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Urinary tract infection is a common disease in pigs and a major reason for sows to be culled. The disease, however, is difficult to diagnose due to lack of distinct clinical signs in the animals. We evaluated the diagnostic value of two commercial urine dipstick tests in 10 pigs using an experimental model of Escherichia coli urinary tract infection. Urine collected at baseline and 48 h after inoculation were analyzed. We show that dipstick tests positive of blood, leucocytes and particularly nitrite are very specific for E. coli UTI with a 100% positive predictive value.

We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy. Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration. All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. Vancomycin and rifampicin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log10 CFU/mL, p = 0.0016). The addition of tPA to vancomycin and rifampicin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log10 CFU/mL, p = 0.26). The cure rate was 16% in the vancomycin + rifampicin group vs. 37.5% cure rate in the vancomycin + rifampicin + tPA group. Whilst interesting, this trend was not significant at our sample size (p = 0.24). We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.

Background Prosthetic joint infections (PJI) are recalcitrant, hard-to-treat infections and severe complications of joint arthroplasty. Therefore, there is a need to develop new effective treatment strategies, and animal models of high clinical relevance are needed. This study aimed to develop a detailed surgical protocol for hip hemiarthroplasty in Göttingen minipigs and a thorough post-mortem sampling protocol to pave the way for creating a minipig PJI model. Methods Three adult female Göttingen minipigs underwent surgery with insertion of a hip hemiarthroplasty, using the anterior approach to the hip joint. After surgery the minipigs were followed closely with daily clinical evaluation and gait scoring. Comprehensive post-mortem analyses were performed with evaluation of macroscopic lesions, microbiology, synovial fluid analysis and histology. Results The study resulted in the first Göttingen minipig with hip hemiarthroplasty and identified several points of awareness when inserting a hip prosthesis in minipigs, especially the high risk of joint dislocation. A spontaneous PJI occurred in one of the minipigs, revealing an impaired ability of the immune cells to reach the bacteria at the bone-prosthesis interface. Conclusion The present study provides a detailed description of surgical technique and post-mortem sampling and validates the suitability of the hip hemiarthroplasty minipig model for future experimental modeling of PJI.

Objective The objective of this study is to characterize bladder mucosal trauma associated with intermittent catheterization with conventional eyelet catheters (CECs) and to assess if a microhole zone catheter (MHZC) design concept reduces this adverse effect. Materials and Methods A porcine model was developed to reflect human catheterization and bladder drainage. Nine pigs were randomized for catheterization with CEC (n = 6) or MHZC (n = 3). The bladder was drained repeatedly 20 times through the catheter. Cystoscopy was performed before and after the procedure, and bladders were analysed by histopathology. Two additional pigs were used for cystoscopy visualization of suction events in vivo. Cystoscopy, gross pathology, histopathological score, leucocyte infiltration, and intracatheter pressure at flow stops during voiding were compared for each group. Results A significant higher pressure gradient was measured inside the CECs compared with MHZCs during flow stop. Consequently, CECs resulted in suction events inflicting bladder trauma characterized by loss of epithelium, oedema, haemorrhage, and neutrophil tissue infiltration. No significant trauma was identified when using MHZC. Conclusions Considerable mucosal bladder trauma is inflicted by CECs which may be an overlooked risk factor for urinary tract infection. Catheters can be designed to minimize mucosal suction and reduce associated trauma. This may be a solution to reduce infection frequency and increase user comfort. Furthermore, the study demonstrates the potential of pigs as an attractive animal model for investigating urinary catheter performances.

We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy. Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log.sup.10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration. All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log.sup.10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.

We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy. Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log.sup.10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration. All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log.sup.10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.

Prosthetic joint infections (PJI) are recalcitrant, hard-to-treat infections and severe complications of joint arthroplasty. Therefore, there is a need to develop new effective treatment strategies, and animal models of high clinical relevance are needed. This study aimed to develop a detailed surgical protocol for hip hemiarthroplasty in Göttingen minipigs and a thorough post-mortem sampling protocol to pave the way for creating a minipig PJI model. Three adult female Göttingen minipigs underwent surgery with insertion of a hip hemiarthroplasty, using the anterior approach to the hip joint. After surgery the minipigs were followed closely with daily clinical evaluation and gait scoring. Comprehensive post-mortem analyses were performed with evaluation of macroscopic lesions, microbiology, synovial fluid analysis and histology. The study resulted in the first Göttingen minipig with hip hemiarthroplasty and identified several points of awareness when inserting a hip prosthesis in minipigs, especially the high risk of joint dislocation. A spontaneous PJI occurred in one of the minipigs, revealing an impaired ability of the immune cells to reach the bacteria at the bone-prosthesis interface. The present study provides a detailed description of surgical technique and post-mortem sampling and validates the suitability of the hip hemiarthroplasty minipig model for future experimental modeling of PJI.

