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1.
J Equine Vet Sci ; 99: 103409, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33781433

RESUMO

BACKGROUND: The breeding prognosis for a mare with fungal (yeast or mold) endometritis is generally considered poor. To our knowledge, however, no reports have been published on the expected pregnancy rate for mares diagnosed with a fungal infection. STUDY DESIGN: Insemination records from 3,223 mares inseminated at two stud farms were retrospectively examined. Mares diagnosed with fungal endometritis were all treated with uterine lavage using physiological saline, intrauterine deposition of 100 mg Clotrimazole vagitorial tablets and oxytocin (10 i.e., i.m.) for three consecutive days. METHODS: From mares with signs of endometritis microbiological culture and cytological assessment were performed on endometrial biopsies. The per season pregnancy results were compared between affected and unaffected mares. RESULTS: A total of 686 mares out of 3,223 mares were considered to have endometritis. Based on the endometrial biopsies obtained, 377 (55%) had no growth, 50 (7.2%) had growth of yeast, 2 (0.3%) had growth of mold and 257 (37.4%) had growth of bacteria recorded. Positive cytology was found in 78.0% of samples diagnosed with yeast endometritis whereas that was the case in 65.6% of samples showing growth of mold or bacteria (P = 0.12). The per-season pregnancy rate was 48% in mares diagnosed with yeast endometritis. The overall per season pregnancy rate in the two stud farms was 76.4% (P < 0.0001, Odds ratio = 3.59, confidence interval 95% = 2.04-6.29). CONCLUSIONS: Yeast can make up a considerable cause of endometritis. The breeding prognosis of a mare with yeast endometritis must be considered worse than that of a normal mare. Following management of the condition approximately 50% of the mares previously diagnosed with an endometrial yeast infection got in foal rendering the breeding prognosis better than initially anticipated.

2.
J Occup Rehabil ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661452

RESUMO

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.

3.
Eur J Med Genet ; 64(4): 104183, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33639313

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable kidney disease. ADPKD leads to cysts, kidney enlargement and end-stage renal disease. ADPKD is mainly caused by variants in PKD1 and PKD2, with truncating PKD1 variants causing the most severe phenotype. This study aimed to characterize variants in Danish patients referred for screening of genes related to cystic kidney disease. METHODS: 147 families were analysed for variants in PKD1, PKD2 and GANAB using next generation sequencing and multiplex ligation-dependent probe amplification. If a variant was identified, relatives were analysed for the specific variant using Sanger sequencing. RESULTS: A pathogenic or possibly pathogenic variant was identified in 87% (103/118) of patients suspected to suffer from ADPKD, according to the requisition form. In total, 112 pathogenic or possibly pathogenic variants were observed, of which 94 were unique; 74 (79%) in PKD1 and 20 (21%) in PKD2, while 41 variants were novel. No variants in GANAB were observed. Ten recurrent variants were observed in 26 (26%) families. These were either PKD2 variants (N = 6) or non-truncating PKD1 variants (N = 4). Five of these were likely founder variants. CONCLUSIONS: The distribution of pathogenic or possibly pathogenic variants in the Danish ADPKD population is similar to that in other populations, except that recurrent truncating PKD1 variants appear to be rare, i.e. founder variants tend to be variant types associated with a mild phenotype. Patients with a mild phenotype may remain undiagnosed, consequently the frequency of founder variants and prevalence of ADPKD may be underestimated.

4.
Vet Res ; 52(1): 27, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596999

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Galinhas , Infecções por Pasteurellaceae/veterinária , Pasteurellaceae/efeitos dos fármacos , Pasteurellaceae/isolamento & purificação , Doenças das Aves Domésticas/microbiologia , Animais , Farmacorresistência Bacteriana Múltipla , Genoma Bacteriano , Irã (Geográfico)/epidemiologia , Infecções por Pasteurellaceae/epidemiologia , Infecções por Pasteurellaceae/microbiologia , Filogenia , Doenças das Aves Domésticas/epidemiologia , Sequenciamento Completo do Genoma
5.
J Zoo Wildl Med ; 51(4): 752-760, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33480555

RESUMO

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.


Assuntos
/isolamento & purificação , Clostridium perfringens/isolamento & purificação , Elefantes/microbiologia , Fezes/microbiologia , Salmonella/isolamento & purificação , Animais , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/veterinária , Europa (Continente)/epidemiologia , Feminino , Masculino , Reação em Cadeia da Polimerase/veterinária , Prevalência , Salmonelose Animal/epidemiologia , Salmonelose Animal/microbiologia
6.
J Zoo Wildl Med ; 51(4): 771-779, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33480557

RESUMO

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.


