intratracheally with either Escherichia coli or sterile vehicle were randomly selected at 2, 4 and 7 days post-infection (dpi) and subjected to biochemical analysis. Samples for bacteriological testing were collected, and all animals were subjected to a full necropsy for disease confirmation. Significantly higher levels of serum amyloid A were evident in the infected birds at 2 and 4 dpi (p < 0.01) compared to the controls. Likewise, haptoglobin (PIT54) levels were significantly elevated at 4 dpi (p < 0.01) in the infected animal, whilst at 2 dpi magnesium and calcium were significantly lower in the infected group (p < 0.05). Gross pathology and bacteriology confirmed the presence of infection in the E. coli inoculated birds. In conclusion, equipment routinely used in other species for rapid analysis of blood samples, successfully differentiated between sick and healthy birds, hereby, showing great potential as an easily added parameter of evaluation in research studies, and as a valuable decision-making tool for poultry veterinarians.

Longitudinal study on background lesions in broiler breeder flocks and their progeny, and genomic characterisation of Escherichia coli.

In broiler breeders, background mortality is rarely addressed, however, it represents the death of a vast number of birds, a constant productivity loss, welfare concerns and it might affect chick quality. The study aimed to unveil lesions leading to mortality in a study population perceived as healthy, combined with whole-genome sequencing (WGS) of Escherichia coli, a well-known contributor to disease problems in poultry. Broiler breeders (n = 340) originating from three distinct, putative healthy flocks and their progeny (n = 154) were subjected to a comprehensive post-mortem examination, bacteriological sampling, and sequencing of 77 E. coli isolates. Productivity data confirmed an exemplary health status of the enrolled flocks, and post-mortem examination further verified the absence of general disease problems. Among the submitted broiler breeders, exudative peritonitis (31.2%) was the most frequent lesion linked to infectious disease, whereas airsacculitis, pericarditis, perihepatitis, and salpingitis occurred in 18.5%, 3.5%, 3.8% and 17%, respectively. Yolksacculitis occurred in 15.6% of the broilers, whilst pericarditis, perihepatitis and peritonitis were diagnosed in 9.7%, 7.1% and 9.1%, respectively. WGS revealed a diverse population where ST95 dominated the population retrieved from broiler breeders, whereas ST10 was highly prevalent among broilers. Both lineages could be isolated from extraintestinal sites of birds without lesions indicative of infection. In general, the genetic diversity within flocks was comparable to the diversity between farms, and the overall occurrence of resistance markers was low. In conclusion, a comprehensive insight into lesions associated with background mortality is presented, together with a vast diversity of E. coli isolated from extraintestinal sites during a non-outbreak situation.

Clarification of large-volume bacterial cultures using a centrifuge-free protocol.

AIMS: To provide a reliable, reproducible and centrifuge-free filtration protocol for clarification of large volumes of bacterial cultures. METHODS AND RESULTS: Four experiments were designed to compare different techniques enabling clarification of Escherichia coli cultures using as a benchmark the concentration and quality of bacterial outer membrane vesicles (OMVs). The experiments were designed to examine the performance of different extraction methods on large volume (≥1 L) filtrations of bacterial culture media. Performance parameters included filtration flow rates, sterility testing and characterization of the filtrates by: (i) SDS-PAGE, (ii) cryogenic transmission electron microscopy, (iii) nanoparticle tracking analysis and (iv) Qubit protein quantification. The experiments revealed that: (i) addition of the filter aid Diatomaceous Earth to the bacterial cultures improved filtration flow rates significantly and eliminated the need for centrifugation prior to filtration; (ii) sterile filtration was successful as no bacterial passage was identified through the membrane filter; (iii) centrifuge-free filtrates contained an increased amount of OMVs compared to centrifuged filtrates. CONCLUSIONS: In comparison to conventional centrifuge-based protocols, the clarification method presented has universal applicability for a broad range of microbial extraction procedures, regardless of the volume of culture harvested. Moreover, the decreased amount of OMVs presented in the filtrates following centrifugation step provides an additional argument in favour of a centrifuge-free approach. SIGNIFICANCE AND IMPACT OF THE STUDY: Sterile filtration is a universal method for the clarification of bacterial cultures. Common challenges related to filtration include filter clogging and long processing times, due to limited centrifugation capacity, which can affect product quality. The proposed protocol is likely to ensure a highly effective filtration process and could be a novel approach in improving the filtrate products without the need of centrifugation.