Background Lung emphysema is a central feature of chronic obstructive pulmonary disease (COPD), a frequent human disease worldwide. Cigarette smoking is the major cause of COPD, but genetic predisposition seems to be an important factor. Mutations in surfactant protein genes have been linked to COPD phenotypes in humans. Also, the catalytic activities of metalloproteinases (MMPs) are central in the pathogenesis of emphysema/COPD. Especially MMP9, but also MMP2, MMP7, and MMP12 seem to be involved in human emphysema. MMP12 − / − mice are protected from smoke-induced emphysema. ITGB6 − / − mice spontaneously develop age-related lung emphysema due to lack of ITGB6-TGF-β1 regulation of the MMP12 expression. Methods A mutated pig phenotype characterized by age-related lung emphysema and resembling the ITGB6 − / − mouse has been described previously. To investigate the emphysema pathogenesis in this pig model, we examined the expression of MMP2, MMP7, MMP9, MMP12, and TGF-β1 by quantitative PCR (qPCR). In addition, immunohistochemical stainings of the lungs with SP-B, SP-C, MMP9, and MMP12 antibodies were performed. The haematologic/immunologic status of the pigs also was studied. Results The qPCR study showed no difference between pigs with and without emphysema, and no systemic differences were indicated by the haematologic and immunologic studies. However, the immunohistochemical stainings showed an increased expression of MMP9 and MMP12 in older, mutated pigs (with emphysema) compared with normal and young mutated pigs (without emphysema). Conclusions The pig model is comparable to human emphysema patients and the ITGB6 − / − mouse model with respect to both morphology and functionality.

Lung emphysema is a central feature of chronic obstructive pulmonary disease (COPD), a frequent human disease worldwide. Cigarette smoking is the major cause of COPD, but genetic predisposition seems to be an important factor. Mutations in surfactant protein genes have been linked to COPD phenotypes in humans. Also, the catalytic activities of metalloproteinases (MMPs) are central in the pathogenesis of emphysema/COPD. Especially MMP9, but also MMP2, MMP7, and MMP12 seem to be involved in human emphysema. MMP12-/- mice are protected from smoke-induced emphysema. ITGB6-/- mice spontaneously develop age-related lung emphysema due to lack of ITGB6-TGF-β1 regulation of the MMP12 expression. A mutated pig phenotype characterized by age-related lung emphysema and resembling the ITGB6-/- mouse has been described previously. To investigate the emphysema pathogenesis in this pig model, we examined the expression of MMP2, MMP7, MMP9, MMP12, and TGF-β1 by quantitative PCR (qPCR). In addition, immunohistochemical stainings of the lungs with SP-B, SP-C, MMP9, and MMP12 antibodies were performed. The haematologic/immunologic status of the pigs also was studied. The qPCR study showed no difference between pigs with and without emphysema, and no systemic differences were indicated by the haematologic and immunologic studies. However, the immunohistochemical stainings showed an increased expression of MMP9 and MMP12 in older, mutated pigs (with emphysema) compared with normal and young mutated pigs (without emphysema). The pig model is comparable to human emphysema patients and the ITGB6-/- mouse model with respect to both morphology and functionality.

Background Reports of dual carriers of pathogenic BRCA1 variants in trans are extremely rare, and so far, most individuals have been associated with a Fanconi Anemia-like phenotype. Methods We identified two families with a BRCA1 in-frame exon 20 duplication (Ex20dup). In one male individual, the variant was in trans with the BRCA1 frameshift variant c.2475delC p.(Asp825Glufs*21). We performed splicing analysis and used a transcription activation domain (TAD) assay to assess the functional impact of Ex20dup. We collected pedigrees and mapped the breakpoints of the duplication by long- and short-read genome sequencing. In addition, we performed a mitomycin C (MMC) assay from the dual carrier using cultured lymphoblastoid cells. Results Genome sequencing and RNA analysis revealed the BRCA1 exon 20 duplication to be in tandem. The duplication was expressed without skipping any one of the two exon 20 copies, resulting in a lack of wild-type transcripts from this allele. TAD assay indicated that the Ex20dup variant has a functional level similar to the well-known moderate penetrant pathogenic BRCA1 variant c.5096G > A p.(Arg1699Gln). MMC assay of the dual carrier indicated a slightly impaired chromosomal repair ability. Conclusions This is the first reported case where two BRCA1 variants with demonstrated functional impact are identified in trans in a male patient with an apparently normal clinical phenotype and no BRCA1- associated cancer. The results pinpoint a minimum necessary BRCA1 protein activity to avoid a Fanconi Anemia-like phenotype in compound heterozygous status and yet still predispose carriers to hormone-related cancers. These findings urge caution when counseling families regarding potential Fanconi Anemia risk. Furthermore, prudence should be taken when classifying individual variants as benign based on co-occurrence in trans with well-established pathogenic variants.