Assuntos
Mordeduras e Picadas , Infecções por Pasteurellaceae/microbiologia , Pasteurellaceae/classificação , Phascolarctidae/microbiologia , Infecção dos Ferimentos/microbiologia , Animais , Austrália/epidemiologia , Genoma Bacteriano , Humanos , Pasteurellaceae/genética , Pasteurellaceae/isolamento & purificação , Filogenia , Infecção dos Ferimentos/epidemiologia , Zoonoses
7.
Pathogens ; 9(12)2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33276526

RESUMO

Production and isolation of recombinant proteins are costly and work-intensive processes, especially in immunology when tens or hundreds of potential immunogens need to be purified for testing. Here we propose an alternative method for fast screening of immunogen candidates, based on genetic engineering of recombinant bacterial strains able to express and expose selected antigens on their outer membrane. In Actinobacillus pleuropneumoniae, a Gram-negative porcine pathogen responsible for extensive economic losses worldwide, we identified a conserved general secretion pathway (GSP) domain in the N-terminal part of the outer membrane protein ApfA (ApfA stem: ApfAs). ApfAs was used as an outer membrane anchor, to which potential immunogens can be attached. To enable confirmation of correct positioning, ApfAs, was cloned in combination with the modified acyl carrier protein (ACP) fluorescent tag ACP mini (ACPm) and the putative immunogen VacJ. The chimeric construct was inserted in the pMK-express vector, subsequently transformed into A. pleuropneumoniae for expression. Flow cytometry, fluorescence imaging and mass spectrometry analysis were employed to demonstrate that the outer membrane of the transformed strain was enriched with the chimeric ApfAs-ACPm-VacJ antigen. Our results confirmed correct positioning of the chimeric ApfAs-ACPm-VacJ antigen and supported this system's potential as platform technology enabling antigenic enrichment of the outer membrane of A. pleuropneumoniae.

8.
BMC Fam Pract ; 21(1): 234, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33203365

RESUMO

BACKGROUND: Meta-analyses suggest that collaborative care (CC) improves symptoms of depression and anxiety. In CC, a care manager collaborates with a general practitioner (GP) to provide evidence-based care. Most CC research is from the US, focusing on depression. As research results may not transfer to other settings, we developed and tested a Danish CC-model (the Collabri-model) for depression, panic disorder, generalized anxiety disorder, and social anxiety disorder in general practice. METHODS: Four cluster-randomized superiority trials evaluated the effects of CC. The overall aim was to explore if CC significantly improved depression and anxiety symptoms compared to treatment-as-usual at 6-months' follow-up. The Collabri-model was founded on a multi-professional collaboration between a team of mental-health specialists (psychiatrists and care managers) and GPs. In collaboration with GPs, care managers provided treatment according to a structured plan, including regular reassessments and follow-up. Treatment modalities (cognitive behavioral therapy, psychoeducation, and medication) were offered based on stepped care algorithms. Face-to-face meetings between GPs and care managers took place regularly, and a psychiatrist provided supervision. The control group received treatment-as-usual. Primary outcomes were symptoms of depression (BDI-II) and anxiety (BAI) at 6-months' follow-up. The incremental cost-effectiveness ratio (ICER) was estimated based on 6-months' follow-up. RESULTS: Despite various attempts to improve inclusion rates, the necessary number of participants was not recruited. Seven hundred thirty-one participants were included: 325 in the depression trial and 406 in the anxiety trials. The Collabri-model was implemented, demonstrating good fidelity to core model elements. In favor of CC, we found a statistically significant difference between depression scores at 6-months' follow-up in the depression trial. The difference was not significant at 15-months' follow-up. The anxiety trials were pooled for data analysis due to inadequate sample sizes. At 6- and 15-months' follow-up, there was a difference in anxiety symptoms favoring CC. These differences were not statistically significant. The ICER was 58,280 Euro per QALY. CONCLUSIONS: At 6 months, a significant difference between groups was found in the depression trial, but not in the pooled anxiety trial. However, these results should be cautiously interpreted as there is a risk of selection bias and lacking statistical power. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02678624 and NCT02678845 . Retrospectively registered on 7 February 2016.