Integrative analyses of probiotics, pathogenic infections and host immune response highlight the importance of gut microbiota in understanding disease recovery in rainbow trout (Oncorhynchus mykiss).

AIMS: Given the pivotal role played by the gut microbiota in regulating the host immune system, great interest has arisen in the possibility of controlling fish health by modulating the gut microbiota. Hence, there is a need to better understand of the host-microbiota interactions after disease responses to optimize the use of probiotics to strengthen disease resilience and recovery. METHODS AND RESULTS: We tested the effects of a probiotic feed additive in rainbow trout and challenged the fish with the causative agent for enteric red mouth disease, Yersinia ruckeri. We evaluated the survival, host immune gene expression and the gut microbiota composition. Results revealed that provision of probiotics and exposure to Y. ruckeri induced immune gene expression in the host, which were associated with changes in the gut microbiota. Subsequently, infection with Y. ruckeri had very little effect on microbiota composition when probiotics were applied, indicating that probiotics increased stabilisation of the microbiota. Our analysis revealed potential biomarkers for monitoring infection status and fish health. Finally, we used modelling approaches to decipher interactions between gut bacteria and the host immune gene responses, indicating removal of endogenous bacteria elicited by non-specific immune responses. CONCLUSIONS: We discuss the relevance of these results emphasizing the importance of host-microbiota interactions, including the protective potential of the gut microbiota in disease responses. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results highlight the functional consequences of probiotic-induced changes in the gut microbiota post infection and the resulting host immune response.

Integrating vocational rehabilitation and mental healthcare to improve the return-to-work process for people on sick leave with depression or anxiety: results from a three-arm, parallel randomised trial.

OBJECTIVE: The aim of this study was to investigate an integrated mental healthcare and vocational rehabilitation intervention to improve and hasten the process of return-to-work of people on sick leave with anxiety and depression. METHODS: In this three-arm, randomised trial, participants were assigned to (1) integrated intervention (INT), (2) improved mental healthcare (MHC) or (3) service as usual (SAU). The primary outcome was time to return-to-work measured at 12-month follow-up. The secondary outcomes were time to return-to-work measured at 6-month follow-up; levels of anxiety, depression, stress symptoms, and social and occupational functioning at 6 months; and return-to-work measured as proportion in work at 12 months. RESULTS: 631 individuals were randomised. INT yielded a higher proportion in work compared with both MHC (56.2% vs 43.7%, p=0.012) and SAU (56.2% vs 45%, p=0.029) at 12-month follow-up. We found no differences in return-to-work in terms of sick leave duration at either 6-month or 12-month follow-up, with the latter being the primary outcome. No differences in anxiety, depression or functioning between INT, MHC and SAU were identified, but INT and MHC showed lower scores on Cohen's Perceived Stress Scale compared with SAU at 12-month follow-up. CONCLUSIONS: Although INT did not hasten the process of return-to-work, it yielded better outcome with regard to proportion in work compared with MHC and SAU. The findings suggest that INT compared with SAU is associated with a few, minor health benefits. Overall, INT yielded slightly better vocational and health outcomes, but the clinical significance of the health advantage is questionable. TRIAL REGISTRATION NUMBER: NCT02872051.

Polar bear-adapted Ursidibacter maritimus are remarkably conserved after generations in captivity.

Most species in the bacterial family of Pasteurellaceae colonize one specific host species. Vertebrates of very different evolutionary descent including fish, turtles, marsupials, eutherians and birds are colonized by different members of Pasteurellaceae. This one-to-one microbial-host species partnership makes Pasteurellaceae species valuable candidates to study biodiversity, bacterial-host co-evolution and host adaptation, and their widespread distribution across vertebrates provide the possibility to collect a wide array of data, where wildlife species are essential. However, obtaining samples from wild animals comes with logistic, technical and ethical challenges, and previous microbiota studies have led to the presumption that captive animals are poor models for microbial studies in wildlife. Here, we show that colonization of polar bears by Ursidibacter maritimus is unaffected by factors related to captivity, reflecting a deep symbiotic bond to the host. We argue that the study of ecological and evolutionary principles in captive wildlife is possible for host-adapted taxa such as those in the Pasteurellaceae family. Moreover, studying captive, often trained animals protects wild populations from the stress associated with obtaining samples.

Clonal spread of multi-resistant Gallibacterium anatis isolates among Iranian broilers and layers.

