| 1. |
- Bai, Xiangning, et al.
(författare)
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Comparative Genomics of Shiga Toxin-Producing Escherichia coli Strains Isolated from Pediatric Patients with and without Hemolytic Uremic Syndrome from 2000 to 2016 in Finland
- 2022
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Shiga toxin-producing Escherichia coli (STEC) is a serious public health burden worldwide which causes outbreaks of gastrointestinal diseases and the fatal hemolytic uremic syndrome (HUS) characterized by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal failure. Understanding the mechanism underlying the disease severity and patient outcome is of high importance. Shiga toxin-producing Escherichia coli (STEC) infection can cause mild to severe illness, such as nonbloody or bloody diarrhea, and the fatal hemolytic uremic syndrome (HUS). The molecular mechanism underlying the variable pathogenicity of STEC infection is not fully defined so far. Here, we performed a comparative genomics study on a large collection of clinical STEC strains collected from STEC-infected pediatric patients with and without HUS in Finland over a 16-year period, aiming to identify the bacterial genetic factors that can predict the risk to cause HUS and poor renal outcome. Of 240 STEC strains included in this study, 52 (21.7%) were from pediatric patients with HUS. Serotype O157:H7 was the main cause of HUS, and Shiga toxin gene subtype stx2a was significantly associated with HUS. Comparative genomics and pangenome-wide association studies identified a number of virulence and accessory genes overrepresented in HUS-associated STEC compared to non-HUS STEC strains, including genes encoding cytolethal distending toxins, type III secretion system effectors, adherence factors, etc. No virulence or accessory gene was significantly associated with risk factors for poor renal outcome among HUS patients assessed in this study, including need for and duration of dialysis, presence and duration of anuria, and leukocyte counts. Whole-genome phylogeny and multiple-correspondence analysis of pangenomes could not separate HUS STEC from non-HUS STEC strains, suggesting that STEC strains with diverse genetic backgrounds may independently acquire genetic elements that determine their varied pathogenicity. Our findings indicate that nonbacterial factors, i.e., characteristics of the host immunity, might affect STEC virulence and clinical outcomes. IMPORTANCE Shiga toxin-producing Escherichia coli (STEC) is a serious public health burden worldwide which causes outbreaks of gastrointestinal diseases and the fatal hemolytic uremic syndrome (HUS) characterized by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal failure. Understanding the mechanism underlying the disease severity and patient outcome is of high importance. Using comparative genomics on a large collection of clinical STEC strains from STEC-infected patients with and without HUS, our study provides a reference of STEC genetic factors/variants that can be used as predictors of the development of HUS, which will aid risk assessment at the early stage of STEC infection. Additionally, our findings suggest that nonbacterial factors may play a primary role in the renal outcome in STEC-infected patients with HUS; further studies are needed to validate this.
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| 2. |
- Hassan, Jasmin, et al.
(författare)
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Reference standards for follicular density in ovarian cortex from birth to sexual maturity
- 2023
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Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 47:4
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Tidskriftsartikel (refereegranskat)abstract
- Research question: Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation?Design: Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1-24 years, mean +/- SD 11 +/- 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values.Results: No difference was observed between Z-scores in samples from untreated patients (0.3 +/- 3.5, n = 30) and patients treated with (0.5 +/- 2.9, n = 48) and without (0.1 +/- 1.3, n = 6) alkylating chemotherapy. Z-scores were not correlated with increasing cumulative exposure to cytostatics. Nevertheless, Z-scores in young treated patients (0-2 years -2.1 +/- 3.1, n = 10, P = 0.04) were significantly lower than Z-scores in older treated patients (11-19 years, 2 +/- 1.9, n = 15). Samples from patients with Turner syndrome differed significantly from samples from untreated patients (-5.2 +/- 5.1, n = 24, P = 0.003), and a Z-score of -1.7 was identified as a cut-off showing good diagnostic value for identification of patients with Turner syndrome with reduced ovarian reserve. When this cut-off was applied to other patients, analysis showed that those with indications for reduced ovarian reserve (n = 15) were significantly younger (5.9 +/- 4.2 versus 10.7 +/- 5.9 years, P = 0.004) and, when untreated, more often had non-malignant haematologic diseases compared with those with normal ovarian reserve (n = 24, 100% versus 19%, P = 0.009).Conclusion: Z-scores allow the estimation of genetic- and treatment-related effects on follicular density in cortical tissue from young patients stored for fertility preservation. Understanding the quality of cryopreserved tissue facilitates its use during patient counselling. More research is needed regarding the cytostatic effects found in this study.