9.
Sci Rep ; 10(1): 16993, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046750

RESUMO

Enteric redmouth disease caused by the bacterial pathogen Yersinia ruckeri is the main reason for antimicrobial prescription, and a cause of substantial economic losses and decreased animal welfare in aquaculture. Given the importance of the intestinal microbiota in digestion and disease, our aim was to investigate whether synbiotic feed supplementation strategies could improve feed performance and disease resistance. Four experimental synbiotic feeds formulated with pre- and probiotics were tested against a commercially available probiotic control feed. Each experimental feed was evaluated for feed performance, effects on gross as well as intestinal morphometrics, and finally their effect on resistance against a waterborne experimental infection with Yersinia ruckeri serotype O1, biotype 2. While co-supplementing Pediococcus acidilactici with citrus flavonoids or bacterial paraprobiotics significantly improved utilization of feed lipid content relative to the control group, a decrease in lipid utilization was observed for feeds that combined P. acidilactici with yeast paraprobiotics. No significant improvements on disease resistance were observed. Still, synbiotic formulations including P. acidilactici led to reduced risks relative to that of the control group, while an increased relative risk was observed for a Bacillus-based formulation. In conclusion, two of the synbiotic supplements significantly improved lipid utilization and contributed to minor increases in disease resistance.

10.
Accid Anal Prev ; 147: 105773, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947176

RESUMO

Road accidents are one of the leading causes of death and injuries among adolescents and young adults. Road safety education programs aim to promote safe traffic behavior through information, skills training or fear appeals. During the last decade, an intervention type using victim testimonials has been developed. These types of programs aim to promote road safety by connecting a personal narrative of choices and consequences to the beliefs and behaviors of the audience. Studies on the effectiveness of this type of road safety programs among youngsters who are not yet drivers are still limited. This study used a cluster-randomized and controlled trial design to examine the effect of a Danish school-based road safety educational program using testimonials for students in lower secondary schools in Denmark on a) knowledge of risks factors in traffic and b) two types of behavior specifically relevant for the pre-driver target group: seatbelt use and safe bicycle behavior. Our analysis sample comprised 1007 students from 57 schools with a matched baseline and four-month follow-up response. Linear regression analyses suggest a small positive effect on the students' knowledge of the three most important risk factors in traffic but not on the age group most at risk. Concerning seatbelt use or overall cycling behavior no effect was found, although a small positive effect was found on helmet use. Neither was the effectiveness modified by gender, parental educational background, or risky cycling behavior at baseline. Although classroom-based interventions using testimonials may have the potential to increase knowledge of risk factors in traffic among adolescents, translating knowledge into safe traffic behavior is challenging. More studies are needed on how to further adapt the intervention to an age group who are not yet drivers. Such research may focus on mechanisms of change including the age-specific relevance of the ambassador's testimonial and on employing strong elements of action guidance.

11.
Toxins (Basel) ; 12(9)2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825511

RESUMO

The RTX toxin GtxA expressed by Gallibacterium anatis biovar haemolytica has been proposed a major virulence factor during disease manifestations in the natural host, the chicken. To better understand the role of GtxA in the pathogenesis of G. anatis, we compared the GtxA expressing wildtype strain with its isogenic ∆gtxA mutant that was unable to express GtxA during exposure to chicken macrophage-like HD11 cells. From adhesion and invasion assays, we showed that GtxA appears to promote adhesion and invasion of HD11 cells. By using quantitative RT-PCR, we also demonstrated that the G. anatis expressing GtxA induced a mainly anti-inflammatory (IL-10) host cell response as opposed to the pro-inflammatory (IL-1ß, IL-6 and TNF-α) response induced by the GtxA deletion mutant. Interestingly, these results, at least partly, resemble recent responses observed from spleen tissue of chickens infected with the same two bacterial strains. The effect of the GtxA toxin on the type of cell death was less clear. While GtxA clearly induced cell death, our efforts to characterize whether this was due to primarily necrosis or apoptosis through expression analysis of a broad range of apoptosis genes did not reveal clear answers.