Gallibacterium anatis is a common cause of reproductive tract infection in chickens, which leads to reduced egg production and increased mortality. This study was undertaken to investigate prevalence of G. anatis in 12 poultry flocks originating from Iranian provinces with leading chicken production and to determine genetic diversity, antimicrobial resistance, and the presence of major antigens of the isolates investigated. Out of the 120 chicken tracheal samples collected and tested, 84 (70%) were positive for G. anatis. Genotyping by Pulse Field Gel Electrophoresis and genome sequencing revealed a total of 24 pulsotypes for 71 strains (at a 87% similarity level) and seven genome clusters comprising 21 strains (97% similarity level), respectively. The combination of the two typing methods confirmed the presence of several genotypes originating from a common ancestor affecting poultry yet also suggested that identical clones were shared among chickens within farms and between different farms. The latter finding is to our knowledge the first example of clonal presence of G. anatis in epidemiologically unrelated farms. The 21 sequenced strains were characterized against a panel of commonly used antibiotics and showed lowered sensitivity to tetracycline (76.2%) and enrofloxacin (90.5%). The widespread presence of multiresistant G. anatis isolates calls for non-antibiotic prophylactics. Three major immunogen genes, gtxA, Gab_1309 and Gab_2312 were detected in the isolates indicating these antigens likely represent effective vaccine targets. A conserved sequence of the gtxA gene across a range of epidemiologically independent strains suggests the use of GtxA for future vaccine development purposes.

Modified MHC Class II-Associated Invariant Chain Induces Increased Antibody Responses against Plasmodium falciparum Antigens after Adenoviral Vaccination.

Adenoviral vectors can induce T and B cell immune responses to Ags encoded in the recombinant vector. The MHC class II invariant chain (Ii) has been used as an adjuvant to enhance T cell responses to tethered Ag encoded in adenoviral vectors. In this study, we modified the Ii adjuvant by insertion of a furin recognition site (Ii-fur) to obtain a secreted version of the Ii. To test the capacity of this adjuvant to enhance immune responses, we recombined vectors to encode Plasmodium falciparum virulence factors: two cysteine-rich interdomain regions (CIDR) α1 (IT4var19 and PFCLINvar30 var genes), expressed as a dimeric Ag. These domains are members of a highly polymorphic protein family involved in the vascular sequestration and immune evasion of parasites in malaria. The Ii-fur molecule directed secretion of both Ags in African green monkey cells and functioned as an adjuvant for MHC class I and II presentation in T cell hybridomas. In mice, the Ii-fur adjuvant induced a similar T cell response, as previously demonstrated with Ii, accelerated and enhanced the specific Ab response against both CIDR Ags, with an increased binding capacity to the cognate endothelial protein C receptor, and enhanced the breadth of the response toward different CIDRs. We also demonstrate that the endosomal sorting signal, secretion, and the C-terminal part of Ii were needed for the full adjuvant effect for Ab responses. We conclude that engineered secretion of Ii adjuvant-tethered Ags establishes a single adjuvant and delivery vehicle platform for potent T and B cell-dependent immunity.

Predictors of work and education among people with severe mental illness who participated in the Danish individual placement and support study: findings from a randomized clinical trial.

PURPOSE: People with severe mental illness experience disproportionately high rates of unemployment. Nonetheless, a substantial amount of research has demonstrated vocational benefits of the Individual Placement and Support (IPS) model and IPS supplemented with cognitive remediation (IPSE). The present study sought to examine demographic and clinical predictors of employment or education among people with severe mental illness and to investigate if IPS or IPSE can compensate for risk factors for unemployment. METHODS: Seven hundred twenty participants were randomly assigned to IPS, IPSE or Service as Usual. During the 18-month follow-up period participants in the two experimental groups obtained significantly more work or education. A series of univariate and multiple logistic regression analyses were conducted to assess the predictive power of demographic and clinical factors for the total population and for the three groups individually. RESULTS: The strongest predictor for vocational recovery, besides treatment allocation, was previous work history (OR = 1.78; 95% CI = 1.28-2.47). Men had a lower probability for vocational recovery compared to women (OR = 0.71; 95% CI = 0.50-0.99) and higher age was also negatively associated with work or education (OR = 0.79; 95% CI = 0.67-0.93). Moreover, vocational recovery was predicted by higher readiness for change, measured on the readiness for change scale (OR = 1.42; 95% CI = 1.19-1.70). Participation in IPS or IPSE could not compensate for negative risk factors such as low cognitive function or negative symptoms. CONCLUSIONS: In a multiple logistic regression analysis age, previous work history and motivation for change were statistically significant predictors of obtaining work or education among people with severe mental illness who participated in the Danish IPS trial.