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| 3. |
- Rodriguez, Patricia Q., et al.
(författare)
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Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Podocytes are critical for the maintenance of kidney ultrafiltration barrier and play a key role in the progression of glomerular diseases. Although mediator complex proteins have been shown to be important for many physiological and pathological processes, their role in kidney tissue has not been studied. In this study, we identified a mediator complex protein 22 (Med22) as a renal podocyte cell-enriched molecule. Podocyte-specific Med22 knockout mouse showed that Med22 was not needed for normal podocyte maturation. However, it was critical for the maintenance of podocyte health as the mice developed progressive glomerular disease and died due to renal failure. Detailed morphological analyses showed that Med22-deficiency in podocytes resulted in intracellular vacuole formation followed by podocyte loss. Moreover, Med22-deficiency in younger mice promoted the progression of glomerular disease, suggesting Med22-mediated processes may have a role in the development of glomerulopathies. This study shows for the first time that mediator complex has a critical role in kidney physiology.
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| 4. |
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| 5. |
- Visuri, Sofia, et al.
(författare)
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Postnatal imaging of prenatally detected hydronephrosis - when is voiding cystourethrogram necessary?
- 2018
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Ingår i: Pediatric nephrology (Berlin, West). - : SPRINGER. - 0931-041X .- 1432-198X. ; 33:10, s. 1751-1757
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate whether grade 4-5 vesicoureteral reflux (VUR) can be predicted from renal ultrasound (RUS) findings and perform voiding cystourethrograms (VCUGs) only on high-risk patients.Methods: The RUS and VCUG images of infants with prenatally detected hydronephrosis admitted to our institution between 2003 and 2013 were re-evaluated. The UTI episodes were collected retrospectively from patient journals. Patients with complex urinary tract anomalies were excluded.Results: One hundred eighty, 44 female and 136 male, patients (352 renal units (RU)), 23 (30 RU) of them having grade 4-5 VUR, were included. The median age of the patients at the time of the RUS was 1.3 (0.1-3.0) months and the median follow-up time was 2.0 (0.1-11.2) years. In multivariate analysis, a visible ureter (OR 12.72; CI 5.33-32.04, p < 0.001) and shorter renal length (OR 2.67; CR 1.504.86, p < 0.001) in RUS predicted grade 4-5 VUR while a visible ureter predicted UTIs (OR 5.75; CI 2.59-12.66, p < 0.001). A three-grade risk score for high-grade VUR was developed based on the RUS findings and the patients were categorized into low-, intermediate-, and high-risk groups. The incidence of grade 4-5 VUR was 2.9% in the low-risk, 12.2% in the intermediaterisk, and 52.2% in the high-risk group. The sensitivity and specificity for detecting grade 4-5 VUR were 79 and 82%, respectively.Conclusions: In patients with antenatally detected hydronephrosis, a visible ureter and reduced renal length in RUS are significant risk factors for high-grade VUR. A RUS-based risk scoring would probably reduce the proportion of unnecessary VCUGs.
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| 6. |
- Visuri, Sofia, et al.
(författare)
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Reduced differential renal function in scintigraphy predicted high-grade vesicoureteral reflux in children with antenatal hydronephrosiss
- 2019
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Ingår i: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 108:4, s. 751-756
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Tidskriftsartikel (refereegranskat)abstract
- Aim: A top-down approach is widely used for detecting vesicoureteral reflux (VUR) in children with febrile urinary tract infections. We evaluated the diagnostic value of renal scintigraphy in predicting VUR in children with antenatal hydronephrosis (AHN).Methods: The voiding cystourethrogram (VCUG) and renal scintigraphy results of 125 AHN patients (76% male) admitted to the Children's Hospital of Helsinki University, Finland, from 2003 to 2013 were analysed. Of those, 94 had nonrefluxing hydronephrosis, nine had low-grade VUR and 22 had high-grade VUR.Results: Scintigraphy was performed at a median age of 1.4 (0.8-15.6) months. In patients with high-grade VUR, the differential renal function (DRF) of the worse kidney was significantly lower than in patients without VUR, with a median of 35% and interquartile range (IQR) of 20-45 versus 47% (IQR: 44-49), (p < 0.001). There was no difference between patients with low-grade VUR and patients without VUR (p = 0.181). DRFs below 44% showed a sensitivity of 73% and specificity of 79% and predicted significantly high-grade VUR (odds ratio 9.82, 95% confidence interval 3.44-28.05, p < 0.001) in the univariate analysis.Conclusion: A DRF below 44% predicted high-grade VUR in patients with AHN and supported the decision to perform VCUG.
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