12.
Poult Sci ; 99(1): 119-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32416793

RESUMO

Apperantly healthy laying hens at the end of production (60 to 91 wk) were investigated for the occurrence of pathology and bacterial infections. In total, 7,477 hens from 15 flocks representing the following production systems: Enriched cages, barn housed layers, and organic/free range layers were necropsied. Indications of bacterial infection were investigated by bacteriological cultivation. The overall prevalence of lesions was 16.60%, including lesions of both infectious and non-infectious origin. The most prevalent lesions were bursitis presternalis (6.65%), reproductive tract lesions (e.g., salpingitis and/or peritonitis and/or oophoritis) (3.50%), serosal scarification (e.g., fibrotic adhesive peritonitis) 1.55%, and neoplasm 1.73%. Significant differences were observed between different production systems and/or flocks in the prevalence of reproductive tract lesions, bursitis presternalis, serosal scarification, skin infections, juvenile hens, and traumas/fractures. No significant difference was observed between different production systems in the prevalence of neoplasia, infection of septicemic etiology, and pododermatitis. In total, 3.4% of the hens were out of lay, with significantly higher rate in organic flocks. Infections of the reproductive tract were the most prevalent lesions with bacterial etiology in all productions systems. In total, 40% of the hens with lesions associated to the oviduct were out of lay and significant difference between production systems were observed. Escherichia coli was the most commonly isolated bacteria and in 90% of the cases they were isolated from the reproductive tract lesions. The second most prevalent bacteria was Gallibacteruim anatis. Significant difference in the prevalence of E. coli positive hens was observed between production systems (P < 0.05). In conclusion, the prevalence of reproductive tract lesions in apparently healthy end-of-lay laying was higher than indicated in previous reports. These findings support the previous suggestions that E. coli and G. anatis are the major pathogens causing reproductive tract lesions.

13.
PeerJ ; 8: e8706, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32181057

RESUMO

Whether through direct supplementation of bacteria or by prebiotic supplementation thought to favour subsets of bacteria, modulation of gut microbiota constitutes an important and promising alternative to the use of prophylactic and growth promoting antibiotics in worldwide aquaculture. We fed a commercial base feed, alone or supplemented with either proprietary ß-glucan, ß-glucan and organic acids, citrus flavonoid or yeast cell wall supplements, to rainbow trout over a period of four weeks. Fish from each feed group were then subjected to experimental, waterborne infection with Yersinia ruckeri O1 biotype 2. Following experimental feeding, the ß-glucan and organic acids supplemented group showed significantly improved feed conversion and lipid efficiency ratios. Furthermore, the ß-glucan, ß-glucan and organic acids and citrus flavonoid supplements proved to significantly reduce the risk of mortality in rainbow trout during experimental infection as shown by hazard ratio analysis. Resulting in 33.2%, 30.6% and 30.5% reduction in risk relative to the non-supplemented base feed, respectively, these three supplements show a promising potential either as stand-alone feed supplements, or as components in complex feed formulations.

14.
Vet Res ; 51(1): 40, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32156313

RESUMO

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.


Assuntos
Proteínas de Bactérias/genética , Galinhas , Infecções por Pasteurellaceae/veterinária , Pasteurellaceae/patogenicidade , Doenças das Aves Domésticas/microbiologia , Fatores de Virulência/genética , Animais , Proteínas de Bactérias/metabolismo , Feminino , Pasteurellaceae/genética , Pasteurellaceae/fisiologia , Infecções por Pasteurellaceae/microbiologia , Fatores de Virulência/metabolismo
15.
Vaccines (Basel) ; 8(1)2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32106599

RESUMO

Protection facilitated by the widespread use of mineral oil adjuvanted injection vaccines in salmonid fish comes with adverse effects of varying severity. In this study, we characterized the immunological profiles of two alternative vaccine formulations, both with proven efficacy and an improved safety profile in rainbow trout. Experimental injection vaccines were prepared on an identical whole-cell Aeromonas salmonicida bacterin platform and were formulated with CpG oligodeoxynucleotides, a liposomal (CAF01) or a benchmark mineral oil adjuvant, respectively. A naïve group, as well as bacterin and saline-injected groups were also included. Following administration, antigen-specific serum antibody titers, the tissue distribution of immune cell markers, and the expression of immune-relevant genes following the in vitro antigenic restimulation of anterior kidney leukocytes was investigated. Immunohistochemical staining suggested prolonged antigen presentation for the particulate formulations and increased mucosal presence of antigen-presenting cells in all immunized fish. Unlike the other immunized groups, the CAF01 group only displayed a transient elevation in specific antibody titers and immunohistochemical observations, and the transcription data suggest an increased role of cell-mediated immunity for this group. Finally, the transcription profile of the CpG formulation approached that of a TH1 profile. When compared to the benchmark formulation, CAF01 and CpG adjuvants induce slight, but distinct differences in the resulting protective immune responses. This is important, as it allows a broader immunological approach for the future development of safer vaccines.