Vocational Outcomes of the Individual Placement and Support Model in Subgroups of Diagnoses, Substance Abuse, and Forensic Conditions: A Systematic Review and Analysis of Pooled Original Data.

PURPOSE: To investigate the effect of Individual Placement and Support (IPS) according to diagnoses of schizophrenia, bipolar disorder, major depression, substance use disorders, or forensic psychiatric conditions. METHODS: A systematic search of the literature was conducted in June 2017 and repeated in December 2020. The systematic review included 13 studies. Analyses of pooled original data were based on the six studies providing data (n = 1594). No studies on forensic psychiatric conditions were eligible. Hours and weeks worked were analyzed using linear regression. Employment, and time to employment was analyzed using logistic regression, and cox-regression, respectively. RESULTS: The effects on hours and weeks in employment after 18 months were comparable for participants with schizophrenia, and bipolar disorder but only statistically significant for participants with schizophrenia compared to services as usual (SAU) (EMD 109.1 h (95% CI 60.5-157.7), 6.1 weeks (95% CI 3.9-8.4)). The effect was also significant for participants with any drug use disorder (121.2 h (95% CI 23.6-218.7), 6.8 weeks (95% CI 1.8-11.8)). Participants with schizophrenia, bipolar disorder, and any drug use disorder had higher odds of being competitively employed (OR 2.1 (95% CI 1.6-2.7); 2.4 (95% CI 1.3-4.4); 3.0 (95% CI 1.5-5.8)) and returned to work faster than SAU (HR 2.1 (95% CI 1.6-2.6); 1.8 (95% CI 1.1-3.1); 3.0 (95% CI 1.6-5.7)). No statistically significant effects were found regarding depression. CONCLUSIONS: IPS was effective regarding schizophrenia, bipolar disorder, and substance use disorder; however, the effect on hours, and weeks worked was not statistically significant regarding bipolar disorder. For people with depression the impact of IPS remains inconclusive. Non-significant results may be due to lack of power. TRIAL REGISTRATION: PROSPERO protocol nr. CRD42017060524.

PREVALENCE OF SALMONELLA SPECIES, CLOSTRIDIUM PERFRINGENS, AND CLOSTRIDIUM DIFFICILE IN THE FECES OF HEALTHY ELEPHANTS (LOXODONTA SPECIES AND ELEPHAS MAXIMUS) IN EUROPE.

Pathogenic Salmonella spp., Clostridium perfringens, and Clostridium difficile have been reported to infect and cause severe enteritis and enterotoxemia in African (Loxodonta spp.) and Asian elephants (Elephas maximus). However, little information exists on whether healthy elephants carry and possibly shed these gastrointestinal organisms. This study was conducted to investigate the prevalence of all three bacteria in feces from healthy elephants in European zoos. Bacterial identification was performed by selective culture on fecal samples and a polymerase chain reaction (PCR) amplification protocol, on the basis of primers targeting the hilA gene (Salmonella spp.), the cpa gene (C. perfringens), and the tpi gene (C. difficile) from deoxyribonucleic acid extracted from elephant feces. The PCR protocol was validated prior to initiation of the investigation. Fecal samples collected from 50 African and 86 Asian elephants originating from 30 European zoologic institutions were investigated. The PCR validation revealed detection limits ranging from 104 to 106 colony-forming units per gram of feces of each gene. Only C. perfringens (one type A and two type E) was detected in the initial sampling (2.2%, three Asian elephants), whereas no Salmonella spp. or C. difficile was detected. At a follow-up sampling from C. perfringens-positive animals and relatives, 2 mo after the initial sampling, three animals were culture positive for Salmonella enterica spp. enterica. All positive samples were obtained with bacterial culture, whereas no PCR reactions were positive. Despite carrying these pathogens, all culture-positive animals were clinically healthy and did not develop signs of gastrointestinal disease during the study period. The findings indicate that prevalence of Salmonella spp., C. perfringens, and C. difficile in feces from healthy Asian and African elephants in Europe is very low.

MOLECULAR IDENTIFICATION OF MEMBERS OF THE FAMILY PASTEURELLACEAE FROM THE ORAL CAVITY OF KOALAS (PHASCOLARCTOS CINEREUS) AND THEIR RELATIONSHIP WITH ISOLATES FROM KOALA BITE WOUNDS IN HUMANS.

