Multilocus variable number tandem repeat analysis as a tool to discern genetic relationships among strains of Yersinia enterocolitica biovar 1A

Aims: To identify variable number tandem repeat (VNTR)-containing loci, and to use multilocus VNTR (MLVA) to discern genetic relationships among strains of Yersinia enterocolitica biovar 1A isolated from diverse sources. Methods and Results: The whole genome sequence of Y. enterocolitica 8081 was analysed and eight VNTR loci with repeat sizes between 4 and 9 bp, and each containing more than four repeat copies were selected for MLVA typing of 88 strains of Y. enterocolitica. Of these, four loci were polymorphic and generated 26 MLVA genotypes among 81 strains of Y. enterocolitica biovar 1A. MLVA was found to be quite discriminatory (DI=0.87). Cluster analysis and population modelling using minimum spanning tree (MST) clearly clustered Y. enterocolitica biovar 1A into two major groups. Conclusions: The MLVA is easy to perform and can be used to discern clonal relationship among strains of Y. enterocolitica. Also the phylogenetic relationships obtained with MLVA genotypes were in good agreement with those established by other typing methods. Significance and Impact of the Study: The MLVA method reported is relatively more discriminatory than the other genotyping methods and has the potential to be used as an epidemiological tool for the study of strains of Y. enterocolitica biovar 1A

Systemic lupus erythematosus and diffuse alveolar hemorrhage, etiology and novel treatment strategies.

Diffuse alveolar hemorrhage is a severe respiratory complication of systemic lupus erythematosus. The illness develops over hours to a few days and is the systemic lupus erythematosus-associated syndrome with highest mortality. Although no specific symptoms have been identified, a number of features are associated with diffuse alveolar hemorrhage, with a drop in blood hemoglobin the most prominent. Dyspnea, blood-stained sputum, diffuse infiltrates identified by chest imaging, elevated single breath-diffusing capacity for monoxide, thrombocytopenia and C3 hypocomplementemia are other commonly reported signs of diffuse alveolar hemorrhage. The etiology is not completely understood but many patients develop diffuse alveolar hemorrhage concomitant with lupus nephritis, suggesting immune complex-driven pathology. Biopsy studies have identified both cases with capillaritis and a bland non-inflammatory phenotype. An animal model of diffuse alveolar hemorrhage has indicated requirement of B lymphocytes and complement receptor-mediated apoptotic body phagocytosis by monocytes as part of the pathogenesis. This review will discuss considerations when diagnosing the condition and available therapies. Infections and other causes of hemorrhage have to be excluded as these require different treatment strategies. Methylprednisolone and cyclophosphamide remain the most commonly used therapies. Plasmapheresis and rituximab are other beneficial treatment options. A few studies have also considered intrapulmonary Factor VII therapy, extracorporeal membrane oxygenation and mesenchymal stem cell therapy. There is an unmet need of better definition of diffuse alveolar hemorrhages etiology and pathology for development of improved treatment strategies

The basic helix-loop-helix transcription factor TCF4 impacts brain architecture as well as neuronal morphology and differentiation

Germline mutations in the basic helix-loop-helix transcription factor 4 (TCF4) cause the Pitt–Hopkins syndrome (PTHS), a developmental disorder with severe intellectual disability. Here, we report findings from a new mouse model with a central nervous system-specific truncation of Tcf4 leading to severe phenotypic abnormalities. Furthermore, it allows the study of a complete TCF4 knockout in adult mice, circumventing early postnatal lethality of previously published mouse models. Our data suggest that a TCF4 truncation results in an impaired hippocampal architecture affecting both the dentate gyrus as well as the cornu ammonis. In the cerebral cortex, loss of TCF4 generates a severe differentiation delay of neural precursors. Furthermore, neuronal morphology was critically affected with shortened apical dendrites and significantly increased branching of dendrites. Our data provide novel information about the role of Tcf4 in brain development and may help to understand the mechanisms leading to intellectual deficits observed in patients suffering from PTHS

Performance characteristics of multiparametric-MRI at a non-academic hospital using transperineal template mapping biopsy as a reference standard

Objectives To evaluate diagnostic accuracy of mpMRI in a non-academic hospital using transperineal template prostate mapping (TPM) biopsy as a reference standard. Secondary objectives included evaluating why mpMRI missed significant cancer. Materials and methods 101 men received pre-biopsy mpMRI and TPM-biopsy over 16 months. Disease status was assigned at hemigland level. Primary histological definition of clinical significance was Gleason grade >/ = 4 + 3 or maximum cancer core length (MCCL) >/ = 6 mm. Positive mpMRI was defined as Prostate Imaging Reporting and Data System (PI-RADS) score >/ = 3. Results Median age 69 (IQR 62–76). Median PSA 7 ng/ml (IQR 4.6–9.8). mpMRI had sensitivity 76.9%, specificity 60.7%, PPV 40.4% and NPV 88.3% at primary definitions. For detecting any Gleason >/ = 7 mpMRI had sensitivity 73.2%, specificity 60.3%, PPV 41.4% and NPV 85.4%. Mean MCCL was lower where significant cancer was missed compared to those correctly identified (5.8 mm versus 7.7 mm respectively, p = 0.035). Conclusion mpMRI performance characteristics were very encouraging when compared to contemporary clinical trials. In a non-academic hospital setting, negative mpMRI was just as good at ruling-out significant disease, though the ability of positive mpMRI to accurately detect significant disease was lower. An mpMRI-guided diagnostic pathway should be accompanied by appropriate mpMRI protocol optimisation, training, and quality control

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

Spontaneous corneal melting in pregnancy: a case report

<p>Abstract</p> <p>Background</p> <p>To report a case of spontaneous corneal melting in pregnancy. We reviewed the literature on corneal melting and the effect of pregnancy on cornea and collagen containing tissues.</p> <p>Case presentation</p> <p>A 29-year-old woman who underwent radial keratotomy in both eyes followed by trabeculectomy in her left eye developed corneal melting in the same eye, in her seventh month of pregnancy. Despite screening, no infectious or immune mediated condition could be identified. She was managed conservatively with cyanoacrylate glue, bandage contact lens, lubricants and antibiotics.</p> <p>Conclusion</p> <p>It may not always be possible to find the underlying cause of corneal melting but the more common underlying causes should be ruled out by proper investigations. Pregnancy with its host of hormonal changes could potentially have some effect on corneal collagen leading to corneal melting in compromised corneas.</p