16.
Vaccines (Basel) ; 8(1)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979285

RESUMO

Gallibacterium anatis is a Gram-negative opportunistic avian pathogen representing an emerging threat to poultry meat and egg production worldwide. To date, no vaccine able to effectively prevent the morbidity associated with G. anatis infections has been developed yet. Our group previously reported that inoculation of different combinations of G. anatis outer membrane vesicles (OMVs), FlfA and GtxA-N proteins is effective in preventing lesions caused by G. anatis infections in layer chickens. Here we report the testing of the efficacy as vaccine prototypes of G. anatis OMVs isolated by hydrostatic filtration, a simple technique that allows the cost-effective isolation of high yields of OMVs. Layer chickens were immunized with OMVs alone or in combination with FlfA and/or GtxA-N proteins. Subsequent challenge with a heterologous G. anatis strain showed that immunization with OMVs alone could significantly reduce the lesions following a G. anatis infection. A second study was carried out to characterize the dose-response (0.25, 2.5 and 25 µg) relationship of G. anatis OMVs as immunogens, showing that 2.5 µg of OMVs represent the optimal dose to elicit protection in the immunized animals after a similar challenge. Additionally, administration of ≥2.5 µg of G. anatis OMVs induced specific IgY titers and possibly vertical transfer of immunity.

18.
Endocr Connect ; 9(1): 34-43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31829966

RESUMO

Objectives: Klinefelter syndrome (KS), 47,XXY, can be viewed as a disease model for investigating the risk of thrombosis in male hypogonadism and the subsequent risk related to testosterone treatment. We describe rates of thrombotic risk factors, thrombosis and thrombosis mortality in KS and the association with testosterone treatment. Methods: National registry-based matched cohort study with follow-up from 1995 to 2016 set in Denmark. For the study, 1155 men with KS were each matched by year and month of birth to 100 men from the background population. First thrombotic events and thrombosis mortality was evaluated by event rates and hazard ratios (HRs) and by applying testosterone treatment as a time-dependent covariate. Results: The KS cohort had higher incidence of venous thromboembolism relative to the comparison cohort (HR, 3.95; 95% CI, 2.83-5.52). Total thrombotic deaths were increased in KS (HR, 1.76; 95% CI, 1.18-2.62), and all-cause mortality was increased in KS following arterial thrombosis (HR 1.73; 95% CI 1.22-2.47). Only 48.7% of men with KS redeemed prescriptions for testosterone. Untreated men with KS were on average born 12 years before those treated, and the majority of untreated men with KS with available biochemistry were hypogonadal. Testosterone treatment in KS was associated with a non-significant decrease in venous thromboembolism and thrombotic deaths. Conclusion: Thrombosis and thrombotic deaths are increased in KS. Only half of the men with KS ever received testosterone treatment, despite overt hypogonadism in the non-treated. Testosterone treatment in Klinefelter syndrome was insignificantly associated with lower incidence rates of venous thrombosis and thrombotic deaths.

19.
NPJ Breast Cancer ; 5: 38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31700994

RESUMO

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.

20.
Int J Surg ; 72: 47-54, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639454

RESUMO

BACKGROUND: Laparoscopic surgery has become increasingly popular in treating perforated peptic ulcer (PPU). However, currently it is not recognized as a prognostic factor for mortality within this group of patients. The aim of this study was to investigate whether laparoscopic surgery was an independent mortality risk factor in patients treated surgically for perforated peptic ulcer. MATERIALS AND METHODS: This was a Danish nationwide cohort study based on prospectively collected data of 1008 patients treated surgically for PPU between September 2011 and December 2015. A propensity score matching analysis, considering most of the known prognostic factors for mortality and baseline characteristics, was used to adjust mortality estimates in patients treated with open and laparoscopic surgery. The primary outcome was postoperative 30-day mortality. RESULTS: The study population comprised 1008 patients; 507 were treated laparoscopically and 501 by open surgery. There was significantly higher mean age, and higher ASA scores, as well as other mortality risk factors in the open surgery group. The unadjusted 30-day mortality was significantly lower in patients undergoing laparoscopic surgery compared to open surgery (HR = 0.48, 95% CI: 0.36-0.65). After matching and weighting controls, the adjusted difference in mortality was reduced and was not significant (HR = 0.82, 95% CI: 0.59-1.15). The 30-day mortality was 13.1% for laparoscopy and 14.7% for the matched controls in the open surgery group. CONCLUSIONS: Compared to open surgery, laparoscopic surgery in patients with PPU does not reduce short term mortality. More well powered randomized clinical trials are needed to investigate the role of laparoscopic surgery in treatment of patients with PPU.


Assuntos
Laparoscopia/mortalidade , Úlcera Péptica Perfurada/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Perfurada/mortalidade , Complicações Pós-Operatórias/mortalidade , Prognóstico , Pontuação de Propensão , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
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