A total of 22 Pasteurellaceae isolates obtained from the oral cavity of koalas (Phascolarctos cinereus) at different wildlife centers in Australia were investigated using amplification and sequencing of two housekeeping genes, rpoA and recN. The available sequences from the Lonepinella koalarum type strain (ACM3666T) and the recent isolates of Lonepinella-like bacteria obtained from human infected wounds associated with koala bites were also included. Phylogenetic analysis was performed on the concatenated rpoA-recN genes and genome relatedness was calculated based on the recN sequences. The oral cavity isolates, the koala bite wound isolates, and L. koalarum ACM3666T resulted in four clusters (Clusters 1-4). Clusters 1-3 were clearly not members of the genus Lonepinella. Cluster 1 was closely related to the genus Fredericksenia, and Clusters 2 and 3 appeared to be novel genera. Cluster 4 consisted of three subclusters: Cluster 4a with one koala bite wound isolate and L. koalarum ACM3666T, Cluster 4b with three oral cavity isolates and two Lonepinella-like wound isolates, and Cluster 4c with three nearly identical oral cavity isolates that may represent a different species within the genus Lonepinella. The rich Pasteurellaceae population, including potential novel taxa in the oral cavity of koalas supports an important role of these highly adapted microorganisms in the physiology of koalas. Moreover, the pathogenic potential of Lonepinella-like species is an important consideration when investigating infected koala bites in humans.

GtxA is a virulence factor that promotes a Th2-like response during Gallibacterium anatis infection in laying hens.

GtxA, a leukotoxic RTX-toxin, has been proposed a main virulence factor of Gallibacterium anatis. To evaluate the impact of GtxA during infection, we experimentally infected laying hens with a G. anatis wild-type (WT) strain and its isogenic gtxA deletion mutant (ΔgtxA), respectively, and monitored the birds during a 6 day period. Birds inoculated with ΔgtxA had significantly reduced gross lesions and microscopic changes compared to the birds inoculated with the WT strain. To assess the host response further, we quantified the expression of pro-inflammatory cytokines and apoptosis genes by RT-qPCR. In the ovarian tissue, the expression levels of IL-4 and TNF-α were significantly lower in the ΔgtxA group compared to the WT group, while IL-6 and IL-10 levels appeared similar in the two groups. In the spleen tissue of ΔgtxA infected chickens, IL-4 expression was also lower compared to the WT infected chickens. The results indicated that GtxA plays a key role in an acute cytokine-mediated Th2-like response against G. anatis infection in the ovary tissue. The pro-inflammatory response in the ovary tissue of birds inoculated with ΔgtxA mutant was thus significantly lower than the wild-type response. This was, at least partly, supported by the apoptosis gene expression levels, which were significantly higher in the ΔgtxA mutant compared to the wild-type infected chickens. In conclusion, GtxA clearly plays an important role in the pathogenesis of G. anatis infections in laying hens. Further investigations into the specific factors regulating the host response is however needed to provide a more complete understanding of the bacteria-host interaction.

Estimating the effect size of the 15Q11.2 BP1-BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice.

BACKGROUND: The 15q11.2 deletion is frequently identified in the neurodevelopmental clinic. Case-control studies have associated the 15q11.2 deletion with neurodevelopmental disorders, and clinical case series have attempted to delineate a microdeletion syndrome with considerable phenotypic variability. The literature on this deletion is extensive and confusing, which is a challenge for genetic counselling. The aim of this study was to estimate the effect size of the 15q11.2 deletion and quantify its contribution to neurodevelopmental disorders. METHODS: We performed meta-analyses on new and previously published case-control studies and used statistical models trained in unselected populations with cognitive assessments. We used new (n=241) and previously published (n=150) data from a clinically referred group of deletion carriers. 15q11.2 duplications (new n=179 and previously published n=35) were used as a neutral control variant. RESULTS: The deletion decreases IQ by 4.3 points. The estimated ORs and respective frequencies in deletion carriers for intellectual disabilities, schizophrenia and epilepsy are 1.7 (3.4%), 1.5 (2%) and 3.1 (2.1%), respectively. There is no increased risk for heart malformations and autism. In the clinically referred group, the frequency and nature of symptoms in deletions are not different from those observed in carriers of the 15q11.2 duplication suggesting that most of the reported symptoms are due to ascertainment bias. CONCLUSIONS: We recommend that the deletion should be classified as 'pathogenic of mild effect size'. Since it explains only a small proportion of the phenotypic variance in carriers, it is not worth discussing in the developmental clinic or in a prenatal setting.